U.S. patent application number 13/844775 was filed with the patent office on 2014-09-18 for reduction in stress cracking of films.
The applicant listed for this patent is MonoSol Rx, LLC. Invention is credited to Beuford Arlie Bogue, Greg Slominski.
Application Number | 20140272220 13/844775 |
Document ID | / |
Family ID | 50631062 |
Filed Date | 2014-09-18 |
United States Patent
Application |
20140272220 |
Kind Code |
A1 |
Bogue; Beuford Arlie ; et
al. |
September 18, 2014 |
REDUCTION IN STRESS CRACKING OF FILMS
Abstract
Methods and packages for storing film strips while reducing or
eliminating stress cracking during storage, including use of
packages having an inner surface made from polymeric materials
exhibiting various physical properties and including films and
pouches that are annealed.
Inventors: |
Bogue; Beuford Arlie;
(Valparaiso, IN) ; Slominski; Greg; (Valparaiso,
IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
MonoSol Rx, LLC; |
|
|
US |
|
|
Family ID: |
50631062 |
Appl. No.: |
13/844775 |
Filed: |
March 15, 2013 |
Current U.S.
Class: |
428/35.2 ;
264/235 |
Current CPC
Class: |
B65D 33/002 20130101;
A61J 1/035 20130101; Y10T 428/1334 20150115; C08J 5/18
20130101 |
Class at
Publication: |
428/35.2 ;
264/235 |
International
Class: |
B65D 33/00 20060101
B65D033/00 |
Claims
1. A pouch for storing a film comprising: a laminate of at least
one first layer and at least one second layer, and a cavity
comprising a film which has been annealed to reduce stress-cracking
of said film, said film comprising at least one polymer and at
least one active, wherein said film exhibits less stress-cracking
when annealed than when not annealed.
2. The pouch of claim 1, wherein the at least one polymer is
selected from the group consisting of polyethylene oxide,
hydroxypropylmethylcellulose, and combinations thereof.
3. The pouch of claim 1, wherein the at least one first layer or
the at least one second layer comprise low density polyethylene,
ethylene acrylic acid, and combinations thereof.
4. The pouch of claim 1, wherein the film does not exhibit stress
cracking or does not exhibit substantial stress cracking from about
1 month to about 3 years.
5. The pouch of claim 4, wherein the film does not exhibit stress
cracking or does not exhibit substantial stress cracking from about
1 month to about 2 years.
6. The pouch of claim 1, said film further comprising an additive
selected from the group consisting of surfactants, plasticizers,
and combinations thereof.
7. A method for reducing stress cracking in a film comprising:
8. (a) providing a film comprising at least one polymer and at
least one active; (b) annealing the film to reduce stress-cracking
of the film; wherein said film exhibits reduced stress cracking as
a result of said annealing.
9. The method of claim 7, wherein said film further comprises an
additive selected from the group consisting of surfactants,
plasticizers, and combinations thereof.
10. The method of claim 9, wherein the additive is present in an
amount from about from about 5% by wt. to about 30% by weight of
the film.
11. The method of claim 7, wherein the film does not exhibit stress
cracking or does not exhibit substantial stress cracking for from
about 1 month to about 3 years.
12. The method of claim 7, wherein the film does not exhibit stress
cracking or does not exhibit substantial stress cracking for from
about 1 month to about 2 years.
13. The method of claim 7, wherein the film is annealed by applying
heat to the film at temperatures of from about 40.degree. C. to
about 90.degree. C.
14. The method of claim 7, wherein the film is heated for from
about 0.5 minutes to about 60 minutes.
15. A method for reducing stress cracking in a film comprising a
continuous and uniform product comprising the steps of: (a)
preparing a film-forming matrix comprising a solvent, an active and
a polymeric material; (b) casting said film-forming matrix and
drying said film-forming matrix to form a dried film; and (c)
annealing said dried film to relieve stresses imposed by the drying
process.
16. The method of claim 15, wherein the film is annealed at a
temperature between 40 degrees C. and 90 degrees C.
17. The method of claim 15, wherein the film is annealed at a time
between 0.5 minutes and 60 minutes.
18. A method for reducing stress cracking in a film comprising a
continuous and uniform product comprising the steps of: (a)
preparing a film-forming matrix comprising a solvent, an active and
a polymeric material; (b) casting said film-forming matrix and
drying said film-forming matrix to form a dried film; (c) packaging
said dried film in a pouch to form a packaged film; and (d)
annealing said pouched film to relieve stresses imposed by the
drying process.
19. The method of claim 18, wherein the packaged film is annealed
at a temperature between 40 degrees C. and 90 degrees C.
20. The method of claim 18, wherein the packaged film is annealed
at a time between 0.5 minutes and 60 minutes. The method of claim
15, wherein the film is annealed by removing the film from the
substrate, annealing the film and rewinding the film onto a
substrate.
22. The method of claim 21, wherein the film is annealed at a
temperature between 40 degrees C. and 90 degrees C.
23. The method of claim 21, wherein the film is annealed at a time
between 0.5 minutes and 60 minutes
24. A continuous and uniform film product with reduced stress
cracking, wherein said film product is formed by a process
comprising: (a) casting a film-forming matrix comprising a solvent,
an active and a polymeric material; (b) drying said film-forming
matrix to form a dried film; and (c) annealing said dried film to
relieve stresses imposed by the drying process to form a reduced
stress cracked film.
25. The film of claim 24, wherein the film is annealed at a
temperature between 40 degrees C. and 90 degrees C.
26. The film of claim 24, wherein the film is annealed at a time
between 0.5 minutes and 60 minutes.
27. A continuous and uniform film product with reduced stress
cracking, wherein said product is formed by a process comprising:
(a) casting a film-forming matrix comprising a solvent, an active
and a polymeric material; (b) drying said film-forming matrix to
form a dried film; (c) packaging said dried film in a pouch to form
a packaged film; and (d) a annealing said pouched film to relieve
stresses imposed by the drying process to form a reduced stress
cracked film.
28. The film of claim 27, wherein the packaged film is annealed at
a temperature between 40 degrees C. and 90 degrees C.
29. The film of claim 27, wherein the packaged film is annealed at
a time between 0.5 minutes and 60 minutes.
30. The film of claim 24, wherein the film is annealed by removing
the film from the substrate, annealing the film and rewinding the
film onto a substrate.
31. The film of claim 30, wherein the film is annealed at a
temperature between 40 degrees C. and 90 degrees C.
32. The film of claim 30, wherein the film is annealed at a time
between 0.5 minutes and 60 minutes
33. The film of claim 24 which is intact with no cracking after 3
weeks in the package
34. The film of claim 24 intact with no cracking after 2 months in
the package
35. The film of claim 24 intact with no cracking after 6 months in
the package
36. The film of claim 24 intact with no cracking after 12 months in
the package
37. The film of claim 24 intact with no cracking after 2 years in
the package
38. The film of claim 24 intact with no cracking after 3 years in
the package
39. The film of claim 30 which is intact with no cracking after 3
weeks in the package
40. The film of claim 30 intact with no cracking after 2 months in
the package
41. The film of claim 30 intact with no cracking after 6 months in
the package
42. The film of claim 30 intact with no cracking after 12 months in
the package
43. The film of claim 30 intact with no cracking after 2 years in
the package
44. The film of claim 30 intact with no cracking after 3 years in
the package
Description
FIELD OF THE INVENTION
[0001] The present invention relates to methods and packages for
storing film strips while reducing or eliminating stress cracking
during storage.
