Note: Descriptions are shown in the official language in which they were submitted.
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LUBRICIOUS SELF-STANDING (INTACT) GEL FOR
ORAL DELIVERY OF BIOLOGICALLY-ACTIVE INGREDIENTS
The present invention relates to a self standing (intact) lubricious (self
lubricating) hydrogel composition comprising gellan gum and a biologically-
active
medicinal ingredient. This invention also relates to a process for preparing
such a
composition comprising gellan gum for subsequent release in a human or animal
whereby a therapeutically effective amount of the biologically-active
ingredient is
1 o provided to and delivered via any one of oral, vaginal and rectal
administration in an
effective useable manner to the recipient (patient}.
BACKGROUND OF THE INVENTION
15 Sometimes it has been difficult to administer oral medicine to persons
who have difficulty swallowing pills like children, elderly persons, paralyzed
persons
and heart attack and stroke victims. Some patients cannot eat from a bowl and
spoon
or have psychological or physical difficulty swallowing whole pills. Patients
weakened by disease and radiation therapy may have trouble taking pills. Some
drug
2o forms cannot or should not be chewed. Pediatric and geriatric patients do
not like to
take pills. Sometimes hospitals crush pills whereby the pill powder is put
into a paper
or plastic medication cup and a suspending vehicle, such as orange juice,
apricot juice,
applesauce, honey or baby food, is added. However care must be taken when
crushing
medications as one medicament could easily become mixed with another
medication.
25 In all instances, the patient must get the full dosage prescribed.
Underdosing a patient can happen when a patient does not getall of
his/her does of an active therapeutic agent. This underdosing fails to provide
the
response sought by the physician. Overdosing can result in adverse reactions
that
3o could be detrimental to the patient. Slow and uncertain response time for
the onset of
an observable reaction to a drug in pill form when taken orally makes it
difficult to
determine when a proper dose for a particular patient has been administered;
the
physician may not learn for an hour whether the patient was underdosed or
overdosed.
w n
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2
Compliance, which is providing the right amount of medication at the
appropriate
intervals, is extremely important to medical personnel and patients.
Injections can sometimes be given to avoid using oral routes of
administration. But injecting a drug (generally intravenously or
intramuscularly) can
result in rapid entry of the drug into the patient's bloodstream. Injection
changes the
removal rate of the drug from the body because the drug is not delivered to
the body's
Iiver at the same rate as with a pill. And injections are not for everyone.
Sometimes
injections can cause psychological stress and worsen a patient's debilitated
condition
1o so that injections may be undesirable in such situations.
This invention provides an alternative to the use of pills and pill-
crushing techniques and inj ections for administering determined {known)
therapeutic
amounts of medication to patients by the use of a self standing (intact)
lubricious gel
containing a determined (known) therapeutic amount of medication for the
patient.
A. M. Bhakoo, S. Woerly and R. Duncan, Release ofAntibiotics and
Antitumour Agents From Alginate and Gellan Gum Gels, Proceed. Intern. Symp.
Control. Rel. Bioact. Mater., 18 ( 199 / ), Controlled Release Society, Inc.,
describes
hydrogels which have been developed as controlled release matrices for
pharmaceutically active chemicals. This references discloses that alginate
(high M or
high G) and gellan gum gels were firstly prepared and then loaded with drugs
(adriamycin, theophylline, ampicillin, amoxicillin, tetracycline and
erthromycin) by
imbition over a period of 24 hours and the degree of entrapment, not known
prior to
2s gel formation, was thereafter determined.
WP09402029-A1 discloses an article of manufacture which consists
of a spongy matrix whose pores are controlled to size and or distribution and
which is
made from a co-processed mixture comprising (a) glucomannan and (b) at least
one
other aqueous gel forming polysaccharide. However, no process appears to be
provided for incorporating drugs or minerals, vitamins or supplements, or
therapeutic
agents or other biologically-active ingredients in such gels.
