U.S. patent application number 14/071125 was filed with the patent office on 2014-02-27 for method and system for optimizing film production and minimizing film scrap.
This patent application is currently assigned to MONOSOL RX, LLC. The applicant listed for this patent is MonoSol Rx, LLC. Invention is credited to Beuford A. Bogue.
Application Number | 20140058550 14/071125 |
Document ID | / |
Family ID | 44354338 |
Filed Date | 2014-02-27 |
United States Patent
Application |
20140058550 |
Kind Code |
A1 |
Bogue; Beuford A. |
February 27, 2014 |
METHOD AND SYSTEM FOR OPTIMIZING FILM PRODUCTION AND MINIMIZING
FILM SCRAP
Abstract
The present invention relates to a method of optimizing
self-supporting film production which includes the steps of:
determining at least one scrap factor which relates to a total
amount of scrap in processing a film product; correlating the at
least one scrap factor to at least one processing parameter; and
adjusting the at least one processing parameter to reduce the total
amount of scrap in processing the film product.
Inventors: |
Bogue; Beuford A.; (New
Carlisle, IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
MonoSol Rx, LLC |
Warren |
NJ |
US |
|
|
Assignee: |
MONOSOL RX, LLC
Warren
NJ
|
Family ID: |
44354338 |
Appl. No.: |
14/071125 |
Filed: |
November 4, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12753152 |
Apr 2, 2010 |
8577488 |
|
|
14071125 |
|
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61303409 |
Feb 11, 2010 |
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Current U.S.
Class: |
700/103 |
Current CPC
Class: |
G05B 13/02 20130101;
B26D 5/00 20130101; B26D 2007/0068 20130101; G05B 15/00 20130101;
A61K 9/7007 20130101; Y10T 428/24405 20150115 |
Class at
Publication: |
700/103 |
International
Class: |
G05B 13/02 20060101
G05B013/02 |
Claims
1. A method of optimizing self-supporting film production
comprising the steps of: (a) determining at least one scrap factor
which relates to a total amount of scrap in processing a film
product; (b) correlating said at least one scrap factor to at least
one processing parameter; and (c) adjusting the at least one
processing parameter to reduce the total amount of scrap in
processing said film product.
2. The method of claim 1, wherein said scrap factor comprises a
scrap for mixing factor.
3. The method of claim 2, wherein said scrap for mixing factor
comprises scrap lost to hoses.
4. The method of claim 2, wherein said scrap for mixing comprises
scrap lost due to coating the mixer.
5. The method of claim 1, wherein said scrap factor comprises a
scrap for coating factor.
6. The method of claim 5, wherein said scrap for coating factor
comprises scrap for start-up of the film forming process.
7. The method of claim 5, wherein said scrap for coating factor
comprises scrap for shut-down of the film forming process.
8. The method of claim 5, wherein said scrap for coating factor
comprises scrap for drying.
9. The method of claim 8, wherein said scrap for drying comprises
scrap related to oven length.
10. The method of claim 1, wherein said scrap factor comprises a
scrap for slitting factor.
11. The method of claim 1, wherein said scrap factor comprises a
scrap for packaging factor.
12. The method of claim 1, further comprising the step of modifying
a processing parameter that relates to a plurality of said scrap
factors.
13. The method of claim 1, wherein the adjusting step further
comprises adjusting a tank size of said film processing.
14. The method of claim 1, wherein the adjusting step further
comprises adjusting a film sheet coating width.
15. The method of claim 1, wherein the adjusting step further
comprises minimizing a hose length from a control volume of mixed
material to a film sheet and construction area.
16. The method of claim 1, wherein the scrap that is reduced
comprises start-up scrap.
17. The method of claim 1, wherein the scrap that is reduced
comprises shut-down scrap.
18. The method of claim 1, wherein the adjusting step is completed
in line.
19. A system for optimizing self-supporting film production
comprising: (a) a film manufacturing apparatus, comprising a mixer,
a film former, and a cutting apparatus; and (b) a computer system
for compiling and processing data related to the film manufacturing
system and at least one product characteristic; wherein the
computer system is capable of controlling at least one processing
parameter to optimize a yield of film dosage product.
20. The system of claim 19, wherein the system is capable of
adjusting the processing parameters in real-time.
21. The system of claim 19, wherein the film manufacturing
apparatus is remotely adjustable.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present invention claims priority to U.S. Provisional
Application No. 61/303,409, filed Feb. 11, 2010, the contents of
which are incorporated by reference herein.
FIELD OF THE INVENTION
[0002] The present invention relates to maximizing the efficiency
and minimizing the cost of producing film that is dosed with agents
and medicaments. Specifically, the present invention relates to a
process and system for minimizing the waste of materials in the
processing of film doses.
BACKGROUND OF THE INVENTION
[0003] When film dosages are manufactured, especially
self-supporting film dosages, the film is generally formed into
individual doses. There is often scrap, either in liquid, mixed
form or in solid form, associated with the manufacturing and
processing steps. This scrap results in unusable and therefore
wasted material. When such wasted material includes precious
material such as active drugs and pharmaceuticals, this wasted
material can be extremely expensive. Current processes and
manufacturing designs employ systems that result in scrap in liquid
and/or solid form. Thus, the current processes and manufacturing
designs are inefficient and ultimately may cost a higher amount to
make individual dosage forms.
[0004] It is desirable to solve the present problems associated
with the art to yield a more efficient manufacturing process to
form individual film doses, especially those containing an active
component.
SUMMARY OF THE INVENTION
[0005] An aspect of the present invention includes a method of
optimizing self-supporting film production which includes the steps
of: determining at least one scrap factor which relates to a total
amount of scrap in processing a self-supporting film product;
correlating the at least one scrap factor to at least one
processing parameter; and adjusting the at least one processing
parameter to reduce the total amount of scrap in processing the
film product.
[0006] Another aspect of the present invention includes a system
for optimizing self-supporting film production which includes: a
self-supporting film manufacturing apparatus; including a mixer, a
film former, and a slitter; a processor for compiling and
processing data related to the self-supporting film manufacturing
system, and at least one process characteristic; wherein the
processor remotely controls at least one parameter to optimize a
yield of self-supporting film dosage product.
[0007] The various aspects of the present invention include
utilizing a computer system in conjunction with the film
manufacturing and processing equipment and apparatus in order to
determine one or more scrap factors, correlate a scrap factor to at
least one processing parameter, and adjust the processing
parameter, where the adjusting step may be prior to initializing
the production process, in-line with production, between runs, or
during various predetermined points in the process. As such, it is
possible to reduce the amount of scrap produced in the
manufacturing of the self-supporting film product, thereby
increasing efficiency in manufacturing as well as yield.
[0008] The present invention with its various embodiments may be
better understood through a study of the following figures and
description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 is a schematic view of an apparatus suitable for
preparation of a pre-mix, addition of an active, and subsequent
formation of the film.
[0010] FIG. 2 is a schematic view of an exemplary drying step for
the film sheet of the present invention.
[0011] FIG. 3 is a representation of a drying process of the
present invention.
[0012] FIG. 4 is a schematic view of the cutting process that may
be employed when the film sheet is reduced to individual doses for
packaging. An exemplary film sheet of film is shown as it goes
through the cutting steps.
[0013] FIG. 5 is a flow chart of a method for determining and
reducing the amount of scrap resulting from the processing of
ingestible film or sheet products.
[0014] FIG. 5A is a block diagram, which depicts a computer system,
which may be employed with the embodiments of the present
invention.
[0015] FIG. 6 is a chart of experimental data, which depicts the
trend between the coating lost to the hoses and tanks as a function
of the total batch size.
[0016] FIG. 7 is a chart depicting the % scrap associated with each
manufacturing step as a function of batch size.
[0017] FIG. 8 is a chart depicting the optimum coating width and
minimum scrap as a function of batch size.
[0018] FIG. 9 is a chart depicting the mixing scrap as a function
of coating width.
[0019] FIG. 10 is a chart depicting the coating scrap as a function
of coating width.
[0020] FIG. 11 is a chart depicting slitting scrap as a function of
coating width.
[0021] FIG. 12 is a chart depicting packaging scrap vs. coating
width as a function of batch size.
[0022] FIG. 13 is a chart depicting total scrap vs. coating width
as a function of batch size.
DETAILED DESCRIPTION OF THE DRAWINGS
[0023] Film systems embody a field of technology that has major
advantages in areas of administering drug, medicament, and various
other active and agent delivery systems to an individual in need
thereof. In order to provide a desirable final product which
exhibits advantageous characteristics and desirable properties, the
processing and manufacturing of film strips and film technology is
technologically demanding and cumbersome.
[0024] As used herein, the terms "pharmaceutical", "medicament",
"drug" and "active agent" may be used interchangeably, and refer to
a substance or composition useful for the prevention or treatment
of a condition. The terms may include pharmaceuticals,
neutraceuticals, cosmetic agents, biologic agents, bioeffective
substances, and the like.
[0025] It will be understood that the term "film" includes delivery
systems of any thickness, including films, sheets, discs, wafers,
and the like, in any shape, including rectangular, square, or other
desired shape. The film may be in the form of a continuous roll of
film or may be sized to a desired length and width. The films
described herein may be any desired thickness and size suitable for
the intended use. For example, a film of the present invention may
be sized such that it may be placed into the oral cavity of the
user. Other films may be sized for application to the skin of the
user, i.e., a topical use. For example, some films may have a
relatively thin thickness of from about 0.1 to about 10 mils, while
others may have a somewhat thicker thickness of from about 10 to
about 30 mils. For some films, especially those intended for
topical use, the thickness may be even larger, i.e., greater than
about 30 mils. In addition, the term "film" includes single-layer
compositions as well as multi-layer compositions, such as laminated
films, coatings on films and the like. The composition in its dried
film form maintains a uniform distribution of components through
the application of controlled drying of the film. Films may include
a pouch or region of medicament between two films.
[0026] In some embodiments of the invention, the films are intended
for oral administration. In other embodiments, the films are
intended for topical administration. As used herein, the term
"topical agent" is meant to encompass active agents that are
applied to a particular surface area. For example, in one
embodiment, a topical agent is applied to an area of the skin. In
other embodiments, the topical agent may also be applied to mucosal
areas of the body, such as the oral (e.g., buccal, sublingual,
tongue), vaginal, ocular and anal areas of the body. In other
embodiments, a topical agent is applied to a hard surface, such as
a particular surface area in need of treatment.
[0027] The medicament may be dispersed throughout the film, or it
may be deposited onto one or more surfaces of the film. In either
way, the amount of medicament per unit area is desirably uniform
throughout the film. It is desired that the films of the present
invention include a uniformity of component distribution throughout
the volume of a given film. Such uniformity includes a
substantially uniform amount of medicament per unit volume of the
film, whether the medicament is within the matrix of the film or
coated, laminated, or stabilized on one or more surfaces thereof.
When such films are cut into individual units, the amount of the
agent in the unit can be known with a great deal of accuracy.
[0028] Uniformity of medicament throughout the film is important in
administering an accurate and effective dose of medicament to a
user. Various methods of forming uniform films, as well as various
additives and fillers, may be used, including those methods and
materials described in U.S. Pat. Nos. 7,425,292 and 7,357,891 and
U.S. Publication No. 2005/0037055, which are herein incorporated by
reference in their entireties.
[0029] Some constituents of the film strip are very expensive, and
thus are desirably used sparingly. For example, active agents may
be extremely expensive, and thus waste of such materials is
preferably limited. A wide variety of medicaments, bioactive active
substances and pharmaceutical compositions may be included in the
dosage forms of the present invention. Such medicaments, bioactive
substances and pharmaceutical compositions may be useful as
topically-administered dosages or as orally-ingestible dosages.
[0030] Examples of useful drugs include ace-inhibitors, antianginal
drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics,
analgesics, anesthetics, anti-convulsants, anti-depressants,
anti-diabetic agents, anti-diarrhea preparations, antidotes,
anti-histamines, anti-hypertensive drugs, anti-inflammatory agents,
anti-lipid agents, anti-manics, anti-nauseants, anti-stroke agents,
anti-thyroid preparations, anti-tumor drugs, anti-viral agents,
acne drugs, alkaloids, amino acid preparations, anti-tussives,
anti-uricemic drugs, anti-viral drugs, anabolic preparations,
systemic and non-systemic anti-infective agents, anti-neoplastics,
anti-parkinsonian agents, anti-rheumatic agents, appetite
stimulants, biological response modifiers, blood modifiers, bone
metabolism regulators, cardiovascular agents, central nervous
system stimulates, cholinesterase inhibitors, contraceptives,
decongestants, dietary supplements, dopamine receptor agonists,
endometriosis management agents, enzymes, erectile dysfunction
therapies, fertility agents, gastrointestinal agents, homeopathic
remedies, hormones, hypercalcemia and hypocalcemia management
agents, immunomodulators, immunosuppressives, migraine
preparations, motion sickness treatments, muscle relaxants, obesity
management agents, osteoporosis preparations, oxytocics,
parasympatholytics, parasympathomimetics, prostaglandins,
psychotherapeutic agents, respiratory agents, sedatives, smoking
cessation aids, sympatholytics, tremor preparations, urinary tract
agents, vasodilators, laxatives, antacids, ion exchange resins,
anti-pyretics, appetite suppressants, expectorants, anti-anxiety
agents, anti-ulcer agents, anti-inflammatory substances, coronary
dilators, cerebral dilators, peripheral vasodilators,
psycho-tropics, stimulants, anti-hypertensive drugs,
vasoconstrictors, migraine treatments, antibiotics, tranquilizers,
anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic
drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants,
neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and
anti-thyroid preparations, diuretics, anti-spasmodics, terine
relaxants, anti-obesity drugs, erythropoietic drugs,
anti-asthmatics, cough suppressants, mucolytics, DNA and genetic
modifying drugs, and combinations thereof.
[0031] Examples of medicating active ingredients contemplated for
use in the present invention include antacids, H.sub.2-antagonists,
and analgesics. For example, antacid dosages can be prepared using
the ingredients calcium carbonate alone or in combination with
magnesium hydroxide, and/or aluminum hydroxide. Moreover, antacids
can be used in combination with H.sub.2-antagonists.
[0032] Analgesics include opiates and opiate derivatives, such as
oxycodone (commercially available as Oxycontin.RTM.); ibuprofen
(commercially available as Motrin.RTM., Advil.RTM., Motrin
Children's.RTM., Motrin IBC), Advil Children's.RTM., Motrin
Infants'.RTM., Motrin Junior.RTM., Ibu-2.RTM., Proprinal.RTM.,
Ibu-200.RTM., Midol Cramp Formula.RTM., Bufen.RTM., Motrin Migraine
Pain.RTM., Addaprin.RTM. and Haltran.RTM.), aspirin (commercially
available as Empirin.RTM., Ecotrin.RTM., Genuine Bayer.RTM., and
Halfprin.RTM.), acetaminophen (commercially available as Silapap
Infant's.RTM., Silapap Children's.RTM., Tylenol.RTM., Tylenol
Children's.RTM., Tylenol Extra Strength.RTM., Tylenol Infants'
Original.RTM., Tylenol Infants'.RTM., Tylenol Arthritis.RTM.,
T-Painol.RTM., Q-Pap.RTM., Cetafen.RTM., Dolono.RTM.,
Tycolene.RTM., APAP.RTM., and Aminofen.RTM.), and combinations
thereof that may optionally include caffeine. Other pain relieving
agents may be used in the present invention, including meperidine
hydrochloride (commercially available as Demerol.RTM.),
hydromorphone hydrochloride (commercially available as
Dilaudid.RTM.), propoxyphene napsylate and acetaminophen
(commercially available as Darvocet-N.RTM.), Fentanyl (commercially
available as Duragesic.RTM. and Fentora.RTM.), sodium hyaluronate
(commercially avialble as Euflexxa.RTM.), adalimumab (commercially
available as Humira.RTM.), sumatriptan succinate (commercially
available as Imitrex.RTM.), fentanyl iontophoretic (commercially
available as Ionsys.RTM.), orphenadrine citrate (commercially
available as Norgesic.RTM.), magnesium salicylate tetrahydrate
(commercially available as Novasal.RTM.), oxymorphone hydrochloride
(commercially available as Opana ER.RTM.), methocarbamol
(commercially available as Robaxin.RTM.), carisoprodol
(commercially available as Soma.RTM.), tramadol hydrochloride
(commercially available as Ultracet.RTM. and Ultram.RTM.), morphine
sulfate (commercially available as MS Contin.RTM.), metaxalone
(commercially available as Skelaxin.RTM.), oxycodone hydrochloride
(commercially available as OxyContin.RTM.), acetaminophen/oxycodone
hydrochloride (commercially available as Percocet.RTM.),
oxycodone/aspirin (commercially available as Percodan.RTM.),
hydrocodone bitartrate/acetaminophen (commercially available as
Vicodin.RTM.), hydrocodone bitartrate/ibuprofen (commercially
available as Vicoprofen.RTM.), nepafenac (commercially available as
Nevanac.RTM.), and pregabalin (commercially available as
Lyrica.RTM.).