BACKGROUND OF THE INVENTION
[0002] Sporadic events of stress cracking in polymeric based film
strips found in finished products but not observed in a 15 minute
in-process check or AQL testing has been an issue with some
polymeric based film products. Stress cracking generally begins to
appear in the film product 2 to 4 weeks after manufacturing and
packaging. Data analysis on lots exhibiting cracking has led to the
conclusion that the problem is probably caused by imparting stress
to the strips during the manufacturing process.
[0003] One source of stress that is imparted to the film during
manufacturing is in the drying process. During drying, the wet film
product is applied or coated to a substrate, and is then dried on
that substrate. In some drying processes, particularly those
including high solvent content, up to 70% of the volume of the wet
film solution is removed in the drying process. This shrinkage
imparts stress to the film, which adheres to the substrate onto
which it is cast and dried. Another source of stress involves the
cutting process. Following the initial drying and shrinkage,
typically the film product is cut into individual rolls or strips.
The film undergoes a number of bending operations as it transits
the tortuous path of a slitting operation.
[0004] Finally, during fabrication and packaging of individual film
strips, the process imparts additional stress by multiple turns
around rollers, stripping the film off the substrate and by the
pull wheels used to move the film product through the
converting/packaging machine. When the strip is individually
packaged in a material with a high surface energy, the film sticks
to the packaging material and is not allowed to move to relieve the
stresses. The stresses are thus relieved at a later time by stress
cracking.
SUMMARY OF THE INVENTION
[0005] In one embodiment, the present invention provides methods
for reducing or substantially reducing stress cracking of polymers
in film products, such as edible film products including an active,
by lowering the surface energy of packaging materials.
[0006] In one embodiment, the present invention provides methods
for reducing or substantially reducing stress cracking of polymers
in film products, such as edible film products including an active,
such as a pharmaceutical active, by annealing the film prior to
storing it in a pouch or package.
[0007] In one embodiment, the present invention provides methods
for reducing or substantially reducing stress cracking of polymers
in film products, such as edible film including an active, such a
pharmaceutical active, by annealing the pouch or package containing
the film.
[0008] In one embodiment, the present invention provides methods
for reducing or substantially reducing stress cracking of polymers
in film products, such as edible film including an active, such as
a pharmaceutical active, by both lowering the surface energy of
packaging materials and by annealing the film prior to storing it
in a pouch or package.
[0009] In one embodiment, the present invention reduces or
substantially reduces stress cracking of polymers in film products,
such as edible film including an active, such a pharmaceutical
active, by both lowering the surface energy of packaging materials
and by annealing the pouch or package in which the film product is
stored.
[0010] In one embodiment, there is provided a package for storing a
film product including an active, such as a pharmaceutical active,
including: (a) a top layer having an inner surface and an outer
surface; and (b) a bottom layer having an inner surface and an
outer surface, the top layer and/or the bottom layer including a
polymeric material, the inner surface of the top layer and/or the
inner surface of the bottom layer having reduced adhesion to a film
product, such as a film; wherein the inner surface of the top layer
is partially sealed to the inner surface of the bottom layer,
wherein a pocket is formed between the top layer and the bottom
layer, and wherein a film product such as a film is stored within
the pocket. Without wishing to be bound by any theory, the inner
surface of the top layer and/or the inner surface of the bottom
layer has reduced adhesion to the film strip due to having (i) a
surface energy measured by a water contact angle test of about 100
degrees or greater; and/or (ii) a surface adhesivity level of less
than about 0.25 lbf as measured by a peel force testing using a
load frame and 1 inch wide packaging tape pulled at 2 inches/minute
and averaged over a distance of 0.75 to 1.75 inches; and/or (iii) a
surface RMS roughness of less than 800 nm as measured by atomic
force microscopy at a 100 micron square sample size square
level.
[0011] In one embodiment, there is provided a package for storing
pharmaceutical active containing film product, including: (a) a top
layer having an inner surface and an outer surface; and (b) a
bottom layer having an inner surface and an outer surface, the
inner surface of the bottom layer including at least one polymeric
material having at least one physical characteristic selected from
the group consisting of: (i) a surface energy measured by a water
contact angle test of about 100 degrees or greater, as; (ii) a
surface adhesivity level of less than about 0.25 lbf as measured by
a peel force testing using a load frame and 1 inch wide packaging
tape pulled at 2 inches/minute and averaged over a distance of 0.75
to 1.75 inches; and (iii) a surface RMS roughness Root Mean Square
(RMS) of less than 800 nm as measured by atomic force microscopy at
a 100 micron square sample size level; where the inner surface of
the top layer is partially sealed to the inner surface of the
bottom layer, forming a pocket between the top layer and the bottom
layer.
[0012] In one embodiment, there is provided a method for reducing
or preventing stress-cracking in a film product, including:
providing a package for storing pharmaceutical active containing
film product, including: (a) a top layer having an inner surface
and an outer surface; and (b) a bottom layer having an inner
surface and an outer surface, at least partially sealing the inner
surface of the top layer to the inner surface of the bottom layer
to form a pocket therebetween, wherein the inner surface of the
bottom layer includes at least one polymeric material having at
least one physical characteristic selected from the group
consisting of: (i) a surface energy measured by a water contact
angle test of about 100 degrees or greater; and/or (ii) a surface
adhesivity level of less than about 0.25 lbf as measured by a peel
force testing using a load frame and 1 inch wide packaging tape
pulled at 2 inches/minute and averaged over a distance of 0.75 to
1.75 inches; and/or (iii) a surface RMS roughness of less than 800
nm as measured by atomic force microscopy at a 100 micron square
sample size level.
[0013] In one embodiment, there is provided a method for reducing
stress cracking in a film including a continuous and uniform
product including the steps of: [0014] (a) preparing a film-forming
matrix including a solvent, an active and a polymeric material;
[0015] (b) forming a dried film by casting the film-forming matrix
and drying the film-forming matrix; [0016] (c) annealing the dried
film to relieve stresses imposed by the drying process.
[0017] In one embodiment, there is provided a method for reducing
stress cracking in a film, such as a film including a continuous
and uniform product, including the steps of: [0018] (a) preparing a
film-forming matrix including a solvent, an active and a polymeric
material; [0019] (b) forming a dried film by casting the
film-forming matrix and drying said film-forming matrix; [0020] (c)
packaging the dried film in a pouch [0021] (d) annealing the
pouched film to relieve stresses imposed by the drying process.
[0022] In one embodiment, there is provided a reduced stress
cracked film product, such as a continuous and uniform film
product, with reduced stress cracking, wherein the film product is
formed by: casting a film-forming matrix including a solvent, and
active, and a polymeric material, drying the film-forming matrix to
form a dried film, and annealing the dried film to relieve stress
imposed by the drying process. The film product has reduced stress
cracking when the film is annealed compared to when the film is not
annealed.
[0023] In one embodiment, there is provided a reduced stress
cracked film product, such as a continuous and uniform reduced
stress cracked film product, wherein the film product is formed by:
casting a film-forming matrix and drying the film-forming matrix to
form a dried film; packaging the dried film into a pouch, and
annealing the pouched film to relieve stresses imposed by the
drying process. The pouched film has reduced stress cracking when
the film is annealed compared to when the film is not annealed.
