U.S. patent application number 11/043634 was filed with the patent office on 2005-06-16 for systems, methods and apparatuses for manufacturing dosage forms.
Invention is credited to Sowden, Harry S..
Application Number | 20050129763 11/043634 |
Document ID | / |
Family ID | 34657909 |
Filed Date | 2005-06-16 |
United States Patent
Application |
20050129763 |
Kind Code |
A1 |
Sowden, Harry S. |
June 16, 2005 |
Systems, methods and apparatuses for manufacturing dosage forms
Abstract
Systems, methods and apparatuses for manufacturing dosage forms,
and to dosage forms made using such systems, methods and
apparatuses are provided. Novel compression, injection molding, and
thermal setting molding modules are disclosed. One or more of such
modules may be linked, preferably via a transfer device, into an
overall system for making dosage forms. The injection molding
module having at least one mold shell with an interior surface
capable of producing non-uniform coatings over compressed cores or
molded inserts contained therein.
Inventors: |
Sowden, Harry S.; (Glenside,
PA) |
Correspondence
Address: |
PHILIP S. JOHNSON
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
34657909 |
Appl. No.: |
11/043634 |
Filed: |
January 26, 2005 |
Related U.S. Patent Documents
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Application
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Filing Date |
Patent Number |
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11043634 |
Jan 26, 2005 |
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10745084 |
Dec 23, 2003 |
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11043634 |
Jan 26, 2005 |
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10432812 |
Dec 4, 2003 |
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11043634 |
Jan 26, 2005 |
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09966939 |
Sep 28, 2001 |
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6837696 |
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Current U.S.
Class: |
424/470 ;
264/109 |
Current CPC
Class: |
A61J 3/005 20130101;
A61K 9/2031 20130101; A61K 9/5084 20130101; A61K 9/2068 20130101;
A61K 9/286 20130101; A61K 9/2013 20130101; B30B 11/08 20130101;
A61J 3/10 20130101; A61K 9/2018 20130101; A61K 9/2081 20130101;
A61K 9/2086 20130101; A61K 9/2893 20130101; A61K 9/284 20130101;
A61K 9/2072 20130101; A61K 9/2826 20130101; A61K 9/2054 20130101;
A61K 9/2095 20130101; A61K 9/2853 20130101; A61K 9/2027 20130101;
A61K 9/209 20130101; A61K 9/2873 20130101; A61K 9/0056 20130101;
A61K 9/2077 20130101; A23G 3/04 20130101; A23G 3/368 20130101; A61K
9/2886 20130101; A61K 9/282 20130101 |
Class at
Publication: |
424/470 ;
264/109 |
International
Class: |
A61K 009/20; A61K
009/26 |
Claims
1. A method of making a coated dosage form comprising: a)
introducing a core into a mold shell; b) injecting a flowable
material under pressure into the mold shell; wherein the mold shell
has an interior surface capable of providing a discontinuous
coating around said dosage form.
2-27. (canceled)
28. A method of making dosage forms, comprising the steps of: a)
compressing a powder into a compressed dosage form in a compression
module; b) transferring said compressed dosage form to a molding
module; c) molding a flowable material around said compressed
dosage form in said molding module; and d) hardening said flowable
material so as to form a coating over said compressed dosage form;
wherein steps (a) through (d) are linked together such that
essentially no interruption occurs between said steps.
29. The method of claim 28, wherein one or more of said steps is
performed on a continuous basis.
30. The method of claim 28, wherein one or more of said steps is
performed on an indexing basis.
31. The method of claim 28, wherein said powder contains a
medicant.
32. The method of claim 28, wherein said flowable material contains
a medicant.
33. The method of claim 28, wherein steps (a) through (d) are
performed simultaneously, such that while coatings are being
hardened on a first group of compressed dosage forms in step (d),
flowable material is being molded around a second group of
compressed dosage forms in step (c), a third group of compressed
dosage forms are being transferred to said molding module in step
(b), and a fourth group of compressed dosage forms are being formed
in step (a).
34. The method according to claim 28, further comprises the steps
of: f) forming an insert; and g) embedding said insert in said
powder prior to compressing said powder into a compressed dosage
form.
35. The method according to claim 34, wherein at least one of said
powder and flowable material comprises a first medicant and said
insert comprises a second medicant.
36. The method according to claim 34, wherein said insert comprises
a thermal setting material.
37. The method according to claim 28, wherein said flowable
material comprises a polymer.
38. The method according to claim 28, wherein said flowable
material comprises a material selected from the group consisting of
sucrose-fatty acid esters; fats, waxes, fat-containing mixtures,
sugars, and low-moisture polymer solutions.
39. The method according to claim 37, wherein said flowable
material comprises a gelatin.
40. The method according to claim 28, wherein step (c) comprises
the steps of: (i) molding a first flowable material around a first
portion of said compressed dosage form; and (ii) molding a second
flowable material around a second portion of said compressed dosage
form.
41. The method according to claim 28, wherein a single motor drives
steps (a) through (d).
42. A dosage form made by the method of claim 28.
43. A method of making dosage forms, comprising the steps of: a)
compressing a first powder into a compressed dosage form in a first
compression module; b) transferring said compressed dosage form to
a molding module; c) molding a flowable material around said
compressed dosage form in said molding module; d) hardening said
flowable material so as to form a coating over said compressed
dosage form; e) transferring said coated compressed dosage form to
a second compression module; and f) compressing a second powder
around said coated compressed dosage form in said second
compression module to form a compressed, coated, compressed dosage
form; wherein steps (a) through (f) are linked together such that
essentially no interruption occurs between said steps.
44. The method of claim 43, wherein one or more of said steps is
performed on a continuous basis.
45. The method of claim 43, wherein one or more of said steps is
performed on an indexing basis.
46. The method of claim 43, further comprising the steps of: g)
transferring said compressed, coated, compressed dosage form to a
second molding module; h) molding a second flowable material around
said compressed, coated, compressed dosage form in said second
molding module; i) hardening said flowable material so as to form a
second coating over said dosage form.
Description
FIELD OF THE INVENTION
[0001] This invention relates generally to systems, methods and
apparatuses for manufacturing dosage forms, and to dosage forms
made using such systems, methods and apparatuses.
BACKGROUND OF THE INVENTION
[0002] A variety of dosage forms, such as tablets, capsules and
gelcaps are known in the pharmaceutical arts. Tablets generally
refer to relatively compressed powders in various shapes. One type
of elongated, capsule-shaped film coated tablet is commonly
referred to as a "caplet." Capsules are typically manufactured
using a two-piece gelatin shell formed by dipping a steel rod into
gelatin so that the gelatin coats the end of the rod. The gelatin
is hardened into two half-shells and the rod extracted. The
hardened half-shells are then filled with a powder and the two
halves joined together to form the capsule. (See Generally, Howard
C. Ansel et al., Pharmaceutical Dosage Forms And Drug Delivery
Systems (7th Ed. 1999).)
[0003] Gelatin-coated tablets, commonly known as geltabs and
gelcaps, are an improvement on gelatin capsules and typically
comprise a tablet coated with a gelatin shell. Several well known
examples of gelcaps are McNeil Consumer Healthcare's acetaminophen
based products sold under the trade name Tylenol.RTM.. U.S. Pat.
Nos. 4,820,524; 5,538,125; 5,228,916; 5,436,026; 5,679,406;
5,415,868; 5,824,338; 5,089,270; 5,213,738; 5,464,631; 5,795,588;
5,511,361; 5,609,010; 5,200,191; 5,459,983; 5,146,730; 5,942,034
describe geltabs and gelcaps and methods and apparatuses for making
them. Conventional methods for forming gelcaps are generally
performed in a batchwise manner using a number of stand-alone
machines operating independently. Such batch processes typically
include the unit operations of granulating, drying, blending,
compacting (e.g., in a tablet press), gelatin dipping or enrobing,
drying, and printing.
[0004] Unfortunately, these processes have certain drawbacks. For
example, because these systems are batch processes, each of the
various apparatuses employed is housed in a separate clean room
that must meet FDA standards. This requires a relatively large
amount of capital in terms of both space and machinery. A process
that would increase and streamline production rates would therefore
provide many economic benefits including a reduction in the size of
facilities needed to mass-produce pharmaceutical products.
Generally, it would be desirable to create a continuous operation
process, as opposed to a batch process, for formation of gelcaps
and other dosage forms.
[0005] Furthermore, gel dipping and drying operations are in
general relatively time consuming. Thus, a process that simplifies
the gelatin coating operation in particular and reduces drying time
would also be advantageous.
[0006] Current equipment for making gelcaps and geltabs is designed
to produce these forms only according to precise specifications of
size and shape. A more versatile method and apparatus, which could
be used to produce a variety of dosage forms to deliver
pharmaceuticals, nutritionals, and/or confections, would therefore
also be advantageous.
[0007] Accordingly, applicants have now discovered that a wide
variety of dosage forms, including compressed tablets, gelcaps,
chewable tablets, liquid fill tablets, high potency dosage forms,
and the like, some of which in and of themselves are novel, can be
made using unique operating modules. Each operating module performs
distinct functions, and therefore may be used as a stand-alone unit
to make certain dosage forms. Alternatively, two or more of the
same or different operating modules may be linked together to form
a continuous process for producing other dosage forms. In essence,
a "mix and match" system for the production of dosage forms is
provided by the present invention. Preferably, the operating
modules may be linked together as desired to operate as a single
continuous process.
SUMMARY OF THE INVENTION
[0008] The present invention relates to a method of making a coated
dosage form by introducing a core into a mold shell and injecting a
flowable material under pressure into the mold shell. The mold
shell has an interior surface capable of providing a discontinuous
coating around said dosage form. For example, the mold shell can
have an interior surface with at least one protrusion that extends
toward the dosage core. Alternatively, the mold shell has an
interior surface with a plurality of protrusions that extend toward
and optionally touch the surface of the core. The plurality of
protrusions can be an integral and inseparable part of the mold
shell. In an alternative embodiment, the core rests on a
spring-biased holding mechanism. In one embodiment, the core can be
a compressed powder containing a medicant.