[0033] The present invention may further include agents such as
NSAIDs, including etodolac (commercially available as Lodine.RTM.),
ketorolac tromethamine (commercially available as Acular.RTM.),
naproxen sodium (commercially available as Anaprox.RTM.,
Naprosyn.RTM.), flurbiprofen (commercially available as
Ansaid.RTM.), diclofenac sodium/misoprostol (commercially available
as Arthrotec.RTM.), celecoxib (commercially available as
Celebrex.RTM.), sulindac (commercially available as Clinoril.RTM.),
oxaprozin (commercially available as Daypro.RTM.), piroxicam
(commercially available as Feldene.RTM.), indomethacin
(commercially available as Indocin.RTM.), meloxicam (commercially
available as Mobic.RTM.), mefenamic acid (commercially available as
Ponstel.RTM.), tolmetin sodium (commercially available as
Tolectin.RTM.), choline magnesium trisalicylate (commercially
available as Trilisate.RTM.), diclofenac sodium (commercially
available as Voltaren.RTM.), and misoprostol (commercially
available as Cytotec.RTM.). Opiate agonists and antagonists, such
as buprenorphine and naloxone are further examples of drugs for use
in the present invention.
[0034] Other preferred drugs for other preferred active ingredients
for use in the present invention include anti-diarrheals such as
loperamide (commercially available as Imodium AD.RTM., Imotil.RTM.,
Kaodene.RTM., Imperim.RTM., Diamode.RTM., QC Anti-Diarrheal.RTM.,
Health Care America Anti-Diarrheal.RTM., Leader A-D.RTM., and
Imogen.RTM.), nitazoxanide (commercially available as Alinia.RTM.)
and diphenoxylate hydrochloride/atropine sulfate (commercially
available as Lomotil.RTM.), anti-histamines, anti-tussives,
decongestants, vitamins, and breath fresheners. Common drugs used
alone or in combination for colds, pain, fever, cough, congestion,
runny nose and allergies, such as acetaminophen, ibuprofen,
chlorpheniramine maleate, dextromethorphan, dextromethorphan HBr,
phenylephrine HCl, pseudoephedrine HCl, diphenhydramine and
combinations thereof, such as dextromethophan HBr and phenylephrine
HCl (available as Triaminic.RTM.) may be included in the film
compositions of the present invention.
[0035] Other active agents useful in the present invention include,
but are not limited to alcohol dependence treatment, such as
acamprosate calcium (commercially available as Campral.RTM.);
Allergy treatment medications, such as promethazine hydrochloride
(commercially available as Phenergan.RTM.), hydrocodone
polistirex/chlorpheniramine polistirex (commercially available as
Tussionex.RTM.), cetirizine hydrochloride (commercially available
as Zyrtec.RTM.), cetirizine hydrochloride/pseudoephedrine
hydrochloride (commercially available as Zyrtec-D.RTM.),
promethazine hydrochloride/codeine phosphate (commercially
available as Phenergan.RTM. with Codeine), pemirolast (commercially
available as Alamast.RTM.), fexofenadine hydrochloride
(commercially available as Allegra.RTM.), meclizine hydrochloride
(commercially available as Antivert.RTM.), azelastine hydrochloride
(commercially available as Astelin.RTM.), nizatidine (commercially
available as Axid.RTM.), desloratadine (commercially available as
Clarinex.RTM.), cromolyn sodium (commercially available as
Crolom.RTM.), epinastine hydrochloride (commercially available as
Elestat.RTM.), azelastine hydrochloride (commercially available as
Optivar.RTM.), prednisolone sodium phosphate (commercially
available as Orapred ODT.RTM.), olopatadine hydrochloride
(commercially available as Patanol.RTM.), ketotifen fumarate
(commercially available as Zaditor.RTM.), and montelukast sodium
(commercially available as Singulair.RTM.); and anti-histamines
such as diphenhydramine HCl (available as Benadryl.RTM.),
loratadine (available as Claritin.RTM.), astemizole (available as
Hismanal.RTM.), nabumetone (available as Relafen.RTM.),
diphenydramine HCL (available as TheraFlu.RTM.) and clemastine
(available as Tavist.RTM.).
[0036] Films of the present invention may further include
Alzheimer's treatment medications, such as tacrine hydrochloride
(commercially available as Cognex.RTM.), galantamine (commercially
available as Razadyne.RTM.), donepezil hydrochloride (commercially
available as Aricept.RTM.), rivastigmine tartrate (commercially
available as Exelon.RTM.), and memantine (commercially available as
Namenda.RTM.); anemia medication, such as cyanocobalamin
(commercially available as Nascobal.RTM.); anesthetics, such as
antipyrine with benzocaine (commercially available as
Auralgan.RTM., Aurodex.RTM. and Auroto.RTM.); angina medication,
such as amlodipine besylate (commercially available as
Norvasc.RTM.), nitroglycerin (commercially available as
Nitro-Bid.RTM., Nitro-Dur.RTM., Nitrolingual.RTM., Nitrostat.RTM.,
Transderm-Nitro.RTM.), isosorbide mononitrate (commercially
available as Imdur.RTM.), and isosorbide dinitrate (commercially
available as Isordil.RTM.); anti-tussives such as guaifensin;
anti-Alzheimer's agents, such as nicergoline; and
Ca.sup.H-antagonists such as nifedipine (commercially available as
Procardia.RTM. and Adalat.RTM.).
[0037] Actives useful in the present invention may also include
anti-asthmatics, such as albuterol sulfate (commercially available
as Proventil.RTM.), ipratropium bromide (commercially available as
Atrovent.RTM.), salmeterol xinafoate (commercially available as
Serevent.RTM.), zafirlukast (commercially available as
Accolate.RTM.), flunisolide (commercially available as
AeroBid.RTM.), metaproterenol sulfate (commercially available as
Alupent.RTM.), albuterol inhalation (commercially available as
Ventolin.RTM.), terbutaline sulfate (commercially available as
Brethine.RTM.), formoterol (commercially available as
Foradil.RTM.), cromolyn sodium (commercially available as
Intal.RTM.), levalbuterol hydrochloride (commercially available as
Xopenex.RTM.), zileuton (commercially available as Zyflo.RTM.),
fluticasone propionate/salmeterol (commercially available as
Advair.RTM.), albuterol sulfate/triamcinolone acetonide
(commercially available as Azmacort.RTM.), dimethylxanthine
(commercially available as Theophylline.RTM.), and beclomethasone
(commercially available as Beclovent.RTM., Beconase.RTM.,
Qvar.RTM., Vancenase.RTM., Vanceril.RTM.); and antibacterial
medications, such as trimethoprim/sulfamethoxazole (commercially
available as Bactrim.RTM.), mupirocin (commercially available as
Bactroban.RTM.), metronidazole (commercially available as
Flagyl.RTM.), sulfisoxazole acetyl (commercially available as
Gantrisin.RTM.), bismuth subsalicylate and
metronidazole/tetracycline hydrochloride (commercially available as
Helidac Therapy.RTM.), nitrofurantoin (commercially available as
Macrodantin.RTM.), norfloxacin (commercially available as
Noroxin.RTM.), erythromycin ethylsuccinate/Sulfisoxazole acetyl
(commercially available as Pediazole.RTM.), and levofloxacin
(commercially available as Levaquin.RTM.).
[0038] The present invention may further include one or more
Antibiotics, including amoxicillin (commercially available as
Amoxil.RTM.), ampicillin (commercially available as Omnipen.RTM.,
Polycillin.RTM. and Principen.RTM.), amoxicillin/clavulanate
potassium (commercially available as Augmentin.RTM.), moxifloxacin
hydrochloride (commercially available as Avelox.RTM.),
clarithromycin (commercially available as Biaxin.RTM.), ceftibuten
(commercially available as Cedax.RTM.), cefuroxime axetil
(commercially available as Ceftin.RTM.), cefprozil (commercially
available as Cefzil.RTM.), ciprofloxacin hydrochloride
(commercially available as Ciloxan.RTM. and Cipro.RTM.),
clindamycin phosphate (commercially available as Cleocin T.RTM.),
doxycycline hyclate (commercially available as Doryx.RTM.),
dirithromycin (commercially available as Dynabac.RTM.),
erythromycin (commercially available as E.E.S..RTM., E-Mycin.RTM.,
Eryc.RTM., Ery-Tab.RTM., Erythrocin.RTM., and PCE.RTM.),
erythromycin topical (commercially available as A/T/S.RTM.,
Erycette.RTM., T-Stat.RTM.), gemifloxacin (commercially available
as Factive.RTM.), ofloxacin (commercially known as Ocuflox.RTM.,
Floxin.RTM.), telithromycin (commercially available as Ketek.RTM.),
lomefloxacin hydrochloride (commercially available as
Maxaquin.RTM.), minocycline hydrochloride (commercially available
as Minocin.RTM.), fosfomycin tromethamine (commercially available
as Monurol.RTM.), penicillin with potassium (commercially available
as Penicillin VK.RTM., Veetids.RTM.), trimethoprim (commercially
available as Primsol.RTM.), ciprofloxacin hydrochloride
(commercially available as Proquin XR.RTM.), rifampin, isoniazid
and pyrazinamide (commercially available as Rifater.RTM.),
cefditoren (commercially available as Spectracef.RTM.), cefixime
(commercially available as Suprax.RTM.), tetracycline (commercially
available as Achromycin V.RTM. and Sumycin.RTM.), tobramycin
(commercially available as Tobrex.RTM.), rifaximin (commercially
available as Xifaxan.RTM.), azithromycin (commercially available as
Zithromax.RTM.), azithromycin suspension (commercially available as
Zmax.RTM.), linezolid (commercially available as Zyvox.RTM.),
benzoyl peroxide and clindamycin (commercially available as
BenzaClin.RTM.), erythromycin and benzoyl peroxide (commercially
available as Benzamycin.RTM.), ciprofloxacin and dexamethasone
(commercially available as Ciprodex.RTM.), polymyxin B
sulfate/neomycin sulfate/hydrocortisone (commercially available as
Cortisporin.RTM.), colistin sulfate/neomycin sulfate/hydrocortisone
acetate/thonzonium bromide (commercially available as
Cortisporin-TC Otic.RTM.), cephalexin hydrochloride (commercially
available as Keflex.RTM.), cefdinir (commercially available as
Omnicef.RTM.), and gatifloxacin (commercially available as
Zymar.RTM.).
[0039] Other useful actives include cancer treatment medications,
including cyclophosphamide (commercially available as
Cytoxan.RTM.), methotrexate (commercially available as
Rheumatrex.RTM. and Trexal.RTM.), tamoxifen citrate (commercially
available as Nolvadex.RTM.), and anastrozole (commercially
available as Arimidex.RTM.); anti-coagulants, such as aspirin with
extended-release dipyridamole (commercially available as
Aggrenox.RTM.), warfarin sodium (commercially available as
Coumadin.RTM.), dipyridamole (commercially available as
Persantine.RTM.), dalteparin (commercially available as
Fragmin.RTM.), danaparoid (commercially available as Orgaran.RTM.),
enoxaparin (commercially available as Lovenox.RTM.), heparin
(commercially available as Hep-Lock, Hep-Pak, Hep-Pak CVC, Heparin
Lock Flush), tinzaparin (commercially available as Innohep.RTM.),
and clopidogrel bisulfate (commercially available as Plavix.RTM.);
antiemetics, such as granisetron hydrochloride (commercially
available as Kytril.RTM.) and nabilone (commercially available as
Cesamet.RTM.), trimethobenzamide hydrochloride (commercially
available as Tigan.RTM.), and ondansetron hydrochloride
(commercially available as Zofran.RTM.); anti-fungal treatment,
such as ketoconazole (commercially available as Nizoral.RTM.),
posaconazole (commercially available as Noxafil.RTM.), ciclopirox
(commercially available as Penlac.RTM.), griseofulvin (commercially
available as Gris-PEG.RTM.), oxiconazole nitrate (commercially
available as Oxistat.RTM.), fluconazole (commercially available as
Diflucan.RTM.), sertaconazole nitrate (commercially available as
Ertaczo.RTM.), terbinafine hydrochloride (commercially available as
Lamisil.RTM.), ciclopirox (commercially available as Loprox.RTM.),
nystatin/triamcinolone acetonide (commercially available as
Mycolog-II.RTM.), econazole nitrate (commercially available as
Spectazole.RTM.), itraconazole (commercially available as
Sporanox.RTM.), and terconazole (commercially available as
Terazol.RTM.).
[0040] Active agents may further include anti-inflammatory
medications, such as hydroxychloroquine sulfate (commercially
available as Plaquenil.RTM.), fluticasone propionate (commercially
available as Cutivate.RTM.), amcinonide (commercially available as
Cyclocort.RTM.), methylprednisolone (commercially available as
Medrol.RTM.), budesonide (commercially available as Entocort
EC.RTM.), anakinra (commercially available as Kineret.RTM.),
diflorasone diacetate (commercially available as Psorcon.RTM.), and
etanercept (commercially available as Enbrel.RTM.); antispasmodic
medication, such as phenobarbital/hyoscyamine sulfate/atropine
sulfate/scopolamine hydrobromide (commercially available as
Donnatal.RTM.); antiviral treatment, such as oseltamivir phosphate
(commercially available as Tamiflu.RTM.); anti-parasites
medication, including tinidazole (commercially available as
Tindamax.RTM.); appetite treatment mediations, such as megestrol
acetate (commercially available as Megace ESC), phentermine
hydrochloride (commercially available as Adipex-P.RTM.), and
diethylpropion hydrochloride (commercially available as
Tenuate.RTM.); arthritis medications, including leflunomide
(commercially available as Arava.RTM.); bladder control medication,
such as trospium chloride (commercially available as
Sanctura.RTM.), desmopressin acetate (commercially available as
DDAVP.RTM.), tolterodine tartrate (commercially available as
Detrol.RTM.), oxybutynin chloride (commercially available as
Ditropan.RTM.), darifenacin (commercially available as
Enablex.RTM.), and solifenacin succinate (commercially available as
VESIcare.RTM.); blood vessel constrictors, such as methylergonovine
maleate (commercially available as Methergine.RTM.); cholesterol
lowering medication, including paricalcitol (commercially available
as Altocor.RTM.), lovastatin, niacin (commercially available as
Advicor.RTM.), colestipol hydrochloride (commercially available as
Colestid.RTM.), rosuvastatin calcium (commercially available as
Crestor.RTM.), fluvastatin sodium (commercially available as
Lescol.RTM.), atorvastatin calcium (commercially available as
Lipitor.RTM.), lovastatin (commercially available as Mevacor.RTM.),
niacin (commercially available as Niaspan.RTM.), pravastatin sodium
(commercially available as Pravachol.RTM.), pavastatin sodium with
buffered aspirin (commercially available as Pravigard PAC.RTM.),
cholestyramine (commercially available as Questran.RTM.),
simvastatin and niacin (commercially available as Simcor.RTM.),
atenolol, chlorthalidone (commercially available as
Tenoretic.RTM.), atenolol (commercially available as
Tenormin.RTM.), fenofibrate (commercially available as
Tricor.RTM.), fenofibrate (commercially available as
Triglide.RTM.), ezetimibe/simvastatin (commercially available as
Vytorin.RTM.), colesevelam (commercially available as
WelChol.RTM.), bisoprolol fumarate (commercially available as
Zebeta.RTM.), ezetimibe (commercially available as Zetia.RTM.),
bisoprolol fumarate/hydrochlorothiazide (commercially available as
Ziac.RTM.), and simvastatin (commercially available as
Zocor.RTM.).
[0041] The actives included herein may also include chronic kidney
disease medication, such as paricalcitol (commercially available as
Zemplar.RTM.); contraceptive agents, including etonogestrel
(commercially available as Implanon.RTM.), norethindrone acetate,
ethinyl estradiol (commercially available as Loestrin 24 FE.RTM.),
ethinyl estradiol, norelgestromin (commercially available as Ortho
Evra.RTM.), levonorgestrel (commercially available as Plan B.RTM.),
levonorgestrel and ethinyl estradiol (commercially available as
Preven.RTM.), levonorgestrel, ethinyl estradiol (commercially
available as Seasonique.RTM.), and medroxyprogesterone acetate
(commercially available as Depo-Provera.RTM.); COPD medication,
such as arformoterol tartrate (commercially available as
Brovana.RTM.) and ipratropium bromide, albuterol sulfate
(commercially available as Combivent.RTM.); cough suppressants,
including benzonatate (commercially available as Tessalon.RTM.),
guaifenesin, codeine phosphate (commercially available as
Tussi-Organidin NR.RTM.), and acetaminophen, codeine phosphate
(commercially available as Tylenol with Codeine.RTM.); medication
for the treatment of diabetes, including pioglitazone
hydrochloride, metformin hydrochloride (commercially available as
ACTOplus met.RTM.), pioglitazone hydrochloride (commercially
available as Actos.RTM.), glimepiride (commercially available as
Amaryl.RTM.), rosiglitazone maleate, metformin hydrochloride
(commercially available as Avandamet.RTM.), rosiglitazone maleate
(commercially available as Avandaryl.RTM.), rosiglitazone maleate
(commercially available as Avandia.RTM.), exenatide (commercially
available as Byetta.RTM.), chlorpropamide (commercially available
as Diabinese.RTM.), pioglitazone hydrochloride, glimepiride
(commercially available as Duetact.RTM.), metformin hydrochloride
(commercially available as Glucophage.RTM.), glipizide
(commercially available as Glucotrol.RTM.), glyburide, metformin
(commercially available as Glucovance.RTM.), metformin
hydrochloride (commercially available as Glumetza.RTM.),
sitagliptin (commercially available as Januvia.RTM.), detemir
(commercially available as Levemir.RTM.), glipizide, metformin
hydrochloride (commercially available as Metaglip.RTM.), glyburide
(commercially available as Micronase.RTM.), repaglinide
(commercially available as Prandin.RTM.), acarbose (commercially
available as Precose.RTM.), nateglinide (commercially available as
Starlix.RTM.), pramlintide acetate (commercially available as
Symlin.RTM.), and tolazamide (commercially available as
Tolinase.RTM.).