[0024] In one embodiment, there is provided a pouch for storing a
film product including an active, such as a pharmaceutical active,
including a laminate of at least one first layer and at least one
second layer, wherein the at least one first layer has an inner
surface and an outer surface; wherein the second layer is
positioned over the first layer; wherein the pouch includes a
cavity including a film such as an edible film including at least
one polymer and including at least one active, such as a
pharmaceutical active, positioned therein, and wherein the pouch is
laminated. The pouch may be made from any suitable material,
including suitable polymeric materials. The film is annealed to
prevent and/or reduce stress cracking in the film contained therein
by applying heat to the film. Thereafter, the film may be placed
and stored in a pouch or package in accordance with the present
invention.
[0025] In one embodiment, there is provided a pouch for storing a
film product including an active, such as a pharmaceutical active,
including a laminate of at least one first layer and at least one
second layer, wherein the at least one first layer has an inner
surface and an outer surface; wherein the second layer is
positioned over the first layer; wherein the pouch includes a
cavity including a film which has been annealed, such as an edible
film which has been annealed and which includes at least one
polymer and including at least one active, such as a pharmaceutical
active, positioned therein, and wherein the pouch is laminated. The
pouch may be made from any suitable material, including suitable
polymeric materials.
[0026] In one embodiment, there is provided a method for reducing
stress cracking in a film product comprising: (a) providing a
sealed pouch including a laminate of at least one first layer and
at least one second layer, wherein the at least one first layer has
an inner surface and an outer surface; wherein the at least one
second layer has an inner surface and an outer surface; wherein the
second layer is positioned over said first layer; and wherein the
pouch includes a cavity including an edible film including at least
one polymer and an active, such as a pharmaceutical active,
positioned therein, and (b) annealing the pouch to prevent and/or
reduce stress-cracking in the film by applying heat to the
pouch.
BRIEF DESCRIPTION OF THE FIGURES
[0027] FIG. 1 shows the results of a comparative foil film peel
test.
[0028] FIG. 2 shows the results of an AFM surface RMS roughness
test for various films.
[0029] FIG. 3 shows the rate of stress cracking of films at various
times.
[0030] FIG. 4 shows the rate of stress cracking of films after a
sixty day period.
[0031] FIG. 5 shows layers for use in forming a package or pouch of
the present invention.
[0032] FIG. 6 is a cross sectional view of a package of the present
invention.
[0033] FIG. 7 is a 2D birefringence map of a "fresh" (1 week old)
film strip (shown at the top of FIG. 7) and "old" (3 week old) film
strip (shown at the bottom of FIG. 7) before anneal.
[0034] FIG. 8 is a 2D birefringence map of a "fresh" (1 week old)
film strip (shown at the top of FIG. 8) and "old" (3 week old) film
strip (shown at the bottom of FIG. 8) after anneal.
DETAILED DESCRIPTION OF THE INVENTION
[0035] As used herein, the term "annealing" means a heat treatment
that alters a material to, among other things, relieve internal
stresses.
[0036] As used herein, the term "stress cracking" means a phenomena
occurring in polymers, where the material is held together by a
combination of weaker Van der Waals forces and stronger covalent
bonds. When sufficient local stress overcomes the Van der Waals
force, a gap is formed resulting in a stress crack. These stress
cracks can start as minute cracks, visible only under a microscope
and depending on the stress in the polymer, can with time separate
a polymer film into 2 or more pieces. If the polymer film is left
unrestrained, the stresses will relieve themselves when the film is
allowed to shrink. However, when the film is restrained by adhesion
to a surface, the film cannot shrink and will subsequently crack.
Stress can also be relieved by annealing, which allows relaxation
of the stresses in the polymer and therefore prevents stress
cracking.
[0037] As used herein, the terms "pharmaceutical", "medicament",
"drug" and "active" 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.
[0038] It will be understood that the terms "film" and "film strip"
include delivery systems of any thickness, including films and film
strips, 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
processing of the film. Films may include a pouch or region of
medicament between two films. The films of the present invention
may have any desired dimension suitable to provide the desired
level of active, and in some embodiments, the films have a length
from about 10 to about 50 mm and a width of from about 10 to about
50 mm, and may take any desired shape, including square and
rectangle.
[0039] The term "patch" as used herein is intended to include
multi-layered film products, where the first layer (or "backing
layer") is a film product that has a slower rate of dissolution
than the second layer (or "active layer"). Patches described herein
generally include the first and second layers adhered or laminated
to each other, where the second layer has a smaller length and/or
width of the first layer, such that at least a portion of the
surface of the first layer is visible outside of the second
layer.
[0040] Film strips may be formed through any desired processing
means, including casting and drying methods as well as extrusion
methods. The film strips may be single-layer films or multiple
layered films. Some examples of methods of forming and drying films
may be found in U.S. Pat. Nos. 7,425,292, 7,666,337, and 7,357,891,
the contents of each of which are incorporated by reference in
their entireties. Any number of active components or pharmaceutical
agents may be included in the films discussed herein. The active
component(s) may be disposed within any layer of film products
formed herein or they may be placed onto one or more surfaces of
the film products.
[0041] Films formed by the present invention may be suitable for
administration to at least one region of the body of the user, such
as mucosal regions or regions within the body of the user, such as
on the surface of internal organs. 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
still other embodiments, the topical agent is applied to an
internal organ or other body surface of the user, such as during
surgery, where the agent may be removed or left within the body
after surgery is complete. In other embodiments, a topical agent is
applied to a hard surface, such as a particular surface area in
need of treatment. In other embodiments, the films of the present
invention are ingestible, and are intended to be placed in the
mouth of the user and swallowed as the film disintegrates.
[0042] The medicament may be dispersed throughout the film, or it
may be deposited onto one or more surfaces of the film. In either
way, it is desirable that the amount of medicament per unit area is
substantially uniform throughout the film. The "unit area" is
intended to include a suitable unit area, such as the area of one
typical dosage unit. It is desired that the films of the present
invention include a uniformity of component distribution throughout
the volume of a given film. That is, the individual film products
(including individual dosages of approximately equal sizes) formed
by the present invention should have approximately the same content
composition as each other film product. 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. For
the films formed herein, it is understood by one of ordinary skill
in the art that the resulting film is not required to be exactly
100% uniform. All that is required is that the film be
"substantially uniform", i.e., a slight amount of non-uniformity is
understood to be acceptable. "Substantially uniform" may include,
for example, a film that is about 90% uniform in content from one
region of the film to another, or a film that is about 95% uniform
in content from one region of the film to another, and most
desirably about 99% uniform in content from one region of the film
to another. In other words, "substantially uniform" may mean that
individual film products should vary by no more than about 10% with
respect to each other. In some embodiments, "substantially uniform"
may mean that individual film products should vary by no more than
about 5% with respect to each other.
[0043] After formation of the film, a plurality of film strips
having similar dimensions, including length, width and depth, may
be cut from the film product. Each film strip is desirably
substantially uniform in content from each other, particularly in
active content. When forming films, the user sets a target active
content, depending upon the desired level of active in the film.