[0009] The present invention also relates to a method of making a
coated dosage form by: a) compressing a powder material into a
compressed core in a compression module; b) transferring said
compressed core from the compression module to an injection molding
module; c) injecting a flowable material into a mold shell having
an interior surface capable of providing a discontinuous coating
around said compressed core; and d) hardening said flowable
material so as to form a discontinuous coating over said compressed
core. Advantageously, steps (a) through (d) are linked together
such that essentially no interruption occurs between said steps.
One or more of said steps can be performed on a continuous
basis.
[0010] In a further embodiment, steps (a) through (d) are performed
simultaneously, such that while coatings are being hardened on a
first group of compressed cores in step (d), flowable material is
being molded around a second group of compressed cores in step (c),
a third group of compressed cores are being transferred to said
injection molding module in step (b), and a fourth group of
compressed cores are being formed in step (a). In a still further
embodiment, step (c) includes the steps of:
[0011] (i) injecting into a first mold shell a first flowable
material around a first portion of said compressed core; and
[0012] (ii) injecting into a second mold shell a second flowable
material around a second portion of said compressed core.
[0013] Either the first mold shell or the second mold shell or both
mold shells have a surface capable of producing a discontinuous
coating over at least a portion of said compressed core.
[0014] The present invention further relates to a mold shell having
a generally global, circular, cylindrical or elliptical shape that
is sized for coating a substrate selected from a compressed core
for health, particularly human, or medicinal purposes and molded
dosage inserts having an interior surface with at least one
protrusion extending toward a resting position for said substrate.
The present invention further relates to a plate having a plurality
of mold shells described above.
[0015] The present invention further relates to a dosage form made
by the method described herein having at least one opening passing
through the coating to expose the compressed core.
[0016] The invention also provides compressed cores containing at
least about 85 percent by weight of a medicant selected from the
group consisting of acetaminophen, ibuprofen, flurbiprofen,
ketoprofen, naproxen, diclofenac, aspirin, pseudoephedrine,
phenylpropanolamine, chlorpheniramine maleate, dextromethorphan,
diphenhydramine, famotidine, loperamide, ranitidine, cimetidine,
astemizole, terfenadine, fexofenadine, loratadine, cetirizine,
antacids, mixtures thereof and pharmaceutically acceptable salts
thereof, and being substantially free of water soluble polymeric
binders, the relative standard deviation in weight of said
compressed cores being less than about 2%.
[0017] The invention also provides compressed cores containing at
least about 85 percent by weight of a medicant and being
substantially free of hydrated polymers, the relative standard
deviation in weight of said compressed cores being less than about
2%, alternatively, the relative standard deviation in weight of
said compressed cores is less than about 1%.
[0018] The invention also provides a dosage form comprising a
substrate having a coating thereon and at least one opening that
exposes the substrate, said coating having a thickness of about 100
to about 400 microns; the relative standard deviation in thickness
of said coating being less than 30%; wherein said coating is
substantially free of humectants. The invention also provides a
dosage form comprising a tablet having a coating thereon and at
least one opening that exposes the substrate, said coating having a
thickness of about 100 to about 400 microns, wherein the relative
standard deviation in thickness of said dosage form is not more
than about 0.35%; and wherein said coating is substantially free of
humectants.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] FIG. 1 is an example of a dosage form made according to the
invention.
[0020] FIGS. 1A, 1B, 1C and ID illustrate alternative dosage
forms.
[0021] FIG. 2 is a plan view, partially schematic, of a system for
manufacturing dosage forms according to the invention.
[0022] FIG. 3 is an elevational view of the system shown in FIG.
3.
[0023] FIG. 4 is top view of a portion of the compression
module.
[0024] FIG. 5 is a cross-section of an injection molding
module.
[0025] FIGS. 6 and 7 illustrate phases of operation for the
injection molding module.
[0026] FIG. 8 illustrates process steps for one embodiment of the
invention.
[0027] FIGS. 9-11 illustrate a preferred process for an injection
molding module.
[0028] FIGS. 12 and 13 illustrate a mold shell capable of producing
a discontinuous coating.
[0029] FIGS. 14-16 are cross-sectional views of a preferred nozzle
system of a center mold assembly.
[0030] FIG. 17 is a cross-sectional view of an upper mold assembly
of the injection molding module showing a cam system thereof.
[0031] FIGS. 18-20 are cross-sectional views of the upper mold
assembly and the center mold assembly of the injection molding
module.
[0032] FIG. 21 illustrates a temperature control system.
[0033] FIG. 22 is a top view of a transfer device according to the
invention.
DETAILED DESCRIPTION OF INVENTION
[0034] The methods, systems, and apparatuses of this invention can
be used to manufacture conventional dosage forms, having a variety
of shapes and sizes, as well as novel dosage forms that could not
have been manufactured heretofore using conventional systems and
methods. In its most general sense, the invention provides an
injection molding process for coating dosage forms using a mold
shell with an interior surface capable of providing a discontinuous
coating around the dosage form. Further, the invention includes the
combination of: 1) a compression module for making compressed cores
from compressible powders, 2) an injection molding module having
the modified interior surface for applying a discontinuous coating
to a substrate, and 3) a transfer device for transferring dosage
forms from one module to another.
[0035] In one embodiment, the inventive process produces a dosage
form 10 comprising a molded coating 18 having at least one,
preferably a plurality, of openings 16 on the outside surface of a
core 12 optionally also containing an insert 14 as shown in FIG. 1.
It may be appreciated from FIG. 1 that the coating is discontinuous
as indentations or holes or openings (as shown) prevent the
coatings from uniformly coating the entire surface.
[0036] FIG. 1 depicts a dosage form 10 according to the invention
comprising a molded coating 18 having a plurality of openings 16.
Openings 16 are shaped as elongated slits, and do not extend all
the way through the molded coating 18 to the core (not shown).
[0037] FIG. 1 depicts another dosage form according to the
invention. The dosage form 10 comprises a core (not shown) having a
first molded coating 18a and a second molding coating 18b. Molded
coating 18a contains a plurality of openings 16a and 16b. Openings
16a are shaped as dimples, while openings 16b are shaped as
letters.
[0038] FIG. 1 illustrates another dosage form according to the
invention. Dosage form 10 comprises a core (not shown) covered by
molded coating 18, which comprises openings 16a and 16b. Openings
16a are shaped as circular holes, while openings 16b are shaped as
letters.
[0039] By way of overview, a preferred system 20 comprises an
optional compression module 100, an injection molding module 200
and an optional transfer device 300 for transferring a core
(optionally made in the compression module 100, or alternately made
in a second molding module) to the injection molding module 200 as
shown in FIGS. 2 and 3.
[0040] In certain preferred embodiments, linkage of the compression
module, transfer device, and the injection molding module in this
manner results in a continuous, multi-station system. In such
embodiments, compression is accomplished in the first module,
molding of a coating around the resulting compressed core is
performed in the second module, and the transfer device
accomplishes transfer of the intermediate dosage form from one
module to the other.
[0041] In other optional embodiments, the system 20 also includes a
thermal setting molding module 400 for forming a molded dosage
form, which may comprise the final dosage form or be an insert for
incorporation into another dosage form. In a preferred embodiment,
the insert comprises a high potency additive. The invention is not
limited to the type or nature of insert. Rather, the term insert is
used simply to denote a pellet-type component embedded in another
dosage form. Such an insert may itself contain a medicant, and
retains its shape while being placed within the powder. The insert
is inserted into uncompressed powder within compression module 100.
After insertion the powder and insert are compressed. The thermal
setting molding module 400 can be separate from or part of the
compression module 100. If the thermal setting molding module is
separate from the compression module 100, a transfer device 700 can
be used to transfer the insert from the thermal setting molding
module 400 to the compression module 100.
[0042] The linked system for creating dosage forms, as well as each
individual operating module, provide many processing advantages.
The operating modules may be used separately or together, in
different sequences, depending on the nature of the dosage form
desired. Two or more of the same operating modules may be used in a
single process. And although the apparatuses, methods and systems
of this invention are described with respect to making dosage
forms, it will be appreciated that they can be used to produce
non-medicinal products as well. For example, they may be used to
make confections or placebos. The molding module can be used with
numerous natural and synthetic materials with or without the
presence of a medicant. Similarly, the compression module can be
used with various powders with or without drug. These examples are
provided by way of illustration and not by limitation, and it will
be appreciated that the inventions described herein have numerous
other applications.
[0043] When linked in a continuous process, the operating modules
can each be powered individually or jointly. In the preferred
embodiment shown in FIGS. 3 and 4, a single motor 50 powers the
compression module 100, the injection molding module 200, and the
transfer device 300. The motor 50 can be coupled to the compression
module 100, the injection molding module 200 and the transfer
device 300 by any conventional drive train, such as one comprising
gears, gear boxes, line shafts, pulleys, and/or belts. Of course,
such a motor or motors can be used to power other equipment in the
process, such as the dryer 500 and the like.
[0044] As used herein, the term "dosage form" applies to any solid
object, semi-solid, or liquid composition designed to contain a
specific pre-determined amount (dose) of a certain ingredient, for
example an active ingredient as defined below. Suitable dosage
forms may be pharmaceutical drug delivery systems, including those
for oral administration, buccal administration, rectal
administration, topical or mucosal delivery, or subcutaneous
implants, or other implanted drug delivery systems; or compositions
for delivering minerals, vitamins and other nutraceuticals, oral
care agents, flavorants, and the like.
[0045] Preferably the dosage forms of the present invention are
considered to be solid, however they may contain liquid or
semi-solid components. In a particularly preferred embodiment, the
dosage form is an orally administered system for delivering a
pharmaceutical active ingredient to the gastrointestinal tract of a
human. In another preferred embodiment, the dosage form is an
orally administered "placebo" system containing pharmaceutically
inactive ingredients, and the dosage form is designed to have the
same appearance as a particular pharmaceutically active dosage
form, such as may be used for control purposes in clinical studies
to test, for example, the safety and efficacy of a particular
pharmaceutically active ingredient.
