Palatable solid pharmaceutical compositions

Lipid-containing, molded pharmaceutical compositions, comprising: PA0 (a) from about 10% to about 50% of a lipid material having a melting point of from about 26.degree. C. to about 37.degree. C.; PA0 (b) from about 10% to about 50% of a particulate dispersant material; PA0 (c) from about 0.1% to about 3% of an emulsifier; and PA0 (d) a safe and effective amount of a pharmaceutical active material; wherein the particulate materials in said composition have a mean particle size of from about 4 microns to about 10 microns, with less than about 10% of the particulates greater than about 30 microns in size. Preferably, the measured viscosity of the compositions is less than about 10,000 cps at about 40.degree. C.

BACKGROUND OF THE INVENTION 
This invention relates to palatable solid pharmaceutical compositions 
useful in humans and other animals. In particular, it relates to highly 
efficacious compositions comprising a pharmaceutical active in a 
lipid-containing matrix. Preferred compositions further relate to highly 
palatable tablets, which are chewable or liquify in the mouth, useful for 
the treatment of gastrointestinal disorders. 
Pharmaceutical compositions may be produced in a variety of dosage forms, 
depending upon the desired route of administration of the active material. 
Oral dosage forms, for example, include such solid compositions as 
tablets, capsules, granules and bulk powders, and such liquid compositions 
as solutions, emulsions, and suspensions. The particular dosage form 
utilized may, of course, depend upon such factors as the solubility and 
chemical reactivity of the pharmaceutical active. Further, the dosage form 
may be selected so as to optimize delivery of the pharmaceutical active 
and/or consumer acceptability of the composition. 
Tablet compositions offer many advantages, including ease of product 
handling, chemical and physical stability, portability (in particular, 
allowing ready availability to the consumer when needed), aesthetic 
acceptability, and dosage precision, (i.e., ensuring consistent and 
accurate doses of the pharmaceutical active). However, liquid formulations 
may offer advantages in the treatment of certain disorders, such as 
disorders of the upper gastrointestinal tract, wherein delivery of an 
active material dissolved or dispersed in a liquid ensures rapid and 
complete delivery to the afflicted area. In an effort to obtain the 
therapeutic advantages associated with liquid formulations as well as the 
broad advantages associated with solids, many chewable tablet formulations 
have been developed and described in the pharmaceutical literature. See, 
for example, L. Lachman, et al., The Theory and Practice of Industrial 
Pharmacy (2nd Ed., 1976). 
Many such compositions are antacids, for the treatment of gastric 
hyperacidity and related disorders. Many antacid compositions in liquid 
form are quite effective due to the ready availability of the antacid 
active material (which is typically water-insoluble) suspended in a liquid 
vehicle. There are also many solid antacid formulations, typically 
chewable tablets, which are designed to deliver small particles of antacid 
active to the stomach after chewing of the tablet. 
Chewable tablets, such as antacid tablets, often contain high levels of 
mannitol or similar binders as well as methylcellulose, glycine, or other 
binding agents. Other chewable tablets are described in the literature 
containing fatty materials. See, for example, U.S. Pat. No. 4,230,693, 
Izzo, et al., issued Oct. 28, 1980, U.S. Pat. No. 4,327,076, Puglia, et 
al., issued Apr. 27, 1982, U.S. Pat. No. 4,327,077, Puglia, et al., issued 
Apr. 27, 1982, U.S. Pat. No. 4,533,543, Morris, et al., issued Aug. 6, 
1985, and U.S. Pat. No. 4,581,381, Morris, et al., issued Apr. 8, 1986. 
Many such solid antacid formulations fail to offer equivalent efficacy to 
liquid antacid compositions, for a variety of reasons. For example, the 
tablets may be incompletely chewed due to poor palatability of the 
composition. This problem is particularly acute with antacids, since the 
active materials in these products often have a metallic flavor and an 
astringent, chalky mouth feel. Such compositions may also have a gummy 
texture, and are subject to "taste fatigue", i.e., the composition is 
perceived to be less palatable after ingestion of multiple doses. Further, 
the binders and other materials used in such chewable tablets may prevent 
rapid and effective delivery of active materials to the stomach. 
It has been found that tablet formulations containing selected lipid 
materials, emulsifiers and particulate materials are highly palatable and 
effective compositions for the delivery of pharmaceutical active 
materials. Such compositions afford better taste, mouth feel, and storage 
stability than compositions known in the art. For example, such 
compositions containing selected materials with selected particle sizes, 
and formulated to have a selected product viscosity, afford improved 
palatability when compared to other lipid containing compositions. 