That target content is referred to as 100% of the target level. For
example, the desired film strip may desirably have 1 mg of active
per unit dose, and thus 1 mg would be the "target content". Each
substantially similarly sized film strip cut from the film product
should be within about 10% of that target content. More desirably,
each substantially similarly sized film strip cut from the film
product should be within about 8% of the target content, or within
6% of the target content, or within 4% of the target content. For a
target content of 1.0 mg per unit dose, substantially uniform films
may have from about 0.90 mg to about 1.10 mg per unit dose. When an
active is introduced to the film, the amount of active per unit
area is determined by the uniform distribution of the film. For
example, when the films are cut into individual dosage forms, the
amount of the active in the dosage form can be known with a great
deal of accuracy. This is achieved because the amount of the active
in a given area is substantially identical to the amount of active
in an area of the same dimensions in another part of the film. The
accuracy in dosage is particularly advantageous when the active is
a medicament, i.e. a drug.
[0044] The active components that may be incorporated into the
films of the present invention include, without limitation
pharmaceutical and cosmetic actives, drugs, medicaments, proteins,
antigens or allergens such as ragweed pollen, spores,
microorganisms, seeds, mouthwash components, flavors, fragrances,
enzymes, preservatives, sweetening agents, colorants, spices,
vitamins and combinations thereof.
[0045] A wide variety of medicaments, bioactive active substances
and pharmaceutical compositions may be included in the dosage forms
of the present invention. 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.
[0046] 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.
[0047] Analgesics include opiates and opiate derivatives, such as
oxycodone (available as Oxycontin.RTM.), ibuprofen, aspirin,
acetaminophen, and combinations thereof that may optionally include
caffeine.
[0048] Other preferred drugs for other preferred active ingredients
for use in the present invention include anti-diarrheals such as
immodium AD, 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, chlorpheniramine maleate,
dextromethorphan, pseudoephedrine HCl and diphenhydramine may be
included in the film compositions of the present invention.
[0049] Also contemplated for use herein are anxiolytics such as
alprazolam (available as Xanax.RTM.); anti-psychotics such as
clozopin (available as Clozaril.RTM.) and haloperidol (available as
Haldol.RTM.); non-steroidal anti-inflammatories (NSAID's) such as
dicyclofenacs (available as Voltaren.RTM.) and etodolac (available
as Lodine.RTM.), anti-histamines such as loratadine (available as
Claritin.RTM.), astemizole (available as Hismanal.TM.), nabumetone
(available as Relafen.RTM.), and Clemastine (available as
Tavist.RTM.); anti-emetics such as granisetron hydrochloride
(available as Kytril.RTM.) and nabilone (available as Cesamet.TM.);
bronchodilators such as Bentolin.RTM., albuterol sulfate (available
as Proventil.RTM.); anti-depressants such as fluoxetine
hydrochloride (available as Prozac.RTM.), sertraline hydrochloride
(available as Zoloft.RTM.), and paroxtine hydrochloride (available
as Paxil.RTM.); anti-migraines such as Imigra.RTM., ACE-inhibitors
such as enalaprilat (available as Vasotec.RTM.), captopril
(available as Capoten.RTM.) and lisinopril (available as
Zestril.RTM.); anti-Alzheimer's agents, such as nicergoline; and
Ca.sup.H-antagonists such as nifedipine (available as
Procardia.RTM. and Adalat.RTM.), and verapamil hydrochloride
(available as Calan.RTM.).
[0050] Erectile dysfunction therapies 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 non-limiting drugs include
sildenafils, such as Viagra.RTM., tadalafils, such as Clalis.RTM.,
vardenafils, apomorphines, such as Uprima.RTM., yohimbine
hydrochlorides such as Aphrodyne.RTM., and alprostadils such as
Caverject.RTM..
[0051] 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.
[0052] 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- or
di-basic calcium phosphate, tricalcium phosphate, potassium
bicarbonate, sodium tartrate, sodium bicarbonate, magnesium
aluminosilicates, tartaric acids and salts. 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.
[0053] An anti-oxidant may also be added to the film to prevent the
degradation of an active, especially where the active is
photosensitive.
[0054] Cosmetic active agents may include breath freshening
compounds like menthol, other flavors or fragrances, especially
those used for oral hygiene, as well as actives used in dental and
oral cleansing such as quaternary ammonium bases. The effect of
flavors may be enhanced using flavor enhancers like tartaric acid,
citric acid, vanillin, or the like.
[0055] Also color additives can be used in preparing the films.
Such color additives include food, drug and cosmetic colors
(FD&C), drug and cosmetic colors (D&C), or external drug
and cosmetic colors (Ext. D&C). These colors are dyes, their
corresponding lakes, and certain natural and derived colorants.
Lakes are dyes absorbed on aluminum hydroxide. Other examples of
coloring agents include known azo dyes, organic or inorganic
pigments, or coloring agents of natural origin. Inorganic pigments
are preferred, such as the oxides or iron or titanium, these
oxides, being added in concentrations ranging from about 0.001 to
about 10%, and preferably about 0.5 to about 3%, based on the
weight of all the components. Flavors may be chosen from natural
and synthetic flavoring liquids. An illustrative list of such
agents includes volatile oils, synthetic flavor oils, flavoring
aromatics, oils, liquids, oleoresins or extracts derived from
plants, leaves, flowers, fruits, stems and combinations thereof. A
non-limiting representative list of examples includes mint oils,
cocoa, and citrus oils such as lemon, orange, grape, lime and
grapefruit and fruit essences including apple, pear, peach, grape,
strawberry, raspberry, cherry, plum, pineapple, apricot or other
fruit flavors.
[0056] The films containing flavorings may be added to provide a
hot or cold flavored drink or soup. These flavorings include,
without limitation, tea and soup flavorings such as beef and
chicken.
[0057] Other useful flavorings include aldehydes and esters such as
benzaldehyde (cherry, almond), citral i.e., alphacitral (lemon,
lime), neral, i.e., beta-citral (lemon, lime), decanal (orange,
lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits),
aldehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond),
2,6-dimethyloctanol (green fruit), and 2-dodecenal (citrus,
mandarin), combinations thereof and the like.
[0058] The film products of the present invention are capable of
accommodating a wide range of amounts of the active ingredient. The
films are capable of providing an accurate dosage amount
(determined by the size of the film and concentration of the active
in the original polymer/water combination) regardless of whether
the required dosage is high or extremely low. Therefore, depending
on the type of active or pharmaceutical composition that is
incorporated into the film, the active amount may be as high as
about 300 mg, desirably up to about 150 mg or as low as the
microgram range, or any amount therebetween.
[0059] Sweeteners for us in the present invention may be chosen
from the following non-limiting list: glucose (corn syrup),
dextrose, invert sugar, fructose, and combinations thereof;
saccharin and its various salts such as the sodium salt; dipeptide
sweeteners such as aspartame; dihydrochalcone compounds,
glycyrrhizin; Stevia Rebaudiana (Stevioside); chloro derivatives of
sucrose such as sucralose; sugar alcohols such as sorbitol,
mannitol, xylitol, and the like. Also contemplated are hydrogenated
starch hydrolysates and the synthetic sweetener
3,6-dihydro-6-methyl-1-1-1,2,3-oxathiazin-4-one-2,2-dioxide,
particularly the potassium salt (acesulfame-K), and sodium and
calcium salts thereof, and natural intensive sweeteners, such as Lo
Han Kuo. Other sweeteners may also be used.
[0060] The film products and methods of the present invention are
well suited for high potency, low dosage drugs. This is
accomplished through the high degree of uniformity of the films.
