Note: Descriptions are shown in the official language in which they were submitted.
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SEMI-SOLID CHEWABLE DOSAGE FORM FOR OVER-THE-COUNTER
MEDICATIONS AND METHOD FOR PRODUCING SAME
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent application claims the benefit of U.S. Provisional
Application No.
62/115,618, filed February 12, 2015, and is a continuation-in-part of U.S.
Patent Application
No. 14/626,897, filed February 19, 2015, which claims the benefit of U.S.
Provisional
Application No. 62/046,712, filed September 5, 2014, which are incorporated
herein by
reference in their entireties for all purposes.
BACKGROUND OF THE INVENTION
[0002] Over-the-counter (OTC) medications are commonly used to treat
various
symptoms associated with allergies, colds, coughs, fever, pain,
gastrointestinal disorders, and
sleep. OTC medications are available in a variety of solid dosage forms that
are taken orally
including tablets, capsules, and soft-gels.
[0003] The oral administration of solid dosage forms is difficult for some
individuals who
have difficulties swallowing any type of pills. This problem is magnified for
solid dosage
forms that need to be taken 2-4 times per day to provide the desired
therapeutic effect. In
addition, solid dosage forms often have an unpleasant after-taste. Moreover,
the need for a
source of water or other liquid to assist with swallowing solid dosage forms
can complicate
administration. All of these problems with traditional solid oral dosage forms
lead to sub-
optimal patient compliance with taking OTC medications resulting in the
patient suffering
symptoms for extended periods of time.
[0004] Liquid suspensions or solutions are sometimes used as an alternative
to solid oral
dosage forms. However, the dosing with liquid dosage forms is not precise
which can lead to
the administration of too little or too much medications. In addition, liquid
dosage forms are
messy and often have a bitter taste which leads to problems with patient
compliance.
[0005] The need remains for alternative dosage forms for OTC medications to
treat
symptoms associated with allergies, colds, coughs, pain, gastrointestinal
disorders and other
common conditions that are suitable for oral administration without an
unpleasant taste or
problem with swallowing to improve patient compliance.
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BRIEF SUMMARY OF THE INVENTION
[0006] An embodiment of the invention provides a semi-solid chewable dosage
form that
contains an active pharmaceutical ingredient, a gelling agent, gelatin, sugar,
a polyol, and a
pH adjusting agent.
[0007] In another embodiment, the invention provides a semi-solid chewable
dosage
form that contains an active pharmaceutical ingredient, a gelling agent,
gelatin, sugar, corn
syrup, and a pH adjusting agent.
[0008] A further embodiment of the invention provides a semi-solid chewable
dosage
form that contains an active pharmaceutical ingredient, a gelling agent,
gelatin, sugar and
corn syrup. In another embodiment, the invention provides a semi-solid
chewable dosage
form that contains an active pharmaceutical ingredient, a gelling agent,
gelatin, sugar, and a
polyol.
[0009] The active pharmaceutical ingredient may be chlorpheniramine
maleate,
phenylephrine hydrochloride, guaifenesin, dextromethorphan hydrobromide,
loratadine,
diphenhydramine, or a combination thereof Alternatively, the active
pharmaceutical
ingredient useful for treating gastrointestinal disorders may be an antacid,
an anti-foaming
agent, a histamine H2-receptor antagonist (commonly known as a H2 antagonist),
proton
pump inhibitor, or a combination thereof. Other active pharmaceutical
ingredients commonly
present in OTC medications are suitable for use in the present invention.
[0010] A method of producing a semi-solid chewable dosage form is provided.
The
method comprises forming a primary blend comprising a gelling agent, sugar, a
polyol and a
pH adjusting agent, cooking the primary blend to obtain a residual moisture
content to
between 5% by weight to 25% by weight, combining the primary blend with a
secondary
blend containing an active pharmaceutical ingredient to yield a final blend,
depositing the
final blend into individual semi-solid chewable dosage forms.
[0011] In a further embodiment, the invention provides a method of
producing a semi-
solid chewable dosage form that comprises forming a primary blend comprising a
gelling
agent, sugar, and corn syrup, cooking the primary blend to obtain a residual
moisture content
to between 5% by weight to 25% by weight, combining the primary blend with a
secondary
blend containing an active pharmaceutical ingredient to yield a final blend,
depositing the
final blend into individual semi-solid chewable dosage forms.
[0012] In another embodiment, the invention provides a method of producing
a semi-
solid chewable dosage form that comprises forming a primary blend comprising a
gelling
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agent, sugar, and a polyol, cooking the primary blend to obtain a residual
moisture content to
between 5% by weight to 25% by weight, combining the primary blend with a
secondary
blend containing an active pharmaceutical ingredient to yield a final blend,
depositing the
final blend into individual semi-solid chewable dosage forms.
[0013] The semi-solid chewable dosage form according to the invention is
useful for
administration to individuals, including both adults and children, to treat
symptoms from
allergies, colds, coughs, pains, fever, gastrointestinal disorders, sleep, and
the like.
[0014] Other embodiments, characteristics, and advantages of the invention
are apparent
after reading the descriptions and examples that follow.
DETAILED DESCRIPTION OF THE INVENTION
[0015] The semi-solid chewable dosage form of the invention (also referred
to as the
semi-solid dosage form) is intended to be chewed by a patient such that it is
broken up into
smaller parts within the oral cavity and then easily swallowed. The semi-solid
dosage form
has a sufficiently high viscosity that it is not pourable and further does not
flow or conform to
its container at room temperature. Typically, the semi-solid dosage form does
not flow at
low shear stress and generally exhibits plastic flow behavior. In general, the
consistency of
the semi-solid dosage form is the same as or similar to gelatin-based or
pectin-based candy
products such as, for example, gummy bears and pectin jellies.
[0016] The dosage form can have any size and shape such that it can be
administered
orally and chewed by a patient. The patient should be able to readily break
apart the dosage
form by chewing and swallow the dosage form without the need for an external
source of
liquid. Typically, the dosage form has a length of about 1 cm to about 5 cm,
width of about 1
cm to about 5 cm and a height of about 1 cm to about 5 cm. Suitable shapes
include, for
example, ovals, spheres, cylinders, rectangular boxes and cubes. The dosage
form may be
formed into unique shapes and figures including, for example, animals for
administration to
children (e.g., under the age of 13) and/or adults.
[0017] Generally, each individual dosage form has a total weight of at
least 100 mg.
Typically, each dosage form has a total weight of from about 1 g to about 20
g. Preferably,
each dosage form has a total weight of from about 1 g to about 15 g.
Preferably each dosage
form has a total weight of from about 1 g to about 10 g, for example, about 1
g to about 1.5 g,
about 1.5 g to about 2 g, about 2 g to about 2.5 g, about 2.5 g to about 3 g,
about 3.5 g to
about 4 g, about 4 g to about 4.5 g, about 4.5 g to about 5 g, about 5 g to
about 5.5 g, about
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5.5 g to about 6 g, about 6 g to about 6.5 g, about 6.5 g to about 7 g, about
7 g to about 7.5 g,
about 7.5 g to about 8 g, about 8 g to about 8.5 g, about 8.5 g to about 9 g,
about 9 g to about
9.5 g, and about 9.5 g to about 10 g. Most preferably, each dosage form has a
total weight of
about 5 g.
[0018] Active pharmaceutical ingredients that are suitable for use in the
semi-solid
dosage form for the invention include, by way of example, anti-allergy,
antihistamines,
antitussives, decongestants, expectorants, anti-cold/flu, analgesics, anti-
inflammatories, sleep
medications, anti-heartburn medications, anti-gas medications, anti-GERD
medications, anti-
diarrheals, laxatives, anti-smoking and/or motion sickness medications. In
some
embodiments, suitable active pharmaceutical ingredients may treat and/or
prevent
gastrointestinal disorders including, for example, antacids, anti-foaming
agents, H2
antagonists, proton pump inhibitors, anti-diarrheals, laxatives, or a
combination thereof.
Suitable active pharmaceutical ingredients useful in the semi-solid dosage
form of the
invention are typically available as over-the-counter medications.
[0019] The semi-solid chewable dosage of the invention is further useful
for
administration to individuals, including both adults and children, to treat
and/or prevent
allergies, colds and coughs, as well as symptoms of these conditions.
Additionally, the semi-
solid chewable dosage form of the invention may be used to treat or prevent
gastrointestinal
disorders and symptoms thereof such as dyspepsia, peptic ulcer,
gastroesophageal reflux
disease, upset stomach, heartburn, excessive gas, and the like along with
symptoms of these
disorders.
[0020] In other embodiments, the semi-solid chewable dosage form of the
invention
includes one or more active pharmaceutical ingredients useful for the
treatment of
gastrointestinal disorders and symptoms thereof Such active ingredients are
typically
available as over-the-counter medications.
[0021] Any suitable active pharmaceutical ingredients may be used in the
semi-solid
dosage form of the present invention to treat or prevent one or more symptoms.
Suitable
active pharmaceutical ingredients are set forth in Table 1:
Table 1
Anti-Allergy
loratadine
diphenhydramine
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cetirizine
fexofenadine
Anti-Cold/Flu
pseudoephedrine
phenylephrine
chlorpheniramine
Analgesics
ibuprofen
aspirin
naproxen
acetaminophen
codeine
Cough Medications
guaifenesin
dextromethorphan
Sleep Medications
diphenhydramine
doxylamine
Heartburn Medications
ranitidine
cimetidine
famotidine
omeprazole
esomeprazole
lansoprazole
calcium carbonate
bismuth subsalicylate
Anti-Diarrheals
lop eramide
Anti-Gas
simethicone
Laxatives
bisacodyl
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Smoking Cessation
nicotine
Motion Sickness
dimenhydrinate
meclazine
[0022]
Combinations of two or more active pharmaceutical ingredients may be used in
the semi-solid dosage form of the invention to treat or prevent one or more
symptoms.