SUMMARY OF THE INVENTION 
The present invention provides lipid-containing, molded pharmaceutical 
compositions, comprising: 
(a) from about 10% to about 50% of a lipid material having a melting point 
of from about 26.degree. C. to about 37.degree. C.; 
(b) from about 10% to about 50% of a particulate dispersant material; 
(c) from about 0.1% to about 3% of an emulsifier; and 
(d) a safe and effective amount of a pharmaceutical active material; 
wherein the particulate materials in said composition have a mean particle 
size of from about 4 microns to about 10 microns, with less than about 10% 
of said particulates greater than about 30 microns in size. Preferably, 
the measured viscosity of said composition is less than about 10,000 cps 
at about 40.degree. C. 
Among the preferred lipid-containing compositions of this invention are 
chewable tablets useful for the treatment of upper gastrointestinal 
disorders, such as an antacid composition containing from about 10% to 65% 
of an acid neutralizing material. The present invention also provides 
coated unit dosage compositions which comprise the lipid-containing solid 
compositions of this invention coated with a solid coating material. 
DESCRIPTION OF THE INVENTION 
The compositions of the present invention contain a pharmaceutical active 
material in a vehicle containing a lipid base material, a dispersant 
material and an emulsifier. In addition, the compositions of the present 
invention may contain optional pharmaceutically-acceptable components 
which may modify their physical characteristics and/or therapeutic 
effects. All components of the present compositions must, of course, be 
pharmaceutically-acceptable. As used herein, a 
"pharmaceutically-acceptable" component is one which is suitable for use 
with humans and/or other animals without undue adverse side effects (such 
as toxicity, irritation and allergic response) commensurate with a 
reasonable benefit/risk ratio. 
The present invention provides lipid-containing, molded pharmaceutical 
compositions, comprising: 
(a) from about 10% to about 50% of a lipid material having a melting point 
of from about 26.degree. C. to about 37.degree. C.; 
(b) from about 10% to about 50% of a particulate dispersant material; 
(c) from about 0.1% to about 3% of an emulsifier; and 
(d) a safe and effective amount of a pharmaceutical active material; 
wherein the particulate materials in said composition have a mean particle 
size of from about 4 microns to about 10 microns, with less than about 10% 
of said particulates greater than about 30 microns in size. Preferably, 
the measured viscosity of said composition is less than about 10,000 cps 
at about 40.degree. C. Except as otherwise stated, all percentages set 
forth herein are by weight of total composition. 
Further, as used herein, the term "safe and effective amount" refers to the 
quantity of a component which is sufficient to yield a desired therapeutic 
response without undue adverse side effects (such as toxicity, irritation 
or allergic response) commensurate with a reasonable benefit/risk ratio 
when used in the manner of this invention. The specific "safe and 
effective amount" will, obviously, vary with such factors as the 
particular condition that is being treated, the severity of the condition, 
the duration of the treatment, the physical condition of the patient, the 
nature of concurrent therapy (if any), and the specific formulation and 
optional components employed. 
Preferably, the lipid base material is present in the present compositions 
at a level of from about 20% to about 40%, more preferably from about 25% 
to about 40%. Also preferably, the dispersant material is present at a 
level of from about 20% to about 40%, more preferably from about 20% to 
about 35%. The emulsifier is preferably present at a level of from about 
0.5% to about 2%, more preferably from about 0.6% to about 1.5%. Specific 
components, and optional materials useful in these chewable tablet 
compositions are further described below. 
These compositions may be provided in unit-dosage form, as molded tablets. 
Molded tablets are produced by forming a liquid product mass, i.e., by 
melting the fatty carrier materials and admixing the other components, 
followed by pouring into tablet-form molds, and cooling to a solid state. 
Although these compositions may be swallowed whole or in part without 
chewing, the present compositions are preferably comprised so as to 
facilitate chewing and/or melting in the mouth. The present compositions 
thereby facilitate dispersion of the pharmaceutical active material in 
saliva and (after swallowing, ultimately) in the gastric fluids of the 
stomach. 
Essential Components 
As described above, the present chewable tablet compositions contain four 
essential components: a lipid base material, a dispersant material, a 
nonionic emulsifier material, and a pharmaceutical active material. These 
compositions may also contain optional components, such as other 
emulsifiers, tempering aids, flavorants and colorants. 
Lipid Material: 
The compositions of the invention contain one or more materials, (herein 
individually and in mixtures referred to as "lipid materials") that are 
substantially water-insoluble, inert, pharmaceutically-acceptable 
hydrocarbon fats or oils, or their derivatives, or mixtures thereof. The 
lipid materials useful herein preferably have a melting point of from 
about 26.degree. C. (80.degree. F.) to about 37.degree. C. (99.degree. 
F.), preferably from about 32.degree. C. (90.degree. F.) to about 
35.degree. C. (95.degree. F.), more preferably about 33.degree. C. 