Therefore, low dosage drugs, particularly more potent racemic
mixtures of actives are desirable. The polymer may be water
soluble, water swellable, water insoluble, or a combination of one
or more either water soluble, water swellable or water insoluble
polymers. The polymer may include cellulose or a cellulose
derivative. Specific examples of useful water soluble polymers
include, but are not limited to, polyethylene oxide (PEO),
pullulan, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl
cellulose (HPC), hydroxypropyl cellulose, polyvinyl pyrrolidone,
carboxymethyl cellulose, polyvinyl alcohol, sodium aginate,
polyethylene glycol, xanthan gum, tragancanth gum, guar gum, acacia
gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer,
carboxyvinyl copolymers, starch, gelatin, and combinations thereof.
Specific examples of useful water insoluble polymers include, but
are not limited to, ethyl cellulose, hydroxypropyl ethyl cellulose,
cellulose acetate phthalate, hydroxypropyl methyl cellulose
phthalate and combinations thereof.
[0061] As used herein the phrase "water soluble polymer" and
variants thereof refer to a polymer that is at least partially
soluble in water, and desirably fully or predominantly soluble in
water, or absorbs water. Polymers that absorb water are often
referred to as being water swellable polymers. The materials useful
with the present invention may be water soluble or water swellable
at room temperature and other temperatures, such as temperatures
exceeding room temperature. Moreover, the materials may be water
soluble or water swellable at pressures less than atmospheric
pressure. Desirably, the water soluble polymers are water soluble
or water swellable having at least 20 percent by weight water
uptake. Water swellable polymers having a 25 or greater percent by
weight water uptake are also useful. Films or dosage forms of the
present invention formed from such water soluble polymers are
desirably sufficiently water soluble to be dissolvable upon contact
with bodily fluids.
[0062] Other polymers useful for incorporation into the films of
the present invention include biodegradable polymers, copolymers,
block polymers and combinations thereof. Among the known useful
polymers or polymer classes which meet the above criteria are:
poly(glycolic acid) (PGA), poly(lactic acid) (PLA), polydioxanoes,
polyoxalates, poly(.alpha.-esters), polyanhydrides, polyacetates,
polycaprolactones, poly(orthoesters), polyamino acids,
polyaminocarbonates, polyurethanes, polycarbonates, polyamides,
poly(alkyl cyanoacrylates), and mixtures and copolymers thereof.
Additional useful polymers include, stereopolymers of L- and
D-lactic acid, copolymers of bis(p-carboxyphenoxy) propane acid and
sebacic acid, sebacic acid copolymers, copolymers of caprolactone,
poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol
copolymers, copolymers of polyurethane and (poly(lactic acid),
copolymers of polyurethane and poly(lactic acid), copolymers of
.alpha.-amino acids, copolymers of .alpha.-amino acids and caproic
acid, copolymers of a-benzyl glutamate and polyethylene glycol,
copolymers of succinate and poly(glycols), polyphosphazene,
polyhydroxy-alkanoates and mixtures thereof. Binary and ternary
systems are contemplated.
[0063] Other specific polymers useful include those marketed under
the Medisorb and Biodel trademarks. The Medisorb materials are
marketed by the Dupont Company of Wilmington, Del. and are
generically identified as a "lactide/glycolide co-polymer"
containing "propanoic acid, 2-hydroxy-polymer with hydroxy-polymer
with hydroxyacetic acid." Four such polymers include
lactide/glycolide 100L, believed to be 100% lactide having a
melting point within the range of 338.degree.-347.degree. F.
(170.degree.-175.degree. C.); lactide/glycolide 100L, believed to
be 100% glycolide having a melting point within the range of
437.degree.-455.degree. F. (225.degree.-235.degree. C.);
lactide/glycolide 85/15, believed to be 85% lactide and 15%
glycolide with a melting point within the range of
338.degree.-347.degree. F. (170.degree.-175.degree. C.); and
lactide/glycolide 50/50, believed to be a copolymer of 50% lactide
and 50% glycolide with a melting point within the range of
338.degree.-347.degree. F. (170.degree.-175.degree. C.).
[0064] The Biodel materials represent a family of various
polyanhydrides which differ chemically.
[0065] Although a variety of different polymers may be used, it is
desired to select polymers to provide a desired viscosity of the
mixture prior to drying. For example, if the active or other
components are not soluble in the selected solvent, a polymer that
will provide a greater viscosity is desired to assist in
maintaining uniformity. On the other hand, if the components are
soluble in the solvent, a polymer that provides a lower viscosity
may be preferred.
[0066] The polymer plays an important role in affecting the
viscosity of the film. Viscosity is one property of a liquid that
controls the stability of the active in an emulsion, a colloid or a
suspension. Generally the viscosity of the matrix will vary from
about 400 cps to about 100,000 cps, preferably from about 800 cps
to about 60,000 cps, and most preferably from about 1,000 cps to
about 40,000 cps. Desirably, the viscosity of the film-forming
matrix will rapidly increase upon initiation of the drying
process.
[0067] The viscosity may be adjusted based on the selected active
depending on the other components within the matrix. For example,
if the component is not soluble within the selected solvent, a
proper viscosity may be selected to prevent the component from
settling which would adversely affect the uniformity of the
resulting film. The viscosity may be adjusted in different ways. To
increase viscosity of the film matrix, the polymer may be chosen of
a higher molecular weight or crosslinkers may be added, such as
salts of calcium, sodium and potassium. The viscosity may also be
adjusted by adjusting the temperature or by adding a viscosity
increasing component. Components that will increase the viscosity
or stabilize the emulsion/suspension include higher molecular
weight polymers and polysaccharides and gums, which include without
limitation, alginate, carrageenan, hydroxypropyl methyl cellulose,
locust bean gum, guar gum, xanthan gum, dextran, gum arabic, gellan
gum and combinations thereof.
[0068] It has also been observed that certain polymers which when
used alone would ordinarily require a plasticizer to achieve a
flexible film, can be combined without a plasticizer and yet
achieve flexible films. For example, HPMC and HPC when used in
combination provide a flexible, strong film with the appropriate
plasticity and elasticity for manufacturing and storage. No
additional plasticizer or polyalcohol is needed for
flexibility.
[0069] Additionally, polyethylene oxide (PEO), when used alone or
in combination with a hydrophilic cellulosic polymer, achieves
flexible, strong films. Additional plasticizers or polyalcohols are
not needed for flexibility. Non-limiting examples of suitable
cellulosic polymers for combination with PEO include HPC and HPMC.
PEO and HPC have essentially no gelation temperature, while HPMC
has a gelation temperature of 58-64.degree. C. (Methocel EF
available from Dow Chemical Co.). Moreover, these films are
sufficiently flexible even when substantially free of organic
solvents, which may be removed without compromising film
properties. As such, if there is no solvent present, then there is
no plasticizer in the films. PEO based films also exhibit good
resistance to tearing, little or no curling, and fast dissolution
rates when the polymer component contains appropriate levels of
PEO.
[0070] To achieve the desired film properties, the level and/or
molecular weight of PEO in the polymer component may be varied.
Modifying the PEO content affects properties such as tear
resistance, dissolution rate, and adhesion tendencies. Thus, one
method for controlling film properties is to modify the PEO
content. For instance, in some embodiments rapid dissolving films
are desirable. By modifying the content of the polymer component,
the desired dissolution characteristics can be achieved.
[0071] In accordance with the present invention, PEO desirably
ranges from about 20% to 100% by weight in the polymer component.