[0046] The dosage form of the present invention preferably contains
one or more active ingredients. Suitable active ingredients broadly
include, for example, pharmaceuticals, minerals, vitamins and other
nutraceuticals, oral care agents, flavorants and mixtures thereof.
Suitable pharmaceuticals include analgesics, anti-inflammatory
agents, antiarthritics, anesthetics, antihistamines, antitussives,
antibiotics, anti-infective agents, antivirals, anticoagulants,
antidepressants, antidiabetic agents, antiemetics, antiflatulents,
antifungals, antispasmodics, appetite suppressants,
bronchodilators, cardiovascular agents, central nervous system
agents, central nervous system stimulants, decongestants, oral
contraceptives, diuretics, expectorants, gastrointestinal agents,
migraine preparations, motion sickness products, mucolytics, muscle
relaxants, osteoporosis preparations, polydimethylsiloxanes,
respiratory agents, sleep-aids, urinary tract agents and mixtures
thereof.
[0047] Suitable flavorants include menthol, peppermint, mint
flavors, fruit flavors, chocolate, vanilla, bubblegum flavors,
coffee flavors, liqueur flavors and combinations and the like.
[0048] Examples of suitable gastrointestinal agents include
antacids such as calcium carbonate, magnesium hydroxide, magnesium
oxide, magnesium carbonate, aluminum hydroxide, sodium bicarbonate,
dihydroxyaluminum sodium carbonate; stimulant laxatives, such as
bisacodyl, cascara sagrada, danthron, senna, phenolphthalein, aloe,
castor oil, ricinoleic acid, and dehydrocholic acid, and mixtures
thereof; H2 receptor antagonists, such as famotadine, ranitidine,
cimetadine, nizatidine; proton pump inhibitors such as omeprazole
or lansoprazole; gastrointestinal cytoprotectives, such as
sucraflate and misoprostol; gastrointestinal prokinetics, such as
prucalopride, antibiotics for H. pylori, such as clarithromycin,
amoxicillin, tetracycline, and metronidazole; antidiarrheals, such
as diphenoxylate and loperamide; glycopyrrolate; antiemetics, such
as ondansetron, analgesics, such as mesalamine.
[0049] Examples of suitable polydimethylsiloxanes, which include,
but are not limited to dimethicone and simethicone, are those
disclosed in U.S. Pat. Nos. 4,906,478, 5,275,822, and 6,103,260,
the contents of each is expressly incorporated herein by reference.
As used herein, the term "simethicone" refers to the broader class
of polydimethylsiloxanes, including but not limited to simethicone
and dimethicone.
[0050] In one embodiment of the invention, at least one active
ingredient may be selected from bisacodyl, famotadine, ranitidine,
cimetidine, prucalopride, diphenoxylate, loperamide, lactase,
mesalamine, bismuth, antacids, and pharmaceutically acceptable
salts, esters, isomers, and mixtures thereof.
[0051] In another embodiment, at least one active ingredient is
selected from analgesics, anti-inflammatories, and antipyretics,
e.g. non-steroidal anti-inflammatory drugs (NSAIDs), including a)
propionic acid derivatives, e.g. ibuprofen, naproxen, ketoprofen
and the like; b) acetic acid derivatives, e.g. indomethacin,
diclofenac, sulindac, tolmetin, and the like; c) fenamic acid
derivatives, e.g. mefenamic acid, meclofenamic acid, flufenamic
acid, and the like; d) biphenylcarbodylic acid derivatives, e.g.
diflunisal, flufenisal, and the like; e) oxicams, e.g. piroxicam,
sudoxicam, isoxicam, meloxicam, and the like; f) cyclooxygenase-2
(COX-2) selective NSAIDs; and g) pharmaceutically acceptable salts
of the foregoing.
[0052] In one particular embodiment, at least one active ingredient
is selected from propionic acid derivative NSAID, which are
pharmaceutically acceptable analgesics/non-steroidal
anti-inflammatory drugs having a free --CH(CH.sub.3)COOH or
--CH.sub.2CH.sub.2COOH or a pharmaceutically acceptable salt group,
such as --CH(CH.sub.3)COO--Na+ or CH.sub.2CH.sub.2COO--Na+, which
are typically attached directly or via a carbonyl functionality to
a ring system, preferably an aromatic ring system.
[0053] Examples of useful propionic acid derivatives include
ibuprofen, naproxen, benoxaprofen, naproxen sodium, fenbufen,
flurbiprofen, fenoprofen, fenbuprofen, ketoprofen, indoprofen,
pirprofen, carpofen, oxaprofen, pranoprofen, microprofen,
tioxaprofen, suprofen, alminoprofen, tiaprofenic acid, fluprofen,
bucloxic acid, and pharmaceutically acceptable salts, derivatives,
and combinations thereof.
[0054] In one embodiment of the invention, the propionic acid
derivative is selected from ibuprofen, ketoprofen, flubiprofen, and
pharmaceutically acceptable salts and combinations thereof. In
another embodiment, the propionic acid derivative is ibuprofen,
2-(4-isobutylphenyl) propionic acid, or a pharmaceutically
acceptable salt thereof, such as the arginine, lysine, or histidine
salt of ibuprofen. Other pharmaceutically acceptable salts of
ibuprofen are described in U.S. Pat. Nos. 4,279,926, 4,873,231,
5,424,075 and 5,510,385, the contents of which are incorporated by
reference.
[0055] In another particular embodiment of the invention, at least
one active ingredient may be an analgesic selected from
acetaminophen, acetyl salicylic acid, ibuprofen, naproxen,
ketoprofen, flurbiprofen, diclofenac, cyclobenzaprine, meloxicam,
rofecoxib, celecoxib, and pharmaceutically acceptable salts,
esters, isomers, and mixtures thereof.
[0056] In another particular embodiment of the invention, at least
one active ingredient may be selected from pseudoephedrine,
phenylpropanolamine, chlorpheniramine, dextromethorphan,
diphenhydramine, astemizole, terfenadine, fexofenadine, loratadine,
desloratadine, cetirizine, mixtures thereof and pharmaceutically
acceptable salts, esters, isomers, and mixtures thereof.
[0057] In another particular embodiment, at least one active
ingredient is an NSAID and/or acetaminophen, and pharmaceutically
acceptable salts thereof.
[0058] The active ingredient or ingredients are present in the
dosage form in a therapeutically effective amount, which is an
amount that produces the desired therapeutic response upon oral
administration and can be readily determined by one skilled in the
art. In determining such amounts, the particular active ingredient
being administered, the bioavailability characteristics of the
active ingredient, the dosing regimen, the age and weight of the
patient, and other factors must be considered, as known in the art.
Typically, the dosage form comprises at least about 1 weight
percent, preferably, the dosage form comprises at least about 5
weight percent, e.g. about 20 weight percent of a combination of
one or more active ingredients. In one preferred embodiment, the
core comprises a total of at least about 25 weight percent (based
on the weight of the core) of one or more active ingredients.
[0059] The active ingredient or ingredients may be present in the
dosage form in any form. For example, one or more active
ingredients may be dispersed at the molecular level, e.g. melted or
dissolved, within the dosage form, or may be in the form of
particles, which in turn may be coated or uncoated. If an active
ingredient is in form of particles, the particles (whether coated
or uncoated) typically have an average particle size of about
1-2000 microns. In one preferred embodiment, such-particles are
crystals having an average particle size of about 1-300 microns. In
another preferred embodiment, the particles are granules or pellets
having an average particle size of about 50-2000 microns,
preferably about 50-1000 microns, most preferably about 100-800
microns.
[0060] In certain embodiments, at least a portion of one or more
active ingredients may be optionally coated with a
release-modifying coating, as known in the art. This advantageously
provides an additional tool for modifying the release profile of
active ingredient from the dosage form. For example, the core may
contain coated particles of one or more active ingredients, in
which the particle coating confers a release modifying function, as
is well known in the art. Examples of suitable release modifying
coatings for particles are described in U.S. Pat. Nos. 4,173,626;
4,863,742; 4,980,170; 4,984,240; 5,286,497; 5,912,013; 6,270,805;
and 6,322,819. Commercially available modified release coated
active particles may also be employed. Accordingly, all or a
portion of one or more active ingredients in the core may be coated
with a release-modifying material.
[0061] In embodiments in which it is desired for at least one
active ingredient to be absorbed into the systemic circulation of
an animal, the active ingredient or ingredients are preferably
capable of dissolution upon contact with a dissolution medium such
as water, gastric fluid, intestinal fluid or the like.
[0062] In one embodiment, the dissolution characteristics of at
least one active ingredient meets USP specifications for immediate
release tablets containing the active ingredient. For example, for
acetaminophen tablets, USP 24 specifies that in pH 5.8 phosphate
buffer, using USP apparatus 2 (paddles) at 50 rpm, at least 80% of
the acetaminophen contained in the dosage form is released
therefrom within 30 minutes after dosing, and for ibuprofen
tablets, USP 24 specifies that in pH 7.2 phosphate buffer, using
USP apparatus 2 (paddles) at 50 rpm, at least 80% of the ibuprofen
contained in the dosage form is released therefrom within 60
minutes after dosing. See USP 24, 2000 Version, 19-20 and 856
(1999). In embodiments in which at least one active ingredient is
released immediately, the immediately released active ingredient is
preferably contained in the shell or on the surface of the shell,
e.g. in a further coating surrounding at least a portion of the
shell.
[0063] In another embodiment, the dissolution characteristics of
one or more active ingredients are modified: e.g. controlled,
sustained, extended, retarded, prolonged, delayed and the like. In
a preferred embodiment in which one or more active ingredients are
released in a modified manner, the modified release active or
actives are preferably contained in the core. As used herein, the
term "modified release" means the release of an active ingredient
from a dosage form or a portion thereof in other than an immediate
release fashion, i.e., other than immediately upon contact of the
dosage form or portion thereof with a liquid medium. As known in
the art, types of modified release include delayed or controlled.