[0042] Other useful agents of the present invention may include
digestive agents, such as sulfasalazine (commercially available as
Azulfidine.RTM.), rabeprazole sodium (commercially available as
AcipHex.RTM.), lubiprostone (commercially available as
Amitiza.RTM.), dicyclomine hydrochloride (commercially available as
Bentyl.RTM.), sucralfate (commercially available as Carafate.RTM.),
lactulose (commercially available as Chronulac.RTM.), docusate
(commercially available as Colace.RTM.), balsalazide disodium
(commercially available as Colazal.RTM.), losartan potassium
(commercially available as Cozaar.RTM.), olsalazine sodium
(commercially available as Dipentum.RTM.), chlordiazepoxide
hydrochloride, clidinium bromide (commercially available as
Librax.RTM.), esomeprazole magnesium (commercially available as
Nexium.RTM.), famotidine (commercially available as Pepcid.RTM.),
lansoprazole (commercially available as Prevacid.RTM.),
lansoprazole and naproxen (commercially available as Prevacid
NapraPAC.RTM.), amoxicillin/clarithromycin/lansoprazole
(commercially available as Prevpac.RTM.), omeprazole (commercially
available as Prilosec.RTM.), pantoprazole sodium (commercially
available as Protonix.RTM.), metoclopramide hydrochloride
(commercially available as Reglan.RTM.), cimetidine (commercially
available as Tagamet.RTM.), ranitidine hydrochloride (commercially
available as Zantac.RTM.), and omeprazole, sodium bicarbonate
(commercially available as Zegerid.RTM.); diuretics, including
spironolactone, hydrochlorothiazide (commercially available as
Aldactazide.RTM.), spironolactone (commercially available as
Aldactone.RTM.). bumetanide (commercially available as Bumex.RTM.),
torsemide (commercially available as Demadex.RTM.), chlorothiazide
(commercially available as Diuril.RTM.), furosemide (commercially
available as Lasix.RTM.), metolazone (commercially available as
Zaroxolyn.RTM.), and hydrochlorothiazide, triamterene (commercially
available as Dyazide.RTM.).
[0043] Agents useful herein may also include treatment for
emphysema, such as tiotropium bromide (commercially available as
Spiriva.RTM.); enema treatments, including aminosalicylic acid
(commercially available as Mesalamine.RTM. and Rowasa.RTM.);
epilepsy medications, including valproic acid (commercially
available as Depakene.RTM.), felbamate (commercially available as
Felbatol.RTM.), lamotrigine (commercially available as
Lamictal.RTM.), primidone (commercially available as
Mysoline.RTM.), oxcarbazepine (commercially available as
Trileptal.RTM.), zonisamide (commercially available as
Zonegran.RTM.), levetiracetam (commercially available as
Keppra.RTM.), and phenytoin sodium (commercially available as
Dilantin.RTM.).
[0044] Erectile dysfunction therapies useful herein include, but
are not limited to, drugs for facilitating blood flow to the penis,
and for effecting autonomic nervous activities, such as increasing
parasympathetic (cholinergic) and decreasing sympathetic
(adrenersic) activities. Useful agents for treatment of erectile
dysfunction include, for example, those agents available as
alprostadil (commercially available as Caverject.RTM.), tadalafil
(commercially available as Cialis.RTM.), vardenafil (commercially
available as Levitra.RTM.), apomorphine (commercially available as
Uprima.RTM.), yohimbine hydrochloride (commercially available as
Aphrodyne.RTM., Yocon.RTM.), and sildenafil citrate (commercially
available as Viagra.RTM.).
[0045] Agents useful herein may further include eye medications and
treatment, such as dipivefrin hydrochloride (commercially available
as Propine.RTM.), valganciclovir (commercially available as
Valcyte.RTM.), bromfenac (commercially available as Xibrom.RTM.),
fluorometholone (commercially available as FML.RTM.), pilocarpine
hydrochloride (commercially available as Pilocar.RTM.),
cyclosporine (commercially available as Restasis.RTM.), brimonidine
tartrate (commercially available as Alphagan P.RTM.), dorzolamide
hydrochloride/timolol maleate (commercially available as
Cosopt.RTM.), bimatoprost (commercially available as Lumigan.RTM.),
timolol maleate (available as Timoptic.RTM.), travoprost
(commercially available as Travatan.RTM.), latanoprost
(commercially available as Xalatan.RTM.), echothiophate iodide
(commercially available as Phospholine Iodide.RTM.), and
ranibizumab (commercially available as Lucentis.RTM.); fluid
controllers, such as acetazolamide (commercially available as
Diamox.RTM.); gallstone medications, including ursodiol
(commercially available as Actigall.RTM.); medication for the
treatment of gingivitis, including chlorhexidine gluconate
(commercially available as Peridex.RTM.); headache medications,
including butalbital/codeine phosphate/aspirin/caffeine
(commercially available as Fiornal.RTM. with Codeine), naratriptan
hydrochloride (commercially available as Amerge.RTM.), almotriptan
(commercially available as Axert.RTM.), ergotamine
tartrate/caffeine (commercially available as Cafergot.RTM.),
butalbital/acetaminophen/caffeine (commercially available as
Fioricet.RTM.), butalbital/aspirin/caffeine (commercially available
as Fiorinal.RTM.), frovatriptan succinate (commercially available
as Frova.RTM.), rizatriptan benzoate (commercially available as
Maxalt.RTM.), isometheptene mucate/dichloralphenazone/acetaminophen
(commercially available as Midrin.RTM.), dihydroergotamine mesylate
(commercially available as Migranal.RTM.), eletriptan hydrobromide
(commercially available as Relpax.RTM.), and zolmitriptan
(commercially available as Zomig.RTM.); and heart treatments,
including quinidine sulfate, isosorbide dinitrate/hydralazine
hydrochloride (commercially available as BiDil.RTM.), digoxin
(commercially available as Lanoxin.RTM.), flecainide acetate
(commercially available as Tambocor.RTM.), mexiletine hydrochloride
(commercially available as Mexitil.RTM.), disopyramide phosphate
(commercially available as Norpace.RTM.), procainamide
hydrochloride (commercially available as Procanbid.RTM.), and
propafenone (commercially available as Rythmol.RTM.).
[0046] Other useful agents include hepatitis treatments, including
entecavir (commercially available as Baraclude.RTM.), hepatitis B
immune globulin (commercially available as HepaGam B.RTM.), and
copegus/rebetol/ribasphere/vilona/virazole (commercially available
as Ribavirin.RTM.); herpes treatments, including valacyclovir
hydrochloride (commercially available as Valtrex.RTM.), penciclovir
(commercially available as Denavir.RTM.), acyclovir (commercially
available as Zovirax.RTM.), and famciclovir (commercially available
as Famvir.RTM.); treatment for high blood pressure, including
enalaprilat (available as Vasotec.RTM.), captopril (available as
Capoten.RTM.) and lisinopril (available as Zestril.RTM.), verapamil
hydrochloride (available as Calan.RTM.), ramipril (commercially
available as Altace.RTM.), olmesartan medoxomil (commercially
available as Benicar.RTM.), amlodipine/atorvastatin (commercially
available as Caduet.RTM.), nicardipine hydrochloride (commercially
available as Cardene.RTM.), diltiazem hydrochloride (commercially
available as Cardizem.RTM.), quinapril hydrochloride (commercially
available as Accupril.RTM.), quinapril
hydrochloride/hydrochlorothiazide (commercially available as
Accuretic.RTM.), perindopril erbumine (commercially available as
Aceon.RTM.), candesartan cilexetil (commercially available as
Atacand.RTM.), candesartan cilexetil/hydrochlorothiazide
(commercially available as Atacand HCT.RTM.),
irbesartan/hydrochlorothiazide (commercially available as
Avalide.RTM.), irbesartan (commercially available as Avapro.RTM.),
amlodipine besylate/olmesartan medoxomil (commercially available as
Azor.RTM.), levobunolol hydrochloride (commercially available as
Betagan.RTM.), betaxolol hydrochloride (commercially available as
Betoptic.RTM.), nebivolol (commercially available as
Bystolic.RTM.), captopril/hydrochlorothiazide (commercially
available as Capozide.RTM.), doxazosin mesylate (commercially
available as Cardura.RTM.), clonidine hydrochloride (commercially
available as Catapres.RTM.), carvedilol (commercially available as
Coreg.RTM.), nadolol (commercially available as Corgard.RTM.),
nadolol/bendroflumethiazide (commercially available as
Corzide.RTM.), valsartan (commercially available as Diovan.RTM.),
isradipine (commercially available as DynaCirc.RTM.), wytensin.
(commercially available as Guanabenz acetate.RTM.), tenex
(commercially available as Guanfacine hydrochloride.RTM.), losartan
potassium/hydrochlorothiazide (commercially available as
Hyzaar.RTM.), propranolol hydrochloride (commercially available as
Indera.RTM.), propranolol hydrochloride/hydrochlorothiazide
(commercially available as Inderide.RTM.), eplerenone (commercially
available as Inspra.RTM.), ambrisentan (commercially available as
Letairis.RTM.), enalapril maleate/felodipine (commercially
available as Lexxel.RTM.), metoprolol tartrate (commercially
available as Lopressor.RTM.), benazepril hydrochloride
(commercially available as Lotensin.RTM.), benazepril
hydrochloride/hydrochlorothiazide (commercially available as
Lotensin HCT.RTM.), amlodipine/benazepril hydrochloride
(commercially available as Lotrel.RTM.), indapamide (commercially
available as Lozol.RTM.), trandolapril (commercially available as
Mavik.RTM.), telmisartan (commercially available as Micardis.RTM.),
telmisartan/hydrochlorothiazide (commercially available as Micardis
HCT.RTM.), prazosin hydrochloride (commercially available as
Minipress.RTM.), amiloride, hydrochlorothiazide (commercially
available as Moduretic.RTM.), fosinopril sodium (commercially
available as ZZXT Monopril.RTM.), fosinopril
sodium/hydrochlorothiazide (commercially available as
Monopril-HCT.RTM.), pindolol (commercially available as
Visken.RTM.), felodipine (commercially available as Plendil.RTM.),
sildenafil citrate (commercially available as Revatio.RTM.),
Nisoldipine (commercially available as Sular.RTM.),
trandolapril/verapamil hydrochloride (commercially available as
Tarka.RTM.), aliskiren (commercially available as Tekturna.RTM.),
eprosartan mesylate (commercially available as Teveten.RTM.),
eprosartan mesylate/hydrochlorothiazide (commercially available as
Teveten HCT.RTM.), moexipril hydrochloride/hydrochlorothiazide
(commercially available as Uniretic.RTM.), moexipril hydrochloride
(commercially available as Univasc.RTM.), enalapril
maleate/hydrochlorothiazide (commercially available as
Vaseretic.RTM.), and lisinopril/hydrochlorothiazide (commercially
available as Zestoretic.RTM.).
[0047] The present invention may include agents useful in the
medication for the treatment of HIV/AIDS, such as amprenavir
(commercially available as Agenerase.RTM.), tipranavir
(commercially available as Aptivus.RTM.),
efavirenz/emtricitabine/tenofovir (commercially available as
Atripla.RTM.), lamivudine/zidovudine (commercially available as
Combivir.RTM.), indinavir sulfate (commercially available as
Crixivan.RTM.), lamivudine (commercially available as Epivir.RTM.),
saquinavir (commercially available as Fortovase.RTM.), zalcitabine
(commercially available as Hivid.RTM.), lopinavir/ritonavir
(commercially available as Kaletra.RTM.), fosamprenavir calcium
(commercially available as Lexiva.RTM.), ritonavir (commercially
available as Norvir.RTM.), zidovudine (commercially available as
Retrovir.RTM.), atazanavir sulfate (commercially available as
Reyataz.RTM.), efavirenz (commercially available as Sustiva.RTM.),
abacavir/lamivudine/zidovudine (commercially available as
Trizivir.RTM.), didanosine (commercially available as Videx.RTM.),
nelfinavir mesylate (commercially available as Viracept.RTM.),
nevirapine (commercially available as Viramune.RTM.), tenofovir
disoproxil fumarate (commercially available as Viread.RTM.),
stavudine (commercially available as Zerit.RTM.), and abacavir
sulfate (commercially available as Ziagen.RTM.); homocysteiene
removers, including betaine anhydrous (commercially available as
Cystadane.RTM.); medications, such as insulin (commercially
available as Apidra.RTM., Humalog.RTM., Humulin.RTM., Iletin.RTM.,
and Novolin.RTM.); and HPV treatment, such as Human papillomavirus
vaccine (commercially available as Gardasil.RTM.);
immunosuppressants, including cyclosporine (commercially available
as Gengraf.RTM., Neoral.RTM., Sandimmune.RTM., and
Apo-Cyclosporine.RTM.).
[0048] Agents useful in the present invention may further include
prolactin inhibitors, such as bromocriptine mesylate (commercially
available as Parlodel.RTM.); medications for aiding in stress
tests, such as regadenoson (commercially available as
Lexiscan.RTM.); baldness medication, including finasteride
(commercially available as Propecia.RTM. and Proscar.RTM.);
pancreatitis treatment, such as gemfibrozil (commercially available
as Lopid.RTM.); hormone medications, such as norethindrone
acetate/ethinyl estradiol (commercially available as femHRT.RTM.),
goserelin acetate (commercially available as Zoladex.RTM.),
progesterone gel (commercially available as Prochieve.RTM.),
progesterone (commercially available as Prometrium.RTM.),
calcitonin-salmon (commercially available as Miacalcin.RTM.),
calcitriol (commercially available as Rocaltrol.RTM.), Synthroid
(commercially available as Levothroid.RTM., Levoxyl.RTM.,
Unithroid.RTM.), testosterone (commercially available as
Testopel.RTM., Androderm.RTM., Testoderm.RTM., and AndroGel.RTM.);
menopause medication, such as estradiol/norethindrone acetate
(commercially available as Activella.RTM.), drospirenone/estradiol
(commercially available as Angeliq.RTM.), estradiol/levonorgestrel
(commercially available as Climara Pro.RTM.),
estradiol/norethindrone acetate (commercially available as
CombiPatch.RTM.), estradiol (commercially available as
Estrasorb.RTM., Vagifem.RTM. and EstroGel.RTM.), esterified
estrogens and methyltestosterone (commercially available as
Estratest.RTM.), estrogen (commercially available as Alora.RTM.,
Climara.RTM., Esclim.RTM., Estraderm.RTM., Vivelle.RTM.,
Vivelle-Dot.RTM.), estropipate (commercially available as
Ogen.RTM.), conjugated estrogens (commercially available as
Premarin.RTM.), and medroxyprogesterone acetate (commercially
available as Provera.RTM.); menstrual medications, including
leuprolide acetate (commercially available as Lupron Depot), and
norethindrone acetate (commercially available as Aygestin); and
muscle relaxants, including cyclobenzaprine hydrochloride
(commercially available as Flexeril.RTM.), tizanidine (commercially
available as Zanaflex.RTM.), and hyoscyamine sulfate (commercially
available as Levsin.RTM.).
[0049] Agents useful herein may also include osteoporosis
medications, including ibrandronate sodium (commercially available
as Boniva.RTM.), risedronate (commercially available as
Actonel.RTM.), raloxifene hydrochloride (commercially available as
Evista.RTM., Fortical.RTM.), and alendronate sodium (commercially
available as Fosamax.RTM.); ovulation enhancers, including
clomiphene citrate (commercially available as Serophene.RTM.,
Clomid.RTM., Serophene.RTM.); Paget's disease treatment, such as
etidronate disodium (commercially available as Didronel.RTM.);
pancreatic enzyme deficiency medications, such as pancrelipase
(commercially available as Pancrease.RTM.); medication for the
treatment of Parkinson's disease, such as pramipexole
dihydrochloride (commercially available as Mirapex.RTM.),
ropinirole hydrochloride (commercially available as Requip.RTM.),
carbidopa/levodopa (commercially available as Sinemet CRC),
carbidopa/levodopa/entacapone (commercially available as
Stalevo.RTM.), selegiline hydrochloride (commercially available as
Zelapar.RTM.), rasagiline (commercially available as Azilect.RTM.),
entacapone (commercially available as Comtan.RTM.), and selegiline
hydrochloride (commercially available as Eldepryl.RTM.); prostate
medication, including flutamide (commercially available as
Eulexin.RTM.), nilutamide (commercially available as
Nilandron.RTM.), dutasteride (commercially available as
Avodart.RTM.), tamsulosin hydrochloride (commercially available as
Flomax.RTM.), terazosin hydrochloride (commercially available as
Hytrin.RTM.), and alfuzosin hydrochloride (commercially available
as UroXatral.RTM.).