In some embodiments, the amount of PEO desirably ranges from about
1 mg to about 200 mg. The hydrophilic cellulosic polymer ranges
from about 0% to about 80% by weight, or in a ratio of up to about
4:1 with the PEO, and desirably in a ratio of about 1:1.
[0072] In some embodiments, it may be desirable to vary the PEO
levels to promote certain film properties. To obtain films with
high tear resistance and fast dissolution rates, levels of about
50% or greater of PEO in the polymer component are desirable. To
achieve adhesion prevention, i.e., preventing the film from
adhering to the roof of the mouth, PEO levels of about 20% to 75%
are desirable. In some embodiments, however, adhesion to the roof
of the mouth may be desired, such as for administration to animals
or children. In such cases, higher levels of PEO may be employed.
More specifically, structural integrity and dissolution of the film
can be controlled such that the film can adhere to mucosa and be
readily removed, or adhere more firmly and be difficult to remove,
depending on the intended use.
[0073] The molecular weight of the PEO may also be varied. High
molecular weight PEO, such as about 4 million, may be desired to
increase mucoadhesivity of the film. More desirably, the molecular
weight may range from about 100,000 to 900,000, more desirably from
about 100,000 to 600,000, and most desirably from about 100,000 to
300,000. In some embodiments, it may be desirable to combine high
molecular weight (600,000 to 900,000) with low molecular weight
(100,000 to 300,000) PEOs in the polymer component.
[0074] For instance, certain film properties, such as fast
dissolution rates and high tear resistance, may be attained by
combining small amounts of high molecular weight PEOs with larger
amounts of lower molecular weight PEOs. Desirably, such
compositions contain about 60% or greater levels of the lower
molecular weight PEO in the PEO-blend polymer component.
[0075] To balance the properties of adhesion prevention, fast
dissolution rate, and good tear resistance, desirable film
compositions may include about 50% to 75% low molecular weight PEO,
optionally combined with a small amount of a higher molecular
weight PEO, with the remainder of the polymer component containing
a hydrophilic cellulosic polymer (HPC or HPMC).
[0076] Desirably, the films of the present invention include
polyethylene oxide (PEO), hydroxypropylmethylcellulose or a
combination thereof.
[0077] The layers of the packages and pouches of the present
invention may include any suitable packaging material. Desirably,
low density polyethylene (LDPE) and/or ethylene acrylic acid may be
product contact layers in packaging material. Once a film strip is
formed and cut to the appropriate and desired size, the film strip
is packaged. Packaging of film strips helps keep the film strips in
a controlled environment so as to maintain the integrity of the
film strip and the active content. Desirably, a single package
houses one single film strip and is sealed so that the film strip
is not exposed to an external environment. Typically, film strip
packages are made from foil, polymeric materials, or combinations
of foil and polymeric materials. In some embodiments, the package
is made from at least one laminated foil, where the foil is
laminated with a polymeric material. The package is capable of
being opened by the user by one or more known methods, including,
for example, tear notches, perforations, or through use of a tool
such as scissors or other blade.
[0078] A representative package suitable for the present invention
is shown in FIG. 6. A top layer 20 including an outer surface 20A
and a bottom surface 20B and a bottom layer 30 including an outer
surface 30A and a bottom layer 30A for use in making the package
are shown in FIG. 5. As shown in FIG. 6, the package 10 includes a
top layer 20 and bottom layer 30. The top layer 20 includes an
outer surface 20A that is exposed to the outside environment, and
an inner surface 20B that is in contact with an interior pocket 40
of the package 10. The bottom layer 30 also includes an outer
surface 30A that is exposed to the outside environment and an inner
surface 30B that is in contact with the interior pocket 40 of the
package. A film strip 50 is contained within the interior pocket 40
of the package 10. The package 10 may be oriented in any direction,
but for ease of explanation FIG. 6 shows the bottom layer 30 under
the top surface 20, such that the film strip 50 rests on the inner
surface 30A of the bottom layer 30. It is understood that in some
embodiments, the film strip 50 may be in at least partial contact
with the inner surface 20A of the top layer 20. Since the film
strip 50 is or may be in contact with the inner surfaces 20A, 30A
of the package 10, the inner surfaces 20A, 30A of the package 10
should be made from a material or materials that are inert with
respect to the film strip 50. The materials forming the inner
surfaces 20A, 30A of the package 10 should not be capable of
reacting with the film strip 50 so as to affect the film strip 50
in a material way.
[0079] After cutting the film strip to the proper and desired size,
it is placed onto the inner surface 30A of the package 10, and the
package 10 is then closed around the film strip 50 and sealed. The
film strip 50 may remain in the package 10 for an extended period
of time, and may be within the package 10 for days, weeks, months,
or even years. In some embodiments, the package 10 is suitable to
house the film strip 50 without detrimental damage to the film
strip 50 for at least 1 week, or for at least 1 month, or for at
least 6 months, or for at least 1 year. In some embodiments, the
film strip 50 suitably remains in the package 10 for about 1 month
to about 2 years without detrimental damage. In some embodiments,
the film strip 50 suitably remains in the package 10 for about 1
month to about 2 years without detrimental damage.
[0080] In some embodiments, the film may be formed directly onto
the inner surface of the package during the manufacturing stage. In
such embodiments, the film strip is formed at the desired
dimensions, smaller than the package.
[0081] When a user wishes to use the film strip, the user opens the
package and removes the film strip. It is important that the film
strip not stick to or adhere to the inner surface of the package,
so as to allow for easy removal of the film strip. However, in
addition to the ease of removal of the film strip, the present
inventors have discovered that the inner surface of the package
should be made from a material that resists formation of stress
cracking in the film strip. This is particularly true when the film
strip is made from a polymeric material or materials that are
susceptible to stress cracking. As will be discussed below, the
inner surface of the package desirably is made from a material or
materials having a low surface energy. In addition, the inner
surface may have a lower surface adhesivity with respect to the
film strip that is housed in the package. Also, or in the
alternative, the inner surface may have a lower root mean square
surface roughness, as measured at the 100 micron square sample size
scale. Each of these properties is discussed below.
[0082] Stress cracking of films is particularly noticeable when
certain polymers are used in the film product. Such polymers
include polymers that are or can become highly crystalline in
nature. One particularly noticeable polymer that causes stress
cracking is polyethylene oxide (PEO). However, polymeric materials
such as PEO offer a number of advantages in a film product, and
thus it is desirable to use PEO and similar materials, either alone
or in combination with other polymeric components, in the formation
of films. For example, PEO may be used in combination with a
cellulosic material, such as HPC or HPMC. Unfortunately, due to its
tendency to cause stress cracking, PEO has been found to cause
problems when the user wishes to use the film. As such, certain
measures should be taken during the preparation and packaging of
the film strips. One such measure is to use packaging materials
that include an inner surface made from a material or materials
that will reduce the likelihood of stress cracking. Desirable
materials include those that have at least one of the following
characteristics: the inner surface of the package being made from a
material or materials having a low surface energy; the inner
surface having a lower surface adhesivity with respect to the film
strip that is housed in the package; and the inner surface having a
lower root mean square surface roughness, as measured at the 100
micron square sample size scale.