Types of controlled release include prolonged, sustained, extended,
retarded, and the like. Modified release profiles that incorporate
a delayed release feature include pulsatile, repeat action, and the
like. As is also known in the art, suitable mechanisms for
achieving modified release of an active ingredient include
diffusion, erosion, surface area control via geometry and/or
impermeable or semi-permeable barriers, and other known
mechanisms.
[0064] In certain embodiments, the dosage form of the present
invention comprises a core and a shell. The core may be any solid
form. The core can be prepared by any suitable method, including
for example compression or molding. Suitable method of
manufacturing solid cores are well known in the art such as the
techniques on pages 1576-1607 of Remington's Pharmaceutical
Sciences, Mack Publishing Company (Fifteenth edition), 1975 the
text of which is hereby incorporated by reference.
[0065] Additionally, the cores are, in one embodiment, provided
with a precoat sealant "subcoat" that covers the entire core before
incorporation of the outer visible coating (shell). The precoat
sealant can be colored, opaque or transparent. The use of
subcoatings is well known in the art and disclosed in, for example,
U.S. Pat. No. 5,234,099, which is incorporated by reference herein.
Any composition suitable for film-coating a tablet may be used as a
subcoating according to the present invention. Examples of suitable
subcoatings are disclosed in U.S. Pat. Nos. 4,683,256, 4,543,370,
4,643,894, 4,828,841, 4,725,441, 4,802,924, 5,630,871, and
6,274,162, which are all incorporated by reference herein.
[0066] Additional suitable subcoatings include one or more of the
following ingredients: cellulose ethers such as
hydroxypropylmethylcellul- ose, hydroxypropylcellulose, and
hydroxyethylcellulose; polycarbohydrates such as xanthan gum,
starch, and maltodextrin; plasticizers including for example,
glycerin, polyethylene glycol, propylene glycol, dibutyl sebecate,
triethyl citrate, vegetable oils such as castor oil, surfactants
such as Polysorbate-80, sodium lauryl sulfate and dioctyl-sodium
sulfosuccinate; polycarbohydrates, pigments, and opacifiers.
[0067] In one embodiment, the subcoating comprises from about 2
percent to about 8 percent, e.g. from about 4 percent to about 6
percent of a water-soluble cellulose ether and from about 0.1
percent to about 1 percent, castor oil, as disclosed in detail in
U.S. Pat. No. 5,658,589, which is incorporated by reference herein.
In another embodiment, the subcoating comprises from about 20
percent to about 50 percent, e.g., from about 25 percent to about
40 percent of HPMC; from about 45 percent to about 75 percent,
e.g., from about 50 percent to about 70 percent of maltodextrin;
and from about 1 percent to about 10 percent, e.g., from about 5
percent to about 10 percent of PEG 400. The dried subcoating
typically is present in an amount, based upon the dry weight of the
core, from about 0 percent to about 5 percent. As used herein,
"core" refers to a material that is at least partially enveloped or
surrounded by another material. Preferably, the core is a
self-contained unitary object, such as a tablet or capsule.
Typically, the core comprises a solid, for example, the core may be
a compressed or molded tablet, hard or soft capsule, suppository,
or a confectionery form such as a lozenge, nougat, caramel,
fondant, or fat based composition. In certain other embodiments,
the core or a portion thereof may be in the form of a semi-solid or
a liquid in the finished dosage form. For example the core may
comprise a liquid filled capsule, or a semisolid fondant material.
In embodiments in which the core comprises a flowable component,
such as a plurality of granules or particles, or a liquid, the core
preferably additionally comprises an enveloping component, such as
a capsule shell, or a coating, for containing the flowable
material. In certain particular embodiments in which the core
comprises an enveloping component, the shell or shell portions of
the present invention are in direct contact with the enveloping
component of the core, which separates the shell from the flowable
component of the core.
[0068] The core of the present invention, depending on the method
by which it is made, typically comprises, in addition to the active
ingredient, a variety of excipients (inactive ingredients which may
be useful for conferring desired physical properties to the core or
dosage form). In embodiments in which the core is prepared by
compression, suitable excipients for compression include fillers,
binders, disintegrants, lubricants, glidants, and the like, as well
as release-modifying compressible excipients, as are well known in
the art. Suitable release-modifying compressible excipients for
making the core, or a portion thereof, by compression include
swellable erodible hydrophilic materials, insoluble edible
materials, pH-dependent polymers, and the like.
[0069] In one embodiment the core is a compressed tablet having a
hardness from about 2 to about 30 kp/cm.sup.2, e.g. from about 6 to
about 25 kp/cm.sup.2. "Hardness" is a term used in the art to
describe the diametral breaking strength of either the core or the
coated solid dosage form as measured by conventional pharmaceutical
hardness testing equipment, such as a Schleuniger Hardness Tester.
In order to compare values across different size tablets, the
breaking strength must be normalized for the area of the break.
This normalized value, expressed in kp/cm.sup.2, is sometimes
referred in the art as tablet tensile strength. A general
discussion of tablet hardness testing is found in Leiberman et al.,
Pharmaceutical Dosage Forms--Tablets, Volume 2, 2.sup.nd ed.,
Marcel Dekker Inc., 1990, pp. 213-217, 327-329.
[0070] The core may have one of a variety of different shapes. For
example, the core may be shaped as a polyhedron, such as a cube,
pyramid, prism, or the like; or may have the geometry of a space
figure with some non-flat faces, such as a cone, truncated cone,
cylinder, sphere, torus, or the like. In certain embodiments, a
core has one or more major faces. For example, in embodiments
wherein a core is a compressed tablet, the core surface typically
has two opposing major faces formed by contact with the upper and
lower punch faces in the compression machine. In such embodiments
the core surface typically further comprises a "belly-band" located
between the two major faces, and formed by contact with the mold
shell walls in the compression machine. A core may also comprise a
multilayer tablet.
[0071] Exemplary core shapes that may be employed include tablet
shapes formed from compression tooling shapes described by "The
Elizabeth Companies Tablet Design Training Manual" (Elizabeth
Carbide Die Co., Inc., p. 7 (McKeesport, Pa.) (incorporated herein
by reference) as follows (the tablet shape corresponds inversely to
the shape of the compression tooling):
[0072] 1. Shallow Concave.
[0073] 2. Standard Concave.
[0074] 3. Deep Concave.
[0075] 4. Extra Deep Concave.
[0076] 5. Modified Ball Concave.
[0077] 6. Standard Concave Bisect.
[0078] 7. Standard Concave Double Bisect.
[0079] 8. Standard Concave European Bisect.
[0080] 9. Standard Concave Partial Bisect.
[0081] 10. Double Radius.
[0082] 11. Bevel & Concave.
[0083] 12. Flat Plain.
[0084] 13. Flat-Faced-Beveled Edge (F.F.B.E.).
[0085] 14. F.F.B.E. Bisect.
[0086] 15. F.F.B.E. Double Bisect.
[0087] 16. Ring.
[0088] 17. Dimple.
[0089] 18. Ellipse.
[0090] 19. Oval.
[0091] 20. Capsule.
[0092] 21. Rectangle.
[0093] 22. Square.
[0094] 23. Triangle.
[0095] 24. Hexagon.
[0096] 25. Pentagon.
[0097] 26. Octagon.
[0098] 27. Diamond.
[0099] 28. Arrowhead.
[0100] 29. Bullet.
[0101] 30. Shallow Concave.
[0102] 31. Standard Concave.
[0103] 32. Deep Concave.
[0104] 33. Extra Deep Concave.
[0105] 34. Modified Ball Concave.
[0106] 35. Standard Concave Bisect.
[0107] 36. Standard Concave Double Bisect.
[0108] 37. Standard Concave European Bisect.
[0109] 38. Standard Concave Partial Bisect.
[0110] 39. Double Radius.
[0111] 40. Bevel & Concave.
[0112] 41. Flat Plain.
[0113] 42. Flat-Faced-Beveled Edge (F.F.B.E.).
[0114] 43. F.F.B.E. Bisect.
[0115] 44. F.F.B.E. Double Bisect.
[0116] 45. Ring.
[0117] 46. Dimple.
[0118] 47. Ellipse.
[0119] 48. Oval.
[0120] 49. Capsule.
[0121] 50. Rectangle.
[0122] 51. Square.
[0123] 52. Triangle.
[0124] 53. Hexagon.
[0125] 54. Pentagon.
[0126] 55. Octagon.
[0127] 56. Diamond.
[0128] 57. Arrowhead.
[0129] 58. Bullet.
[0130] 59. Barrel.
[0131] 60. Half Moon.
[0132] 61. Shield.
[0133] 62. Heart.
[0134] 63. Almond.
[0135] 64. House/Home Plate.
[0136] 65. Parallelogram.
[0137] 66. Trapezoid.
[0138] 67. FIG. 8/Bar Bell.
[0139] 68. Bow Tie.
[0140] 69. Uneven Triangle.