[0050] Films of the present invention may further include
psychiatric medications, including alprazolam (available as
Niravam.RTM., Xanax.RTM.), clozopin (available as Clozaril.RTM.),
haloperidol (available as Haldol.RTM.), fluoxetine hydrochloride
(available as Prozac.RTM.), sertraline hydrochloride (available as
Zoloft.RTM.), and paroxtine hydrochloride (available as
Paxil.RTM.), aripiprazole (commercially available as Abilify.RTM.),
Amphetamines and methamphetamines (commercially available as
Adderall.RTM. and Desoxyn.RTM.), clomipramine hydrochloride
(commercially available as Anafranil.RTM.), Buspirone hydrochloride
(commercially available as BuSpar.RTM.), citalopram hydrobromide
(commercially available as Celexa.RTM.), duloxetine hydrochloride
(commercially available as Cymbalta.RTM.), methylphenidate
(commercially available as Ritalin, Daytrana.RTM.), divalproex
sodium (Valproic acid) (commercially available as Depakote.RTM.),
dextroamphetamine sulfate (commercially available as
Dexedrine.RTM.), venlafaxine hydrochloride (commercially available
as Effexor.RTM.), selegiline (commercially available as
Emsam.RTM.), carbamazepine (commercially available as
Equetro.RTM.), lithium carbonate (commercially available as
Eskalith.RTM.), fluvoxamine maleate/dexmethylphenidate
hydrochloride (commercially available as Focalin.RTM.), ziprasidone
hydrochloride (commercially available as Geodon.RTM.), ergoloid
mesylates (commercially available as Hydergine.RTM.), escitalopram
oxalate (commercially available as Lexapro.RTM.), chlordiazepoxide
(commercially available as Librium.RTM.), molindone hydrochloride
(commercially available as Moban.RTM.), phenelzine sulfate
(commercially available as Nardil.RTM.), thiothixene (commercially
available as Navane.RTM.), desipramine hydrochloride (commercially
available as Norpramin.RTM.), benzodiazepines (such as those
available as Oxazepam.RTM.), nortriptyline hydrochloride
(commercially available as Pamelor.RTM.), tranylcypromine sulfate
(commercially available as Parnate.RTM.), prochlorperazine,
mirtazapine (commercially available as Remeron.RTM.), risperidone
(commercially available as Risperdal.RTM.), quetiapine fumarate
(commercially available as Seroquel.RTM.), doxepin hydrochloride
(commercially available as Sinequan.RTM.), atomoxetine
hydrochloride (commercially available as Strattera.RTM.),
trimipramine maleate (commercially available as Surmontil.RTM.),
olanzapine/fluoxetine hydrochloride (commercially available as
Symbyax.RTM.), imipramine hydrochloride (commercially available as
Tofranil.RTM.), protriptyline hydrochloride (commercially available
as Vivactil.RTM.), bupropion hydrochloride (commercially available
as Wellbutrin.RTM., Wellbutrin SR.RTM., and Wellbutrin XR.RTM.),
and olanzapine (commercially available as Zyprexa.RTM.).
[0051] Agents useful herein may also include uric acid reduction
treatment, including allopurinol (commercially available as
Zyloprim.RTM.); seizure medications, including gabapentin
(commercially available as Neurontin.RTM.), ethotoin (commercially
available as Peganone.RTM.), and topiramate (commercially available
as Topamax.RTM.); treatment for shingles, such as zoster vaccine
live (commercially available as Zostavax.RTM.); skin care
medications, including calcipotriene (commercially available as
Dovonex.RTM.), isotretinoin (commercially available as
Accutane.RTM.), hydrocortisone/iodoquinol (commercially available
as Alcortin.RTM.), sulfacetamide sodium/sulfur (commercially
available as Avar.RTM.), azelaic acid (commercially available as
Azelex.RTM., Finacea.RTM.), benzoyl peroxide (commercially
available as Desquam-E.RTM.), adapalene (commercially available as
Differin.RTM.), fluorouracil (commercially available as
Efudex.RTM.), pimecrolimus (commercially available as Elidel.RTM.),
topical erythromycin (commercially available as A/T/S.RTM.,
Erycette.RTM., T-Stat.RTM.), hydrocortisone (commercially available
as Cetacort.RTM., Hytone.RTM., Nutracort.RTM.), metronidazole
(commercially available as MetroGel.RTM.), doxycycline
(commercially available as Oracea.RTM.), tretinoin (commercially
available as Retin-A.RTM. and Renova.RTM.), mequinol/tretinoin
(commercially available as Solage.RTM.), acitretin (commercially
available as Soriatane.RTM.), calcipotriene hydrate/betamethasone
dipropionate (commercially available as Taclonex.RTM.), tazarotene
(commercially available as Tazorac.RTM.), fluocinonide
(commercially available as Vanos.RTM.), desonide (commercially
available as Verdeso.RTM.), miconazole nitrate/Zinc oxide
(commercially available as Vusion.RTM.), ketoconazole (commercially
available as Xolegel.RTM.), and efalizumab (commercially available
as Raptiva.RTM.).
[0052] Other agents useful herein may include Sleep disorder
medications, including zaleplon (available as Sonata.RTM.) and
eszopiclone (available as Lunesta.RTM.), zolpidem tartrate
(commercially available as Ambient, Ambien CR.RTM.), lorazepam
(commercially available as Ativan.RTM.), flurazepam hydrochloride
(commercially available as Dalmane.RTM.), triazolam (commercially
available as Halcion.RTM.), clonazepam (commercially available as
Klonopin.RTM.), barbituates, such as Phenobarbital.RTM.), Modafinil
(commercially available as Provigil.RTM.), temazepam (commercially
available as Restoril.RTM.), ramelteon (commercially available as
Rozerem.RTM.), clorazepate dipotassium (commercially available as
Tranxene.RTM.), diazepam (commercially available as Valium.RTM.),
quazepam (commercially available as Doral.RTM.), and estazolam
(commercially available as ProSom.RTM.); smoking cessation
medications, such as varenicline (commercially available as
Chantix.RTM.), nicotine, such as Nicotrol.RTM., and bupropion
hydrochloride (commercially available as Zyban.RTM.); and steroids,
including alclometasone dipropionate (commercially available as
Aclovate.RTM.), betamethasone dipropionate (commercially available
as Diprolene.RTM.), mometasone furoate (commercially available as
Elocon.RTM.), fluticasone (commercially available as Flonase.RTM.,
Flovent.RTM., Flovent Diskus.RTM., Flovent Rotadisk.RTM.),
fluocinonide (commercially available as Lidex.RTM.), mometasone
furoate monohydrate (commercially available as Nasonex.RTM.),
desoximetasone (commercially available as Topicort.RTM.),
clotrimazole/betamethasone dipropionate (commercially available as
Lotrisone.RTM.), prednisolone acetate (commercially available as
Pred Forte.RTM., Prednisone.RTM., Budesonide Pulmicort.RTM.,
Rhinocort Aqua.RTM.), prednisolone sodium phosphate (commercially
available as Pediapred.RTM.), desonide (commercially available as
Tridesilon.RTM.), and halobetasol propionate (commercially
available as Ultravate.RTM.).
[0053] Films of the present invention may further include agents
useful for thyroid disease treatment, such as hormones TC and TD
(commercially available as Armour Thyroid.RTM.); potassium
deficiency treatment, including potassium chloride (commercially
available as Micro-K.RTM.); triglycerides regulators, including
omega-3-acid ethyl esters (commercially available as Omacor.RTM.);
urinary medication, such as phenazopyridine hydrochloride
(commercially available as Pyridium.RTM.) and methenamine,
methylene blue/phenyl salicylate/benzoic acid/atropine
sulfate/hyoscyamine (commercially available as Urised.RTM.);
prenatal vitamins (commercially available as Advanced
Natalcare.RTM., Materna.RTM., Natalins.RTM., Prenate Advance.RTM.);
weight control medication, including orlistat (commercially
available as Xenical.RTM.) and sibutramine hydrochloride
(commercially available as Meridia.RTM.).
[0054] The popular H.sub.2-antagonists which are contemplated for
use in the present invention include cimetidine, ranitidine
hydrochloride, famotidine, nizatidien, ebrotidine, mifentidine,
roxatidine, pisatidine and aceroxatidine.
[0055] Active antacid ingredients include, but are not limited to,
the following: aluminum hydroxide, dihydroxyaluminum aminoacetate,
aminoacetic acid, aluminum phosphate, dihydroxyaluminum sodium
carbonate, bicarbonate, bismuth aluminate, bismuth carbonate,
bismuth subcarbonate, bismuth subgallate, bismuth subnitrate,
bismuth subsilysilate, calcium carbonate, calcium phosphate,
citrate ion (acid or salt), amino acetic acid, hydrate magnesium
aluminate sulfate, magaldrate, magnesium aluminosilicate, magnesium
carbonate, magnesium glycinate, magnesium hydroxide, magnesium
oxide, magnesium trisilicate, milk solids, aluminum mono-ordibasic
calcium phosphate, tricalcium phosphate, potassium bicarbonate,
sodium tartrate, sodium bicarbonate, magnesium aluminosilicates,
tartaric acids and salts.
[0056] The pharmaceutically active agents employed in the present
invention may include allergens or antigens, such as, but not
limited to, plant pollens from grasses, trees, or ragweed; animal
danders, which are tiny scales shed from the skin and hair of cats
and other furred animals; insects, such as house dust mites, bees,
and wasps; and drugs, such as penicillin.
[0057] Wasted constituent in the manufacturing process results in
direct loss of profitability and efficiency. As such, it is
desirable to limit any waste in the manufacturing process in order
to conserve costs and promote efficiency in production. One way to
minimize cost is to limit the amount of wasted film composition.
Some waste may be from the formation and processing of the film
into the final individual-sized delivery modules, while other scrap
may be due, for example, to malfunctioning packaging equipment.
This may be attributed to wasted film composition in either the mix
or batch (liquid) or the final individual film dose product.
[0058] The present invention embodies methods of optimizing film
production. As used herein, the term "optimizing" refers to
processes and methods that minimize waste that may be generated
during the formation of the film product (thus, resulting in a
higher yield percentage). For example, one may desirably adjust the
parameters of manufacturing and production in order to minimize the
scrap film, which is one waste product. Through the present
invention, production parameters may be adjusted based on various
system components, known variables, and devisable factors. Thus,
the present invention of optimizing film production may result in
various advantages, including a greater efficiency in
manufacturing, including less wasted product, and lower cost per
individual film strip or sheet dosage. Thus, in focusing on
reducing the attributable errors and scrap in the processing and
manufacturing steps, a greater number of film strips or film sheets
may be produced at the same, or lower total cost in a given process
design.
[0059] To appreciate the present invention, it is helpful to
understand the general characteristics of individual film strip
doses, the processing and manufacturing of the film strips, as well
as the factors and variables, which may be related to the methods
and systems of the present invention. It is known and appreciated
that additional characteristics of film strips and methods of
making the same are possible and foreseeable in combination with
desirable properties and characteristics listed herein, as may be
desired. Thus, the present disclosure, by way of example, in no way
limits the various embodiments of the present invention.
[0060] Each individual film strip dose may be characterized in that
it may have a strip weight, a strip width, a strip length, and a
strip thickness. These parameters may be varied in order to yield a
dosage, which dissolves, for example, quickly, slowly, over a
period of predetermined length, and combinations thereof. Further,
the size and compositional make-up of the dosage may attribute
different levels or amounts of active ingredient(s) or agent(s),
which may be delivered to an individual. Thus, various film strip
shapes and varying thicknesses are included in the film strip
dosages of the present invention. In order to manufacture a film
strip which meets the rigors for commercialization and regulatory
approval, factors including consistency, quality, and efficacy must
be maintained throughout processing and manufacture.
Forming the Film
[0061] A film forming matrix, including, for example, a
film-forming polymer, polar solvent, any additives, and the active
ingredient may be formed in a number of steps. For example, the
various components may all be initially added together, or
pre-mixes of different materials may separately be prepared. One
advantage of a pre-mix is that all ingredients, except for the
active, may be combined in advance, with the active added just
prior to formation of the film. This is especially important for
actives that may degrade with prolonged exposure to water, air or
another polar solvent.
[0062] Mixing techniques may play a role in manufacturing of a
pharmaceutical film that is suitable for commercialization and
regulatory approval. For example, if air is trapped in the
composition during the mixing process (or later during the film
making process), it can leave voids in the film product as the
moisture evaporates during the drying stage. This may result in
film collapse around the voids, which causes an uneven film surface
and ultimately, attributes to a non-uniform final film product,
which may have inconsistent properties and component distribution.
Uniformity may still be affected even if the voids in the film
caused by air bubbles do not collapse. This situation also provides
a non-uniform film in that the spaces, which are not uniformly
distributed, are occupying area that would otherwise be occupied by
the film composition. Once uniformity is compromised, having a
consistent dosage of active from one strip to another is much more
difficult to achieve.
[0063] FIG. 1 shows an apparatus 20 suitable for the preparation of
a pre-mix, addition of an active, and the subsequent formation of a
film or sheet. The pre-mix or master batch 22, which includes the
film-forming polymer, polar solvent, and any other additives except
a drug active may be added to the master batch feed tank 24.
[0064] The components for pre-mix or master batch 22 are desirably
formed in a mixer (not shown) prior to their addition into the
master batch feed tank 24. Then a pre-determined amount of the
master batch may be controllably fed via a first metering pump 26
and control valve 28 to either or both of the first and second
mixers, 30, 30'. The present invention, however, is not limited to
the use of two mixers, 30, 30', and any number of mixers may
suitably be used. Moreover, the present invention is not limited to
any particular sequencing of the mixers 30, 30', such as parallel
sequencing as depicted in FIG. 5 (discussed below), and other
sequencing or arrangements of mixers, such as series or combination
of parallel and series, may suitably be used.
[0065] The required amount of the drug or other ingredient, such as
a flavor, may be added to the desired mixer through an opening, 32,
32', in each of the mixers, 30, 30'. Desirably, the residence time
of the pre-mix or master batch 22 is minimized in the mixers 30,
30'. While complete dispersion of the drug into the pre-mix or
master batch 22 is desirable, excessive residence times may result
in leaching or dissolving of the drug, especially in the case for a
soluble drug. Thus, the mixers 30, 30' are often smaller, with
lower residence times required to achieve the desired level of
mixing, as compared to the primary mixers (not shown) used in
forming the pre-mix or master batch 22.
[0066] After the drug has been blended with the master batch
pre-mix for a sufficient time to provide a uniform matrix, a
specific amount of the uniform matrix may then fed to the pan 36
through second metering pumps, 34, 34'. A metering roller 38 may be
used to determine the thickness of the wet film 42 and apply it to
the application roller. Thus, the metering roller 38 may be
adjusted to form a very thin film, a thick film, or other
variations as may be desired. Once the wet film 42 is formed on the
substrate 44, the film 42 may be carried away or conveyed onto
further processing via the support roller 46.
[0067] The combination of the multi-component matrix, which
includes the polymer, water, and an active (or other components as
desired), may be formed into a sheet or film used other equipment,
instruments, or techniques commonly known in the art besides those
depicted in FIG. 1.
[0068] In addition to the aforementioned film forming method, any
method known in the art such as extrusion, coating, spreading,
casting, spraying or drawing the multi-component matrix may be used
to form the film or sheet. Although a variety of different
film-forming techniques may be used, it is desirable to select a
method that will provide a self-supporting, flexible film, such as
reverse roll coating. The flexibility of the film allows for the
sheets of film to be rolled and transported without breaking once
they are formed. Film rolls may be stored for a period of time
prior to being cut, or may be easily transported across a room or
facility. Desirably, the films will also be self-supporting or able
to maintain their integrity and structure in the absence of a
separate support. Furthermore, the films of the present invention
may be selected from materials that are edible, ingestible,
biodegradable, biocompatible, and or pharmaceutically
acceptable.
[0069] Multi-layered films or sheets may be formed by co-extruding
more than one combination of components (of the same or different
combination), or by a multi-step coating, spreading, casting,
drawing, or combinations thereof. As another example, a
multi-layered film may also be achieved by coating, spreading, or
casting a combination onto an already formed film layer.
[0070] Coating or casting methods are particularly useful for the
purpose of forming the films of the present invention. Specific
examples of forming the film may include: (1) reverse roll coating;
(2) gravure coating; (3) immersion or dip coating; (4) metering rod
or meyer bar coating; (5) slot die or extrusion coating; (6) gap or
knife over roll coating; (7) air knife coating; (8) curtain
coating; or combinations thereof. Combinations of one or more of
the aforementioned may be employed when the formation of a
multi-layered film is desired.