Suitable combinations of active pharmaceutical ingredients are set forth in
Table 2:
Table 2
Anti-Allergy
loratadine/pseudoephedrine
diphenhydramine/phenylephrine, diphenhydramine/pseudoephedrine
cetirizine/pseudoephedrine
fexofenadine/pseudoephedrine
Anti-Cold/Flu
chlorpheniramine/phenylephrine
ibuprofen/phenylephrine
dextromethorphan/ibuprofen/phenylephrine
dextromethorphan/acetaminophen/phenylephrine
acetaminophen/phenylephrine, acetaminophen/pseudoephedrine
doxylamine/dextromethorphan/acetaminophen
acetaminophen/dextromethorphan/guifenesin/phenylephrine
Analgesics
ibuprofen/caffeine
aspirin/caffeine
naproxen/caffeine
acetaminophen/caffeine
diphenhydramine/ibuprofen
diphenhydramine/acetaminophen
diphenhydramine/naproxen
acetaminophen/caffeine/aspirin
Antitussives
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guaifenesin/dextromethorphan
Sleep Medications
diphenhydramine/ibuprofen
diphenhydramine/aspirin
diphenhydramine/naproxen
diphenhydramine/acetaminophen
Anti-Gas
simethicone/calcium carbonate
[0023] Pharmaceutically acceptable salts of any suitable active
pharmaceutical
ingredients may also be used.
[0024] Preferably, the active pharmaceutical ingredients used in the semi-
solid chewable
dosage form of the invention include chlorpheniramine maleate, phenylephrine
hydrochloride, guaifenesin, dextromethorphan hydrobromide, loratadine,
diphenhydramine,
or a combination thereof In one embodiment, the dosage form contains a
combination of
chlorpheniramine maleate and phenylephrine hydrochloride. In another
embodiment, the
dosage form contains a combination of dextromethorphan hydrobromide and
phenylephrine
hydrochloride.
[0025] Chlorpheniramine maleate is a pharmaceutically acceptable salt of
chlorpheniramine. Chlorpheniramine has the following chemical structure:
1 : .,.
,,,,,,--,..,,,.., Pi
1..,
(5' N
L)
1 I
,,,,,
[0026] In some embodiments, the amount of chlorpheniramine maleate present
in each
dosage form is from about 0.1 mg to about 30 mg. Preferably, the amount of
chlorpheniramine maleate present in each dosage form is from about 1 mg to
about 10 mg.
More preferably, the amount of chlorpheniramine maleate present in each dosage
form is
about 1 mg to about 5 mg. Most preferably, the amount of chlorpheniramine
present is about
2 mg or about 4 mg in each dosage form that has a total weight of about 5 g.
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[0027] Alternatively, chlorpheniramine maleate may be present in the dosage
form in
amount from about 0.01% by weight to about 1.0% by weight, and preferably
about 0.02% to
about 0.2% by weight. For an adult dose, chlorpheniramine maleate is
preferably present in
an amount from about 0.06% by weight to about 0.1% by weight. For a pediatric
dose (e.g.,
children under 13), chlorpheniramine maleate is preferably present in an
amount from about
0.03% by weight to about 0.05% by weight.
[0028] Phenylephrine hydrochloride is a pharmaceutically acceptable salt of
phenylephrine. Phenylephrine has the following chemical structure:
Oi i
H . 1. g
11
[0029] In some embodiments, the amount of phenylephrine hydrochloride
present in each
dosage form is from about 0.1 mg to about 20 mg. Preferably, the amount of
phenylephrine
hydrochloride present is from about 2 mg to about 15 mg. More preferably, the
amount of
phenylephrine hydrochloride present is from about 3 mg to about 12 mg. Most
preferably,
the amount of phenylephrine hydrochloride present is about 5 mg or about 10 mg
in each
dosage form that has a total weight of about 5 g.
[0030] Alternatively, phenylephrine hydrochloride may be present in the
dosage form in
amount from about 0.01% by weight to about 1% by weight, and preferably 0.01%
to about
0.5% by weight. For an adult dose, phenylephrine hydrochloride is preferably
present in an
amount from about 0.15% by weight to about 0.25% by weight. For a pediatric
dose (e.g.,
children under 13), phenylephrine hydrochloride is preferably present in an
amount from
about 0.05% by weight to about 0.15% by weight.
[0031] Guaifenesin has the following chemical structure:
11
)3 OH
,
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[0032] In some embodiments, the amount of guaifenesin present in each
dosage form is
from about 10 mg to about 1,500 mg. Preferably, the amount of guaifenesin
present in each
dosage form is from about 200 mg to about 1,200 mg. More preferably, the
amount of
guaifenesin present in each dosage form is about 100 mg to about 400 mg. Most
preferably,
the amount of guaifenesin present is about 100 mg, 200 mg or about 400 mg in
each dosage
form that has a total weight of about 5 g.
[0033] Alternatively, guaifenesin may be present in the dosage form in
amount from
about 0.1% by weight to about 20% by weight, and preferably about 0.5% to
about 10% by
weight. For an adult dose, guaifenesin is preferably present in an amount from
about 0.5%
by weight to about 5% by weight. For a pediatric dose (e.g., children under
13), guaifenesin
is preferably present in an amount from about 0.1% by weight to about 4% by
weight.
[0034] Dextromethorphan hydrobromide is a pharmaceutically acceptable salt
of
dextromethorphan. Dextromethorphan has the following chemical structure:
= 1-k-
40-4`,`'= ,
14414,H
N., s
[0035] In some embodiments, the amount of dextromethorphan hydrobromide
present in
each dosage form is from about 1 mg to about 100 mg. Preferably, the amount of
guaifenesin
present in each dosage form is from about 5 mg to about 60 mg. More
preferably, the amount
of guaifenesin present in each dosage form is about 10 mg to about 30 mg. Most
preferably,
the amount of guaifenesin present is about 10 mg or about 20 mg in each dosage
form that
has a total weight of about 5 g.
[0036] Alternatively, dextromethorphan hydrobromide may be present in the
dosage form
in amount from about 0.01% by weight to about 2% by weight, and preferably
about 0.1% to
about 1% by weight. For an adult dose, guaifenesin is preferably present in an
amount from
about 0.1% by weight to about 1% by weight. For a pediatric dose (e.g.,
children under 13),
guaifenesin is preferably present in an amount from about 0.1% by weight to
about 0.8% by
weight.
[0037] Loratadine has the following chemical structure:
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Ci
0 0
[0038] In some embodiments, the amount of loratadine present in each dosage
form is
from 1 mg to about 100 mg. Preferably, the amount of loratadine present in
each dosage
form is from about 5 mg to about 50 mg. More preferably, the amount of
loratadine present
in each dosage form is from about 10 mg to about 30 mg. Most preferably, the
amount of
loratadine present is about 10 mg in each dosage form that has a total weight
of about 5 g.
[0039] Alternatively, loratadine may be present in the dosage form in
amount from about
0.01% by weight to about 2% by weight, and preferably about 0.1% to about 1%
by weight.
For an adult dose, loratadine is preferably present in an amount from about
0.1% by weight to
about 1% by weight. For a pediatric dose (e.g., children under 13), loratadine
is preferably
present in an amount from about 0.1% by weight to about 0.5% by weight.
[0040] Diphenhydramine hydrochloride is a pharmaceutically acceptable salt
of
diphenhydramine. Diphenhydramine has the following chemical structure:
[0041] In some embodiments, the amount of diphenhydramine hydrochloride
present in
each dosage form is from 1 mg to about 100 mg. Preferably, the amount of
diphenhydramine
hydrochloride present in each dosage form is from about 5 mg to about 50 mg.
More
preferably, the amount of diphenhydramine hydrochloride present in each dosage
form is
from about 10 mg to about 30 mg. Most preferably, the amount of
diphenhydramine
hydrochloride present is about 12.5 mg or 25 mg.
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[0042] Alternatively, diphenhydramine hydrochloride may be present in the
dosage form
in amount from about 0.01% by weight to about 2% by weight, and preferably
about 0.1% to
about 1% by weight. For an adult dose, diphenhydramine hydrochloride is
preferably present
in an amount from about 0.1% by weight to about 1% by weight. For a pediatric
dose (e.g.,
children under 13), diphenhydramine hydrochloride is preferably present in an
amount from
about 0.1% by weight to about 0.5% by weight.
[0043] Chlorpheniramine maleate and phenylephrine hydrochloride may
optionally both
be present in combination in the dosage form. Preferably, in such embodiments,
chlorpheniramine maleate is present in an amount of about 2 mg and
phenylephrine
hydrochloride is present in an amount of about 5 mg. Alternatively,
chlorpheniramine
maleate is present in an amount of about 4 mg and phenylephrine hydrochloride
is present in
an amount of about 10 mg. Typically, a pediatric dose contains about 2 mg
chlorpheniramine
maleate and 5 mg phenylephrine hydrochloride and an adult dose contains about
4 mg
chlorpheniramine maleate and 10 mg phenylephrine hydrochloride.
[0044] In embodiments in which dextromethorphan hydrobromide and
phenylephrine
hydrochloride are both present in the dosage form, preferably dextromethorphan
hydrobromide is present in an amount of about 10 mg and phenylephrine
hydrochloride is
present in an amount of about 5 mg. Alternatively, dextromethorphan
hydrobromide is
present in an amount of about 20 mg and phenylephrine hydrochloride is present
in an
amount of about 10 mg.
[0045] In other embodiments, the active pharmaceutical ingredient is an
antacid, anti-
foaming agent, histamine H2-antagonist, proton pump inhibitor, anti-diarrheal,
laxative, or
combination thereof, that are useful for the treatment and/or prevention of
gastrointestinal
disorders or symptoms thereof
[0046] Suitable antacids including, but are not limited to, potassium
bicarbonate, sodium
bicarbonate, calcium bicarbonate, aluminum bicarbonate, magnesium bicarbonate,
magnesium hydroxide, calcium carbonate, aluminum hydroxide, and combinations
thereof
[0047] In a preferred embodiment, the antacid is calcium carbonate. Calcium
carbonate
has the formula Ca2CO3. The calcium carbonate can be anhydrous calcium
carbonate or a
hydrate thereof
[0048] Suitable histamine H2-receptor antagonists include, but are not
limited to,
cimetidine, ranitidine, famotidine, and nizatidine.
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[0049] In a preferred embodiment, the histamine H2-receptor antagonist is
famotidine.
Famotidine has the structure:
H2N 00
NH2
[0050] Suitable proton pump inhibitors include, but are not limited to,
omeprazole,
lansoprazole, dexlansoprazole, esomeprazole, pantoprazole, rabeprazole, and
ilaprazole.
[0051] In a preferred embodiment, the proton pump inhibitor is omeprazole.