(91.degree. F.). (As used herein "melting point" refers to the capillary 
melting point, at which essentially all of the fat is in a liquid state.) 
The particular lipid material employed may be selected in order to obtain 
desired product characteristics. These characteristics include such 
factors as rheology (mouth feel), appearance, flavor and compatibility 
with the pharmaceutical active. 
Among the lipid materials useful herein are those which are commercially 
available and commonly used in confectionery and other food products. Such 
lipid materials include, for example, cocoa butter, hydrogenated tallow, 
hydrogenated vegetable oils, and derivatives and mixtures thereof. 
Hydrogenated vegetable oils (such as hydrogenated palm kernel oil), cocoa 
butter, and cocoa butter substitutes are among the preferred useful lipid 
materials. Lipid materials among those useful in this invention are 
described in the following documents, all incorporated by reference 
herein: U.S. Pat. No. 2,903,363, Farr, issued Sept. 8, 1959; British 
Patent Specification No. 827,176, Best et al., published Feb. 3, 1960; 
U.S. Pat. No. 3,012,891, Best et al., issued Dec. 12, 1961; U.S. Pat. No. 
3,093,480, Arnold, issued June 11, 1963; U.S. Pat. No. 3,492,130, Harwood, 
issued Jan. 27, 1970; U.S. Pat. No. RE 28,737, Yetter reissued Mar. 16, 
1976; European Patent Application No. 23,062, Cotton et al., published 
Jan. 28, 1981; U.S. Pat. No. 4,276,322, Padley et al., issued June 30, 
1981; U.S. Pat. No. 4,283,436, Soeters et al., issued Aug. 31, 1981; U.S. 
Pat. No. 4,364,868, Hargreaves, issued Dec. 21, 1982; and U.S. Pat. No. 
4,581,381, Morris et al., issued Apr. 8, 1986; and U.S. Pat. No. 
4,594,259, Baker et al., issued June 10, 1986. 
Particularly preferred lipid materials are those that melt sharply at about 
33.degree. C. (91.degree. F.). Such fats which melt "sharply" are those 
with melting profiles similar to cocoa butter, which is a solid at ambient 
temperatures, but is entirely liquid at a point just below mouth 
temperature (approximately 34.degree. C.). 
A commercially available material having such a preferred melting profile 
is Hydrokote, SP1, manufactured by Capital Cities Products Co. (Division 
of Stokely-VanCamp, Inc.). The solid fat index of this lipid material 
shows that the fat melts sharply at just below 34.degree. C.; being about 
65% to 69% solid at about 21.degree. C. (70.degree. F.), about 52% to 56% 
solid at about 26.degree. C. (80.degree. F.), and less than about 1% solid 
at about 33.5.degree. C. (92.degree. F.). 
Another particularly preferred lipid material is described in U.S. Pat. No. 
4,594,259, Baker et al., issued June 10, 1986. Solid pharmaceutical 
compositions containing these particularly preferred materials are 
described in U.S. patent application Ser. No. 916,061, filed Oct. 6, 1986. 
Such particularly preferred compositions contain one or more materials, 
herein "lipid base materials", which together with all other mono-, di- 
and tri-glycerides (if any) in the compositions form the "lipid component" 
of the chewable tablet compositions. The lipid component of the present 
composition thus preferably contains certain key triglycerides: 
saturated-oleic-saturated ("SOS"), saturated-unsaturated-saturated 
("SUU"), unsaturated-unsaturated-unsaturated ("UUU"), 
saturated-lineolic-saturated ("SLS"), saturated-saturated-oleic ("SSO"), 
and saturated-saturated-saturated ("SSS") triglycerides, i.e., referring 
to the chemical structure of the fatty acid moiety of each glyceride in 
the key triglyceride. As used herein, "S" refers to the stearic ("St") or 
palmitic ("P") fatty acid residues of the glyceride molecule and ("U") 
refers to the oleic ("O") or linoleic ("L") fatty acid residues of the 
glyceride molecule. 
Specifically, the lipid component of such particularly preferred 
composition contains at least about 70% of SOS triglycerides, and from 
about 4% to about 20% of combined SUU/UUU/SLS triglycerides, where the 
St:P weight ratio is about 0.8 or less. (These percentages are by weight 
of the lipid component, not by weight of total composition.) Preferably 
the lipid component contains about 8% or less of SLS triglycerides, about 
9.5% or less of SSO triglycerides, about 2.5% or less of SSS 
triglycerides, and about 4% or less of other triglycerides. The lipid 
component of the present invention preferably is comprised entirely of a 
fat having a low St:P ratio (about 0.2 or less). A POP fat is particularly 
preferred. A preferred source of POP fat is through a triple stage solvent 
fractionation of palm oil. This process is described in U.S. Pat. No. 