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3
Japanese Patent Application 89-0724239, "Transparent Gel-Like
Composition", discloses a 0.1-1.3 wt. % high-MW polysaccharide based on the
total
amount of a composition that is added to water and the mixture is heated
(e.g., at 90°
C), stirred, dissolved and then cooled (e.g., at about SO° C) whereby a
volatile
substance selected from perfumes, deodorants, mothproofing agents,
insecticides and
repellents, a proper amount of a surface active agent (e.g., nonionic
substance) for
solubilization and, if necessary, an anti-freezing agent (e.g., polyhydric
alcohol) and
an antiseptic agent are added therefore and the mixture is furthermore
stirred, left for
cooling (e.g., to about 40° C), filled in a container and furthermore
left for cooling to
1o room temperature to obtain the composition.
Japanese Patent Application 87-126943, "Heat-Resistant Water-based
Gel", discloses that an aqueous suspension of gellan gum is heated at about
95° C
above the solution-forming temperature to obtain a homogeneous aqueous
solution, to
the solution is added an acid (e.g., citric acid, fruit juice, etc.) and
calcium chloride,
etc., and the solution is reportedly gelatinized by cooling below the gelling
temperature to obtain the objective heat resistant water-based gel.
Japanese Patent Application 87-126942, "Gelation of Gellan Gum",
2o discloses a mixture of water and gellan gum which is reported to be a kind
of
polysaccharide which is produced beforehand and heated at about 85° C
which is a
solution-forming temperature of gellan gum. The produced aqueous solution of
gellan
gum is added with an acid (e.g., citric acid, fruit juice) and the mixture is
cooled
below the gelatinization temperature to effect the gelatinization of the
solution and
obtain the obj ective aqueous gel of gellan gum. The amount of the acid is
preferably
about 15% of the gellan gum.
Japanese Patent Application 88-309150, "Production of Instant
Gelatinous Substance", discloses compositions of gellan gum dissolved in after
3o heating or dispersed and suspended in water at ambient temperature to
prepare about a
0.1-2 wt. % aqueous solution of gellan gum. An alkaline earth metal salt
and/or
alkaline metal salt and/or an acidic substance, such as organic or inorganic
acid, and
acid salts are disclosed to induce gellation at ambient temperature. The
utility is said
to be foods, medicines, industrial chemicals, etc.
~ I
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4
United States Patent No. 5,342,626, which issued to Philip E. Winston
Jr., et al. on August 30, 1994 discloses "Composition and Process for Gelatin-
Free
Soft Capsules", and relates to a polymer composition comprised of gellan,
carrageenan and mannan gums and a process for producing flexible films for
encapsulation comprising the gellan, carrageenan and mannan gum composition.
Such films reportedly can be used for the production of capsules or
microcapsules.
Capsules are believed to be characterized by a dry outer phase (film membrane)
containing a different liquid or solid ingredient in the inner phase.
U.S. Patent 4,857,331 which issued to James J. Shaw et al on August.
15, 1989, discloses pectin/algin/gelatin self standing gels requiring a
structuring agent
to increase gel strength and in particular this patent also discloses a
sugarless
ingestible gel confectionery delivery system which includes a pectin gel
component,
an algin gel component and a polymer network gel component in amounts Buff
cient
to form a gel confectionery unit. The delivery system may also include a
further active
ingredient such as a drug, medicament, or nutritional supplement.
However, the industry has continued to recognize the need for an
2o improved method of providing compliance with the delivery of 'drugs to
patients
which is provided by this invention.
OBJECTS OF THE INVENTION
It is an object of the invention to provide a novel system and a method
as a utility for effectively delivering a known effective amount of medication
such as
a unit amount, to patients who are unable to tolerate presently available
medication
delivery systems and methods.
Yet another obj ect of this invention is to administer a pharmaceutical
preparation which is nonsticky, palatable, easy-to-swallow , or easy to
breakdown if
need be, of a unit dose, to persons of all ages (e.g., pediatric or geriatric
patients) and
to animals thus achieving compliance with the desired medication.
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It is another object of the invention to provide an effective medication
delivery system for those whose cannot tolerate medication containing
pastilles,
tablets, capsules, trouches, lollipops and chewing gum and the like.
It is yet another object of the invention to provide a useful method for
delivering medication to persons who have difficulty in swallowing.
Another objection of this invention is to provide a gel easy to break if
desired for mixing with food or producing smaller pieces easy to swallow for
humans
1 o and animals.