Omeprazole
has the structure:
N
0 ¨
0 41111" N
./?
[0052] A suitable anti-diarrheal includes, but is not limited to,
loperamide.
[0053] A suitable laxative includes, but is not limited to, bisacodyl.
[0054] A suitable anti-gas agent includes, but is not limited to,
simethicone. Simethicone
has the following structure:
cts
,
ti3C t-CH3 E802
cH3 cH3
[0055] The amount of active pharmaceutical ingredient in the semi-solid
dosage form
will vary for each different active depending on its use. The amount present
will usually be
less for semi-solid dosage forms that are intended to be administered to
children. For semi-
solid dosage forms for use with gastrointestinal disorders, the active
ingredient may be
present in an amount sufficient to treat and/or prevent gastrointestinal
disorders and
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symptoms thereof (e.g., bloating, discomfort and/or pain) including, for
example, dyspepsia,
peptic ulcer, gastroesophageal reflux disease, upset stomach, heartburn, and
excessive gas.
[0056] Typically, the semi-solid dosage form contains about 0.1 mg to 1 g
of the active
pharmaceutical ingredient. Alternatively, the semi-solid dosage form contains
one or more
active pharmaceutical ingredients in an amount from about 0.01% by weight to
about 10% by
weight.
[0057] The semi-solid dosage form of the invention may be administered once
per day or
multiple times per day to provide relief for various symptoms affecting an
individual. For
example, chlorpheniramine maleate may be administered to treat symptoms of
allergic
rhinitis or sinusitis. Phenylephrine hydrochloride may be administered to
treat symptoms of
nasal congestion. Typical dosing of chlorpheniramine maleate for adults is 4
mg every 4-6
hours and for children (i.e., 6-11 years old) is 2 mg every 4-6 hours. Typical
dosing of
phenylephrine hydrochloride for adults is 10 mg every 4-6 hours and for
children (i.e., 6-11
years old) is 5 mg every 4-6 hours.
[0058] Guaifenesin may be administered to treat symptoms of congestion in
the chest and
throat. Typical dosing of guaifenesin for adults is 200 mg to 400 mg every 4-6
hours and for
children (i.e., 6-11 years old) is 100 mg to 200 mg every 4-6 hours.
[0059] Dextromethorphan hydrobromide may be administered to treat symptoms
of a
cough. Typical dosing of dextromethorphan hydrobromide for adults is 10 mg to
30 mg
every 4-8 hours and for children (i.e., 6-11 years old) is 5 mg to 10 mg every
4 hours.
[0060] Loratadine may be administered to treat symptoms of allergic
rhinitis and
urticaria. Typical dosing of loratadine for adults and children (i.e., 6-11
years old) is 10 mg
per day.
[0061] In embodiments where the active pharmaceutical ingredient is an
antacid, the
amount of antacid present in each dosage form is from about 10 mg to about 2
g. Preferably,
the amount of antacid present in each dosage form is from about 100 mg to
about 1 g. More
preferably, the amount of antacid present in each dosage form is about 500 mg
to about 1 mg.
Most preferably, the amount of antacid present is about 750 mg or about 800 mg
in each
dosage form that has a total weight of about 5 g.
[0062] Alternatively, the antacid may be present in the dosage form in
amount from about
1% by weight to about 30% by weight, and preferably about 5% to about 20% by
weight.
[0063] In embodiments where the active pharmaceutical ingredient is an anti-
foaming
agent (also referred to herein as an anti-gas agent), the amount of anti-
foaming agent present
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in each dosage form is from about 1 mg to about 500 mg. Preferably, the amount
of
anti-foaming agent present is from about 5 mg to about 250 mg. More
preferably, the amount
of anti-foaming agent present is from about 10 mg to about 100 mg. Most
preferably, the
amount of anti-foaming agent present is about 20 mg or about 80 mg in each
dosage form
that has a total weight of about 5 g.
[0064] Alternatively, the anti-foaming agent may be present in the dosage
form in
amount from about 0.01% by weight to about 5% by weight, and preferably 0.1%
to about
5% by weight. For an adult dose, the anti-foaming agent is preferably present
in an amount
from about 0.15% by weight to about 0.25% by weight. For a pediatric dose
(e.g., children
under 13), the anti-foaming agent is preferably present in an amount from
about 0.05% by
weight to about 0.15% by weight.
[0065] In some embodiments, the active pharmaceutical ingredient is a
histamine
H2-receptor antagonist. In these embodiments, the amount of histamine H2-
receptor
antagonist present in each dosage form is from about 1 mg to about 500 mg.
Preferably, the
amount of histamine H2-receptor antagonist is from about 5 mg to about 250 mg.
More
preferably, the amount of histamine H2-receptor antagonist present is from
about 10 mg to
about 100 mg. Most preferably, the amount of histamine H2-receptor antagonist
present is
about 20 mg or about 80 mg in each dosage form that has a total weight of
about 5 g.
[0066] In some embodiments, the active pharmaceutical ingredient is a
proton pump
inhibitor. In these embodiments, the amount of proton pump inhibitor present
in each dosage
form is from about 1 mg to about 500 mg. Preferably, the amount of proton pump
inhibitor is
from about 5 mg to about 250 mg. More preferably, the amount of proton pump
inhibitor
present is from about 10 mg to about 100 mg. Most preferably, the amount of
proton pump
inhibitor present is about 20 mg or about 80 mg in each dosage form that has a
total weight of
about 5 g.
[0067] The semi-solid dosage form of the invention includes a gelling
agent. Any
suitable gelling agent may be used to provide the dosage form with the desired
characteristics
including, for example, semi-solid structure, shape and texture. The gelling
agent is typically
a USP (U.S. Pharmacopeia) grade gelling agent. Preferably, the gelling agent
is pectin.
[0068] Pectin is a purified carbohydrate obtained by aqueous extraction
from citrus peel
or apple pomace. Any suitable type of pectin may be use in the dosage form
including, for
example, high-methoxy pectin and low-methoxy pectin and combinations thereof.
Low-
methoxy pectin may be amidated which is often referred to as LMA pectin.
Examples of
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suitable pectins are Genu citrus pectin USP/100 and Genu citrus pectin
USP/200 from CP
Kelco.
[0069] Pectin may be generally present in the semi-solid dosage form in an
amount of
from about 0.01% by weight to about 10% by weight. Preferably, pectin is
present in an
amount of from about 0.5% by weight to about 7% by weight, for example from
about 0.5%
to about 1%, from about 1% to about 1.5%, from about 1.5% to about 2%, from
about 2% to
about 2.5%, from about 2.5% to about 3%, from about 3% to about 3.5%, from
about 3.5% to
about 4%, from about 4% to about 4.5%, from about 4.5% to about 5%, from about
5% to
about 5.5%, from about 5.5% to about 6%, from about 6% to about 6.5%, and from
about
6.5% to about 7%. More preferably, pectin is present in an amount from about
1% by weight
to about 5% by weight.
[0070] In some embodiments, the semi-solid dosage form of the invention
includes
gelatin. Without being bound by any theory, it is believed that the presence
of gelatin assists
with gelling of the semi-solid dosage form and further serves to mask the
taste of the active
ingredients.
[0071] Any suitable type of gelatin may be present in the dosage form. For
example, the
gelatin may be animal-derived gelatin, chemically-modified gelatin, physically-
modified
gelatin, and combinations thereof Animal-derived gelatin may be derived from
any suitable
source such as, for example, pigskin or bovine bone.
[0072] Alternatively, the gelatin may be hydrolyzed gelatin. Hydrolyzed
gelatin is also
commonly known as hydrolyzed collagen, collagen hydrolysate, and collagen
peptide.
Hydrolyzed gelatin having a molecular weight ranging from about 2,500 to about
5,000 may
be used. An example of a suitable hydrolyzed gelatin is Peptiplus powder from
Gelita.
[0073] Gelatin may be generally present in the semi-solid dosage form in an
amount from
about 0.01% by weight to about 15% by weight. Preferably, gelatin is present
in an amount
of from about 0.5% by weight to about 8% by weight, for example from about
0.5% to about
1%, from about 1% to about 1.5%, from about 1.5% to about 2%, from about 2% to
about
2.5%, from about 2.5% to about 3%, from about 3% to about 3.5%, from about
3.5% to about
4%, from about 4% to about 4.5%, from about 4.5% to about 5%, from about 5% to
about
5.5%, from about 5.5% to about 6%, from about 6% to about 6.5%, from about
6.5% to about
7%, from about 7% to about 7.5%, and from about 7.5% to about 8%. More
preferably,
gelatin is present in an amount from about 1% by weight to about 5% by weight.
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[0074] The semi-solid dosage form of the invention includes sugar.
Generally, sugar is
present in an amount from about 30% by weight to about 99% by weight of the
dosage form.
Preferably, sugar is present in an amount from about 40% by weight to about
95% by weight,
for example, from about 40% to about 45%, from about 45% to about 50%, from
about 50%
to about 55%, from about 55% to about 60%, from about 60% to about 65%, from
about 65%
to about 70%, from about 70% to about 75%, from about 75% to about 80%, from
about 80%
to about 85%, from about 85% to about 90%, and from about 90% to about 85%.
[0075] In some embodiments of the invention, the semi-solid dosage form
includes a
polyol. Polyols are also referred to as sugar alcohols. Without being bound by
any theory,
the presence of a polyol is believed to promote the stability of the semi-
solid dosage form of
the invention.
[0076] Suitable polyols include, for example, hydrogenated starch
hydrolysates, isomalt,
lactitol, maltitol, mannitol, sorbitol, erythritol, and xylitol. Combinations
of polyols may be
used. Preferably, the polyol is hydrolyzed starch hydrolysates (HSH). HSH
typically
contains substantial quantities of hydrogenated oligo- and poly-saccharides in
addition to
monomeric and dimeric polyols. HSH is commonly known to include polyglycitol.
An
example of a commercially available HSH is Hystar 3375 syrup (75% solids),
Hystar 4075
and Hystar 6075 supplied by SPI Polyols. Other commercially available HSH
include
75/400 from Roquette and Stabilite liquid HSH and Stabilite powdered HSH
supplied by
Corn Products Specialty Ingredients.