[0071] Roll coating, or more specifically reverse roll coating, is
particularly desired when forming films in accordance with the
present invention. This procedure provides excellent control and
uniformity of the resulting films, which is desired in the present
invention. In this procedure, the coating material is measured onto
the applicator roller by the precision setting of the gap between
the upper metering roller and the application roller below it. The
coating is transferred from the application roller to the substrate
as it passes around the support roller adjacent to the application
roller. Both three roll and four roll processes are common.
[0072] The gravure coating process relies on an engraved roller
running in a coating bath, which fills the engraved dots or lines
of the roller with the coating material. The excess coating on the
roller may be wiped off by a doctor blade and the coating is then
deposited onto the substrate as it passes between the engraved
roller and a pressure roller. Offset Gravure is common, where the
coating is deposited on an intermediate roller before transfer to
the substrate.
[0073] In the simple process of immersion or dip coating, the
substrate is dipped into a bath of the coating, which is normally
of a low viscosity, to enable the coating to run back into the bath
as the substrate emerges.
[0074] In the metering rod coating process, an excess of the
coating is deposited onto the substrate as it passes over the bath
roller. The wire-wound metering rod, sometimes known as a Meyer
Bar, allows the desired quantity of the coating to remain on the
substrate. The quantity is determined by the diameter of the wire
used on the rod.
[0075] In the slot die process, the coating is squeezed out by
gravity or under pressure through a slot and onto the substrate. If
the coating is 100% solids, the process is termed "extrusion" and
in this case, the line speed is frequently much faster than the
speed of the extrusion. This enables coatings to be considerably
thinner than the width of the slot. In addition, slot die coating
may be beneficial in that it may reduce or altogether eliminate the
requirement for edge trimming from the film. A similar embodiment
includes using parallel slots to coat film products in the same
coating head. In this embodiment, it is possible to coat with one
solution without an active on one side of the coating head until
the proper gap setting and oven temperature is reached. At this
point, the coating head can be switched to the active side,
allowing the active to be coated at the right setting and oven
temperature.
[0076] The gap or knife over roll process relies on a coating being
applied to the substrate, which then passes through a "gap" between
a "knife" and a support roller. As the coating and substrate pass
through, the excess is scraped off.
[0077] Air knife coating is where the coating is applied to the
substrate and the excess is "blown off" by a powerful jet from the
air knife. This procedure is useful for aqueous coatings.
[0078] In the curtain coating process, a bath with a slot in the
base allows a continuous curtain of the coating to fall into the
gap between two conveyors. The object to be coated is passed along
the conveyor at a controlled speed and so receives the coating on
its upper face.
[0079] While viscosity, uniformity, stability, and casting are
important aspects of the film formation process, the method of
removing the moisture from the wet film to create a dried product
is also an important factor. That is, a quick, controlled drying
process ensures that the uniformity of content of the film is
rapidly achieved and will be maintained within the film once the
film is dry. In one embodiment, a viscoelastic mass is rapidly
formed, which "locks in" the uniformity of content of the film
matrix. The viscoelastic mass may then be further dried to fully
form the self-supporting film dosage.
[0080] Once the film strip is formed, any water or aqueous
components of the wet film are desirably removed in order to
provide a final product which is in a self-supporting condition,
and which may maintain a certain shape or conformation. Further,
the active agent may desirably be evenly or uniformly distributed
throughout the film strip product. In order to promote an exact
dosing of active ingredient or agent in each film strip, it may be
desirably to make each film strip substantially uniform in surface
and consistency. As such, it may be desirable to control one or
more processing parameters in order to ensure that there air
bubbles, ridges, and or pockets may be eliminated prior to and
during the film formation and the drying process (if any) employed
therewith.
Processing the Wet Film Product to Remove Excess Moisture
[0081] The films of the present invention may contain particles
that are sensitive to temperature, such as flavors, which may be
volatile, or drugs, which may have a low degradation temperature.
In such cases, the drying techniques used to form the film may be
varied in order to adequately dry the uniform films of the present
invention. Drying the wet film product may be desirable in order to
remove excess moisture from the film product.
[0082] A modification to the drying step may be to reduce the
amount of time that a wet film is potentially exposed to
contaminants, and the amount of time from processing to packaging
(i.e. a more efficient manufacturing process). Excess water,
solvent, or moisture in the film product may contribute to a
non-uniform product and/or degradation of active components within
the film or sheet. Drying may be through the evaporation of excess
water at ambient or other desired temperatures over a length of
time. The film may be dried at low or negative pressures (i.e.
vacuum dried), or the film may be dried by air blowers, fans, and
the like. The drying step may reduce any aggregation or
conglomeration of the film components as it is formed into a solid
structure. The drying process may further permit exposure of the
film to temperatures above that at which the active ingredient
typically would degrade without loss of a desired level of
activity. Any of these drying methods may be varied as desired.
[0083] The wet film may optionally be dried using controlled bottom
drying or controlled microwave drying, desirably in the absence of
external air currents or heat on the top (exposed) surface of the
film 48. Controlled bottom drying or controlled microwave drying
advantageously allows for vapor release from the film.
[0084] Conventional convection air drying from the top is not
preferably employed as it initiates drying at the top uppermost
portion of the film, thereby forming a barrier against fluid flow,
such as the evaporative vapors, and thermal flow, such as the
thermal energy for drying. Such dried upper portions serve as a
barrier to further vapor release as the portions beneath are dried,
which results in non-uniform films. As previously mentioned, some
top air flow can be used to aid the drying of the films of the
present invention, but it preferable does not create a condition
that would cause particle movement or a rippling effect in the
film, both of which would result in non-uniformity. If top air is
employed, it is preferably balanced with the bottom air drying to
avoid non-uniformity and prevent film lift-up on the carrier belt.
A balanced top and bottom air flow may be suitable where the bottom
air flow functions as the major source of drying and the top air
flow is the minor source of drying. The advantage of some top air
flow is to move the exiting vapors away from the film thereby
aiding in the overall drying process. The use of any top air flow
or top drying, however, is preferably be balanced by a number of
factors including, but not limited, to rheological properties of
the composition and mechanical aspects of the processing. Any top
fluid flow, such as air, also preferably does not overcome the
inherent viscosity of the film-forming composition. In other words,
the top air flow cannot break, distort or otherwise physically
disturb the surface of the composition. Moreover, air velocities
are desirably below the yield values of the film, i.e., below any
force level that can move the liquids in the film-forming
compositions. For thin or low viscosity compositions, low air
velocity must be used. For thick or high viscosity compositions,
higher air velocities may be used. Furthermore, air velocities are
desirably low so as to avoid any lifting or other movement of the
film formed from the compositions.
[0085] In bottom drying, the evaporating vapors more readily carry
heat away from the film as compared to top drying which lowers the
internal film temperature. Such lower internal film temperatures
often result in decreased drug degradation and decreased loss of
certain volatiles, such as flavors.
[0086] During film preparation, it may be desirable to dry films at
high temperatures. High heat drying produces uniform films, and
leads to greater efficiencies in film production. Films containing
sensitive active components, however, may face degradation problems
at high temperatures. Degradation is the "decomposition of a
compound . . . exhibiting well-defined intermediate products." The
American Heritage Dictionary of the English Language (4.sup.th ed.
2000). Degradation of an active component is typically undesirable
as it may cause instability, inactivity, and/or decreased potency
of the active component. For instance, if the active component is a
drug or bioactive material, this may adversely affect the safety or
efficacy of the final pharmaceutical product. Additionally, highly
volatile materials will tend to be quickly released from this film
upon exposure to conventional drying methods.
[0087] Degradation of an active component may occur through a
variety of processes, such as, hydrolysis, oxidation, and light
degradation, depending upon the particular active component.
Moreover, temperature has a significant effect on the rate of such
reactions. The rate of degradation typically doubles for every
10.degree. C. increase in temperature. Therefore, it is commonly
understood that exposing an active component to high temperatures
will initiate and/or accelerate undesirable degradation
reactions.
[0088] During the drying process of the present invention, several
factors produce uniformity within the film while maintaining the
active component at a safe temperature, i.e., below its degradation
temperature. First, the films of the present invention have an
extremely short heat history, usually only about minutes, so that
total temperature exposure is minimized to the extent possible.
Second, the films are controllably dried to prevent aggregation and
migration of components, as well as preventing heat build up
within. Third, the films are desirably dried from the bottom, as
controlled bottom drying, as described herein, prevents the
formation of a polymer film, or skin, on the top surface of the
film. As heat is conducted from the film bottom upward, liquid
carrier, e.g., water, rises to the film surface. The absence of a
surface skin permits rapid evaporation of the liquid carrier as the
temperature increases, and thus, concurrent evaporative cooling of
the film. Due to the short heat exposure and evaporative cooling,
the film components such as drugs or volatile actives remain
unaffected by high temperatures. In contrast, skinning on the top
surface traps liquid carrier molecules of increased energy within
the film, thereby causing the temperature within the film to rise
and exposing active components to high, potentially deleterious
temperatures.
[0089] Although the inventive process is not limited to any
particular apparatus for the above-described desirable drying, one
particular useful drying apparatus 50 is depicted in FIG. 2. Drying
apparatus 50 is a nozzle arrangement for directing hot fluid, such
as but not limited to hot air, towards the bottom of the film 42,
which is disposed on a substrate 44. The substrate 44 may include
any material on which the film 42 can be coated. Two preferred
substrates include Mylar and silicone coated paper, however other
substrates may be used if desired. For example, the substrate may
include a metal belt, any number of polymer materials, other films,
and the like. In one embodiment, the substrate may include a
packaging foil, which may allow the film to be applied to the
substrate and packaged immediately after drying, without the need
to separately form and package the film 42.
[0090] In one embodiment, depicted in FIG. 2, hot air is allowed to
enter the entrance end 52 of the drying apparatus and travel
vertically upward, as depicted by vectors 54, towards an air
deflector 56. The use of an air deflector 56 is optional, but may
be desired, as it is capable of redirecting the air movement to
minimize upward force on the film 42. Thus, the air is tangentially
directed, as indicated by vectors 60 and 60' as the air passes by
air deflector 56 and travels through chamber portions 58 and 58' of
the drying apparatus 50. With the hot air flow being substantially
tangential to the film 42, lifting of the film as it is being dried
is thereby minimized.
[0091] While the air deflector 56 is depicted as a roller type of
device, other devices and geometries for deflecting air or hot
fluid may suitable be used, including, for example, cylindrical,
triangular, and other type of geometries for deflecting fluid. The
exit ends 62 and 62' of the drying apparatus 50 are desirably
flared downwardly. Downward flaring provides a downward force or
downward velocity vector, as indicated by vectors 64 and 64', which
tend to provide a pulling or drag effect of the film 42 to prevent
undesirable lifting of the film 42. Lifting of the film 42 may not
only result in non-uniformity in the film or otherwise, but may
also result in non-controlled processing of the film 42 as the film
42 and/or substrate 44 lift away from the processing equipment.
[0092] FIG. 3 is a sequential representation of a drying process
useful in the present invention. After mechanical mixing, the film
may be placed on a conveyor for continued thermal mixing during the
drying process. At the outset of the drying process, depicted in
Section A, the wet film forming matrix 71 is heated, optionally
from the bottom 70, as it is travels via conveyor (not shown). Heat
may be supplied to the film by a heating mechanism, such as, but
not limited to, the dryer depicted in FIG. 2.
[0093] As the film is heated, any liquid carriers, or volatiles
("V") present in the wet film, begin to evaporate, as shown by
upward arrow 78. Thermal mixing also initiates as hotter liquid,
depicted by arrow 74, rises and cooler liquid, depicted by arrow
76, takes its place. Because there is no skin formation on the top
surface 72 of the film 1, (as shown in Section B), the volatile
liquid continues to evaporate 78 and thermal mixing 74/76 continues
to distribute thermal energy throughout the film. Once a sufficient
amount of the volatile liquid has evaporated, thermal mixing has
produced uniform heat diffusion throughout the wet film forming
matrix 71. The resulting dried film 79 is a visco-elastic solid, as
depicted in Section C. Desirably, the components are locked into a
uniform distribution throughout the film. Minor amounts of liquid
carrier, i.e., water or solvent, may remain subsequent to formation
of the visco-elastic solid 79. If desired, the visco-elastic solid
79 may be dried further without resulting in movement of the
particles. As can be seen, during the drying process (i.e., from
Section A to Section C), the thickness of the matrix is reduced,
due to evaporation of the volatiles present in the matrix 71.
[0094] The drying step(s) remove the liquid carriers from the film
in a manner such that the uniformity, or more specifically, the
non-self-aggregating uniform heterogeneity, that is obtained in the
wet film is maintained. The temperature of the oven, the length of
drying time and the amount of humidity in the ambient air may be
controllable factors in the drying process. The amount of energy,
temperature and length and speed of the conveyor can be balanced to
accommodate such actives and to minimize loss, degradation or
ineffectiveness in the final film. Desirably, the drying oven (or
ovens) is first turned on and is allowed to run until the
temperature within the oven has stabilized at the set point before
coating is started. The length of the drying oven may be altered as
necessary to achieve the drying desired. For example, when a
smaller batch size is used, or when the coating is narrow, the
length of the drying time may be reduced. The drying time may be
changed via the speed at which the film travels, or the number of
ovens through which the film travels. For example, in one
embodiment, the drying process includes passing the film through at
least two ovens, or at least five ovens. Any number of ovens may be
used in the drying process to achieve the desired film.
[0095] Monitoring and control of the thickness of the film also
contributes to the production of a uniform film by providing a film
of uniform thickness. The thickness of the film may be monitored
with gauges, such as Beta or Gamma Gauges. A gauge may be coupled
to another gauge at the end of the drying apparatus, i.e. drying
oven or tunnel, to communicate through feedback loops to control
and adjust the opening in the coating apparatus, resulting in
control of uniform film thickness. Desirably, the film is
formulated so that the dimensional changes incurred during drying
are to the film's thickness and not its width. As such, monitoring
of the film's thickness may be helpful in maintaining a suitable
product.
Cutting and Packaging the Sheet or Film Product
[0096] Once the film or sheet is mixed, formed, and dried into a
thin film or sheet product, the film or sheet may be cut into
certain shapes, dimensions, and the like, and packaged in a
desirable contaminant-preventing and shelf-life promoting packaging
material. In preferred embodiments, the film is maintained in a
package that is suitable for protecting products including active
components, and most desirably is approved by any regulatory agency
that may be applicable.
[0097] In the cutting process, the equipment may generally include
a slitter and a package machine. The slitter cuts or trims the
edges of the film product as desired, necessarily resulting in some
degree of scrap. The film may be shaped and sized into a continuous
roll of film, or it may be cut into individual pieces of film
product. Once the film product is cut, the cut film product may be
delivered directly to the customer. In some embodiments, after the
film is cut, the cut film may be provided to an outside packager,
where the material may be finally cut to its desired length (i.e.,
film strips) and may be placed into an individual package, such as
a cassette or other protective packaging. Still other cut products
may be provided to contract packagers who may then cut the film
product to the desired length, and then package the cut film
products in foil pouches with custom build pouching machine. In a
preferred embodiment, after cutting the sheet of film into
individual film products, the film products are packaged in
individual foil pouches via a pouching machine. These individually
packaged products may then be distributed to customers or
distributors for use. Any combination of a coating apparatus,
slitter and pouching machine may be used as desired, and in a
preferred embodiment, the coating apparatus, slitter and pouching
machine are used in combination with each other.
[0098] FIG. 4 generally depicts a schematic for cutting or trimming
a film product down into individual film strips or sheets. In FIG.
4, the drying apparatus 50 (referred to in FIG. 2) is depicted as
an oven 80. Generally, once the film 1 is mixed and reverse roll
coated into the film sheet, the film sheet 1 is dried. Here, the
sheet is oven-dried by oven 80.
[0099] The exemplary film sheet 1 depicted in FIG. 4 has a coated
width of about 31'' wide (where 1 inch=2.54 cm). Though the sheet 1
is shown as a rectangle, discontinuous regions along the length 82
of the film 1 denote that the film 1 may be of any length,
generally dependent upon the batch size, thickness of the film, and
coating width 84 of the film 1. Once the sheet 1 leaves the oven
80, the sheet 1 is fed onto the slitter 90. On the slitter 90, an
outer edge 88 measuring about 1/2'' is trimmed from each side of
the sheet 1 in order to remove any inconsistencies along the
outer-most edge 88 of the film 1. Then, the slitter 90 also cuts
the sheet 1 down into individual rolls 86, or "daughter" rolls, as
the rolls stem from the same mother sheet. The daughter rolls are
labeled 86. Thus, once the outer-edge trim 88 (measuring about
1/2'') is removed from each edge, the film sheet 1 is a total of
30'' wide, while each daughter roll 86 is roughly 1/4 of the total
width, or, in one embodiment, about 7.5'' wide, per roll. The cuts
on the sheet which yield the daughter rolls 86 are depicted as
dashed lines on FIG. 4, as the daughter rolls 86 are further
processed. The outer-edge trims 88, however, are removed from the
sheet and discarded as scrap. It should be noted that the rolls of
film 86 forms from the sheet of film are generally self-supporting
and flexible in nature, such that the films may be rolled over and
onto itself to form a daughter roll. These rolls may be stored;
however, ultimately, these rolls are preferably processed by
feeding the rolls onto the package machine 92.