Still another object of this invention is to provide an intact lubricious
gel easy to administer for oral, and/or vaginal and/or rectal applications.
15 It is an additional object of this invention to provide an effective
medication delivery system for animals.
These and other objects are met in the invention which is hereinafter
described more particularly in detail.
BRIEF SUMMARY OF THE INVENTION
This invention comprises a self standing (intact) lubricious gel and a
process for the production of a self standing (intact), lubricious gel
containing an
effective known amount of a biologically-active (medicinal) ingredient for
subsequent
effective providing to and release in a human or animal biological system of a
therapeutic amount of a biologically-active medicinal ingredient whereby the
biologically active ingredient is delivered to the biological systems of the
patient for
effective medical relief to the patient. These lubricious self standing gels
can be used
3o for any one of oral, vaginal or rectal administration. The product and
method of the
present invention also includes a composition in which the gel delivery system
can be
molded directly in or shaped to accommodate the receptacle which is used to
dispense
and provide the medication unit to the consumer.
~ I
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6
The process for preparation of the gels of this invention comprises
admixing gellan gum with water to a concentration from about 0.05% to about 5%
and preferably from about 0.25% to about 2.5% by weight of said gum to form a
gum
containing composition, with or without a sequestrant, and maintaining said
gum
composition at a temperature sufficiently warm to achieve hydration of said
gum in a
warm solution such that gelation will occur upon subsequent cooling and
admixing a
known amount of biologically-active medicinal ingredient with said warm
solution
and optionally admixing therewith solubilizing and suspending aids and
optionally
admixing therewith rations and thereafter cooling said warm solution
containing said
to biologically-active ingredient to a temperature in the range sufficient to
induce
gelation in molds of desired shapes whereby said self standing (intact)
lubricious gel
is formed containing a known amount of active.
DETAILED DESCRIPTION OF THE INVENTION
This invention comprises a process for the production of an
self standing (intact) lubricious gel containing an effective known amount of
a
biologically-active ingredient for subsequent release in a human or animal
biological
system which comprises admixing gellan gum with water to a concentration from
2o about 0.05% to about 5% and preferably from about 0.25% to about 2.5% by
weight
of said gum to form a gum containing composition, with or without a
sequestrant, and
maintaining said gum composition at a temperature sufficiently warm to achieve
hydration of said gum such that gelation will occur upon subsequent cooling
and
admixing a biologically-active ingredient with said warm solution and
optionally
admixing therewith solubilizing and suspending aids (for the biologically
active
ingredient, i.e. the drug) and optionally admixing therewith other polymers or
additives if desired to alter gel strength or release characteristics and
optionally
admixing therewith rations and thereafter cooling said warm solution
containing said
biologically-active ingredient to a temperature in the range sufficient to
induce
3o gelation whereby said self standing (intact) lubricious gel is formed.
As employed herein, the term "self standing" includes but is not
limited to a gel or gels which are capable of standing or staying in an erect
mode and
are generally not pourable or flowable.
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7
As employed herein, the term "lubricious" includes but is not limited
to a gel which has a moist, substantially moist (wet) or partially moist
surface at or
near surface such that the gel has the feel of a wet surface to the patient
(or handfeel
for suppositories).
Gellan Gum is a known naturally occurring polysaccharide that is
produced by inoculating a carefully formulated fermentation medium with the
microorganism Sphingomonas elodea (ATTC 31461 ). Gellan Gum is available in
clarified forms (KELCOGEL~) and (GELRITE~) available from Monsanto
Company, U.S.A. The gelling mechanism of Gellan Gum is based on cation-induced
macromolecular chain association. As employed herein, the term Gellan gum
includes non-clarified, clarified, and partially-clarified, native, deacylated
and
partially deacylated forms as well as mixtures thereof. Useful Gellan Gum{s)
include
those available commercially but are not limited to those which are sold
commercially
by Monsanto Company, 800 North Lindbergh Blvd., St. Louis, Missouri, 63167,
U.S.A. Processes for preparing gellan gum include those described in U.S.