[0077] One or more polyols may be present in the semi-solid dosage form in
an amount
from about 30% by weight to about 99% by weight. Preferably, one or more
polyols may be
present in an amount from about 40% by weight to about 90% by weight, for
example, about
40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to
about
80%, and about 80% to about 90%. Alternatively, one or more polyols may be
present in an
amount from about 40% by weight to about 60% by weight.
[0078] In embodiments in which one or more polyols are present, the ratio
of polyol to
sugar is typically from about 1:10 to about 10:1 by dry weight. Preferably,
the ratio of polyol
to sugar is from about 1:2 to about 2:1 by dry weight, for example, from about
1:1.5 to about
1:5.1.
[0079] In other embodiments, the ratio of polyol to gelling agent is from
about 40:1 to
about 1:1 by dry weight. Preferably, the ratio of polyol to gelling agent is
from about 30:1 to
about 10:1 by dry weight.
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[0080] In some embodiments, the semi-solid dose form includes corn syrup.
Corn syrup
may be present without a polyol. Alternatively, corn syrup may be present in
addition to a
polyol. Any suitable corn syrup may be used, for example, corn syrup having 36-
65 DE
(dextrose equivalents), preferably corn syrup 42-43 DE. Corn syrup may contain
about 50%
by weight to about 90% by weight solids, preferably about 80% solids.
[0081] Corn syrup may be present in the semi-solid dosage form in an amount
from about
30% by weight to about 99% by weight. Preferably, corn syrup may be present in
an amount
from about 40% by weight to about 90% by weight, for example, about 40% to
about 50%,
about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, and
about 80%
to about 90%.
[0082] In embodiments in which corn syrup is present, the ratio of corn
syrup to sugar is
typically from about 1:10 to about 10:1 by dry weight. Preferably the ratio of
corn syrup to
sugar is from about 1:2 to about 2:1 by dry weight, for example, from about
1:1.5 to about
1:5.1.
[0083] In other embodiments, the ratio of corn syrup to gelling agent is
from about 20:1
to about 1:1 by dry weight. Preferably, the ratio of corn syrup to gelling
agent is from about
10:1 to about 2:1 by dry weight.
[0084] The semi-solid dosage form may optionally include a pH adjusting
agent. Any
suitable pH adjusting agent may be used that is sufficient to adjust the pH
during the
manufacture of the dosage form to yield the desired pH. By way of example, the
pH
adjusting agent may be sodium citrate, citric acid, sodium ascorbate and
ascorbic acid. Two
or more pH adjusting agents may be used. The pH adjusting agent may be
supplied in solid
form (e.g., as a powder) or in aqueous solution. For example, citric acid may
be supplied in a
50% solution. Preferably, the pH adjusting agent is sodium citrate or citric
acid. More
preferably, both sodium citrate and citric acid are included in the semi-solid
dosage form as
pH adjusting agents.
[0085] The pH adjusting agent may be present in the semi-solid dosage form
in an
amount from about 0.1% by weight to about 5% by weight. Preferably, the pH
adjusting
agent may be present in an amount from about 1% to about 5% by weight, for
example, from
about 1% to about 1.5%, from about 1.5% to about 2%, from about 2% to about
2.5%, from
about 2.5% to about 3%, from about 3% to about 3.5%, from about 3.5% to about
4.0%, from
about 4% to about 4.5%, and from about 4.5% to about 5%.
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[0086] In some embodiments, sodium citrate is present in an amount from
about 0.1% by
weight to about 1% by weight. Preferably, sodium citrate is present in an
amount from about
0.1% by weight to about 0.5% by weight, for example, from about 0.1% to about
0.2%, from
about 0.2% to about 0.3%, from about 0.3% to about 0.4%, and from about 0.4%
to about
0.5%.
[0087] In other embodiments, citric acid is present (as 50% aqueous
solution) in an
amount from about 0.5% by weight to about 3% by weight, for example from about
0.5% to
about 1%, from about 1% to about 1.5%, from about 1.5% to about 2%, from about
2% to
about 2.5%, and from about 2.5% to about 3%.
[0088] In certain embodiments, the semi-solid dosage form contains
glycerin, also
commonly known as glycerol. Without being bound by any theory, glycerin is
believed to
function as an emollient to stability the dosage form during its preparation.
Preferably,
glycerin USP is used. In some embodiments, glycerin is present in the semi-
solid dosage
form in addition to the absence of gelatin.
[0089] Glycerin may be present in the semi-solid dosage form in an amount
from about
0.1% by weight to about 10% by weight. Preferably, glycerin is present in an
amount from
about 0.5% by weight to about 5% by weight, for example from about 0.5% to
about 1%,
from about 1% to about 1.5%, from about 1.5% to about 2.0%, from about 2.0% to
about
2.5%, from about 2.5% to about 3.0%, from about 3.0% to about 3.5%, from about
3.5% to
about 4.0%, from about 4.0% to about 4.5%, and from about 4.5% to about 5.0%.
[0090] In some embodiments, the semi-solid dosage form contains a
flavorant. Any
suitable food-grade flavorant may be used to suppress the bitterness of the
active ingredients
to provide a pleasant taste to the dosage form upon chewing and swallowing. A
mixture of
two or more flavorants may be used to yield the desired taste characteristic.
[0091] Suitable flavorants include artificial sweeteners such as, for
example, sucralose,
acesulfame potassium, stevia, sodium saccharine, erythritol, and aspartame.
Another suitable
flavorant may be a fraction of the lactone group such as, for example,
decalactone and
dodecalactone (e.g., gamma dodecalactone). Lactone fractions are typically
supplied in a
propylene glycol solution, in particular from 0.5% to 1% in propylene glycol
solution. The
flavorant may be orange or cherry flavors. Alternatively, the flavorant may be
menthol.
[0092] Preferably, the flavorant is an artificial sweetener. More
preferably, the artificial
sweetener is sucralose.
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[0093] The flavorant may be present in an amount up to about 1% by weight,
preferably
up to about 0.5% by weight, for example, up to about 0.01%, up to about 0.05%,
up to about
0.1%, up to about 0.2%, up to about 0.3%, up to about 0.4%, and up to about
0.5%. In
certain embodiments, the amount of flavorant present is in a range bounded by
any of the
foregoing values. Fractions of the lactone group may be present in an amount
of from about
1 ppm to 50 ppm, preferably from about 2 ppm to about 10 ppm, and more
preferably from
about 3 ppm to about 9 ppm.
[0094] A colorant may optionally be added to provide a suitable appearance
for the semi-
solid dosage form. Examples of suitable colorants include red or yellow dyes
such as FD&C
Red #40 and FD&C Yellow #6. Two or more colorants may be combined.
[0095] The semi-solid chewable dosage form of the invention generally has a
water
content, also referred to as a residual moisture content, of less than about
15% by weight,
e.g., about 14% or less, about 13% or less, about 12% or less, about 11% or
less, about 10%
or less, about 9% or less, about 8% or less, about 7% or less, about 6% or
less, or about 5% or
less. In other embodiments, the water content of the semi-solid dosage form is
in a range
bounded by any of the foregoing values. Preferably, the water content of the
semi-solid
dosage form is from about 8% by weight to about 15% by weight.
[0096] In some embodiments, the semi-solid chewable dosage form comprises
one or
more active pharmaceutical ingredients, a gelling agent, gelatin, sugar, a
polyol, and a pH
adjusting agent. In other embodiments, the semi-solid chewable dosage form
comprises one
or more active pharmaceutical ingredients, a gelling agent, gelatin, sugar,
corn syrup, and a
pH adjusting agent. In other embodiments, the semi-solid chewable dosage form
comprises
one or more active pharmaceutical ingredients, a gelling agent, sugar, a
polyol, glycerin, and
a pH adjusting agent.
[0097] In some embodiments, the semi-solid chewable dosage form comprises
one or
more active pharmaceutical ingredients, pectin, sugar, hydrolyzed starch
hydrolysate,
hydrolyzed gelatin, and a pH adjusting agent. In other embodiments, the semi-
solid chewable
dosage form comprises one or more active pharmaceutical ingredients, pectin,
sugar, corn
syrup, hydrolyzed gelatin, and a pH adjusting agent.
[0098] In some embodiments, the semi-solid chewable dosage form comprises
one or
more active pharmaceutical ingredients, pectin, sugar, hydrolyzed starch
hydrolysate,
glycerin, and a pH adjusting agent.
[0099] In some embodiments, the semi-solid chewable dosage form comprises:
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one or more active pharmaceutical ingredients in an amount from about 0.01% by
weight to about 10% by weight;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
hydrolyzed starch hydrolysate in an amount from about 40% by weight to about
90% by weight;
hydrolyzed gelatin in an amount from about 0.5% by weight to about 8% by
weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0100] In some embodiments, the semi-solid chewable dosage form comprises:
one or more active pharmaceutical ingredients in an amount from about 0.01% by
weight to about 10% by weight;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
corn syrup in an amount from about 40% by weight to about 90% by weight;
hydrolyzed gelatin in an amount from about 0.5% by weight to about 8% by
weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0101] In some embodiments, the semi-solid chewable dosage form comprises:
one or more active pharmaceutical ingredients in an amount from about 0.01% by
weight to about 10% by weight;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
hydrolyzed starch hydrolysate in an amount from about 40% by weight to about
90% by weight;
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glycerin in an amount from about 0.1% by weight to about 5% by weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0102] In some embodiments, the semi-solid chewable dosage form comprises:
chlorpheniramine maleate;
phenylephrine hydrochloride;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
hydrolyzed starch hydrolysate in an amount from about 40% by weight to about
90% by weight;
hydrolyzed gelatin in an amount from about 0.5% by weight to about 8% by
weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0103] In some embodiments, the semi-solid chewable dosage form comprises:
chlorpheniramine maleate;
phenylephrine hydrochloride;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
corn syrup in an amount from about 40% by weight to about 90% by weight;
hydrolyzed gelatin in an amount from about 0.5% by weight to about 8% by
weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
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[0104] In some embodiments, the semi-solid chewable dosage form comprises:
diphenhydramine hydochloride;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
hydrolyzed starch hydrolysate in an amount from about 40% by weight to about
90% by weight;
hydrolyzed gelatin in an amount from about 0.5% by weight to about 8% by
weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0105] In some embodiments, the semi-solid chewable dosage form comprises:
loratadine;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
hydrolyzed starch hydrolysate in an amount from about 40% by weight to about
90% by weight;
glycerin in an amount from about 0.1% by weight to about 5% by weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0106] In some embodiments, the semi-solid chewable dosage form comprises:
an active pharmaceutical ingredient selected from the group consisting of an
antacid,
an anti-foaming agent, a histamine H2-receptor antagonist, a proton pump
inhibitor, or a
combination thereof in an amount from about 0.01% by weight to about 10% by
weight;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
hydrolyzed starch hydrolysate in an amount from about 40% by weight to about
90%
by weight;
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hydrolyzed gelatin in an amount from about 0.5% by weight to about 8% by
weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0107] In some embodiments, the semi-solid chewable dosage form comprises:
an active pharmaceutical ingredient selected from the group consisting of an
antacid,
an anti-foaming agent, a histamine H2-receptor antagonist, a proton pump
inhibitor, or a
combination thereof in an amount from about 0.01% by weight to about 10% by
weight;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
corn syrup in an amount from about 40% by weight to about 90% by weight;
hydrolyzed gelatin in an amount from about 0.5% by weight to about 8% by
weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0108] In some embodiments, the semi-solid chewable dosage form comprises:
calcium carbonate, simethicone, famotidine, or omeprazole;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
hydrolyzed starch hydrolysate in an amount from about 40% by weight to about
90%
by weight;
hydrolyzed gelatin in an amount from about 0.5% by weight to about 8% by
weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0109] In some embodiments, the semi-solid chewable dosage form comprises:
calcium carbonate, simethicone, famotidine, or omeprazole;
pectin in an amount from about 0.5% by weight to about 7% by weight;
sugar in an amount from about 40% by weight to about 95% by weight;
corn syrup in an amount from about 40% by weight to about 90% by weight;
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hydrolyzed gelatin in an amount from about 0.5% by weight to about 8% by
weight;
sodium citrate in an amount from about 0.1% by weight to about 1% by weight;
and
citric acid in an amount from about 0.5% by weight to about 3% by weight,
wherein the water content of the semi-solid dosage form is from about 8% by
weight to about
15% by weight.