[0083] It has been noticed by the present inventors that films
including PEO as either the sole or as one of the polymeric
materials in the film can suffer from stress cracking. Such films
have suffered from stress cracking even on a number of different
packaging materials. Stress cracking is undesirable as it has an
unappealing appearance, thus causing the user of the film strip to
question its integrity and usefulness. The present inventors have
noticed that films including PEO as a polymeric component tended to
adhere to various packaging materials, thus causing more stress
cracking as observed when the package was opened. One such
packaging material that demonstrated noticeable stress cracking in
films was a material having an inner surface made from ethylene
acrylic acid. Up to 63% of films that were prepared on such
packaging materials demonstrated stress cracking.
[0084] The present inventors have discovered, however, that a film
including polymers that are or can become highly crystalline in
nature as a polymeric component can be formed without stress
cracking when stored on a packaging material made from a material
having a lower surface energy, having lower surface adhesivity, or
having a lower surface roughness. The surface energy of a product
may be measured by a water contact angle test, described below. The
desired surface energy is about 100 degrees or greater, as measured
by the water contact angle test.
[0085] Surface adhesivity may be measured by peel force testing
using a load frame and packaging tape. Using such a test, the
desired surface has an average peel force of less than about 0.25
lbf, and more desirably less than about 0.20 lbf. Finally, surface
RMS roughness may be measured by atomic force microscopy at a 100
micron square sample size level. At the 100 micron square sample
size level, the desired surface RMS roughness of the package
material should be less than about 800 nm, and desirably less than
about 700 nm.
[0086] One such packaging material having a lower surface energy
includes materials made from low density polyethylene (LDPE). When
the inner surface of the package is made from a material including
LDPE, the film strips were found to have reduced or eliminated
stress cracking. Such inner surfaces have a surface energy of about
100 degrees or greater as measured by the water contact angle test,
a surface adhesivity of about 0.25 lbf or less as measured by peel
force testing, and a surface RMS roughness of about 800 nm or less
as measured by atomic force microscopy at a 100 micron square
sample size level.
[0087] Desirably, less than 10% of film strips stored in the
inventive package exhibit stress cracking after storage of about
three months at temperatures of about 25.degree. C. to about
30.degree. C.
[0088] Surface roughness was measured using Atomic force microscopy
(AFM). AFM scans were completed with three scans of each film, one
100 .mu.m square, one 25 .mu.m square, and one 5 .mu.m square. As
the scan size decreases, the lateral resolution of the images
increases, allowing the small scan sizes to make out smaller
features.
[0089] Water contact angle tests were conducted by applying a 5
microliter drop of purified water on the film using a
micro-pipette. Images were taken of each drop and image processing
was used to capture the shape of each drop's surface, and the data
was processed to calculate the contact angle.
[0090] Peel tests were conducted with packaging tape applied to
sampled films. Test samples were one inch wide. The ends of the
tape and the substrate films were clamped by grips of an MTS load
frame (tensile tester), manufactured by MTS Systems Corporation.
The tests were run at 2 inches per minute speed. The load rises as
the specimen ends are pulled until the sample is taught and peeling
progresses. Once peeling is initiated, the load is variable, based
on the local bond strength between packaging tape and the substrate
film. The data became more stable after a moderate opening length,
and the test data was averaged over on opening distance of 0.75
inches to 1.75 inches.
[0091] In some embodiments, additives may optionally be included in
the films of the present invention to assist in ameliorating
internal stresses in the film structure. Such additives may
include, for example, surfactants, plasticizers, and vitamin E,
TPGS, and combinations thereof. Such additives may be present in
any suitable amount. Suitable amounts of such additives include,
for example, from about 1% by weight to about 50% or higher by
weight of a film. In some embodiments, a plasticizer may be present
in an amount from about 5% by weight to about 30% by weight of a
film. In some embodiments, a plasticizer may be present in an
amount from about 2% by weight to about 30% by weight of a film. In
some embodiments, a plasticizer may be present in an amount of
about 5% by weight of a film.
[0092] The present invention also reduces the tendency and
likelihood of stress cracking through certain measures taken in the
packaging stage of formation.
[0093] In some embodiments, a film may be annealed to reduce or
substantially reduce stress cracking in the film prior to being
stored in a package or pouch. In some embodiments, a film is
annealed at a temperature between 40 degrees C. and 90 degrees C.
In some embodiments, the film is annealed at a time between 0.5
minutes and 60 minutes.
[0094] In some embodiments, a film is annealed by removing the film
from a substrate, annealing the film and rewinding the film onto a
substrate. In some embodiments, a film is annealed at a temperature
between 40 degrees C. and 90 degrees C. In some embodiments, a film
is annealed at a time between 0.5 minutes and 60 minutes In some
embodiments, a film is intact with no cracking after 3 weeks in a
package.
[0095] In some embodiments, a film is intact with no cracking after
2 months in a package. In some embodiments, a film is intact with
no cracking after 6 months in a package. In some embodiments, a
film is intact with no cracking after 12 months in a package. In
some embodiments, a film is intact with no cracking after 2 years
in a package. In some embodiments, a film is intact with no
cracking after 3 years in a package. In some embodiments, a film is
intact with no cracking after 3 weeks in a package. In some
embodiments, a film is intact with no cracking after 2 months in a
package. In some embodiments, a film is intact with no cracking
after 6 months in a package. In some embodiments, a film is intact
with no cracking after 12 months in a package. In some embodiments,
a film is intact with no cracking after 2 years in a package. In
some embodiments, a film is intact with no cracking after 3 years
in a package.
[0096] In some embodiments, a package or pouch including a film
product, such as a polymeric film, may be annealed to prevent
and/or reduce stress-cracking in the film. In some embodiments, the
package or pouch including the product is annealed by placing the
sealed pouches of the product in an oven. The package or pouch may
be heat annealed for any suitable length of time, including from
about 0.5 to about 120 minutes. Moreover, the package or pouch may
be annealed at any suitable temperature, including from about
40.degree. C. to about 90.degree. C. In some embodiments, the
packaged film is annealed at a temperature between 40 degrees C.
and 90 degrees C.
[0097] Desirably, a package or pouch of the present invention is
heat annealed at 70.degree. C. for 25 minutes. In some embodiments,
a packaged film is annealed at a time between about 0.5 minutes and
about 60 minutes. In some embodiments, a packaged film is annealed
at a time between 0.5 minutes and 60 minutes.
EXAMPLES
Example 1
Comparative Testing Between Two Materials
[0098] Two materials were tested for peel force using a load frame
and packaging tape. The first material ("Material A") was a
packaging product having a surface made from ethylene acrylic acid,
and the second material ("Material B") was a packaging product
having a surface made from LDPE. FIG. 1 demonstrates the foil film
peel test results for these two materials.
[0099] Test samples were one inch wide. The ends of the tape and
the substrate films were clamped by grips of an MTS load frame. The
tests were run at 2 inches per minute speed. The load rises as the
specimen ends are pulled until the sample is taught and peeling
progresses. Once peeling is initiated, the load is variable based
on the local bond strength between packaging tape and the substrate
film. The data became more stable after a moderate opening length,
and the test data was averaged over on opening distance of 0.75
inches to 1.75 inches.
[0100] Water contact angle tests were then run on the surfaces of
the two materials. These tests were conducted by applying a 5
microliter drop on the product contact surface using a
micro-pipette. Images were taken of each drop, and image processing
was used to capture the shape of each drop's surface, and the data
was processed to calculate the contact angle.