Patents
Nos 4,326,052 and 4,236, 053 to Kang both of which are incorporated herein by
reference in their entirety.
The process of preparing a gel composition of this invention is
preferably carried out at a temperature in step 1 (a) from about 50 °C
to about 100 ° C
and maintained at that temperature or near that temperature until the gum
hydrates or
substantially hydrates. Alternatively, hydration can be achieved at room
temperature
in the presence of appropriate sequestrants. The hydration process is carried
out until
complete or substantially complete which is when the gum is fully or nearly or
sufficiently hydrated, usually resulting in a clear or substantially clear
solution.
The process of admixing the biologically-active medicinal ingredient
3o above is typically carned out at a temperature above the gel setting point
for a time as
it necessary to effectively solubilize or suspend said biologically-active
ingredient.
Thus the biologically active ingredient is within or in the gel.
~ I
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8
If desired other polymers (organic or natural} or additives can be added
to the composition to alter texture and/or release characteristics of the
gels. Such
polymers include but are not limited to one or more of the following, xanthan
gum,
cellulose derivatives, carrageenan, glucan, curdlan, agar, gelatin, alginates,
starch,
s pectin, blends of xanthan gum with galactomannans and/or glucomannans,
mixtures
thereof and the like.
An illustrative xanthan gum which may be employed herein include
xanthan gums) which is(are) sold and registered trademarks) owned by Monsanto
1o Company, 800 North Lindbergh Blvd, St. Louis, Missouri, 63167 U.S.A.
Xanthan
gum is an exocellular heteropolysaccharide typically produced by a
fermentation
process from the bacterium Xanthomonas campestris.
If desired, suitable sequestrants which may be employed herein include
i 5 sodium citrate, sodium hexametaphosphate (SHMP), disodium phosphate,
mixtures
thereof and the like. The amount of sequestrant employed may be about 0.05
wt.% to
about 0.5 wt.%. Greater and lesser amounts of sequestrant may be employed if
desired.
20 Preferred range for additional optimal ration use level herein is in
general from about 0.5 to about 500 mM, or about (0.5 to about 15 mM for
divalent
rations and about 10 to about 500 mM for monovalent rations for example).
If desired solubilizing aids (which without being bound by theory are
25 believed to help solubilize the biologically active ingredient(s)) maybe
employed and
preferably selected from the group consisting of ionic or nonionic surfactants
and
cyclodextrins, mixtures thereof and the like. In an embodiment wherein rations
are
employed with the process of this invention those preferred rations are those
selected
from the group consisting of alkali metals, alkaline earth metals and
ammonium. In
3o another embodiment of the invention, it is preferred that the rations used
are part of
the biologically active ingredient if desired. The amount of any solubilizing
aid
employed depends on the application. This can range from about 0.1% to about
50%
or more.
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9
The biologically-active ingredient is not limited and includes but is not
limited to a biologically active ingredient{s) which provides) therapeutic
and/or
medicinal and/or pharmacological value to a recipient either by itself of
through an
active metabolite and/or active derivative. The biologically active ingredient
includes
any ingredients) or similar ingredient which provide such or similar value in
whole or
part, initially or later, directly or indirectly as through active metabolites
or active
derivatives of any kind, in whole or in part, mixtures thereof, to a
recipient.