[0110] The semi-solid chewable dosage form of the invention can be prepared
by any
suitable method including, for example, a batch process or a continuous
process. In some
embodiments, the components of the dosage form are first combined together in
a suitable
vessel. The components can be combined in any suitable order.
[0111] During manufacturing, water is typically added to the combination of
some or all
of the components to form a mixture that is the base for the semi-solid dosage
form. In some
embodiments, pectin, sugar, a polyol, and a pH adjusting agent are combined
with water to
form the base. Alternatively, pectin, sugar, corn syrup, and a pH adjusting
agent are
combined with water to form the base. Any amount of water may be added to
prepare a
suitable mixture. In some embodiments, a sufficient amount of water is added
to dissolve
water-soluble components, for example, sugar, and uniformly disperse non-water-
soluble
components to form a mixture.
[0112] Following the preparation of the base containing the components of
the semi-solid
dosage form along with water, the base typically has a water content of from
about 10% by
weight to about 90% by weight. Preferably, the base has a water content of
from about 20%
by weight to about 50% by weight, for example, about 20% to about 25%, about
25% to
about 30%, about 30% to about 35%, about 35% to about 40%, about 40% to about
45%, and
about 45% to about 50%.
[0113] In some embodiments, the base is cooked at a suitable temperature to
remove a
portion of the water present. By reducing the water content through cooking,
the base may be
converted into a semi-solid chewable dosage form having the desired physical
characteristics,
in particular consistency and texture. The base may be cooked by any suitable
means
including, for example, with a steam-jacketed vessel or a conventional heat
exchanger.
Cooking may optionally be carried out with the aid of a vacuum.
[0114] The base may be cooked at any suitable temperature and for a
sufficient length of
time to yield a molten mass having the desired water content. Generally,
following cooking,
the base has a residual moisture content from about 5% by weight to about 25%
by weight.
Preferably, the base has a residual moisture content after cooking from about
9% by weight to
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about 20% by weight, for example, about 9% to about 10%, about 10% to about
11%, about
11% to about 12%, about 12% to about 13%, about 13% to about 14%, and about
14% to
about 15%, about 15% to about 16%, about 16% to about 17%, about 17% to about
18%,
about 18% to about 19%, and about 19% to about 20%. In certain aspects, the
residual
moisture content of the base after cooking is an amount to provide a semi-
solid dosage form
containing about 0.01% by weight to about 2% by weight of the active
ingredients.
[0115] Generally, the base is cooked at a temperature of from about 220 F
to about 265
F. Preferably, the base may be cooked at a temperature of about 230 F to
about 250 F, for
example, about 230 F to about 235 F, about 235 F to about 240 F, about 240
F to about
245 F, and about 245 F to about 250 F.
[0116] After the base is cooked for a sufficient time to yield a molten
mass, any
remaining components of the semi-solid dosage form may be added such as, for
example, the
active pharmaceutical ingredients chlorpheniramine maleate and phenylephrine
hydrochloride, hydrolyzed gelatin, glycerin, a flavorant, and a colorant to
form the final
blend. These additional components may be added to the base by any suitable
means using,
for example, mass flow meters and static mixers.
[0117] A pH adjusting agent, such as citric acid, may be added to the base
to provide a
suitable pH for the final blend that contains all of the components of the
semi-solid dosage
form. The pH of the final blend is generally from about 4 to about 6,
preferably from about
4.5 to about 5.5.
[0118] In some embodiments, different blends of components are prepared
separately and
then combined together to form a final blend from which the semi-solid dosage
form is
obtained. For example, a primary blend may be combined with a secondary blend
to form the
final blend. A separate blend containing flavorants and/or colorants and an
acid solution may
optionally be added in the preparation of the final blend.
[0119] In one embodiment, a primary blend is prepared by combining pectin,
sugar, a
polyol, and a pH adjusting agent with water. Alternatively, the primary blend
may be
prepared by combining pectin, sugar, corn syrup, and a pH adjusting agent with
water. The
amount of water and corn syrup. A pH adjusting agent such as, for example,
sodium citrate
may optionally be added to the primary blend. In some embodiments, the primary
blend has
a pH from about 2 to about 6, preferably from about 2.5 to about 4, and more
preferably from
about 2.8 to about 3.8.
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[0120] In certain aspects, the primary blend is cooked at an appropriate
temperature and
for an appropriate length of time to provide the primary blend with any
suitable moisture
content for further processing. Preferably, the primary blend has a moisture
content after
cooking from about 5% by weight to about 25% by weight. Preferably, the
primary blend has
a residual moisture content after cooking from about 9% by weight to about 20%
by weight,
for example, about 9% to about 10%, about 10% to about 11%, about 11% to about
12%,
about 12% to about 13%, about 13% to about 14%, and about 14% to about 15%,
about 15%
to about 16%, about 16% to about 17%, about 17% to about 18%, about 18% to
about 19%,
and about 19% to about 20%. Generally, the primary blend may be cooked at a
temperature
of about 230 F to about 250 F, for example, about 230 F to about 235 F,
about 235 F to
about 240 F, about 240 F to about 245 F, and about 245 F to about 250 F.
[0121] A secondary blend may be added to the primary blend after cooking is
completed.
The secondary blend may contain one or more components of the semi-solid
dosage form. In
some embodiments, the secondary blend includes chlorpheniramine maleate,
phenylephrine
hydrochloride, and hydrolyzed gelatin. In other embodiments, the secondary
blend includes
calcium carbonate, simethicone, famotidine, or omeprazole, and hydrolyzed
gelatin. Water
may be added to the secondary blend to dissolve water-soluble components
and/or form a
homogenous mixture. Other components may be added to the secondary blend
including, for
example, glycerin, flavorants and colorants. Alternatively, an additional
blend may be
prepared containing glycerin, flavorants and colorants. An acid solution may
further be
prepared containing citric acid to obtain the desired pH of the final blend.
The final blend
may be obtained by combining the primary blend, secondary blend, additional
blend and
citric acid in any order.
[0122] The final blend may be further processed as needed prior to
preparation of the
semi-solid dosage form. For example, the final blend may be transferred to a
depositor
hopper having a jacket to maintain a temperature of from about 180 F to about
210 F,
preferably about 190 to about 200 F. After a suitable amount of time, the
final blend may
be dispensed from the depositor hopper to product the semi-solid chewable
dosage form of
the invention.
[0123] The semi-solid chewable dosage form may be obtained by depositing
the final
blend into pre-formed plastic molds using conventional techniques. Preferably,
the plastic
molds are blister packs having multiple cavities that provide for unit dose
packaging of the
semi-solid dosage form without having to transfer the dosage form from a mold
to a separate
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container. The dosage form solidifies in the plastic molds which serve as the
final packaging.
As the temperature of the dosage form cools, the dosage form takes its final
shape in the
cavities of the blister pack. The blister pack is preferably sealed, for
example, using foil.
One or more blister packs may be packaged in containers. Alternatively, the
dosage forms
may be prepared in molds and transferred to other suitable containers.
[0124] Advantageously, a pre-determined amount
of the final blend, for example based
on weight, is dispensed into each cavity to form individual pieces. The
individual pieces
contain the desired amount of the active ingredients as described herein. For
example,
individual pieces may contain 4 mg chlorpheniramine maleate and 10 mg
phenylephrine
hydrochloride for an adult dose and 2 mg chlorpheniramine maleate and 5 mg
phenylephrine
hydrochloride for a pediatric dose.
[0125] The following examples further illustrate the invention but, of
course, should not
be construed as in any way limiting its scope.
EXAMPLE 1
[0126] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 2 mg of
chlorpheniramine maleate and 5 mg of phenylephrine hydrochloride.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 40.17 80.34
Corn Syrup (dry) 41.43 82.86
Sodium Citrate (powder) 0.39 0.78
USP Citrus Pectin 200 (high methoxy) 1.97 3.94
Residual Water 11.13 22.26
Chlorpheniramine Maleate 0.04 0.08
Phenylephrine Hydrochloride 0.10 0.20
Hydrolyzed Gelatin 1.48 2.96
Artificial sweetener (Sucralose) 0.30 0.6
Dodecalactone (1% in PG sol) 0.01 0.02
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Ingredient Formula Batch
% by weight 200 g
FD&C Yellow #6 0.01 0.02
Glycerin USP 1.97 3.94
Orange Flavor FFS (211P52) 0.20 0.40
Menthol 0.05 0.1
Citric Acid (powder) 0.75 1.5
[0127] A primary blend is prepared that contains sugar, corn syrup, sodium
citrate, pectin
and water. The primary blend is cooked to produce a residual moisture content
of about 11%
by weight. A secondary blend is prepared that contains chlorpheniramine
maleate,
phenylephrine hydrochloride, hydrolyzed gelatin, sucralose and dodecalactone
(1% in
propylene glycol solution). An additional blend is prepared that contains
glycerin, colorants
and flavorants. An acid solution is prepared that contains citric acid.