[0101] Film contact angle results show that Material B, having a
surface made from LDPE, demonstrated the highest contact angle and
therefore the lowest surface energy of the materials tested. The
higher surface energy of Material A (having a surface made from
ethylene acrylic acid) results in better wet-out and a greater
tendency for other materials (e.g. film strips) to stick to the
surface. This is again consistent with observations that film
strips tend to stick to Material A. The results are set forth in
Table 1 below:
TABLE-US-00001 TABLE 1 Film Contact Angle Results Sample Contact
Angle (deg) Material A 95.6 95.4 88.9 89.2 88 89.3 Material B 100.7
104.7 106.8 109.5 109.2 106.3
[0102] Atomic force microscope (AFM) scans were completed on both
films to gain additional insight into the physical structure of
each. Three scans of each film, one 100 .mu.m square, one 25 .mu.m
square, and one 5 .mu.m square were done. As the scan size
decreases, the lateral resolution of the images increases, allowing
the small scan sizes to make out smaller features. FIG. 2 shows the
AFM surface RMS roughness of the films.
[0103] The results indicate that at the 100 micron square same size
scale, the Material A shows the highest surface roughness,
approximately 30% more rough than Material B. This is consistent
with the Material A having higher surface energy and higher
adhesivity to other materials. The data then can be summarized as
the peel force testing, contact angle measurement and surface RMS
roughness measurements by AFM all suggest that the Material A
packaging material has a higher surface adhesivity (peel force), a
higher surface energy (lower contact angle) and a higher surface
RMS roughness at a 100 micron square sample size scale.
[0104] These results are consistent with observations that film
strips are often found sticking to Material A when opened for
examination. It is believed that this tendency to stick to Material
A is directly related for the film strips' tendency to crack while
in the Material A package. The results are also consistent with the
observation that the film strips have seldom been found to stick to
the Material B and the strips experience much less stress cracking
when packaged in this material. Since Material B has a lower
surface energy and roughness, the strips do not tend to stick and
subsequently crack when packaged into this material.
Example 2
Comparative Testing
[0105] Two lots of film product, both including PEO as a polymeric
component, were manufactured and packaged in two separate packaging
materials. The first packaging material included an inner surface
made from ethylene acrylic acid and the second packaging material
included an inner surface made from LDPE. These lots were inspected
after 20 weeks for stress cracked strips.
[0106] After twenty weeks, the first lot packaged in the ethylene
acrylic acid packaging showed 30.4% stress cracking, and the first
lot packaged in the LDPE packaging showed 4.2% stress cracking.
Also after twenty weeks, the second lot packaged in the ethylene
acrylic acid packaging showed 46.4% stress cracking, and the first
lot packaged in the LDPE packaging showed 0% stress cracking.
Example 3
Use of LDPE Packaging Material
[0107] Five lots of film material, each including PEO as a
polymeric component, were packaged in a packaging material
including an inner surface made from LDPE and placed in a 36 month
stability program. The samples were stored at either 25.degree. C.
or 30.degree. C. At the end of the 36 months, samples were
inspected for stress cracking. The results are presented in Table 2
below:
TABLE-US-00002 TABLE 2 Stress cracking after 36 months storage at
different temperature conditions. Storage temperature Percentage
with Lot No. Number of Samples (.degree. C.) Stress Cracking 1 25
25 0% 2 25 25 0% 3 25 25 0% 4 25 25 0% 5 25 25 0% 1 25 30 0% 2 25
30 0% 3 25 30 0% 4 25 30 0% 5 25 30 0%
Example 4
Use of LDPE Packaging Material
[0108] Nine lots of three different strengths of film, each
including PEO, were manufactured and packaged in a packaging
material having an inner surface made from LDPE. The films were
inspected for stress cracking after 5 months. The results are shown
in Table 3 below:
TABLE-US-00003 TABLE 3 Frequency of stress cracking in experimental
lots. Lot No. Percentage with Stress Cracking 1 0% 2 0% 3 0% 4 0% 5
0% 6 0.67% 7 0.20% 8 0% 9 0%
Example 5
Comparative Testing
[0109] Twelve lots of film, each including PEO as a polymeric
component, were packaged in a packaging material having an inner
surface made from ethylene acrylic acid, and thirty-three lots were
packaged in a packaging material having an inner surface made from
LDPE. The films were all inspected after 3 weeks for stress
cracking. The two populations were then compared using a 2 sided
test. The results are shown in Table 4. The value of 0.005 for p
indicates a high probability the data sets are different
populations.
TABLE-US-00004 TABLE 4 Results of t test on populations Packaging
Material Defect Rate Ethylene acrylic acid Mean 8.38% SD 6.3% LDPE
Mean 2.01% SD 1.4% p 0.005
Example 6
Comparative Testing
[0110] Samples from 22 lots of film, all including PEO as polymeric
component, were packaged in a packaging material including an inner
surface made from ethylene acrylic acid and samples from 32 lots of
film, each including PEO as polymeric component, were packaged in a
packaging material including an inner surface made from LDPE. The
films were inspected at different times after packaging. The data
is shown in FIG. 3. To more clearly differentiate the rate of
stress cracking at the earlier times, a second plot (FIG. 4) shows
data obtained after 60 days.
Example 7
[0111] Film strips were individually packaged in foil/PET laminate
pouches. Some of the product was heat annealed by placing the
sealed pouches of product in an oven at 70 degrees .degree. C. for
25 minutes. The product was then inspected over time for stress
cracking. For each week (post packaging) 2000 samples were opened
and inspected. The results are shown in Table 5.
TABLE-US-00005 TABLE 5 Comparison of stress cracking in annealed
and not annealed film Week 2 Week 3 Week 4 Lot A, not annealed 0.9%
3.3% 4.0% Lot A, annealed 0.00% 0.00% 0.00% Lot B, not annealed
1.0% 8.4% 5.7% Lot B, annealed 0.25% 0.00% 0.00%
Based upon the data in Table 5, it is apparent that not annealed
material consistently has more stress cracking than the annealed
product, which exhibits essentially no stress cracking or minimal
stress cracking.
Example 8
[0112] Fresh (1 week old) and old (3 month old) of individual film
strips packaged in a foil/PET laminate pouch were examined using a
Hinds near infrared birefringence systems using a measurement
wavelength of 1310 nanometers. This wavelength surprisingly showed
anisotropic and isotropic changes while other birefringence
instruments and wavelengths were not able to see any birefringence.
Mild heating at 70.degree. C. for 1 hour surprisingly resulted in a
complete reduction of the stress as is apparent from comparing the
2D birefringence map before anneal (top: Fresh, Bottom: Old) shown
in FIG. 7 to the 2D birefringence map after anneal (top: Fresh,
Bottom: Old) shown in FIG. 8. The yellow and red areas indicate
higher internal stress while the green indicates the lowest stress.
It is evident from this experiment that both old and fresh films
exhibit internal stress before the annealing process and that heat
annealing lowers the internal stress of both the fresh and old
samples.
Example 9
[0113] A film in accordance with the present invention is coated
onto a substrate and dried in accordance with drying methods as
disclosed in U.S. Pat. Nos. 7,425,292, 7,666,337, and 7,357,8912.
Before, during or after slitting, the film is continuously
delaminated from the substrate, heated to an annealing temperature,
preferably 70 degrees C. (range of 40-90 degrees) for a period of
10 minutes (range 0.5-60 minutes) and rewound onto a substrate. The
film is then cut and packaged on standard packaging machine into
any type of packaging material.
* * * * *