The biologically active ingredient is preferably (but not limited to) one
or more selected from the group consisting of nutritional supplements (e.g.,
vitamins,
minerals, mineral supplements, plant extracts, amino acids, electrolytes, and
proteins),
anti-inflammatory (e.g., NSAIDS such as ibuprofen, ketoprofen, fenoprofen,
indomethacin, meclofentamate, mefenamic acid, naproxen, phenylbutazone,
piroxicam, tolmetin, sulindac, and dimethyl sulfoxide), analgesics,
antipyretics,
anesthetics including benzocaine, pramoxine, dibucaine, diclonine, lidocaine,
mepiracaine, prilocaine, and tetracaine; demulcents (including benzoin,
acacia,
tragacanth, polyvinyl alcohol and glycerin); analgesics including opiate
analgesics
(e.g., codeine or hydrocodone), non-opiate analgesics, (e.g., meperidine or
methadone), non-narcotic analgesics including acetaminophen and astringent
2o including calamine, zinc oxide, tannic acid, Hamamelis water, zinc sulfate;
(e.g.,
benzalkonium chloride, carbamate peroxide, tannic acid, salicylic acid
triclosan,
benzoyl peroxide, and boric acid); natural or synthetic steroids including
triamcinolone, acetonide, perdnisone, beclomethasone dipropionate; asthmatic
drugs
including terbutaline sulfate, albuterol, leukotriene receptor antagonists;
electrolytes,
metals and minerals; antiaxiety and antidepressant agents; antimicrobial and
antiviral
agents (e.g., acyclovir, neomycin, bacitracin, polymyxin B, vidarabine,
trifluridine,
zidovucine, methenamine, nonoxynol sulfonamides and other antibiotics); (e.g.,
fish
oils, shark liver oil, castor oil, sucralfate and liver yeast cell
derivatives);
antihistamines and respiratory agents (e.g., diphenhydramine, promethazine,
cromolyn, cyproheptadine and azatadine); immune-suppression agents;
cholesterol-
lowering agents; cardiac and high-blood pressure agents, cardiovascular and
diuretic,
hormone, protein, and enzyme active agents, anti neopolastics,
gastrointestinal agents,
adriamycin, theophylline, ampicillin, amoxicillin, tetracycline and
erthromycin and
a i~
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mixtures thereof and the like. Mixtures of any one or more than one of any of
these
and any acceptable ingredients may be employed.
Illustrative but non limiting examples of useful biologically active
5 ingredients which may be employed herein include those without limit as
recited in
American society of Health-System Pharmacists, 1997, [AFHS Drug Information
97]
Edited by Gerald K. McEvoy, Bethesda, MD; American Society of Health-System
Pharmacists which is incorporated herein in its entirety by reference.
Illustrative non
limiting examples of useful biologically active ingredients herein also
include those
1o without limit as disclosed in Hardman, G.G; [Goodman & Gilman's The
Pharmacological basis of Therapeutics], 9''' Edition, 1996; New York; McGraw-
Hill,
Health Professions Division which is also incorporated herein by reference in
its
entirety. After reading this specification including the Examples those of
skill in the
art will recognize that a wide range of such biologically active ingredients
may be
employed in the practice of this invention.
A nonlimiting example of a useful biologically-active ingredient is a
nutritional supplement and a nonlimiting example thereof is a vitamin. Vitamin
C
may be employed herein as a vitamin in the practice of this invention.
Potassium
2o chloride is a nonlimiting example of a mineral useful herein.
Other nonlimiting useful biologically-active ingredients include
sodium naproxen, sodium salicylate and ibuprofen, mixtures thereof and the
like.
Additional nonlimiting examples are shown in the Table page 16.
A therapeutically effective amount of a biologically active ingredient is
preferably employed in the gels) of this invention.
Typically the amount of biologically active ingredient employed in
3o each gel is that amount which is deemed therapeutically effective for the
use etc and is
also that amount which the gel will handle. Greater and lesser loadings of
active
ingredient in the gels) may be employed if desired. Typically for sodium
naproxen,
one may be employ from about 50mg/ml. to about 125mg/ml (mg of active / ml of
gel
(see examples). Greater and lesser amounts may be employed if desired
depending on
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11
the use, drug, and other factors. Unit or partial unit dosages may be employed
in one
or more gels in practicing this invention.
The gel compositions) of this invention may be conveniently molded
or shaped into various shapes) or mixtwes of shapes which are not critical.
Preferred
shapes are those which are pleasing to patients and of a size and form and
shape that is
desirable to and swallowable or easy to administer for rectal and vaginal
administration to and by the patient or with assistance.
1o Illustratively, the composition is poured into a suitable mold where the
gelation occurs, resulting in a molded composition accepting the shape of the
mold
and suitable for the patient. Compositions of this invention may then be
removed
from the mold and administered to patients and animals. Administration can be
orally,
vaginally and rectally via suppository with or without an applicator assist.