[0128] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly.
The final blend
is transferred to a depositor hopper. From the depositor hopper, individual
pieces are
deposited into pre-formed plastic molds.
EXAMPLE 2
[0129] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 2 mg of
chlorpheniramine maleate and 5 mg of phenylephrine hydrochloride.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 42.75 85.50
Hydrogenated Starch Hydrolysate (HSH) (dry) 38.77 77.54
Sodium Citrate (powder) 0.35 0.70
USP Citrus Pectin 200 (high methoxy) 1.99 3.98
Residual Water 11.20 22.40
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Ingredient Formula Batch
% by weight 200 g
Chlorpheniramine Maleate 0.04 0.08
Phenylephrine Hydrochloride 0.10 0.20
Hydrolyzed Gelatin 1.49 2.98
Artificial sweetener (Sucralose) 0.30 0.6
Dodecalactone (1% in PG sol) 0.01 0.02
FD&C Yellow #6 0.01 0.02
Glycerin USP 1.99 3.98
Orange Flavor FFS (211P52) 0.20 0.40
Menthol 0.05 0.10
Citric Acid (powder) 0.75 1.50
[0130] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin and water. The primary blend is cooked to produce a
residual moisture
content of about 11% by weight. A secondary blend is prepared that contains
chlorpheniramine maleate, phenylephrine hydrochloride, hydrolyzed gelatin,
sucralose and
dodecalactone (1% in propylene glycol solution). An additional blend is
prepared that
contains glycerin, colorants and flavorants. An acid solution is prepared that
contains citric
acid.
[0131] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly.
The final blend
is transferred to a depositor hopper. From the depositor hopper, individual
pieces are
deposited into pre-formed plastic molds.
EXAMPLE 3
[0132] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 4 mg of
chlorpheniramine maleate and 10 mg of phenylephrine hydrochloride.
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Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 40.12 80.24
Corn Syrup (dry) 41.37 82.74
Sodium Citrate (powder) 0.39 0.78
USP Citrus Pectin 200 (high methoxy) 1.97 3.94
Residual Water 11.10 22.20
Chlorpheniramine Maleate 0.08 0.16
Phenylephrine Hydrochloride 0.20 0.4
Hydrolyzed Gelatin 1.48 2.96
Artificial sweetener (Sucralose) 0.30 0.6
Dodecalactone (1% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin USP 1.97 3.94
Cherry Flavor FFS (223G12) 0.20 0.40
Menthol 0.05 0.1
Citric Acid (powder) 0.75 1.5
[0133] A primary blend is prepared that
contains sugar, corn syrup, sodium citrate, pectin
and water. The primary blend is cooked to produce a residual moisture content
of about 11%
by weight. A secondary blend is prepared that contains chlorpheniramine
maleate,
phenylephrine hydrochloride, hydrolyzed gelatin, sucralose and dodecalactone
(1% in
propylene glycol solution). An additional blend is prepared that contains
glycerin, colorants
and flavorants. An acid solution is prepared that contains citric acid.
[0134] The secondary blend, additional blend
and acid solution are combined with the
primary blend to form the final blend. The final blend is mixed thoroughly.
The final blend
is transferred to a depositor hopper. From the depositor hopper, individual
pieces are
deposited into pre-formed plastic molds.
EXAMPLE 4
[0135] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
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in this example. Each individual piece weighs 5 grams and contains 4 mg of
chlorpheniramine maleate and 10 mg of phenylephrine hydrochloride
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 42.69 85.38
Hydrogenated Starch Hydrolysate (HSH) (dry) 38.72 77.44
Sodium Citrate (powder) 0.35 0.70
USP Citrus Pectin 200 (high methoxy) 1.99 3.98
Residual Water 11.17 22.34
Chlorpheniramine Maleate 0.08 0.16
Phenylephrine Hydrochloride 0.20 0.40
Hydrolyzed Gelatin 1.49 2.98
Artificial sweetener (Sucralose) 0.30 0.6
Dodecalactone (1% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin USP 1.99 3.98
Cherry Flavor FFS (223G12) 0.20 0.40
Menthol 0.05 0.10
Citric Acid (powder) 0.75 1.50
[0136] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin and water. The primary blend is cooked to produce a
residual moisture
content of about 11% by weight. A secondary blend is prepared that contains
chlorpheniramine maleate, phenylephrine hydrochloride, hydrolyzed gelatin,
sucralose and
dodecalactone (1% in propylene glycol solution). An additional blend is
prepared that
contains glycerin, colorants and flavorants. An acid solution is prepared that
contains citric
acid.
[0137] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly.
The final blend
is transferred to a depositor hopper. From the depositor hopper, individual
pieces are
deposited into pre-formed plastic molds.
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EXAMPLE 5
[0138] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 200 mg of
guaifenesin.
Ingredient Formula Batch
% by weight 200 gr
Sugar (powder) 34.00 68.00
Hydrogenated Starch Hydrolysate (HSH) (dry) 38.00 76.00
Sodium Citrate (powder) 0.40 0.80
USP Citrus Pectin 200 (high methoxy) 2.99 5.98
Residual Water 13.79 27.58
Guaifenesin (USP) powder 4.00 8.00
Hydrolyzed Gelatin 3.00 6.00
Artificial sweetener (Sucralose) 0.50 1.00
Dodecalactone (1% in PG sol) 0.02 0.04
FD&C Red #40 0.01 0.02
Glycerin USP 1.99 3.98
Cherry Flavor FFS (223G12) 0.20 0.40
Menthol 0.10 0.20
Citric Acid (powder) 1.00 2.00
[0139] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin and water. The primary blend is cooked to produce a
residual moisture
content of about 14% by weight. A secondary blend is prepared that contains
guaifenesin,
hydrolyzed gelatin, sucralose and dodecalactone (1% in propylene glycol
solution). An
additional blend is prepared that contains glycerin, colorants and flavorants.
An acid solution
is prepared that contains citric acid.
[0140] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly.
The final blend
is transferred to a depositor hopper. From the depositor hopper, individual
pieces are
deposited into pre-formed plastic molds.
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EXAMPLE 6
[0141] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 10 mg of
dextromethorphan HBr and 5 mg of phenylephrine hydrochloride.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 40.10 80.20
Corn Syrup (dry) 41.37 82.74
Sodium Citrate (powder) 0.39 0.78
USP Citrus Pectin 200 (high methoxy) 1.97 3.94
Residual Water 11.10 22.20
Dextromethorphan Hydrobromide 0.20 0.40
Phenylephrine Hydrochloride 0.10 0.20
Hydrolyzed Gelatin 1.48 2.96
Artificial sweetener (Sucralose) 0.30 0.6
Dodecalactone (1% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin USP 1.97 3.94
Cherry Flavor FFS (223G12) 0.20 0.40
Menthol 0.05 0.1
Citric Acid (powder) 0.75 1.5
[0142] A primary blend is prepared that
contains sugar, corn syrup, sodium citrate, pectin
and water. The primary blend is cooked to produce a residual moisture content
of about 11%
by weight. A secondary blend is prepared that contains dextromethorphan
hydrobromide,
phenylephrine hydrochloride, hydrolyzed gelatin, sucralose and dodecalactone
(1% in
propylene glycol solution). An additional blend is prepared that contains
glycerin, colorants
and flavorants. An acid solution is prepared that contains citric acid.
[0143] The secondary blend, additional blend
and acid solution are combined with the
primary blend to form the final blend. The final blend is mixed thoroughly.
The final blend
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is transferred to a depositor hopper. From the depositor hopper, individual
pieces are
deposited into pre-formed plastic molds.
EXAMPLE 7
[0144] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 10 mg of
dextromethorphan hydrobromide.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 40.20 80.40
Corn Syrup (dry) 41.37 82.74
Sodium Citrate (powder) 0.39 0.78
USP Citrus Pectin 200 (high methoxy) 1.97 3.94
Residual Water 11.10 22.20
Dextromethorphan Hydrobromide 0.20 0.40
Hydrolyzed Gelatin 1.48 2.96
Artificial sweetener (Sucralose) 0.30 0.60
Dodecalactone (1% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin USP 1.97 3.94
Cherry Flavor FFS (223G12) 0.20 0.40
Menthol 0.05 0.10
Citric Acid (powder) 0.75 1.50
[0145] A primary blend is prepared that
contains sugar, corn syrup, sodium citrate, pectin
and water. The primary blend is cooked to produce a residual moisture content
of about 11%
by weight. A secondary blend is prepared that contains dextromethorphan
hydrobromide,
hydrolyzed gelatin, sucralose and dodecalactone (1% in propylene glycol
solution). An
additional blend is prepared that contains glycerin, colorants and flavorants.
An acid solution
is prepared that contains citric acid.
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[0146] The secondary blend, additional blend
and acid solution are combined with the
primary blend to form the final blend. The final blend is mixed thoroughly.
The final blend
is transferred to a depositor hopper. From the depositor hopper, individual
pieces are
deposited into pre-formed plastic molds.
EXAMPLE 8
[0147] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 10 mg of
loratadine.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 40.20 80.40
Corn Syrup (dry) 41.37 82.74
Sodium Citrate (powder) 0.39 0.78
USP Citrus Pectin 200 (high methoxy) 1.97 3.94
Residual Water 11.10 22.20
Loratadine 0.20 0.40
Hydrolyzed Gelatin 1.48 2.96
Artificial sweetener (Sucralose) 0.30 0.60
Dodecalactone (1% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin USP 1.97 3.94
Cherry Flavor FFS (223G12) 0.20 0.40
Menthol 0.05 0.10
Citric Acid (powder) 0.75 1.5
[0148] A primary blend is prepared that
contains sugar, corn syrup, sodium citrate, pectin
and water. The primary blend is cooked to produce a residual moisture content
of about 11%
by weight. A secondary blend is prepared that contains loratadine, hydrolyzed
gelatin,
sucralose and dodecalactone (1% in propylene glycol solution). An additional
blend is
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prepared that contains glycerin, colorants and flavorants. An acid solution is
prepared that
contains citric acid.