[0100] As the roll 86 is fed onto the package machine 92, the
package machine 92 may also perform a cutting function. The package
machine 92 may trim another section (approximately 1/4'') off each
side, to yield another about 1/2'' of scrap. Thus, after this
cutting, the roll is trimmed down to about 7'' width. The package
machine also cuts each daughter roll down into individual lanes 96.
As depicted in FIG. 4, the daughter roll 86 may be cut into a
plurality of individual lanes. In one embodiment, the daughter roll
86 may be cut into about 8 lines, such that each lane has a total
with of 7/8''. Thus, in this embodiment, each individual film strip
or sheet dosage may have a total width of 7/8''. Other sizes may be
used if desired, for example, the daughter roll may be cut into
from about 2 to about 10 lanes, if desired. Each lane 96 may then
be cut along a predetermined length in order to yield the finished
film strip product. Typically, the film strip is immediately
packaged once the final cut is made from the individual lane,
although the cut film strip may be stored until packaged.
Optimization of Film or Sheet Production Method(s)
[0101] While various processing parameters have been discussed in
the aforementioned paragraphs, the present inventors have
determined a set of common denominators or variables in processing
techniques that may be controlled in order to optimize the
manufacturing and processing of film or sheet dosage production
while minimizing the scrap (or waste) that is produced. These
variables are defined in the following Table 1, which sets for the
variable abbreviation, a description of the variable, the source of
the variable, and the units in which the variable is expressed:
TABLE-US-00001 TABLE I List of Variables Variable Description
Source Units L.sub.O Oven Length Equipment Train Meters V.sub.M
Mixer Volume Equipment Train Liters W.sub.P Packaging Roll Width
Equipment Train Meters N.sub.S Number of slit Independent No Units
rolls/master roll Variable W.sub.C Coating Width Independent Meters
Variable W.sub.PT Packaging Trim Width Independent Meters Variable
W.sub.ST Slitting Trim Width Independent Meters Variable % S.sub.F
Formula % Solids Formulation % C.sub.Si Coating Solution
Formulation Kg (Batch Size) C.sub.T Total Coated Film Area
Formulation Square Meters C.sub.W Coating Weight Formulation
Kg/Square Meter % S.sub.M Measured % Solids Empirical Data % K
Coating Loss Parameter Empirical Data No Units P.sub.SS Packaging
Start/Stop Loss Empirical Data Meters S.sub.SS Slitting Start/Stop
Loss Empirical Data Meters % W.sub.PT % Packaging Trim Width
Calculated Meters % M.sub.LM % Mixing Losses Mass Calculated Kg %
P.sub.SS % Packaging Start/Stop Loss Calculated Meters % S.sub.SS %
Coating Start/Stop Losses Calculated Meters % W.sub.ST % Edge Trim
Calculated % C.sub.Sf Coated Solution Calculated Kg C.sub.SS
Coating Start/Stop Losses Calculated Meters L.sub.T Total length of
film Calculated Meters M.sub.LA Mixing Losses Area Calculated
Square Meters M.sub.LM Mixing Losses Mass Calculated Kg S.sub.F
Solids in Formulation Calculated Kg S.sub.L Slitting Loss
Calculated Square Meters T.sub.S Total Scrap Calculated Square
Meters
[0102] During production and manufacturing of the film, the various
components are mixed in one or more mixers, as previously
discussed. The mixer size may be defined by its working volume
(V.sub.M) in liters. The contents of the mixer may be referred to
as the "batch size" or the coating solution volume (C.sub.Si). The
mixer size may be larger than the batch size, as desired. For
example, the batch size may be less than the mixer size by
including proper agitation in the mixer. Further, the present
invention may be employed with various batch sizes, including bench
top, pilot plant size, and commercial size applications, with
particular reference to batch applications. Each batch includes a
percentage of the total weight in solids (percent solids), which
may include powders (such as polymers and actives) and non-aqueous
liquids (such as ethanol and flavors). Of the total solids, the
portion of the liquids which can evaporate in the drying oven is
defined as the percentage of volatile liquids (% volatile
components). Batch size, as used herein, is an independent
variable, which may be used in the inventive formulation to
calculate the amount of each component that is needed for a
suitable batch. Once the desired batch size is specified, the
required total solids (S.sub.F) may be calculated by the product of
the batch size (C.sub.Si) and the percentage of solids (% S.sub.F)
in the below equation (Eq. 1):
S.sub.F(kg)=C.sub.Si(kg).times.% S.sub.F (eq.1)
[0103] The term "total solids" generally refers to the total weight
of solids (including non-aqueous liquids such as flavors) in the
pre-mix batch. The total solids is intended to be measured in kg,
but other measurements may be used if desired.
[0104] The term "formula percent (%) solids" (% S.sub.F) generally
refers to the fractional ratio, or percentage of solids out of the
total amount of the pre-mix batch, measured in a fractional
percent. Formula percent solids is the fraction of total solids
(kg), including both dry solids and non-aqueous ingredients such as
flavors, out of the total coating solution (kg) in the mixer (which
is then multiplied by 100 to give a percentage).
[0105] The term "measured % solids" (% S.sub.M) refers to the
measurement of percentage of solids in the coating solution, which
may be measured by a suitable loss-in-weight instrument. The
measured percentage of solids is intended to not include all of the
volatile components of the formula, such as flavors, but only those
solids that are not driven off by the measurement.
Mixing Losses
[0106] As used herein, the term "mixing scrap" generally refers to
the scrap material that may be attributed to the mixing process.
This term includes, for example, material that is lost and not
recoverable because it coats the tank and/or the hoses, and
ultimately is not transferred to the film. Scrap for mixing is
measured in kg of solution, which is a function of the surface area
of the mixer and/or hoses, which is correlated to the size of the
mixer. The loss is generally a function of the mixer design, size
and plumbing used to connect the equipment to the coater. In order
to apply this optimization to a given coating line, the mixer(s)
used in the process should be evaluated, and the amount of solution
lost correlated to the mixer size.
[0107] Once the amount of lost solution (mixing scrap) (M.sub.LM)
is identified, one can then calculate the % lost solution (%
M.sub.LM) by the following equation (Eq. 2):
% M.sub.LM=M.sub.LM(kg)/C.sub.Si(kg)*100 (eq. 2)
[0108] In order to convert Scrap for mixing into a comparable
number (with the other scrap factors, including Coating and
Slitting) it may be useful to convert Scrap for Mixing in kg into
an area, (or m.sup.2). Therefore, assuming that the total mass of
lost solution is converted into a coating, one could simply
multiply the percentage of mixing loss and the total area of film
produced (C.sub.T) to get the area loss (M.sub.LA) in square meters
(Eq. 3):
M.sub.LA=% M.sub.LM*C.sub.T(m.sup.2) (eq. 3)
Coating Losses
[0109] Once the film-forming composition is completely processed,
it may then be coated or otherwise laid out into a desired film
width, and then dried to form the final film. As explained above,
the film may be coated, rolled, extruded, sprayed, or any other
desired means of laying out the composition into a film form.
Further to the present invention, if desired, the actives,
polymers, and other film-forming matrix components may be formed
into a large sheet of material prior to processing for packaging.
The sheet may be coated, rolled, extruded, spread, or otherwise
dispersed onto a generally flat area for drying prior to further
processing and packaging.
[0110] The "coated Solution" (C.sub.S, measured in kg) is the
amount of solution that becomes part of the final dosage form, and
may be defined by the following formula (Eq. 4):
C.sub.Sf(kg)=C.sub.Si(kg)-M.sub.LM(kg) (eq. 4)
[0111] The term "coating solution" generally refers to the
completed mixture of all film-forming components, which are mixed
and ready to be coated, cast, extruded, rolled, or otherwise spread
in order to form a wet film or sheet. The term "coated solution"
generally refers to the wet film product that has been formed, but
has not yet completed drying. The coated solution may be any size
and thickness desired to achieve the intended final product
size.
[0112] The "Scrap for Coating" is generally a function of the
coating width of the film sheet, i.e. the film sheet formation by
dispensing the liquid matrix into a wet sheet (pre-drying). The
term "scrap for coating" as used herein generally refers to the
scrap that is attributable to forming the film, including the
drying step. An example of scrap for coating may generally include
the stop scrap and/or the start-up scrap, and the scrap which
results from film product which is not completely set or which does
not fully dry (for example, if the oven is not optimized prior to
the drying process beginning). Start-up scrap may include the very
beginning length of the wet sheet, which may not fully dry into a
formable film. Start-up scrap may be typically 80-100 m in length,
regardless of the width of the material employed. In part, this is
because the oven should first come to a steady state to impart
drying through a phase shift to the wet film. Thus, the thickness
of the film or sheet, as well as the moisture content, should
desirably be consistent over a given length of film. This
consistency helps promote a uniform product having the desired
level of dispersed active throughout the film, i.e., a film that
has uniformity of content. Scrap for Coating is measured as surface
area (m.sup.2).
[0113] The start/stop scrap (C.sub.SS) for coating may be defined
by the following formula (Eq. 5)
C.sub.SS(m.sup.2)=K*L.sub.O(m)*W.sub.C(m) (Eq. 5)
where K is an empirical constant developed by evaluating historical
data for a specific coating system and L.sub.O is the length of the
drying oven. The constant K is the number of oven passes required
to reach steady state at the required in process conditions in
drying the film
[0114] The term "coating width" (W.sub.C) generally refers to the
width of a sheet of film before it is dried (i.e., after it is cast
or rolled), where the width is measured from side to side of the
cast film as it exits the rollers on the substrate. Coating width
and coating length may be variable parameters that may be adjusted
to optimize yield (or to minimize waste). For example, the coating
width may generally be constant for a given manufacturing
apparatus, while the coating length may be variable. Alternatively,
the coating width may be variable and the coating length generally
constant. In other embodiments, both the coating width and coating
length may be variable, or both may be constant.
[0115] As the batch size increases, the fixed scrap generally stays
the same and the variable scrap generally increases. As the coating
width is increased, the coating scrap increases but the trim scrap
decreases.
[0116] The term "Coating Weight" (C.sub.W) generally refers to the
weight per unit area of the film and is generally proportional to
the thickness of the coating, which may be varied based on the
coating method and equipment employed.
[0117] The term "total length of coated film" generally refers to
the total length of the final film product, measured as it is
collected on master rolls at the end of the coating equipment. The
total length of coated film may be a function of the batch size,
thickness of the coating, and width of the coating. Thus, after the
film is formed, the film may be cut to yield an identical dosage
size and a uniform product surface, in predetermined shapes and
dimensions, in order to be fitted into the desired dosage and/or
packaging.
[0118] The Total Length of Coated Film (L.sub.T) may be defined by
the following equation (eq. 6):
L.sub.T(m)=C.sub.Si(kg)*% S.sub.M/(C.sub.W(kg/m2)*W.sub.C(m)) (eq.
6)
[0119] For formulations where there are many volatile components in
the coating solution, the percent of solids measurement may not be
indicative of the actual percent of solids that exits the oven in
the form of film. In such an instance, the specific formulations
must be evaluated to determine the actual square meters of film
each formulation will produce.
Slitting Losses
[0120] The term "slitting losses" as used herein generally refers
in part to the scrap that is a result of cutting a formed and dried
film sheet into smaller rolls from which the individual doses to be
packaged. The term "edge trim" as used herein generally refers to
the outermost edge of the "coating width" of the coated film, which
is trimmed off.
[0121] Trimming the edges of the coating width (i.e., the "edge
trim") reduces or altogether eliminates inconsistencies along the
outermost edges of the film due to the coating/casting/rolling
process. Such inconsistencies are removed in order to provide a
uniform and consistent product. Slitting edge trim is measured as
the outside cut from the edge of the film sheet as it goes through
the slitter. The width of this cut is an independent variable
(W.sub.ST). The percentage of edge trim scrap is then defined as
the width of the edge trim divided by the starting width of the
film. As the width of the edge trim is independent of the total
film width, the percentage of edge trim scrap is inversely
proportional to the coating width, as demonstrated in the below
equation (eq. 7):
% W.sub.ST=W.sub.ST(m)/W.sub.C(m).*100 (eq. 7)
[0122] Notably, additional scrap (S.sub.SS) may be produced at the
slitter at the startup and shut down of the batch. The length of
this scrap is normally constant and independent of film width. The
percentage of start/stop scrap (% S.sub.SS) is therefore inversely
proportional to the total length of film (batch size), and is
proportional to the width of the film, as set forth in the below
equation (eq. 8):
% S.sub.SS=S.sub.SS(m)/L.sub.T(m)*100 (eq. 8)
[0123] It will be understood, of course, that there can be other
scrap associated with slitting, i.e. web breaks, equipment failures
and other processing issues. This other scrap is referred to herein
as scrap due to error. Scrap due to error is not a function of
batch size or coating width, but tends to be generally random and
is therefore not considered in this optimization method. Desirably,
there is no scrap due to error, and thus the final product is
optimized.
[0124] Scrap for slitting (S.sub.L) or slitting losses may be
defined by the formula (eq. 9):
S.sub.L(m.sup.2)=W.sub.ST(m)*L.sub.T(m)+S.sub.SS (eq. 9)
[0125] As the edge trim is removed from the sheet, the sheet may
also be slit into individual rolls for ease of packaging.
Packaging Losses
[0126] In some embodiments, the slit rolls may be fed into a
packaging machine for final packaging. In such embodiments, as the
slit rolls are fed onto the package machine, each roll may be
subjected to another edge trim to remove any final inconsistencies
which may have resulted in the transport and or storage of the
film. Desirably, such edge trim will be nominal, since the roll has
already been trimmed to its desired size. In addition, the package
machine may also cut each roll into an individual dosage width.
Lengths may be cut as the individual lanes enter the packaging. In
general, there are 3 main types of scrap associated with a standard
packaging machine. The first type of scrap is packaging edge trim,
which is a constant percentage, independent of batch size or
coating width. The percentage of packaging edge trim is defined as
the width of the packaging edge trim (W.sub.PT) divided by the
width of the slit roll being packaged (eq. 10):
% W.sub.PT=W.sub.PT(m)/W.sub.P(m).times.100 (eq. 10)
[0127] The second scrap includes the length of film that is wasted
during the start up of the packaging machine. The film used up at
the start up of the packaging machine includes film that may be
wasted for various alignment and consistency reasons, such as for
the alignment of the packaging material, adjustment of printers,
adjusting static charges, and other processing parameters. For a
given batch, the packaging start up scrap (P.sub.SS) is desirably a
reasonably constant number and independent of batch size or coating
width. Therefore the percentage of packaging start up scrap (%
P.sub.SS) is inversely proportional to the batch size (eq. 11),
where N.sub.S is the number of slit rolls per master roll:
% P.sub.SS=P.sub.SS(m)/(L.sub.T(m)*N.sub.S)*100 (eq. 11)
[0128] The third typical scrap associated with packaging is a
result of malfunctions in the process, such as web breaks, printers
drifting out of alignment, registration drift of the packaging
material and other processing issues. As with the other scrap due
to error, this scrap is desirably limited to the least amount
possible, and is not a function of the batch size and coating
width. Since this error scrap is not a function of the batch size
and coating width, it is therefore not pertinent to the optimized
yield analysis of the present invention.
Analysis of Data
[0129] The term "total scrap" (T.sub.S) as used herein generally
refers to the total scrap of the film or sheet due to
manufacturing, which includes any or all of the scrap lost to
mixing, the scrap lost to coating, the scrap lost to slitting and
the scrap due to packaging. Total scrap is the total scrap from the
processing and trimming of the film dosage products. Total Scrap
may be defined by the following formula (eq. 12):
T.sub.S(m.sup.2)=M.sub.LA(m.sup.2)+[(C.sub.SS+S.sub.SS+P.sub.SS]*W.sub.C-
)(m.sup.2) (eq. 12)
[0130] By utilizing the various relationships of manufacturing
steps as set forth herein, it is possible to optimize the coating
width in order to minimize the scrap produced in the manufacturing
of film products. Therefore, the basis of the invention is to pick
the ideal width to coat at which minimizes the scrap. Through use
of the inventive method for optimizing film production, it is
possible to optimize the process of film production in order to
minimize the scrap byproduct for any sheet or slab of film dosage
produced.
Optimization of Scrap
[0131] There are four types of scrap attributed to the present
method of film production, including: (1) scrap for mixing; (2)
scrap for coating; (3) scrap for slitting (or cutting) and (4)
scrap for packaging. Of the four types of scrap, scrap for mixing,
coating, slitting and packaging, two of the scrap factors are
directly tied to the width of the coating. Specifically, the scrap
for coating is a function of coating width, which is attributed to
the start up and shut down losses associated with the present
operating system.