[0141] A shell surrounds the cores. The shell comprises one or more
openings or indentations therein. In certain embodiments, the
opening or openings provide a passageway for communication between
the core and the exterior of the dosage form. The openings may
extend completely through the thickness of the shell to contact the
core, or only partially through the shell. Each opening may have
dimensions, e.g., length, width, or diameter, in the range of about
0.1% to about 100%, of the diameter of the dosage form, or of any
dimension (e.g. diameter, length, or width) of a major face of the
dosage form. The diameter or width of each opening is preferably
from about 0.5% to about 5% of the diameter of the dosage form, or
of any dimension (e.g. diameter, length, or width) of a major face
of the dosage form. In certain embodiments the diameter or width of
the openings may range from about 200 to about 2000 microns. The
length of the openings may range from about 1% to about 100% of the
diameter of the dosage form, or of the diameter of a major face of
the dosage form. In certain particular embodiments, the length or
diameter of a major face of the dosage form is from about 10,000 to
about 20,000 microns. In one particular embodiment, the length of
the openings is from about 100 to about 20,000 microns. The depth
of the openings is typically from about 75% to about 100% of the
thickness of the shell at the location of the openings. In certain
embodiments, the thickness of the shell at the location of the
openings typically ranges from about 20 to about 800 microns, e.g.
from about 100 to about 400 microns. In one particular embodiment,
the depth of the openings is from about 75 to about 400 microns. If
a plurality of openings is present, they are typically spaced from
one another by at least about one half, e.g. at least about one,
times the smallest dimension of the smallest opening. The openings
may have a variety of shapes, or be arranged in a variety of
different patterns, and may have similar or different sizes. In one
embodiment, the size of the openings is small enough to prevent the
core from being tasted, yet the number of openings is large enough
to provide communication between a certain percentage of surface
area of the core and the exterior of the dosage form.
[0142] The shell thickness at various locations may be measured
using a microscope, for example, an environmental scanning electron
microscope, model XL 30 ESEM LaB6, Philips Electronic Instruments
Company, Mahwah, Wis. The shell thickness is measured at 6
different locations on a single dosage form. The relative standard
deviation (RSD) is calculated as the sample standard deviation,
divided by the mean, times 100 as known in the art (i.e. the RSD is
the standard deviation expressed as a percentage of the mean). The
RSD in shell thickness provides an indication of the variation in
the thickness of the shell on a single dosage form. In certain
optional embodiments of the invention, the relative standard
deviation in shell thickness is less than about 40%, e.g. less than
about 30%, or less than about 20%.
[0143] The shell may be substantially unitary and continuous with
the exception of the openings therein, or the shell may comprise
multiple portions, e.g. a first shell portion and a second shell
portion. In certain embodiments the shell or shell portions are in
direct contact with the core. In certain other embodiments, the
shell or shell portions are in direct contact with a subcoating
that substantially surrounds the core. In embodiments in which the
shell comprises a first and second shell portion, at least a first
shell portion comprises openings therein.
[0144] In certain embodiments the first shell portion and second
shell portion are compositionally different. As used herein, the
term "compositionally different" means having features that are
readily distinguishable by qualitative or quantitative chemical
analysis, physical testing, or visual observation. For example, the
first and second shell portions may contain different ingredients,
or different levels of the same ingredients, or the first and
second shell portions may have different physical or chemical
properties, different functional properties, or be visually
distinct. Examples of physical or chemical properties that may be
different include hydrophylicity, hydrophobicity, hygroscopicity,
elasticity, plasticity, tensile strength, crystallinity, and
density. Examples of functional properties which may be different
include rate and/or extent of dissolution of the material itself or
of an active ingredient therefrom, rate of disintegration of the
material, permeability to active ingredients, permeability to water
or aqueous media, and the like. Examples of visual distinctions
include size, shape, topography, or other geometric features,
color, hue, opacity, and gloss.
[0145] In one embodiment, the dosage form of the invention
comprises: a) a core containing an active ingredient; b) an
optional subcoating that substantially covers the core; and c) a
shell comprising first and second shell portions residing on the
surface of the subcoating, the first shell portion comprising one
or more openings, and the first shell portion being readily soluble
in gastrointestinal fluids. As used herein, "substantially covers"
shall mean at least about 95 percent of the surface area of the
core is covered by the subcoating.
[0146] In one embodiment, the dosage form has a subcoating that is
transparent such that the underlying core is visible through the
one or more openings provided in the molded coating. Alternatively,
the subcoating has the appearance of being translucent or opaque.
Colorants, such as pigments, or coloring agents, such as dyes, can
be used to modify the coloristic properties of the subcoating. The
thickness of the subcoat would be expected to influence the degree
of opacity, as well as the timing for dissolution and/or
disintegration of the molded coating.
[0147] In certain other embodiments, the apparatus and processes
described herein can produce a molded dosage form per se.
[0148] FIG. 4 generally depicts the preferred compression module
100. Other compression systems are suitable for use herein,
particularly when a non-continuous process or system is employed.
For example, the compressed cores can be prepared in a separate
system and then manually delivered to the injection molding module.
Of course, such a system lacks the productivity advantages of the
preferred system described herein. The remainder of the description
will be directed to the preferred system. The preferred compression
module 100 is a rotary device that performs the following
functions: feeding powder to a cavity, compacting the powder into a
compressed core and then ejecting the compressed core. When the
compression module is used in conjunction with the injection
molding module 200, upon ejection from the compression module the
compressed core may be transferred to the molding module either
directly or through the use of a transfer device, such as transfer
device 300 described below. Optionally, an insert formed by another
apparatus, such as the thermal setting molding module 400 described
below, can be inserted into the powder in the compression module
before the powder is compressed into the compressed core.
[0149] In order to accomplish these functions the compression
module 100 preferably has a plurality of zones or stations, as
shown schematically in FIG. 4, including a fill zone 102, an
insertion zone 104, a compression zone 106, an ejection zone 108
and a purge zone 110. Thus, within a single rotation of the
compression module 100 each of these functions are accomplished and
further rotation of the compression module 100 repeats the cycle.
The particulars of the preferred compression module are known and
described in Ser. No. 09/966,939, filed Sep. 28, 2001, now U.S.
Pat. No. ______ which is incorporated herein by reference.
[0150] The rotary portion of the compression module generally
includes an upper rotor, a circular die table, a lower rotor, a
plurality of upper and lower punches, an upper cam, a lower cam,
and a plurality of dies. The upper rotor 112, die table 114 and
lower rotor 116 are rotatably mounted about a common shaft 101
shown in FIG. 2.
[0151] Each of the rotors and the die table include a plurality of
cavities that are disposed along the circumferences of the rotors
and die table. Preferably, there are two circular rows of cavities
on each rotor. The cavities of each rotor are aligned with a cavity
in each of the other rotors and the die table. There are likewise
preferably two circular rows of upper punches and two circular rows
of lower punches.
[0152] Conventional rotary tablet presses are of a single row
design and contain one powder feed zone, one compression zone and
one ejection zone. This is generally referred to as a single sided
press since tablets are ejected from one side thereof. Presses
offering a higher output version of the single row tablet press
employing two powder feed zones, two tablet compression zones and
two tablet ejection zones are commercially available. These presses
are typically twice the diameter of the single sided version, have
more punches and dies, and eject tablets from two sides thereof.
They are referred to as double-sided presses.
[0153] In a preferred embodiment of the invention the compression
module described herein is constructed with two concentric rows of
punches and dies as shown in FIG. 4. This double row construction
provides for an output equivalent to two single side presses, yet
fits into a small, compact space roughly equal to the space
occupied by one conventional single sided press. This also provides
a simplified construction by using a single fill zone 102, a single
compression zone 106, and a single ejection zone 108. A single
ejection zone 108 is particularly advantageous in the linked
process of the invention, because the complexity of multiple
transfer devices 300, 700 having double sided construction is
avoided. Of course, a compression module with one row or more than
two rows can also be constructed.
[0154] The upper punches extend from above the cavities in the
upper rotor through the cavities in the upper rotor and, depending
on their position, either proximal to or within the cavities of the
die table 114. Similarly, the lower punches extend from beneath the
cavities in the lower rotor and into the cavities in the die
table.
[0155] Disposed within each of the cavities of the die table is a
die. Preferably, the dies are metallic, but any suitable material
will suffice. Each die may be retained by any of a variety of
fastening techniques within the respective cavity of the die table
114. For example, the dies may be shaped so as to have a flange
that rests on a seating surface formed in the die table 114 and a
pair of o-rings and grooves.
[0156] Each die comprises a die cavity for receiving the upper and
lower punches. The die cavities and the lower punches that extend a
distance into the die cavities define the volume of powder to be
formed into the compressed core and hence the dosage amount. Thus,
the size of die cavity and the degree of insertion of the punches
into the die cavities can be appropriately selected or adjusted to
obtain the proper dosage.
[0157] Powder is fed into the die cavities in the fill zone 102.
The powder may preferably consist of an active ingredient dispersed
throughout a matrix containing various excipients, such as binders,
disintegrants, lubricants, fillers and the like, as is
conventional, or other particulate material of a medicinal or
non-medicinal nature, such as inactive placebo blends for
tableting, confectionery blends, and the like.
[0158] Suitable excipients for compressed cores include fillers,
which include water-soluble compressible carbohydrates such as
dextrose, sucrose, mannitol, sorbitol, maltitol, xylitol, lactose,
and mixtures thereof, water insoluble plastically deforming
materials such as microcrystalline cellulose or other cellulosic
derivatives, water-insoluble brittle fracture materials such as
dicalcium phosphate, tricalcium phosphate, and the like; other
conventional dry binders such as polyvinyl pyrrolidone,
hydroxypropylmethylcellulose, and the like; sweeteners such as
aspartame, acesulfame potassium, sucralose, and saccharin;
lubricants, such as magnesium stearate, stearic acid, talc, and
waxes; and glidants, such as colloidal silicon dioxide. The mixture
may also incorporate pharmaceutically acceptable adjuvants,
including, for example, preservatives, flavors, antioxidants,
surfactants, and coloring agents. In one embodiment, the powder is
substantially free of water-soluble polymeric binders and hydrated
polymers.
[0159] After the punches leave the fill zone 102 they enter the
insertion zone 104. In this zone the lower punches may retract
slightly to allow for an optional insert to be embedded into the
soft uncompressed powder in the die cavity via a transfer device
700.
[0160] After continued rotation and before entering the compression
zone 106, the upper punch is pushed into the die cavity by a cam
track. Following this, the upper and lower punches engage the first
stage rollers 180 where force is applied to the powder via the
first stage rollers. After this initial compression event, the
punches enter the second stage rollers 182. The second stage
rollers drive the punches into the die cavity to further compress
the powder into the desired compressed core. Once past the
compression zone the upper punches retract from the die cavity and
the lower punches begin to move upward prior to entering the
ejection zone 108.