[0149] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly.
The final blend
is transferred to a depositor hopper. From the depositor hopper, individual
pieces are
deposited into pre-formed plastic molds.
EXAMPLE 9
[0150] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 750 mg of
calcium
carbonate and 80 mg of simethicone.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 24.45 48.90
Corn Syrup (dry) 32.20 64.40
Amidated Pectin 100 (USP) 5.00 10.00
Residual Water 18.75 37.50
Precipitated Calcium Carbonate 15.00 30.00
Simethicone (USP) 1.60 3.20
Hydrolyzed Gelatin 1.48 2.96
Artificial sweetener (Sucralose) 0.20 0.40
Dodecalactone (0.5% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin (USP) 1.00 2.00
Cherry Flavor FFS (223G12) 0.25 0.50
Menthol 0.05 0.10
[0151] A primary blend is prepared that contains sugar, corn syrup, pectin,
calcium
carbonate and water. The primary blend is cooked to 230 F to obtain a
residual moisture
content of about 18%-19% by weight. A secondary blend is prepared that
contains
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simethicone, hydrolyzed gelatin, sucralose and dodecalactone (0.5% in
propylene glycol
solution). An additional blend is prepared that contains glycerin, colorants
and flavorants.
[0152] The secondary blend and additional blend are combined with the
primary blend to
form the final blend. The final blend is mixed thoroughly. The final blend is
transferred to a
depositor hopper. From the depositor hopper, individual pieces are deposited
into pre-formed
plastic molds.
EXAMPLE 10
[0153] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 80 mg of
simethicone.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 34.45 69.10
Corn Syrup (dry) 37.20 74.40
Amidated Pectin 100 (USP) 5.00 10.00
Residual Water 18.75 37.50
Simethicone (USP) 1.60 3.20
Hydrolyzed Gelatin 1.48 2.96
Artificial sweetener (Sucralose) 0.10 0.20
Dodecalactone (0.5% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin (USP) 1.00 2.00
Cherry Flavor FFS (223G12) 0.25 0.50
Menthol 0.05 0.10
[0154] A primary blend is prepared that contains sugar, corn syrup, pectin,
and water.
The primary blend is cooked to 230 F to obtain a residual moisture content of
about 18%-
19% by weight. A secondary blend is prepared that contains simethicone,
hydrolyzed gelatin,
sucralose and dodecalactone (0.5% in propylene glycol solution). An additional
blend is
prepared that contains glycerin, colorants and flavorants.
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[0155] The secondary blend and additional blend are combined with the
primary blend to
form the final blend. The final blend is mixed thoroughly. The final blend is
transferred to a
depositor hopper. From the depositor hopper, individual pieces are deposited
into pre-formed
plastic molds.
EXAMPLE 11
[0156] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 200 mg of
aluminum
hydroxide, 200 mg of magnesium hydroxide, and 20 mg of simethicone.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 34.45 69.10
Corn Syrup (dry) 30.28 60.56
Amidated Pectin 100 (USP) 5.00 10.00
Residual Water 18.75 37.50
Simethicone (USP) 0.40 0.80
Aluminum Hydroxide (USP) 4.00 8.00
Magnesium Hydroxide (USP) 4.00 8.00
Hydrolyzed Gelatin 1.50 3.00
Artificial sweetener (Sucralose) 0.20 0.40
Dodecalactone (0.5% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin (USP) 1.00 2.00
Cherry Flavor FFS (223G12) 0.25 0.50
Menthol 0.05 0.10
[0157] A primary blend is prepared that contains sugar, corn syrup, pectin,
and water.
The primary blend is cooked to 230 F to obtain a residual moisture content of
about 18%-
19% by weight. A secondary blend is prepared that contains simethicone,
aluminum
hydroxide, magnesium hydroxide, hydrolyzed gelatin, sucralose and
dodecalactone (0.5% in
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propylene glycol solution). An additional blend is prepared that contains
glycerin, colorants
and flavorants.
[0158] The secondary blend and additional blend are combined with the
primary blend to
form the final blend. The final blend is mixed thoroughly. The final blend is
transferred to a
depositor hopper. From the depositor hopper, individual pieces are deposited
into pre-formed
plastic molds.
EXAMPLE 12
[0159] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 800 mg of
calcium
carbonate, 165 mg of magnesium hydroxide, and 10 mg of famotidine.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 25.00 50.00
Corn Syrup (dry) 28.63 57.26
Amidated Pectin 100 (USP) 5.00 10.00
Residual Water 18.75 37.50
Famotidine (USP) 0.20 0.40
Calcium Carbonate (USP) 16.00 32.00
Magnesium Hydroxide (USP) 3.30 6.60
Hydrolyzed Gelatin 1.50 3.00
Artificial sweetener (Sucralose) 0.30 0.60
Dodecalactone (0.5% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin (USP) 1.00 2.00
Cherry Flavor FFS (223G12) 0.25 0.50
Menthol 0.05 0.10
[0160] A primary blend is prepared that contains sugar, corn syrup, pectin,
and water.
The primary blend is cooked to 230 F to obtain a residual moisture content of
about 18%-
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19% by weight. A secondary blend is prepared that contains famotidine, calcium
carbonate,
magnesium hydroxide, hydrolyzed gelatin, sucralose and dodecalactone (0.5% in
propylene
glycol solution). An additional blend is prepared that contains glycerin,
colorants and
flavorants.
[0161] The secondary blend and additional blend are combined with the
primary blend to
form the final blend. The final blend is mixed thoroughly. The final blend is
transferred to a
depositor hopper. From the depositor hopper, individual pieces are deposited
into pre-formed
plastic molds.
EXAMPLE 13
[0162] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 10 mg of
famotidine.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 40.00 80.00
Corn Syrup (dry) 32.93 65.86
Amidated Pectin 100 (USP) 5.00 10.00
Residual Water 18.75 37.50
Famotidine (USP) 0.20 0.40
Hydrolyzed Gelatin 1.50 3.00
Artificial sweetener (Sucralose) 0.30 0.60
Dodecalactone (0.5% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin (USP) 1.00 2.00
Cherry Flavor FFS (223G12) 0.25 0.50
Menthol 0.05 0.10
[0163] A primary blend is prepared that contains sugar, corn syrup, pectin,
and water.
The primary blend is cooked to 230 F to obtain a residual moisture content of
about 18%-
19% by weight. A secondary blend is prepared that contains famotidine,
hydrolyzed gelatin,
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sucralose and dodecalactone (0.5% in propylene glycol solution). An additional
blend is
prepared that contains glycerin, colorants and flavorants.
[0164] The secondary blend and additional blend are combined with the
primary blend to
form the final blend. The final blend is mixed thoroughly. The final blend is
transferred to a
depositor hopper. From the depositor hopper, individual pieces are deposited
into pre-formed
plastic molds.
EXAMPLE 14
[0165] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 20 mg of
omeprazole.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 40.00 80.00
Corn Syrup (dry) 32.73 65.46
Amidated Pectin 100 (USP) 5.00 10.00
Residual Water 18.75 37.50
Omeprazole (USP) 0.40 0.80
Hydrolyzed Gelatin 1.50 3.00
Artificial sweetener (Sucralose) 0.30 0.60
Dodecalactone (0.5% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin (USP) 1.00 2.00
Cherry Flavor FFS (223G12) 0.25 0.50
Menthol 0.05 0.10
[0166] A primary blend is prepared that contains sugar, corn syrup, pectin,
and water.
The primary blend is cooked to 230 F to obtain a residual moisture content of
about 18%-
19% by weight. A secondary blend is prepared that contains omeprazole,
hydrolyzed gelatin,
sucralose and dodecalactone (0.5% in propylene glycol solution). An additional
blend is
prepared that contains glycerin, colorants and flavorants.
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[0167] The secondary blend and additional blend are combined with the
primary blend to
form the final blend. The final blend is mixed thoroughly. The final blend is
transferred to a
depositor hopper. From the depositor hopper, individual pieces are deposited
into pre-formed
plastic molds.
EXAMPLE 15
[0168] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 80 mg of
simethicone.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 38.51 77.02
Hydrogenated Starch Hydrolysate (dry) 37.20 74.40
Sodium Citrate (powder) 0.40 0.80
USP Citrus Pectin 200 (high methoxyl) 2.99 5.98
Residual Water 13.79 27.58
Simethicone (USP) 1.60 3.20
Hydrolyzed Gelatin 2.00 4.00
Artificial sweetener (Sucralose) 0.20 0.40
Dodecalactone (1.0% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin (USP) 1.99 3.98
Cherry Flavor FFS (223G12) 0.20 0.40
Menthol 0.10 0.20
Citric Acid (powder) 1.00 2.00
[0169] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin, and water. The primary blend is cooked to 230 F to
obtain a residual
moisture content of about 13%-14% by weight. A secondary blend is prepared
that contains
simethicone, hydrolyzed gelatin, sucralose and dodecalactone (1.0% in
propylene glycol
solution). An additional blend is prepared that contains glycerin, colorants
and flavorants.
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[0170] The secondary blend, additional blend and citric acid are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly.
The final blend
is transferred to a depositor hopper. From the depositor hopper, individual
pieces are
deposited into pre-formed plastic molds.
EXAMPLE 16
[0171] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A 200 g batch
is produced
in this example. Each individual piece weighs 5 grams and contains 750 mg of
calcium
carbonate.
Ingredient Formula Batch
% by weight 200 g
Sugar (powder) 25.05 50.10
Hydrogenated Starch Hydrolysate (dry) 33.30 66.40
Amidated Pectin 100 (USP) 5.00 10.00
Residual Water 18.75 37.50
Precipitated Calcium Carbonate 15.00 30.00
Hydrolyzed Gelatin 1.48 2.96
Artificial sweetener (Sucralose) 0.20 0.40
Dodecalactone (0.5% in PG sol) 0.01 0.02
FD&C Red #40 0.01 0.02
Glycerin (USP) 1.00 2.00
Cherry Flavor FFS (223G12) 0.25 0.50
Menthol 0.05 0.10
[0172] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
pectin, calcium carbonate, and water. The primary blend is cooked to 230 F to
obtain a
residual moisture content of about 18%-19% by weight. A secondary blend is
prepared that
contains hydrolyzed gelatin, sucralose and dodecalactone (0.5% in propylene
glycol
solution). An additional blend is prepared that contains glycerin, colorants
and flavorants.