The
~ 5 method of administering compositions of this invention is carried out by
the patient,
an assistant assisting the patient or a combination thereof. The shape,
texture
(hardness of gel), amount of ingredient, size and other features of the gel
will be
adjusted by those of skill in the art depending on the administration,
patient, patient
age and conditions, doctor preferences, drug employed and many other factors
2o depending on the use.
The biologically-active ingredients) employed in this invention
includes both water soluble and water insoluble biologically-active
ingredients
without limit. An effective (therapeutic) amount of biologically-active
ingredient is
25 preferably employed. The effective (therapeutic) amount of such ingredient
will be
that amount which is effective for the recipient patient who is receiving
medication in
the practice of this invention and is typically that which is recited on the
label of the
medication or prescribed by a medical doctor or veterinarian. Delivery
hereunder is
achieved in an effective manner and time and takes into account the patient,
the drug,
3o and the ability of the patient to be receptive to the manner of delivery of
and the
ingredient, among many factors.
The patient may swallow or otherwise consume (e.g. rectal and vaginal
administration) the gel composition of this invention comprising at least one
t I
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12
biologically-active ingredient. The medication is thus provided to the patient
internally and thus made available to the patient's gastrointestinal tract or
other areas
for beneficial use by the patient as for example when taken orally. The
administration
of gels via vaginal and rectal administration will be apparent to those of
skill in the art
following known procedures for administering gels via vaginal and rectal
(suppository) administration with and without applicator assist.
In another embodiment, this invention comprises a method employed
by a patient of easing the swallowing of a biologically-active ingredient
which
1 o comprises administering a gel prepared by the process of this invention to
a human or
animal. Illustrative animals which may be given and provided effectively gels
of this
invention include cats, dogs, horses, sheep, fish, swine, cattle and the like.
One or
more gels of this invention may be administered and taken at a time to provide
an
effective and safe amount of medication during consumption.
In another embodiment, this invention comprises a method for a patient
to ease breaking a gel and mixing it with food for humans and animals. The gel
of
this invention can be made easy to break, if need be, and can be mixed with
food or
produce smaller entities easier to swallow by a human.
In another embodiment, this invention comprises a method to ease
vaginal or rectal administration of a lubricious gel of this invention. The
texture of
the gels) of this invention may be modified appreciably depending on the
method of
administration contemplated and the recipient desired.
The shape can be molded into those shapes which are aesthetically
pleasing if desired or color coded or marked to provide increased compliance
measures. The shape and texture of the gel can also be configured and
texturized to
provide such increased compliance measures. For example, the mold could
contain
3o the name of drug dosage, form, etc.
EXAMPLES
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13
The examples produced herein are only illustrations of various
embodiments of this invention and are not intended to limit it in any way.
Example 1
s Preparation of Na-Naproxen Gellan Gels
A 0.5% solution of GELRITE~ gelling agent (GELRITE~ is a
registered trademark of Monsanto Company, 800 North Lindbergh Blvd., St.
Louis,
Missouri, 63167, U.S.A. in distilled water is prepared by adding 0.125 g of
1 o GELRITE~ to 25 milliliters of distilled water with agitation from a stir
bar. The
GELRITE~ solution is heated to 90 -95 °C for 3-5 minutes to hydrate the
GELRITE~
Gum and produce a clear solution. The GELRITE~ gelling agent is cooled to
about 75
-78 °C and mixed with 2.5 g of Na-Naproxen until the drug is completely
dissolved.
This produces a drug concentration of 100 mg/ml of solution. The warm drug
15 solution is poured into molds and allowed to cool. Solutions gel as the
temperature
drops below 40° C and forms free-standing (intact) lubricious gels,
easy to mold gel
containing sodium naproxen illustrative of a biologically active ingredient.
(Na-
naproxen is an approved medication which is sold over the counter as an anti-
inflammatory medicine.) This produced a gel containing a biologically active
2o ingredient illustrative of this invention. For example when 2m1 solution
were poured
in mold, final gels contained 200 mg sodium naproxen.
The following examples were prepared following the general
procedure in Example 1.