[0132] The present method of film production is batch oriented with
an oven-based drying step. Achieving the proper consistency through
drying is important in the present invention. If the film is not
dried to the right consistency, the film may be considered waste,
and thus will not be packaged for selling/distribution.
[0133] Further, it is noted that changes to the operating
parameters may result in a new set of scrap. This is because, after
a change to any of the operating parameters is made, the film at
the new conditions must first go through the coater (1 coater
length), and then the resulting film may be tested for coat weight
and moisture, among other final properties. Based on these test
results, one can make an adjustment and run another test batch to
arrive at the proper final film. This repeated testing obviously
results in scrap generated. It is understood by those of ordinary
skill that longer ovens have the possibility to generate more scrap
through such testing. The processing parameters set forth herein
are optimized for specified coat weight and moisture, not for
scrap.
[0134] While the scrap for mixing is not directly related to the
coating width, it should be noted that batch or tank size is often
selected based on pre-existing roller/coating equipment, ovens, and
packaging equipment, etc. Thus, the coating width may be idealized
along with an increased batch size in order to efficiently produce
an increased number of film strips while reducing the total scrap
(including scrap due to mixing, coating, slitting and
packaging).
[0135] A method of optimizing self-supporting film production is
shown, for example, in FIG. 5. The method of optimizing a
self-supporting film dosage 100 includes the steps of: determining
110 at least one scrap factor, correlating 120 at least one scrap
factor to at least one processing parameter, and adjusting 130 the
processing parameter. Once the processing parameter is adjusted,
the method is used to lower or reduce at least one scrap factor. As
at least one scrap factor is reduced, there is an additive effect,
which desirably results in an overall reduction in the total scrap
produced in making a film or sheet product. An adjustment in
certain processing parameters, for example, is intended to reduce
more than one scrap factor, thus having an additive effect on the
reduction of total scrap. This is the case when adjusting one
processing parameter affects more than one scrap factor.
[0136] The at least one scrap factor may generally refer to one or
more of the classes of scrap discussed supra, including, scrap for
mixing, scrap for coating, scrap for cutting (slitting) and scrap
for packaging. Similarly, within these classes of scrap are
subclasses of scrap. For example, the scrap for mixing may
generally include the subclasses of the scrap lost to hoses and the
scrap lost to coating the mixer. The scrap for coating may
generally include the scrap subclasses of the scrap for start-up
and shut-down of the film forming process, and scrap for the drying
step(s), including oven length and various coefficients related to
drying. The scrap for cutting may include the scrap subclasses of
the scrap for slitting and the scrap for a packing machine, if
used. Other sources of scrap due to error may exist, which are not
currently scrap factors in the total scrap formula of eq. 12.
Although these error factors are not taken into account in the
present invention, these scrap factors may additionally be deemed a
scrap factor for purposes of the present invention and incorporated
into the consideration of the total scrap for manufacturing
self-supporting film products. Some of these error-based scrap
factors may also include, for example, scrap lost to volatiles,
scrap due to the degradation of the components, and scrap due to
packaging loses, and scrap due to non-calibrated equipment and
instruments. If desired, these other scrap factors may be included
in the optimization method 100 described herein.
[0137] The determining step 110 may further include determining a
scrap due to mixing factor; determining a scrap due to coating
factor; determining a scrap due to slitting (or cutting) factor,
determining a scrap due to packaging factor, determining one of the
subcategories of scrap factors, and combinations thereof. Scrap
factors may be determined by reviewing the losses in the
manufacturing process, analyzing the processing parameters for
losses in yield, or in comparing the theoretical number of strips
to the actual number of strips produced.
[0138] The correlating step 120 may be achieved by attributing the
at least one scrap factor to one or more processing parameters. The
processing parameters generally include the manufacturing
specifications for a run. Example processing parameters may include
the components used in the batch (solids, liquids, actives, etc.),
tank size, length of hoses, film formation equipment, film
thickness, film uniformity, film dryness, drying parameters
(including equipment, temperature, duration), coating width,
coating length, size of the final film product, and combinations
thereof, as may be desired. These scrap factor(s) may be correlated
to process parameters by incorporating the process parameters into
the equations (eq. 1 through 12) previously provided, or
alternatively, by identifying the relationship between the scrap
factor(s) and the processing parameter(s). The equations may be
manipulated in order to define how much scrap is attributed to
various process parameters, or alternatively, how process
parameters may be modified in order to reduce the amount of scrap
associated with one or more process parameters. The equations set
forth previously (eq. 1 through 12) may aid in defining the
relationship between the processing parameters and the various
scrap factors, and in the step 120 of correlating at least one
scrap factor to at least one processing parameter in accordance
with the method 100.
[0139] The adjusting step 130 of the present method may include
adjusting at least one processing parameter in order to reduce or
lower at least one scrap factor of the manufacturing process. Thus,
the adjusting step 130 may include, for example, modifying,
eliminating, increasing, or decreasing the characteristics of one
or more process parameters in order to put the scrap factor under a
desired target or within a desired range.
[0140] In one particular example, the coating width of the film
sheet may be increased or decreased. Varying the coating width of
the film sheet may be performed so as to reduce the amount of edge
trim needed to reduce the non-uniform edges from the film sheet 1.
Varying the coating width may also reduce the amount of edge trim
needed from each slit roll 86 in order to ensure that the end
individual lanes are the desired width, for example to fit into the
packaging machine properly and into the packaging materials/pouches
(see, e.g. FIG. 4). Similarly, the coating width and thickness may
be adjusted in order to make a more desirable product or
manufacturing process.
[0141] As still another example, the adjusting step 130 may further
include the step of minimizing a hose length from a tank or mixer,
thus holding a control volume of mixed film material to be coated.
This minimization of hose length may ultimately reduce the standard
amount of material that is lost to the hoses as a result of
coating.
[0142] As yet another example, the adjusting step 130 may further
include increasing a drying temperature, a drying duration, or an
oven length in order to promote a desired level of drying in the
final film product. The adjusting step 130 seeks to modify one or
more processing parameters so as to provide a desirable end product
(i.e., one that is uniform and fully dried), while reducing the
waste material generated by the process. In some instances, the
drying parameters (i.e., temperature, length, duration, etc.) may
be increased. In other instances, such parameters may be
shortened.
[0143] The examples of adjusting provided herein are intended to be
non-limiting in nature, and are presented for illustrative purposes
of the diverse number of processing parameters that may be modified
in order to reduce a scrap factor associated with the method 100 of
the present invention. The adjustment and modification of various
other processing parameters is intended to be included herewith as
may be desired.
[0144] With reference to FIG. 5, it should be noted that one or
more steps of the invention of the present method may be repeated
or reiterated as may be desired until a certain target or range may
be achieved. Thus, it is possible to identify more than one scrap
factor to be correlated against processing parameters in order to
reduce more than one scrap factor in the total amount of scrap. In
some instances, it may be undesirable to modify/adjust many
processing parameters at a single time, as changing multiple
variables at once may create other problems in manufacturing. For
example, on a first pass through the method, a scrap for mixing may
be reduced, while on subsequent passes, other scrap factors may be
reduced. Thus, the method 100 may be evolving and improving, while
the desirable parameters may be tracked or logged for use in other
products. For example, certain processing parameters may be
advantageous for processing films of one composition, but not as
advantageous for processing films of a different compositional
make-up, a different thickness, or differing in other physical or
chemical properties. The particular adjustments made in the present
method 100 are specific to the particular final dosage form
desired, including the components and properties of the final
dosage.
[0145] Similarly, it is possible to reduce the amount of scrap
iteratively over a desired number of calculations (modeling the
manufacturing process) or during one or more runs in order to
continually achieve an improved result over previous runs. An
example of this may include, for example, adjusting the coating
width enough so that an edge trim may be employed to cut off any
non-uniform edges along the film sheet, where the edge trim is
limited to only non-uniform film material, and no uniform film
product is sacrificed to the scrap for cutting area.
[0146] One or more of the steps of the present method may be
completed throughout the manufacturing process in order to ensure
that desirable film products are produced. Thus, the method may be
completed in-line as the film is being manufactured and produced,
or with real-time measurements taken, to be determined, correlated,
and adjusted in accordance with the method 100. Alternatively, the
method 100 may be completed as a modeling process prior to
manufacture in order to plan efficient process design for various
final film products. The method 100 may also be completed prior to
initializing the manufacturing as a calibration or quality control
step to ensure the most efficient and economical usage of actives
and ingredients in the film. The method 100 may be completed at the
end of a run, either to aid in the diagnosis or trouble shooting of
unknown problems or errors, or to supplement other measurements
with respect to the manufacturing specifications and parameters.
One or more steps of the method 100 may be completed through
iterative calculations, comparisons, or through the aid of a
computer system 150, shown for example, in FIG. 5A.
[0147] The present invention may further comprise a system for
optimizing the production of self-supporting film. The system
includes a manufacturing apparatus for a film product, and a
computer system 150, which may run the method 100 with respect to
the process design of the manufacturing system.
[0148] The manufacturing apparatus may include one or more of the
instruments and equipment discussed supra. For example, the
manufacturing equipment of the system may include a mixer, a film
former, a drying apparatus, and a cutting apparatus, as well as all
intervening components. As further examples of the manufacturing
equipment that may be used in the present invention: the mixer may
desirably include a mother/daughter mixer; the film former may
desirably include a reverse roll coating apparatus; the drying
apparatus may desirably include an oven; and the cutting apparatus
may desirably include a slitter and/or a packaging machine.
[0149] The computer system 150 may execute the method 100,
including tracking of processing parameters and scrap produced in a
system of optimizing self-supporting film production. The computer
system 150 may be generally defined by the elements included in the
block diagram of FIG. 5A.
[0150] The computer system 150 may be integral to the manufacturing
equipment or remotely associated to the manufacturing equipment
through wireless connections or remote data entry. The computer
system 150 may constantly (or intermittently) acquire various data
from the manufacturing system, taking readings of the various
processing parameters, scrap factors, and the like. The computer
system 150 may monitor at least one product characteristic to
further provide information on whether a final product with
desirable characteristics is achieved. The computer system 150 may
control at least one processing parameter in order to promote the
production of a desirable final product and an efficient process
(with reduced total scrap).
[0151] The system 150 may be adjustable in-line to comport with
real-time processing and manufacture of film. It may also be
desirable for the system 150 to include a film manufacturing
apparatus which may be remotely adjustable.
[0152] The system 150 of FIG. 5A may be used for optimizing a
method of film production 100, in accordance with method 100 and
system of the present invention. In one embodiment, the computer
system 150 may include a processor 151, an input device 152 coupled
to the processor 151, an output device 153 coupled to the processor
151, and one or more memory devices 154 and 155 each coupled to the
processor 151.
[0153] The processor 151 performs computation and control functions
of computing unit or computer system 150, and may include a single
processing unit, or may be distributed across one or more
processing units in one or more locations.
[0154] The input device 152 may be, inter alia, a keyboard, a
mouse, a keypad, a touchscreen, a voice recognition device, a
sensor, a network interface card (NIC), a Voice/video over Internet
Protocol (VOIP) adapter, a wireless adapter, a telephone adapter, a
dedicated circuit adapter, etc.
[0155] The output device 153 may be, inter alia, a printer, a
plotter, a computer screen, a magnetic tape, a removable hard disk,
a floppy disk, a NIC, a VOIP adapter, a wireless adapter, a
telephone adapter, a dedicated circuit adapter, an audio and/or
visual signal generator, a light emitting diode (LED), and the
like.
[0156] The memory devices 154 and 155 may be, inter alia, a cache,
a dynamic random access memory (DRAM), a read-only memory (ROM), a
hard disk, a floppy disk, a magnetic tape, an optical storage such
as a compact disk (CD) or a digital video disk (DVD), etc. The
memory device 155 preferably includes a computer code 157, which is
a computer program that comprises computer-executable instructions.
The computer code 157 may include, inter alia, an algorithm used
for utilizing generational file names according to the present
invention.
[0157] Memory may comprise any known type of data storage and/or
transmission media, including bulk storage, magnetic media, optical
media, random access memory (RAM), read-only memory (ROM), a data
cache, a data object, and the like. Cache memory elements provide
temporary storage of at least some program code in order to reduce
the number of times code must be retrieved from bulk storage during
execution. The storage unit is, for example, a magnetic disk drive
or an optical disk drive that stores data. Moreover, similar to
processor 151, memory may reside at a single physical location,
comprising one or more types of data storage, or be distributed
across a plurality of physical systems in various forms. Further,
memory can include data distributed across, for example, a LAN, WAN
or storage area network (SAN) (not shown).
[0158] The processor 151 executes the computer code 157. The memory
device 154 includes input data 156. The input data 156 includes
input required by the computer code 157. The output device 153
displays output from the computer code 157. Either or both memory
devices 154 and 155 (or one or more additional memory devices not
shown in FIG. 5A) may be used as a computer usable storage medium
(or a computer readable storage medium or a program storage device)
having a computer readable program embodied therein and/or having
other data stored therein. The computer readable program comprises
the computer code 157. Generally, a computer program product (or,
alternatively, an article of manufacture) of the computer system
150 may include computer usable storage medium (or program storage
device).
[0159] While FIG. 5A shows the computer system 150 as a particular
configuration of hardware and software, any configuration of
hardware and software may be utilized for the purposes in
conjunction with the particular computer system 150 of FIG. 5A, as
may be desired. For example, the memory devices 154 and 155 may be
portions of a single memory device rather than separate memory
devices.
[0160] The computer system 150 can take the form of an entirely
hardware embodiment, an entirely software embodiment or an
embodiment containing both hardware and software elements. In a
preferred embodiment, the invention may be implemented in software.
Furthermore, the computer system 150 can take the form of a
computer program product accessible from a computer-usable or
computer-readable medium providing program code for use-by or
in-connection with a computing system or any instruction execution
system to provide and facilitate the capabilities of the present
invention. For the purposes of this description, a computer-usable
or computer-readable medium can be any apparatus that can contain,
store, communicate, propagate, or transport the program for use by
or in connection with the instruction execution system, apparatus,
or device.
EXAMPLES
Example I
Correlating Lost Coating to the Tank Size
[0161] In order to understand the coating lost to the mixer and
hoses, 192 runs on various sized tanks were completed. The amount
of coating solution lost was tabulated for each run. Then, average
solution lost was computed for each tank size over the total number
of runs reviewed. Below is a listing of the data from the 192 runs
at tank sizes including 40 liter, 120 liter, 400 liter, 1,000 liter
and 2,000 liter The trend of tank size versus solution lost is
depicted in FIG. 6, which correlates the trend observed from the
data into the formula: y=3.3988 Ln(x)-6.9467, where y includes the
coating lost to hoses and tank surfaces, and x includes the tank
size.
[0162] The average mixing losses, which are depicted on FIG. 6, are
set forth in Table II below:
TABLE-US-00002 TABLE II Mixer Losses (kg) Tank size Average
(liters) solution lost (kg) 40 4.83 120 10.76 400 12.49 1000 16.91
1,2000 18.67
[0163] Seventeen runs were completed on a 40 liter Tank. Table III
below depicts the total batch size (kg) and the total solution lost
to the mixer and hoses (kg).
TABLE-US-00003 TABLE III Run No. Batch size Kg lost 1 38 3.02 2 38
3.26 3 38 3.58 4 38 3.95 5 38 4.01 6 38 4.15 7 38 4.17 8 38 4.20 9
38 4.30 10 38 4.30 11 38 4.70 12 38 5.30 13 38 5.30 14 38 5.50 15
38 5.62 16 38 7.71 17 41 9.03
[0164] Forty-one runs were then completed on a 120 liter Tank.
Table IV below depicts the total batch size (kg) and the total
solution lost to the mixer and hoses (kg).
TABLE-US-00004 TABLE IV Run No. Batch size Kg lost 1 80 28.00 2 101
2.10 3 101 23.40 4 115 4.60 5 115 4.60 6 115 5.10 7 115 5.50 8 115
6.08 9 115 7.00 10 115 7.10 11 115 7.40 12 115 8.00 13 115 8.40 14
115 9.20 15 115 9.30 16 115 9.30 17 115 9.30 18 115 9.30 19 115
9.30 20 115 9.30 21 115 9.60 22 115 9.60 23 115 9.60 24 115 9.60 25
115 9.90 26 115 10.20 27 115 10.60 28 115 11.20 29 115 11.30 30 115
11.50 31 115 11.80 32 115 12.20 33 115 12.20 34 115 12.20 35 115
12.20 36 115 12.70 37 115 14.70 38 115 17.40 39 115 17.90 40 115
29.60 41 121 2.94
[0165] Seventy runs were then completed on a 400 liter Tank. Table
V below depicts the total batch size (kg) and the total solution
lost to the mixer and hoses (kg).