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[0173] The secondary blend and additional blend are combined with the
primary blend to
form the final blend. The final blend is mixed thoroughly. The final blend is
transferred to a
depositor hopper. From the depositor hopper, individual pieces are deposited
into pre-formed
plastic molds.
EXAMPLE 17
[0174] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A semi-solid
chewable
dosage form containing about 4 mg of chlorpheniramine maleate and about 10 mg
of
phenylephrine hydrochloride is prepared.
Ingredient Formula
% by weight
Sugar (granular) 40.44
Hydrogenated Starch Hydrolysate 49.54
(HSH 3375 75% solids) (dry basis)
Sodium Citrate (powder) 0.15
Pectin USP L-200 (powder) 2.02
Chlorpheniramine Maleate 0.09
Phenylephrine Hydrochloride 0.22
Hydrolyzed Gelatin (Gelita Peptiplus) 1.42
Artificial sweetener (Sucralose) 0.30
Cherry Flavor FFS (223G12) 0.20
FD&C Red #40 0.05
Citric Acid (50/50 solution) (dry basis) 1.62
Water 3.95
[0175] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin and water. The primary blend is cooked to yield a Brix
value of about
85 . A secondary blend is prepared that contains chlorpheniramine maleate,
phenylephrine
hydrochloride, hydrolyzed gelatin, and sucralose. An additional blend is
prepared that
contains colorants and flavorants. An acid solution is prepared using citric
acid.
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[0176] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly to
yield a Brix
value of about 81 to about 83 . The final blend is transferred to a depositor
hopper. From
the depositor hopper, individual pieces are deposited into pre-formed plastic
molds.
EXAMPLE 18
[0177] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A semi-solid
chewable
dosage form containing about 2 mg of chlorpheniramine maleate and about 5 mg
of
phenylephrine hydrochloride is prepared.
Ingredient Formula
% by weight
Sugar (granular) 39.94
Hydrogenated Starch Hydrolysate 50.45
(HSH 3375 75% solids) (dry basis)
Sodium Citrate (powder) 0.16
Pectin USP L-200 (powder) 2.10
Chlorpheniramine Maleate 0.04
Phenylephrine Hydrochloride 0.11
Hydrolyzed Gelatin (Gelita Peptiplus) 1.47
Artificial sweetener (Sucralose) 0.11
Orange Flavor FFS (221P52) 0.29
FD&C Yellow #6 0.13
Citric Acid (50/50 solution) (dry basis) 1.68
Water 3.52
[0178] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin and water. The primary blend is cooked to yield a Brix
value of about
85 . A secondary blend is prepared that contains chlorpheniramine maleate,
phenylephrine
hydrochloride, hydrolyzed gelatin, and sucralose. An additional blend is
prepared that
contains colorants and flavorants. An acid solution is prepared using citric
acid.
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[0179] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly to
yield a Brix
value of about 81 to about 83 . The final blend is transferred to a depositor
hopper. From
the depositor hopper, individual pieces are deposited into pre-formed plastic
molds.
EXAMPLE 19
[0180] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A semi-solid
chewable
dosage form containing about 25 mg of diphenhydramine hydrochloride is
prepared.
Ingredient Formula
% by weight
Sugar (granular) 40.66
Hydrogenated Starch Hydrolysate 49.25
(HSH 3375 75% solids) (dry basis)
Sodium Citrate (powder) 0.16
Pectin USP L-200 (powder) 2.10
Diphenhydramine Hydrochloride 0.55
Hydrolyzed Gelatin (Gelita Peptiplus) 1.43
Artificial sweetener (Sucralose) 0.23
Grape Flavor FFS (227U64) 0.27
FD&C Red #40 0.16
FD&C Blue #1 0.01
Citric Acid (50/50 solution) (dry basis) 1.57
Water 3.64
[0181] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin and water. The primary blend is cooked to yield a Brix
value of about
85 . A secondary blend is prepared that contains diphenhydramine
hydrochloride,
hydrolyzed gelatin, and sucralose. An additional blend is prepared that
contains colorants
and flavorants. An acid solution is prepared using citric acid.
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[0182] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly to
yield a Brix
value of about 81 to about 83 . The final blend is transferred to a depositor
hopper. From
the depositor hopper, individual pieces are deposited into pre-formed plastic
molds.
EXAMPLE 20
[0183] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A semi-solid
chewable
dosage form containing about 12.5 mg of diphenhydramine hydrochloride is
prepared.
Ingredient Formula
% by weight
Sugar (granular) 40.80
Hydrogenated Starch Hydrolysate 49.42
(HSH 3375 75% solids) (dry basis)
Sodium Citrate (powder) 0.16
Pectin USP L-200 (powder) 2.10
Diphenhydramine Hydrochloride 0.28
Hydrolyzed Gelatin (Gelita Peptiplus) 1.43
Artificial sweetener (Sucralose) 0.23
Grape Flavor FFS (227U64) 0.27
FD&C Red #40 0.16
FD&C Blue #1 0.01
Citric Acid (50/50 solution) (dry basis) 1.57
Water 3.57
[0184] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin and water. The primary blend is cooked to yield a Brix
value of about
85 . A secondary blend is prepared that contains diphenhydramine
hydrochloride,
hydrolyzed gelatin, and sucralose. An additional blend is prepared that
contains colorants
and flavorants. An acid solution is prepared using citric acid.
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[0185] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly to
yield a Brix
value of about 81 to about 83 . The final blend is transferred to a depositor
hopper. From
the depositor hopper, individual pieces are deposited into pre-formed plastic
molds.
EXAMPLE 21
[0186] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A semi-solid
chewable
dosage form containing about 10 mg of loratadine is prepared.
Ingredient Formula
% by weight
Sugar (granular) 39.78
Hydrogenated Starch Hydrolysate 50.25
(HSH 3375 75% solids) (dry basis)
Sodium Citrate (powder) 0.16
Pectin USP L-200 (powder) 2.09
Loratadine 0.22
Glycerin USP 1.88
Cherry Flavor FFS (223G12) 0.27
FD&C Red #40 0.19
Citric Acid (50/50 solution) (dry basis) 1.57
Water 3.59
[0187] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin and water. The primary blend is cooked to yield a Brix
value of about
85 . A secondary blend is prepared that contains loratadine and glycerin. An
additional
blend is prepared that contains colorants and flavorants. An acid solution is
prepared using
citric acid.
[0188] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly to
yield a Brix
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value of about 81 to about 83 . The final blend is transferred to a depositor
hopper. From
the depositor hopper, individual pieces are deposited into pre-formed plastic
molds.
EXAMPLE 22
[0189] This example demonstrates a semi-solid chewable dosage form and its
method of
preparation in accordance with an embodiment of the invention. A semi-solid
chewable
dosage form containing about 10 mg of loratadine is prepared.
Ingredient Formula
% by weight
Sugar (granular) 39.78
Hydrogenated Starch Hydrolysate 50.25
(HSH 3375 75% solids) (dry basis)
Sodium Citrate (powder) 0.16
Pectin USP L-200 (powder) 2.09
Loratadine 0.22
Glycerin USP 1.88
Grape Flavor FFS (227U64) 0.21
FD&C Red #40 0.16
FD&C Blue #1 0.01
Citric Acid (50/50 solution) (dry basis) 1.57
Water 3.67
[0190] A primary blend is prepared that contains sugar, hydrogenated starch
hydrolysate,
sodium citrate, pectin and water. The primary blend is cooked to produce a
residual moisture
content of about 85% solids. A secondary blend is prepared that contains
loratadine and
glycerin. An additional blend is prepared that contains colorants and
flavorants. An acid
solution is prepared using citric acid.
[0191] The secondary blend, additional blend and acid solution are combined
with the
primary blend to form the final blend. The final blend is mixed thoroughly to
yield a Brix
value of about 81 to about 83 . The final blend is transferred to a depositor
hopper. From
the depositor hopper, individual pieces are deposited into pre-formed plastic
molds.
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[0192] All references, including publications, patent applications, and
patents, cited
herein are hereby incorporated by reference to the same extent as if each
reference were
individually and specifically indicated to be incorporated by reference and
were set forth in
its entirety herein.
[0193] The use of the terms "a" and "an" and "the" and "at least one" and
similar
referents in the context of describing the invention (especially in the
context of the following
claims) are to be construed to cover both the singular and the plural, unless
otherwise
indicated herein or clearly contradicted by context. The use of the term "at
least one"
followed by a list of one or more items (for example, "at least one of A and
B") is to be
construed to mean one item selected from the listed items (A or B) or any
combination of two
or more of the listed items (A and B), unless otherwise indicated herein or
clearly
contradicted y context. The terms "comprising," "having," "including," and
"containing" are
to be construed as open-ended terms (i.e., meaning "including, but not limited
to,") unless
otherwise noted. Recitation of ranges of values herein are merely intended to
serve as a
shorthand method of referring individually to each separate value falling
within the range,
unless otherwise indicated herein, and each separate value is incorporated
into the
specification as if it were individually recited herein. All methods described
herein can be
performed in any suitable order unless otherwise indicated herein or otherwise
clearly
contradicted by context. The use of any and all examples, or exemplary
language (e.g., "such
as") provided herein, is intended merely to better illuminate the invention
and does not pose a
limitation on the scope of the invention unless otherwise claimed. No language
in the
specification should be construed as indicating any non-claimed element as
essential to the
practice of the invention.
[0194] Preferred embodiments of this invention are described herein,
including the best
mode known to the inventors for carrying out the invention. Variations of
those preferred
embodiments may become apparent to those of ordinary skill in the art upon
reading the
foregoing description. The inventors expect skilled artisans to employ such
variations as
appropriate, and the inventors intend for the invention to be practiced
otherwise than as
specifically described herein. Accordingly, this invention includes all
modifications and
equivalents of the subject matter recited in the claims appended hereto as
permitted by
applicable law. Moreover, any combination of the above-described elements in
all possible
variations thereof is encompassed by the invention unless otherwise indicated
herein or
otherwise clearly contradicted by context.