[0161] Following the formation of the compressed core in the
compression zone 106, the respective die cavity rotates to ejection
zone 108 as shown in FIG. 4. The upper punches move upward due to
the slope of the cam tracks. The lower punches move upward and into
the die cavities until eventually the lower punches eject the
compressed core out of the die cavity and optionally into a
transfer device 300 as shown in FIG. 3. In the purge zone 110,
excess powder is removed from the filters after the compressed core
has been ejected from the die cavities by blowing air through or
placing suction pressure.
[0162] The injection molding module 200 generally includes a rotor
202, as shown in FIGS. 2 and 3, around which a plurality of mold
units 204 are disposed. As the rotor 202 revolves, the mold units
204 receive compressed cores, preferably from a transfer device
such as transfer device 300. However, as noted earlier, the
compressed cores can be delivered via manual transfer. Next,
flowable material is injected into the mold units to coat the
compressed cores. After the compressed cores have been coated, the
coating may be further hardened or dried if required. They may be
hardened within the mold units or they may be transferred to
another device such as a dryer. Continued revolution of the rotor
202 repeats the cycle for each mold unit.
[0163] The injection molding module 200 includes at least one
reservoir 206 containing the flowable material, as shown in FIG. 3.
There may be a single reservoir for each mold unit, one reservoir
for all the mold units, or multiple reservoirs that serve multiple
mold units. In a preferred embodiment, flowable material of two
different colors is used to make the coating, and there are two
reservoirs 206, one for each color. The reservoirs 206 may be
mounted to the rotor 202 such that they rotate with the rotor 202,
or be stationary and connected to the rotor via a rotary union 207
as shown in FIG. 3. The reservoirs 206 can be heated to assist the
flowable material in flowing. The temperature to which the flowable
material should be heated of course depends on the nature of the
flowable material. Any suitable heating means may be used, such as
an electric (induction or resistance) heater or fluid heat transfer
media. Any suitable tubing 208 may be used to connect the
reservoirs 206 to the mold unit 204. In a preferred embodiment,
tubing 208 extends through each of the shafts 213 for each of the
center mold assemblies 212.
[0164] A preferred embodiment of a mold unit 204 is shown in FIG.
5. The mold unit 204 includes a lower retainer 210, an upper mold
assembly 214, and a center mold assembly 212. Each lower retainer
210, center mold assembly 212, and upper mold assembly 214 are
mounted to the rotor 202 by any suitable means, including but not
limited to mechanical fasteners. Although FIG. 5 depicts a single
mold unit 204 all of the other mold units 204 are similar. The
lower retainer 210 and the upper mold assembly 214 are mounted so
that they can move vertically with respect to the center mold
assembly 212. The center mold assembly 212 is preferably rotatably
mounted to the rotor 202 such that it may rotate 180 degrees.
[0165] The lower retainer 210 is mounted to the rotor 202 as shown
in FIG. 5 in any suitable fashion and comprises a plate 216 and a
dosage form holder 217. Each dosage form holder can be connected to
the plate by any one of a variety of fastening techniques including
without limitation snap rings and groves, nuts and bolts, adhesives
and mechanical fasteners. The lower retainer preferably has a total
of eight dosage form holders.
[0166] FIG. 6 is a section through one of the mold units. At the
beginning of the cycle, the upper mold assembly 214 and the center
mold assembly 212 are in the open position. As the rotor continues
to revolve the mold assemblies close to form a mold cavity. After
the mold assemblies close, hot flowable material is injected from
the upper mold assembly, the center mold assembly, or both into the
mold cavity. After the flowable material hardens, the mold
assemblies open. Upon further revolution of the rotor, the finished
molded dosage forms are ejected thus completing one full revolution
of the rotor. FIG. 7 is a section through one of the mold units
showing upper mold assembly 214 and center mold assembly 212. Note
that the center mold assembly 212 in this embodiment is capable of
rotation about its axis.
[0167] At the beginning of the molding cycle, the mold assemblies
are in the open position. Center mold assembly 212 has received a
compressed core, for example from a compression module according to
the invention transferred via a transfer device also according to
the invention. As the rotor continues to revolve, the upper mold
assembly 214 closes against center mold assembly 212. Next,
flowable material is injected into the mold cavity created by union
of the mold assemblies to apply a shell to the first half of the
compressed core. The flowable material is cooled in the mold
cavity. The mold assemblies open with the half coated compressed
cores remaining in the upper mold assembly 214. Upon further
revolution of the rotor, the center mold assembly rotates 180
degrees. As the rotor moves past 180 degrees the mold assemblies
again close and the uncoated half of the compressed core is covered
with flowable material. The mold assemblies again open and the
coated compressed core is ejected from the injection molding
module.
[0168] FIG. 8 depicts the sequence of steps for using a preferred
embodiment of the injection molding module to form a coating over a
compressed core. In this embodiment, part of a compressed core is
coated in the mold cavity created by union of the lower retainer
and the center mold assembly 212 during revolution of the rotor
between 0 and 360 degrees. Simultaneously, the remainder of a
second compressed core, the first part of which has already been
coated during a previous revolution of the rotor, is coated in the
mold cavity created by the union of the center mold assembly and
the upper mold assembly 214. Compressed cores transit through the
injection molding module in a helix, receiving partial coatings
during a first full rotation of the rotor, and then the remainder
of their coatings during a second full rotation of the rotor.
Compressed cores are therefore retained in the injection molding
module for two revolutions of the rotor (720 degrees) prior to
being ejected as finished products.
[0169] FIG. 9 is a section through one of the mold units. At the
beginning of the cycle (0 degrees rotation of the rotor) the mold
units are in the open position. The lower mold assembly 210
receives an uncoated compressed core, for example from a
compression module 100 via a transfer device 300. In the next step
illustrated by FIG. 10, upon rotation of the rotor the center mold
assembly 212 rotates 180 degrees about its axis, which is radial to
the rotor. This presents the partially coated compressed core to
the upper mold assembly 214, which is empty. The partially coated
compressed core is then disposed between the upper and center mold
assemblies 212, 214. As the rotor continues to rotate, the mold
units close. The lower retainer 210 and center mold assembly 212
create a seal around the uncoated compressed core.
[0170] Flowable material is injected into the mold cavity created
between the lower retainer 210 and the center mold assembly 212
over the uncoated compressed core to cover a part thereof. In a
preferred embodiment, the flowable material coats about half of the
uncoated compressed core, preferably the top half. Simultaneously
with the mating of the lower retainer 210 and the center mold
assembly 212, the center 212 and upper 214 mold assemblies mate to
create seals around the partially coated compressed core. Flowable
material is injected through the upper mold assembly 214 into the
mold cavity created by the center mold assembly and the upper mold
assembly to coat the remaining portion of the partially coated
compressed core, the top portion. The lower retainer 210 and upper
mold assembly 214 are mated with the center mold assembly 212
simultaneously. Accordingly, when an uncoated compressed core is
being partially coated between the lower retainer 210 and the
center mold assembly 212, the remainder of a partially coated
compressed core is being coated between the center 212 and upper
mold assemblies 214. See FIG. 10.
[0171] Following this, the lower retainer and the mold assemblies
separate. The fully coated compressed core is retained in the upper
mold assembly 214. The partially coated compressed core is retained
in the center mold assembly 214. The fully coated compressed core
is then ejected from the upper mold assembly 214 as shown
schematically in FIG. 11. Following this, an uncoated compressed
core is transferred to the lower retainer 210, such that the lower
retainer 210, center mold assembly 212, and upper mold assembly 214
return to the position of FIG. 9. The process then repeats
itself.
[0172] In the preferred embodiment shown, each mold unit can coat
eight compressed cores. Of course, the mold units can be
constructed to coat any number of compressed cores. Additionally
and preferably, the compressed cores are coated with two different
colored flowable materials. Any colors can be used. Alternatively,
only a portion of the compressed core may be coated while the
remainder is uncoated.
[0173] The molds may also be constructed to impart regular or
irregular, continuous or discontinuous, coatings, i.e., of various
portions and patterns, to the dosage forms. For example, dimple
patterned coatings, similar to the surface of a golf ball, can be
formed using a molding module comprising mold insert having dimple
patterns on their surfaces. Alternatively, a circumferential
portion of a dosage form can be coated with one flowable material
and the remaining portions of the dosage form with another flowable
material. Still another example of an irregular coating is a
discontinuous coating comprising holes of uncoated portions around
the dosage form. For example, the mold insert may have elements
covering portions of the dosage form so that such covered portions
are not coated with the flowable material. Letters or other symbols
can be molded onto the dosage form. Finally, the present molding
module allows for precise control of coating thickness on a dosage
form.
[0174] One form of a mold shell 270 having a mold cavity capable of
imparting a patterned coating to the dosage form is exemplified in
FIGS. 12 and 13. The mold cavity shown therein includes multiple
protrusions 266B extending as fixed elements from the surface of
mold shell 270 towards core 12. Such protrusions can be sized to
extend part way to the core or physically touch the core.
Additionally, while multiple protrusions 266B are exemplified, the
effect could just as easily be achieved with only one protrusion.
The shape of protrusions 266B is not significant and may form any
geometric shape or representation within or through the gelatin
coating.
[0175] In one embodiment, shown in FIG. 12, center support stem
222, contains a spring mechanism 222b that is formed from a metal,
elastomeric material, gas bladder, bevel washers, or the like; in
communication with a plunger 222A. When the mold closes, at least a
portion of protrusions 266B contacts compressed core 12, pressing
compressed core 12 against plunger 222A, causing spring mechanism
222b to compress. In one embodiment, the spring applies a pressure
to seal core 12 against protrusions 266B such that when flowable
material is injected in the gaps between the core and the
protrusions, the areas of contact are thereby masked. The pressure
applied by the spring resists an opposing pressure caused by the
injection of flowable material that would otherwise tend to
separate the core from protrusions or masking members 266B thereof.