TABLE-US-00005 TABLE V Run No. Batch size Kg lost 1 205 8.30 2 227
5.30 3 227. 13.90 4 227. 16.70 5 250 8.40 6 250 8.70 7 250 9.40 8
250 9.50 9 250 9.50 10 250 10.80 11 250 10.80 12 250 12.00 13 250
13.10 14 250 14.40 15 250 14.90 16 250 15.00 17 250 17.90 18 250
20.10 19 265 9.30 20 265 9.60 21 265 9.60 22 265 9.90 23 265 9.90
24 265 10.00 25 265 10.00 26 265 10.20 27 265 10.50 28 265 10.89 29
265 10.89 30 265 12.00 31 265 12.00 32 265 14.20 33 265 17.45 34
265 19.30 35 275 4.62 36 280 3.10 37 280 4.09 38 280 6.30 39 280
6.80 40 280 7.30 41 280 7.90 42 280 8.40 43 280 8.40 44 280 8.70 45
280 10.70 46 280 11.50 47 280 11.90 48 280 11.90 49 280 12.00 50
280 12.00 51 280 12.30 52 280 12.90 53 280 13.90 54 280 14.00 55
280 15.10 56 280 15.70 57 280 17.00 58 280 17.90 59 280 19.00 60
280 23.90 61 280 24.40 62 380 11.93 63 380 11.93 64 380 12.00 65
380 12.00 66 380 17.70 67 380 17.70 68 380 18.30 69 380 23.40 70
380 23.40
[0166] Fifty-four runs were completed on a 1000 liter Tank. Table
VI below depicts the total batch size (kg) and the total solution
lost to the mixer and hoses (kg).
TABLE-US-00006 TABLE VI Run No. Batch size Kg lost 1 850 9.00 2 850
11.20 3 850 11.30 4 850 12.00 5 850 12.00 6 850 12.00 7 850 12.00 8
850 12.00 9 850 12.00 10 850 12.00 11 850 12.00 12 850 12.00 13 850
12.00 14 850 13.10 15 850 13.69 16 850 13.69 17 850 13.80 18 850
13.80 19 850 15.20 20 850 15.70 21 850 15.70 22 850 17.30 23 850
17.90 24 850 18.00 25 850 18.80 26 850 19.10 27 850 20.20 28 850
20.20 29 850 20.50 30 850 20.50 31 850 21.60 32 850 21.60 33 850
23.20 34 850 23.20 35 850 23.90 36 850 23.90 37 850 25.40 38 850
28.12 39 850 28.12 40 850 38.80 41 950 9.00 42 950 10.60 43 950
11.20 44 950 11.70 45 950 12.00 46 950 12.00 47 950 12.00 48 950
12.00 49 950 12.00 50 950 15.30 51 950 17.70 52 950 22.00 53 950
28.00 54 950 31.20
[0167] Nine runs were completed on a 2000 liter Tank. Table VII
below depicts the total batch size (kg) and the total solution lost
to the mixer and hoses (kg).
TABLE-US-00007 TABLE VII Run No. Batch size Kg lost 1 1,380 12 2
1,380 12 3 1,380 12 4 1,700 12 5 1,900 24 6 1,900 24 7 1,900 24 8
1,900 24 9 1,900 24
[0168] To determine mixer loses, data was compiled from the above
192 batches. Lost solution was determined to be a function of tank
size. Thus, even if a mixer is run at half capacity (i.e. half
full), the same total solution is lost (Lost Solution) in the pumps
and hoses of the process. The resulting function of these batches,
plotted on a chart of tank size (in kg) by mixer losses (in kg) is
the relationship depicted in FIG. 6. The scrap for mixing refers to
the amount of solution that is lost to hoses and mixer.
[0169] The scrap for mixing may be further defined by the formula
(eq.13):
M.sub.LM(Kg)=(3.4031 Ln(V.sub.M(Kg)))-6.8207 (eq. 13)
[0170] As explained above, other scrap associated with mixing,
including errors such as spills, equipment failures and other
processing issues. This other error-based scrap is not a function
of batch size or coating width, but tends to be more or less random
and is therefore not considered in this optimization method.
Example II
Determining Coating Losses as Related to Start-Up/Shut-Down
[0171] In order to understand the coating losses which are
attributed to the start-up and shut-down of the oven/drying
process, the amount of coated solution lost was tabulated over 206
runs. As scrap in some of these runs were high as a result of one
time anomalies, one hundred of the most ideal runs (lowest scrap)
lots were used as examples for this calculation. Efficiency in the
start-up and shut-down is an area in which constant efforts are
made to improve. The amount of scrap film was tracked for each run.
"Scrap film" refers to that film which did not have the proper
uniformity/consistency upon the completion of the drying process,
thus it was discarded. For the runs in this Example, the oven
length was a standard length of 9 m. The average total scrap for
each run was 87 m, regardless of the batch size. Thus, 87 m of
scrap, divided by 9 m of oven length is 9.7, which is the
coefficient of equation 5 (eq. 5), a variable in the determination
of Scrap for Coating. That is, regardless of the batch size, the
average loss for start-up/shut-down was determined to be 87 meters
in length, which is 9.7 times the oven length. Currently 9 meters,
this length is the amount of material that must typically be run
through the oven to be initialized before the end film sheet
product has the most desirable characteristics obtained. Thus, the
amount of scrap for coating is also a direct function of the
coating width selected. While the coating width is minimized, the
start up/shut down scrap will also be minimized.
[0172] The scrap for coating may be defined by the formula:
C.sub.SS(m.sup.2)=9.7*L.sub.O(m)*W.sub.C(m) (eq. 5)
[0173] It is noted that 9.7 is the coefficient generated from the
analysis of a select 100 runs (set forth below in Table VIII). To
determine the coating losses at start-up and shut down of the
process, the average of the best 100 runs were used. This average
is in accordance with the results that are accomplished on a
routine basis. The average loss of coating from these 100 runs was
87 meters. It is understood that this coefficient can vary with
different formulations and different drying ovens, and will need to
be evaluated for any specific product. The "% coating scrap" is
defined by the scrap for coating (m.sup.2) divided by the total
square meters of film produced times 100.
[0174] There can be other scrap associated with coating, i.e. web
breaks, equipment failures and other processing issues. This scrap
is not a function of batch size or coating width, but tends to be
more or less random and is therefore not considered in this
optimization method.
[0175] The term "oven length" generally refers to the total length
under which moisture and/or water is removed from the wet film or
cast film, before the film is completed into the final film product
or film sheet product. The oven length was 9 meters for these 100
runs.
TABLE-US-00008 TABLE VIII Run Scrap Batch size No. (M) (kg) 1 38.7
265 2 38.7 265 3 39.7 265 4 41.1 265 5 41.1 265 6 43.2 38 7 43.2 38
8 44.2 38 9 44.2 38 10 44.3 115 11 44.3 115 12 44.3 115 13 44.3 115
14 47.0 280 15 50.5 38 16 50.6 41 17 57.3 38 18 58.3 38 19 58.7 38
20 59.9 280 21 63.8 280 22 64.3 38 23 64.9 265 24 64.9 265 25 65.0
115 26 65.3 280 27 65.9 115 28 65.9 115 29 65.9 115 30 65.9 115 31
70.2 280 32 71.1 280 33 72.3 115 34 72.3 115 35 72.3 115 36 72.3
115 37 72.4 265 38 72.4 265 39 72.7 115 40 72.9 115 41 72.9 115 42
73.7 280 43 73.9 101 44 74.4 38 45 75.3 265 46 75.4 115 47 77.8 280
48 79.9 115 49 81.2 265 50 82.5 280 51 84.0 250 52 86.8 280 53 87.3
280 54 90.3 275 55 90.5 227 56 90.9 280 57 92.3 250 58 92.5 115 59
94.5 280 60 95.4 265 61 96.8 380 62 96.8 380 63 97.1 38 64 97.5 38
65 97.6 250 66 98.6 250 67 98.7 280 68 99.6 280 69 99.8 115 70
102.0 280 71 104.0 115 72 104.2 38 73 108.6 115 74 110.6 38 75
113.3 280 76 115.4 250 77 115.8 280 78 115.8 115 79 116.8 280 80
119.6 115 81 121.7 250 82 122.4 115 83 122.8 850 84 122.9 250 85
124.2 115 86 124.5 250 87 127.2 850 88 128.5 850 89 129.0 280 90
130.1 850 91 130.2 280 92 130.6 38 93 132.9 380 94 132.9 380 95
137.0 250 96 144.8 280 97 144.9 280 98 145.3 250 99 149.3 115 100
152.9 280
Example III
Exemplary Film or Sheet Process with Exemplary Scrap
[0176] Table IX below depicts, for tank sizes of 40 liter, 120
liter, 400 liter, 1000 liter and 2000 liter, the possible results
of a batch of solution, which is coated, dried, cut and packaged.
The film manufacturing process along these metrics has scrap
computed for it, including a scrap for mixing, a scrap for coating,
a scrap for slitting and a scrap for packaging. For the purposes of
this example, the optimum coating width discussed above was
used.
TABLE-US-00009 TABLE IX Tank Size (liters) 40 100 400 1000 2000
Total Batch .sup. 38 .sup. 115 380 950 1900 wt (kg) Theoretical
152,000 460,000 1,520,000 3,800,000 7,600,000 Strips strips to
129,767 422,693 1,466,423 3,733,950 7,524,515 coater % Mixing 14.6%
8.1% 3.5% 1.7% 1.0% Scrap strips to 99,742 359,155 1,344,932
3,514,856 7,181,920 slitter % Coating 19.8% 13.8% 8.0% 5.8% 4.5%
scrap strips to 92,101 344,761 1,311,369 3,451,292 7,057,676
packaging % Slitting 5.0% 3.1% 2.2% 1.7% 1.6% Scrap total 82,123
317,778 1,219,331 3,215,231 6,578,897 packaged strips % Packaging
6.6% 5.9% 6.1% 6.2% 6.3% Scrap % total 46% 31% 20% 15% 13%
scrap
Example IV
Impact of Batch Size on Scrap
[0177] Using the data from Example III above, one can evaluate the
relationship between batch size and the four main types of scrap.
This data is represented in FIG. 7. The results of this data
indicate the following:
[0178] Mixing Scrap is a strong function of Batch size; Coating
Scrap is a strong function of Batch size; Slitting Scrap is a
moderate function of Batch size; and Packaging Scrap is a minimal
function of Batch size.
[0179] With reference to FIG. 7, the percentage of scrap is
depicted with use of an optimum width. The percentage of scrap is
depicted with respect to the batch size in kg. The optimum coating
width refers to the width that will yield the least amount of scrap
for a given batch size.
[0180] FIG. 8 depicts the optimum coating width and process scrap
as a function of batch size. The curved solid line from left to
right is optimum coating width where the master roll is slit into
the final product width, while the stepped dashed line refers to
the optimum width for products where the master roll is slit into
daughter rolls for a 8 lane packaging machine and a product 22 mm
wide. The curved dashed line represents the minimum amount of scrap
that can be expected using the optimum width
[0181] The data depicted on the graph of FIG. 8 is based on the
film product that is formed, dried, cut, and then packaged on a
pouching machine. Thus, it is possible to optimize the width of
coating in order to minimize scrap. In the present system of
manufacturing, there is both fixed scrap and variable scrap.
[0182] It should, of course, be noted that there may be waste or
"scrap" attributable to other variables, including errors such as
improper packaging, improper cutting, or improper compositional
makeup of the film, or such other scrap may be due to volatiles,
degradation of one or more actives, as well as standard errors
including the calibration of the equipment and instruments.
However, these "other" factors, which may attribute to scrap and
error are desirably minimized, and are not the focus of the present
invention. It is desirable that such "other" factors should be
minimized as much as possible to optimize the final amount of
usable film.
Example V
Mixing Scrap as a Function of Coating Width
[0183] Using the methods set forth in the present application, one
can evaluate the impact of coating width on Mixing Scrap for
various Batch Sizes. This evaluation is shown in FIG. 9. As shown
in FIG. 9, there appears to be minimal impact on the Mixing Scrap
by changing the coating width.
Example VI
Coating Scrap as a Function of Coating Width
[0184] Using the methods set forth in the present application, one
can evaluate the impact of coating width on Coating Scrap for
various Batch Sizes. This evaluation is shown in FIG. 10. As shown
in FIG. 10, the following impact is observed. For all batch sizes,
the relationship between Coating Scrap and Coating Width is linear,
with the greater slop associated with the smaller batches.
Example VII
Slitting Scrap as a Function of Coating Width
[0185] Using the methods set forth in the present application, one
can evaluate the impact of coating width on Slitting Scrap for
various Batch Sizes. This evaluation is shown in FIG. 11. As shown
in FIG. 11, there appears to be a strong inverse relationship
between Slitting Scrap and Coating Width at the narrower widths,
with much less of a correlation with batch size.
Example VIII
Packaging Scrap as a Function of Coating Width
[0186] Using the methods set forth in the present application, one
can evaluate the impact of coating width on packaging scrap. This
evaluation is shown in FIG. 12. FIG. 12 shows the predominately
independent nature of the packaging scrap as a function of the
coating width.
Example IX
Overall Scrap as a Function of Coating Width
[0187] Using the methods set forth in the present application, one
can evaluate the impact of coating width on overall scrap. FIG. 13
shows the presence of an optimum width/minimum scrap for the
smaller batch sizes.
[0188] Data for Examples IV-IX is set forth in the following table
(Table X):
TABLE-US-00010 TABLE X Batch Coating Width size 100.0 200.0 300.0
400.0 500.0 600.0 700.0 800.0 900.0 1000.0 % mixing loss 38 15.1%
15.1% 15.1% 15.1% 15.1% 15.1% 15.1% 15.1% 15.1% 15.1% % mixing loss
115 8.2% 8.2% 8.2% 8.2% 8.2% 8.2% 8.2% 8.2% 8.2% 8.2% % mixing loss
380 3.6% 3.6% 3.6% 3.6% 3.6% 3.6% 3.6% 3.6% 3.6% 3.6% % mixing loss
950 1.8% 1.8% 1.8% 1.8% 1.8% 1.8% 1.8% 1.8% 1.8% 1.8% % mixing loss
1900 1.0% 1.0% 1.0% 1.0% 1.0% 1.0% 1.0% 1.0% 1.0% 1.0% % coating
scrap 38 8.8% 17.5% 26.3% 35.1% 43.9% 52.6% 61.4% 70.2% 79.0% 87.7%
% coating scrap 115 2.9% 5.8% 8.7% 11.6% 14.5% 17.4% 20.3% 23.2%
26.1% 29.0% % coating scrap 380 0.9% 1.8% 2.6% 3.5% 4.4% 5.3% 6.1%
7.0% 7.9% 8.8% % coating scrap 950 0.4% 0.7% 1.1% 1.4% 1.8% 2.1%
2.5% 2.8% 3.2% 3.5% % coating scrap 1900 0.2% 0.4% 0.5% 0.7% 0.9%
1.1% 1.2% 1.4% 1.6% 1.8% % scrap slitting 38 25.6% 13.7% 10.4% 9.4%
9.5% 10.6% 12.7% 16.7% 24.3% 43.6% % scrap slitting 115 25.2% 12.9%
8.9% 7.0% 6.0% 5.4% 5.0% 4.9% 4.8% 4.8% % scrap slitting 380 25.1%
12.6% 8.5% 6.5% 5.3% 4.5% 3.9% 3.6% 3.3% 3.1% % scrap slitting 950
25.0% 12.5% 8.4% 6.3% 5.1% 4.3% 3.7% 3.3% 3.0% 2.7% % scrap
slitting 1900 25.0% 12.5% 8.4% 6.3% 5.1% 4.2% 3.6% 3.2% 2.9% 2.6% %
packaging scrap 38 16.3% 15.8% 15.6% 15.6% 15.5% 15.5% 15.5% 15.5%
15.5% 15.6% % packaging scrap 115 13.6% 13.5% 13.4% 13.4% 13.4%
13.4% 13.4% 13.4% 13.4% 13.4% % packaging scrap 380 12.7% 12.7%
12.6% 12.6% 12.6% 12.6% 12.6% 12.6% 12.6% 12.6% % packaging scrap
950 12.5% 12.4% 12.4% 12.4% 12.4% 12.4% 12.4% 12.4% 12.4% 12.4% %
packaging scrap 1900 12.4% 12.4% 12.4% 12.4% 12.4% 12.4% 12.4%
12.4% 12.4% 12.4% total scrap 38 51.7% 49.1% 52.7% 57.8% 63.6%
69.6% 75.8% 82.2% 88.6% 95.0% total scrap 115 42.4% 34.8% 33.9%
34.7% 36.1% 37.9% 39.8% 41.9% 44.1% 46.3% total scrap 380 37.5%
27.7% 24.9% 24.0% 23.7% 23.8% 24.0% 24.4% 24.9% 25.5% total scrap
950 35.7% 25.3% 22.0% 20.6% 19.8% 19.4% 19.2% 19.1% 19.2% 19.2%
total scrap 1900 35.1% 24.4% 20.9% 19.3% 18.4% 17.8% 17.4% 17.2%
17.1% 17.0%
[0189] While particular embodiments of the present invention have
been described herein for purposes of illustration, many
modifications and changes will become apparent to those skilled in
the art. Accordingly, the appended claims are intended to encompass
all such modifications and changes as fall within the true spirit
and scope of this invention.
* * * * *