GELRITE~ Resulting
dose
Example Solution Na-Naproxen of naproxen
in
Number Concentration Concentration2m1 gels
2 0.25 % 125 mg/mL 250 mg
3 0.50 % 125 mg/mL 250 mg
4 0.50 % 62 mg/mL 124 mg
5 1.00 % 125 mg/mL 250 mg
6 1.00 % 62 mg/mL 124 mg
7 0.50 % 100 mg/mL 200 mg
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14
Examples 8-20
Various biologically-active materials (Na-Naproxen, ascorbic acid,
ibuprofen, penicillin etc.) were incorporated into the Gehzte~ gelling agent
to illustrate
preparing a gel of this invention. In all cases, the preparation of the gel
containing an
illustrative biologically active ingredient in these Examples followed the
procedure
described in Example 1. Hardnesses were measured on an Instron Model 4201.
Data
is given in lbs. which represent the rupture point of the gels under test in
the Instron.
io (Instron Test Instrument Model 4201, Instron, 100 Royale Street, Canton,
Massachusetts, 02021, U.S.A.) The rupture point was measured to show the gels
of
this invention are free standing and can be broken in smaller pieces if
needed.
Initial
GELRITE~ Biologically-ActiveActive Hardness
Example ConcentrationMaterial Concentration lbs.
7* 0.50% Na-Naproxen 100 mglmL 2.1
8 0.50% Potassium Chloride25 mg/mL 1.8
9 0.75% Potassium Chloride25 mg/mL 4.3
1.00% Potassium Chloride25 mg/mL 5.2
11 0.50% Iron Sulfate 100 mg/mL 1.4
12 0.75% Iron Sulfate 100 mg/mL 2.4
13 1.00% Iron Sulfate 100 mg/mL 3.0
14 0.50% Ascorbic Acid 250 mg/mL 1.0
0.75% Ascorbic Acid 250 mg/mL 1.7
16 1.00% Ascorbic Acid 250 mg/mL 2.7
17 0.75% Ibuprofen 75 mg/mL 2.1
18 0.25% Ibuprofen 150 mg/mL 0.96
19 0.50% Penicillin G 100 mg/mL 1.2
0.75% Penicillin G 250 mg/mL 1.3
21 1.00% Penicillin G 250 mg/mL 1.8
* Same as previous page (with hardness given)
I5
CA 02273206 1999-OS-27
WO 98123292 PCT/US97121408
Other Examples 22-27 below were prepared as previously described,
by adding calcium chloride to the warm solution, so that the overall calcium
concentration in the gel was 6mM.
Initial
GELRITE~ Biologically-ActiveActive Hardness
Example ConcentrationMaterial Concentration 1
22 0.75 Pseudoephedrine 30 mg/mL 4.26
HCl
23 0.75 Phenylpropanolamine12.5 mg/mL 4.29
HCl
24 0.75 Chlorpherinamine 2 mg/mL 5.06
0.75 Bromopheniramine 2 mg/mL 5.85
26 0.75 Dextrometorphan 5 mg/mL 5.08
27 0.75 Diphenhydramine HCl 12.5 mg/mL 4.73
28 0.75 Acetaminophen 100 mg/mL 5.42
5
By comparison, commercially available soft-gels (e.g., Pfizer~
Unisom Sleepgels) Registered trademark Pfizer, Inc., distributed by Consumer
Health
Care Group, Pfizer, Inc., New York, NY, 10017 U.S.A. or Gelcaps (Vons~ Liquid-
Gelcaps) Cough & cold Liquid Liquid-Gelcaps, The Von Companies, Inc., P.O. Box
l0 3338, Los Angeles, CA 90051, U.S.A. could not be ruptured in the Instron
(e.g., force
limit is 100 lbs.)
Thus, it is apparent that there has been provided, in accordance with
the instant invention, a novel composition, drug delivery system, a process
and a
15 methods) for easing the swallowing and/or administration of
pharmaceutically active
drug{s) or metabolites or derivatives or medicine that fully satisfies the
objects and
advantages set forth herein above. While the invention has been described with
respect to various specific examples and embodiments thereof, it is understood
that
the invention is not limited thereto and many alternatives, modifications and
2o variations will be apparent to those skilled in the art in light of the
foregoing
description. Accordingly, it is intended to embrace all such alternatives,
modifications and variations as fall within the spirit and broad scope of the
invention.