The compliance (or resilience or flexibility) of the spring
achieves a relatively uniform masking pressure regardless of
variation in core thickness.
[0176] In another embodiment, a debossed core 12, pressed by spring
222b and plunger 222A against a substantially smooth mold surface
266A, will provide gaps, which will be filled with flowable
material. In another embodiment the spring may be designed (wire
diameter, material, and geometry) to provide a lower force than the
resultant opposing force of the pressure caused by the influx of
flowable material during the injection event in order to create a
partial or incomplete masking effect, such as a dimpled surface
texture.
[0177] In another embodiment, flowable materials having elastic
properties such as those selected from the group consisting of
gels, rubbers, silicones, and the like) can provide the resilient
feature to avoid breakage of the core and provide masking of the
desired patterned area, eliminating the necessity for a spring.
This particular embodiment is particularly useful in a 2-step
molding process in which the first shell portion comprises the
elastic or gel-like material, and the second shell portion includes
the desired openings or surface pattern. In another embodiment, the
core composition may provide sufficient ductility to avoid breakage
under the pressure of the masking members (266B) of the mold
surface 266A. Protrusions 266B may be pins, slots, pads, text, or
the like.
[0178] In an alternate embodiment, molding of the shell may be
accomplished in a single injection, eliminating the need for lower
retainer 210, half of center mold 212. Cores are deposited directly
into the center mold 212 and they rest upon protrusions 266B. When
upper mold 214 with its mold surface 266A and protrusions 266B
closes, core 12 will be suspended by such protrusions or any
features on the core or mold surface, which create a flow path for
the flowable material.
[0179] Closing the feed valve prematurely while injecting the first
shell portion can create a unique aesthetic. This causes the first
shell material to cover a portion of the first face of the core.
Consequently, when the second shell flowable material is injected,
it flows until it is stopped by the edge of the first shell
material. The resulting dosage form has the first shell material
covering a portion of a first face, and the second shell material
covering the second face and the entire belly band, and a portion
of the first face.
[0180] Another unique aesthetic or functionality can be created by
placing a gasketing or masking device between the center mold 212
and the upper mold 214 after injection of the first shell portion
and prior to closing of the upper mold against the center mold. The
midsection, e.g. bellyband if the core is a compressed tablet
oriented with major faces proximal to each mold surface, or a
section at about the center of the longitudinal axis, if the core
is a capsule-shaped form oriented with ends proximal to the center
of the upper and lower mold cavities, of the resulting dosage forms
may be uncoated, exposing the core surface. The exposed core
surface may have the form of a continuous band, or a pattern, e.g.
dots, dashes, variable thickness lines, or shapes.
[0181] Because the flowable material is injected from above the
core 12, as viewed in FIG. 11, the edge of an elastomeric collet
stops flow of the flowable material. Consequently, only the portion
of core 12 that is above the elastomeric collet will be coated when
the lower retainer 210 and center mold assembly 210 are mated. This
permits a first flowable material to be used to coat one part of
the dosage form, and a second flowable material to coat the
remainder of the dosage form-that portion which is beneath the
elastomeric collet. Although the elastomeric collet is shaped so
that about half of the dosage form will be coated at one time, the
elastomeric collet can be of any desired shape to achieve a coating
on only a certain portion of the dosage form.
[0182] When two halves of a dosage form are coated with different
flowable materials, the two flowable materials may be made to
overlap, or if desired, not to overlap. With the present invention,
very precise control of the interface between the two flowable
materials on the dosage form is possible. Accordingly, the two
flowable materials may be made flush with each other with
substantially no overlap. Or the two flowable materials may be made
with a variety of edges, for example to allow the edges of the
flowable materials to interlock.
[0183] The center mold assembly comprises a series of back-to-back,
identical insert assemblies 230. The center mold assembly 212
rotates partially coated dosage forms from their downwardly
oriented positions to upwardly oriented positions. The upwardly
pointing portions of the dosage forms, which have been coated with
flowable material, can now receive the remainder of their coatings
once the center mold assembly 212 mates with the upper mold
assembly 214. Also, the insert assemblies previously pointing
upward now point downward. Thus they are now in a position to mate
with the lower retainer 210 to receive uncoated dosage forms.
Rotation of the center mold assembly may be accomplished, for
example, using the system shown in FIG. 40 of application Ser. No.
09/966,939, filed Sep. 28, 2001, now U.S. Pat. No. ______, which is
incorporated herein by reference.
[0184] Each insert assembly 230 preferably comprises a stationary
part, which includes a center insert 254, and a moveable part,
which is in essence a nozzle and comprises a valve body 260, a
valve stem 280 and valve body tip 282, as shown best in FIG. 14.
Although FIGS. 14, 15 and 16 illustrate one nozzle or valve
assembly, in a preferred embodiment there are preferably sixteen
such nozzles or valve assemblies per center mold assembly 212,
eight facing the upper mold assembly and eight facing the lower
retainer. FIG. 15 depicts the insert assembly 230 in its closed
position. FIG. 14 shows the insert assembly 230 positioned for
injection of flowable material. FIG. 16 illustrates the insert
assembly 230 in the dosage form transfer position.
[0185] The center insert 254 may be mounted to its manifold plate
by any suitable means, and is preferably sealed with o-rings 262
and grooves 264 to prevent leakage of flowable material, as shown
in FIG. 14. The coolant channels 238 are defined between the first
manifold plate 234 and the center insert 254. The center insert 254
is constructed from a material that has a relatively high thermal
conductivity, such as stainless steel, aluminum, beryllium-copper,
copper, brass, or gold.
[0186] The movable portion of the insert assembly 230 includes the
valve body 260, the valve stem 280, and the valve body tip 282. See
FIG. 14. Valve stem 280 is independently moveable. Valve stem 280
and valve body 260 are slidably mounted within insert assembly 230.
In the preferred embodiment shown, a plurality of o-rings 284 and
grooves 286 seal the moveable portions of insert assembly to the
stationary portion of the insert assembly. Disposed around valve
stem 280 and valve body tip 282 is a flowable material path through
which flowable material traveling through the second manifold plate
236 flows when the insert assembly is in the open position (FIG.
14).
[0187] Although the center mold assembly 212 is constructed with
identical insert assemblies 230 on both sides of its rotary axis,
each insert assembly 230 performs a different function depending on
whether it is oriented in the up or in the down position. When
facing down, the insert assemblies 230 are actuated to inject
flowable material to coat a first portion of a dosage form. The
insert assemblies 230 that are facing up are presenting partially
coated dosage forms to the upper mold assembly 214. During this
time, the upward facing insert assemblies are in a neutral
position. Prior to the molds opening however, the upward facing
insert assemblies are actuated to allow compressed air to enter the
center cavity 266. This ejects the now completely coated dosage
forms from the upward facing insert assemblies. Thus the completed
dosage forms remain seated or held in the upper mold assembly
230.
[0188] Downward facing valve stem 280 is spring loaded to the
closed position of FIG. 15 by spring 290. Downward facing valve
stem 280 is moveable between the closed position of FIG. 15 and the
open position of FIG. 14. Spring 290 is mounted within the valve
stem 280 to spring load the valve stem 280 to the closed
position.
[0189] Actuator plate 292 moves upward and opens the downward
facing insert assemblies as viewed in FIG. 14 by moving and pulling
the downward facing valve stems 280 against the bias of spring 290
from the position of FIG. 15 to the position of FIG. 14. Opening of
the downward facing valve stems ports flowable material to dosage
forms disposed between the center mold assembly 212 and the lower
retainer 210. Due to the bias of spring 290, the downward facing
valve stems 280 move to the closed position of FIG. 15 to stop the
flow of flowable material.
[0190] When actuator plate 292 moves up as viewed in FIG. 14, the
upward facing insert assemblies 230 remain stationary and closed.
The upward facing valve stems 280 are compressed against spring 290
and do not open. No flowable material is provided to the upward
facing insert assemblies 230. Dosage forms in the upward facing
insert assemblies are coated by the upper mold assembly 214,
described below. Similarly, no air is provided to the downward
facing insert assemblies because dosage forms are only released
from the upward facing insert assemblies.
[0191] After the flowable material has been ported and the downward
facing insert assemblies 230 return to the position of FIG. 15, cam
followers and an air actuator plate initiate movement of the valve
body tip 282 and valve stem 280 of the upward facing insert
assemblies 230. This provides a path for air through the center
mold insert. In particular, the upward facing valve body tip 282
and valve stem 280 move from the position of FIG. 15 to the
position of FIG. 16 due to movement of cam followers. After the
application of air, cam followers move downward with the air
actuator plate, permitting the upward facing insert assemblies 230
to return to the position of FIG. 15, ready for another cycle. The
air actuator plate does not move the downward facing insert
assemblies 230 during this cycle. They do not receive air.
[0192] FIG. 16 depicts an upward facing insert assembly 230 in the
transfer position. In this position, the upward facing valve stem
280 and valve body tip 282 are withdrawn. The upward facing valve
stem 280 rests against the upward facing valve body tip 282 to stop
the flow of flowable material. With the valve body tip 282
withdrawn, however, air from can flow to the mold. After the dosage
forms have been transferred from the center mold assembly, the air
actuator plate returns up to release the upward facing valve body
260, valve body tip 282 and valve stem 280 to the closed position
of FIG. 15.
[0193] The upper mold assembly 214, which is shown in FIG. 17, is
similar in construction to half of the center mold assembly 212.
Like the center mold assembly 212, the upper mold assembly 214
directs flowable material to at least partially coat a compressed
core. In particular, the upper mold assembly 214 has a plurality of
upper insert assemblies 296 (eight in the preferred embodiment)
that mate with corresponding insert assemblies 230.
[0194] Although the upper mold assembly is similar to the center
mold assembly, the upper mold assembly does not rotate. Rather, the
upper mold assembly 214 moves vertically up and down to mate with
the center mold assembly via suitable controls. Preferably, cam
follower 299, cam track 298, and connector arm 293 (FIG. 17) are
used to control the movement of the upper mold assembly 214. Small
cam follower 289 and small cam track 288 control upper actuator
plate 291. Cam follower 299, cam track 298, small cam follower 289,
and small cam track 288 are similar in construction to the
corresponding elements of the lower retainer 210.
[0195] The upper mold assembly 214 moves during rotation of the
rotor 202 via cam follower 299 to mate with the center mold
assembly 212. After this, the cam follower 299 separates the upper
mold assembly 214 from the center mold assembly 212 so that the
finished, fully coated dosage form can be ejected and transferred
from the injection molding module as shown in FIG. 11.
[0196] The upper mold assembly 214 comprises an upper second
manifold plate 251 that ports flowable material to upper insert
assemblies 296 and is similar in construction to the second
manifold plate of the center mold assembly 212. An upper first
manifold plate 253 provides cooling to the upper insert assemblies
296 and is similar in construction to the first manifold plate of
the center mold assembly 212.
[0197] A seal around each dosage form is preferably created by
contact between the upward facing insert assembly 230 of the center
mold assembly 212 and the upper insert assembly 296 of the upper
mold assembly 214. An upper insert assembly 296 is depicted in
FIGS. 18-20 in the closed, open and eject positions, respectively.
Similar to the insert assemblies 230, each upper insert assembly
296 includes a stationary portion that includes an upper insert 265
and an upper flanged insert 258 and a moveable portion that is
basically a nozzle. The latter comprises an upper valve body 273,
upper valve stem 297 and upper valve body tip 295. The upper valve
stem 297 is moveable between open and closed positions to control
flow of the flowable material to the dosage form. The upper valve
body, upper valve stem and upper valve body tip define the flow
path for the flowable material.
[0198] One difference between the upper insert assembly 296 and the
insert assembly 230 is that the upper valve body tip 295 forms part
of the seal around the dosage form as shown in FIGS. 18-20 and
moves outward rather than inward to eject a dosage form after it
has been fully coated. FIG. 20 depicts the upper valve body tip 295
positioned to eject a dosage form. FIG. 18 depicts the upper valve
body tip 295 positioned to receive a dosage form.
[0199] As the rotor 202 rotates, cam follower 289 riding in a cam
track, moves up, causing the upper actuator plate 291 to rise and
pull upper valve stem 297 against the bias of spring 269 and hence
move it from the closed position of FIG. 18 to the open position of
FIG. 19. After this, cam follower 289 moves down and causes upper
actuator plate 291 to move upper valve stem 297 to the closed
position of FIG. 18.
[0200] Next, cam follower 289 moves down and causes upper actuator
plate 291 to move further down. When upper actuator plate 291 moves
down, it depresses upper valve stem 297, which pushes upper valve
body 273 and upper valve body tip 295 against the bias of spring
271. Upper valve body tip 295 thus assumes the position of FIG. 20
to eject a dosage form. In addition, as upper valve body tip 295
moves down air is ported around it from the compressed air path
267. As with the center mold assembly, compressed air in the upper
mold assembly ensures that the coated dosage form does not stick to
the upper insert 265 when it is ejected.
[0201] After the coated dosage form is ejected, it may be sent to a
transfer device, dryer, or other mechanism. Following this, cam
follower 289 and upper actuator plate 291 move back up. This in
turn moves upper valve stem 297 and upper valve body tip 295 back
to the position of FIG. 18 due to the bias of spring 271.
[0202] The mold assemblies, particularly mold plates 258, are
maintained at a temperature below the melting or gel temperature of
the flowable material. A heat sink and temperature control system
are provided to regulate the temperature of the mold assemblies.
Examples of heat sinks include but are not limited to chilled air,
Ranque Effect cooling, and Peltier effect devices. Electrically
powered Freon chillers provide the heat sink for the heat transfer
fluid.
[0203] FIG. 21 depicts a temperature control system 600 for the
center mold assemblies and upper mold assemblies. Although only one
mold assembly 214/212 is depicted, all mold assemblies are
connected to the temperature control system in a similar fashion.
The tubing system includes a cold loop 608 for cooling mold
assembly 214/212. Defined within the flow passageway between
fitting 603 and fitting 605 is a flow path in the mold assembly
214/212. An alternative flow pattern that has been found to produce
enhanced temperature control employs a single inlet passageway that
splits into two distinct pathways, each pathway flowing separately
in the vicinity of four mold cavities and exiting separately from
the mold assembly. Valves 620 and 622, which may be solenoid or
mechanically operated, control the flow of cool heat transfer fluid
through the mold assembly 214/212. The system also includes a
chiller 612, which provides a chilled fluid source for the cold
loop. Outlet ports 612A and inlet ports 612B of the chiller can be
connected to multiple molds, so that a single chiller can support
all of the upper molds 214 and center molds 212. Valves 620 and
622, when the molds are in operation, start the flow of chilled
heat transfer fluid therethrough. As described above, valves 620
and 622 of the temperature control system can be of various designs
known in art, such as spool, plug, ball, or pinch valves. These
valves can be actuated by suitable means such as air, electrical
solenoids, or by mechanical means such as cam tracks and cam
followers. In one embodiment, the valves are pinch valves and are
actuated by mechanical cam tracks and cam followers as the
injection molding module rotates. Known pinch valves are relatively
simple devices comprising a flexible section of tubing and a
mechanism that produces a pinching or squeezing action on the
tubing. This tubing is compressed or "pinched" to block fluid flow
therethrough. Release of the tubing allows fluid to flow.
Accordingly, the pinch valve functions as a two-way valve.
[0204] Known tablet presses use a simple stationary "take-off" bar
to remove and eject tablets from the machine. Since the turrets of
these machines rotate at fairly high speeds (up to 120 rpm), the
impact forces on the tablets as they hit the stationary take-off
bar are very significant. Dosage forms produced on these machines
must therefore be formulated to possess very high mechanical
strength and have very low friability just to survive the
manufacturing process.
[0205] In contrast with prior art devices, the present transfer
device is capable of handling dosage forms having a higher degree
of friability, preferably containing little or no conventional
binders. Thus, a preferred formulation for use with present
invention comprises one or more medicants, disintegrants, and
fillers, but is substantially free of binders. Dosage forms having
a very high degree of softness and fragility may be transferred
from any one of the operating modules of the invention as a
finished product using the transfer device, or transferred from one
operating module to another for further processing.
[0206] The present transfer device is a rotating device. It
comprises a plurality of transfer units 304. It is preferably used
for transferring dosage forms or inserts within a continuous
process of the invention comprising one or more operating modules,
i.e., from one operating module to another. For example, dosage
forms may be transferred from a compression module 100 to an
injection molding module 200, or from a thermal setting molding
module 400 to a compression module 100. Alternatively, the transfer
device can be used to transfer dosage forms or other medicinal or
non-medicinal products between the devices used to make such
products, or to discharge fragile products from such machines.
[0207] Transfer devices 300 and 700 are substantially identical in
construction. For convenience, transfer device 300 will be
described in detail below. Each of the transfer units 304 are
coupled to a flexible conveying means, such as a belt, which may be
made of any suitable material. One example of a suitable material
is a composite consisting of a polyurethane toothed belt with
reinforcing cords of polyester or poly-paraphenylene
terephthalamide (Kevlar.RTM., E.I. duPont de Nemours and Company,
Wilmington, Del.). The belt runs around the inner periphery of the
device 300. The transfer units 304 are attached to the belt as
described below.
[0208] The transfer device can take any of a variety of suitable
shapes. However, when used to transfer dosage forms or inserts
between operating modules of the present invention, transfer device
is preferably generally dog bone shaped so that it can accurately
conform to the pitch radii of two circular modules, enabling a
precision transfer.
[0209] The transfer device can be driven to rotate by any suitable
power source such as an electric motor. In a preferred embodiment,
the transfer device is linked to operating modules of the invention
and is driven by mechanical means through a gearbox, which is
connected, to the main drive motor 50. In this configuration the
velocity and positions of the individual transfer units of the
transfer device can be synchronized with the operating modules. In
a preferred embodiment the drive train includes a drive pulley 309
and an idler pulley 311 which are in the preferred embodiment
disposed inside of the transfer device 300. The drive shaft 307
connects the main drive train of the overall linked system to the
drive pulley 309 of the transfer device. The drive shaft 307 drives
the drive pulley 309 to rotate as shown in FIG. 3. The drive pulley
309 has teeth 309A that engage teeth disposed on the interior of
belt, which in turn rotates the transfer device. The idler pulley
311 has teeth 311A that engage belt, which causes the idler to
rotate with the belt. Other flexible drive systems, such as chains,
linked belts, metal belts, and the like can be used to convey the
transfer units 304 of the transfer device 300.
[0210] The radii of the cam track, the pitch distance between the
transfer units, the pitch of the toothed belt, and the gear ratio
between the drive pulley and the main drive of the linked system
are all selected such that the transfer device is precisely aligned
with the operating modules linked to it. As each operating module
rotates, the transfer device remains synchronized and phased with
each, such that a precise and controlled transfer from one
operating module to another is achieved. The velocity and position
of the transfer unit is matched to the velocity and position of the
operating module along the concave portions of the cam track.
Transfers are accomplished along this arc length. The longer the
length of the arc, the greater the time available to complete a
transfer.
[0211] Dosage forms that have been coated with flowable material in
the injection molding module are relatively hard compared with
dosage forms that have coated using conventional dipping processes.
Thus, the amount of drying needed after molding a coating onto a
dosage form using the injection molding module is substantially
less than that required with known dipping processes. Nevertheless,
they may still require hardening, depending upon the nature of the
flowable material.
[0212] Preferably, dosage forms coated in the injection molding
module are relatively hard so that they can be tumble hardened
relatively quickly. Alternatively, an air dryer may be used. Any
suitable dryers may be used, while a variety of such dryers are
generally understood in the art.
* * * * *