4,588,604, Baker et al., issued May 13, 1986 (incorporated by reference 
herein). 
Dispersant Material: 
The compositions of this invention also contain a hydrophilic material, 
herein "dispersant material", which serves to aid dispersion of the 
pharmaceutical active and other materials of the composition in the mouth 
and/or stomach. Many dispersants among those useful herein are known in 
the pharmaceutical arts. Dispersant materials among those useful herein 
include sugars (such as sucrose, mannitol, sorbitol, dextrose, maltose, 
and lactose), starches and starch derivatives (such as corn starch and 
maltodextrin), microcrystalline cellulose, and mixtures thereof. Among the 
preferred dispersant materials useful herein are sucrose, sorbitol, 
mannitol, and mixtures thereof. 
Emulsifier Material: 
The compositions of this invention also contain one or more emulsification 
materials (herein individually and in mixtures referred to as 
"emulsifiers"). Emulsifiers may be characterized by their 
hydrophilic/lipophilic behavior. This behavior can be numerically 
expressed for a given emulsifier by its hydrophilic-lipophilic balance 
(HLB). The HLB value of an emulsifier can be determined experimentally or 
computed (particularly for polyoxyethylene ethers) from its structural 
formula. In general, emulsifiers with high HLB values are more 
hydrophilic, and tend to favor formation of oil-in-water emulsions, as 
opposed to emulsifiers with lower HLB values. 
Among the emulsifiers useful herein are the alkyl aryl sulfonates, alkyl 
sulfates, sulfonated amides and amines, sulfated and sulfonated esters and 
ethers, alkyl sulfonates, polyethoxylated esters, mono- and diglycerides, 
diacetyl tartaric esters of monoglycerides, polyglycerol esters, sorbitan 
esters and ethoxylates, lactylated esters, propylene glycol esters, 
sucrose esters, and mixtures thereof. 
Many such emulsifiers are known in the pharmaceutical arts. See, for 
example, M. Riegler, "Emulsions", The Theory and Practice of Industrial 
Pharmacy (L. Lachman, et al., ed. 1976), incorporated by reference herein. 
Emulsifiers among those useful herein are also described in McCutcheon's 
Emulsifiers and Detergents, North American Edition (1983), incorporated by 
reference herein. 
Preferably the emulsifier used in the present compositions includes a "low 
HLB emulsifier", i.e., an emulsifier having an HLB of from about 4 to 
about 10, more preferably from about 6 to about 10. Such low HLB 
emulsifiers are preferably included at a level of from about 0.1% to about 
1%, more preferably from about 0.1% to about 0.5%. Also preferably, the 
present compositions are essentially free (e.g., containing less than 
about 0.1%) of emulsifiers having HLB values less than about 4. 
Many low HLB emulsifiers are commercially available. Such emulsifiers among 
those useful herein include: Caprol 6G2S (hexaglycerol distearate), 
manufactured by Capital Cities Products Co.; Artodan (sodium stearoyl 
lactylates), manufactured by Grinsted Products; Myvatem 30 (monoglyceride 
diacetyl tartaric acid esters), manufactured by Eastman Chemical Products, 
Inc.; Polyaldo HGDS (hexaglycerol distearate) and Polyaldo TGMS 
(triglycerol monostearate), manufactured by Glyco Inc.; and Span 60 
(sorbitan monostearate) and Span 80 (sorbitan monooleate), manufactured by 
ICI Americas, Inc. 
The compositions of this invention also preferably contain one or more high 
HLB emulsifiers as a part of the emulsifier component. In particular, the 
present compositions preferably contain from about 0.1% to about 3%, more 
preferably from about 0.5% to about 2%, more preferably from about 0.6% to 
about 1.5% of a nonionic emulsifier having an HLB of at least about 10. 
Preferably, the high HLB emulsifier has an HLB of at least about 11. Many 
such nonionic emulsifiers are commercially available. Such emulsifiers 
include, for example: Caprol PGE860 (Decaglycerol mono-dioleate), 
manufactured by Capital Cities Products Co.; Hodag PSMS-20 
(polyoxyethylene sorbitan) and Hodag SVO-9 (polyoxyethylene sorbitan 20 
monooleate), manufactured by Hodag Chemical Corp.; Liposorb L-20 
(polysorbate 20), Liposorb 0-20 (polysorbate 80), and Liposorb S-20 
(polysorbate 60), manufactured by Lipo Chemicals, Inc.; Pluronic F69 
(block copolymer of propylene oxide and ethylene oxide), manufactured by 
BASF Wyandotte Corp.; Santone 8-1-S (polyglycerol esters of fatty acids), 
manufactured by Durkee Industrial Foods Group of SCM Corp.; and Tween 20 
(polyoxyethylene 20 sorbitan monolaurate), Tween 60 (polyoxyethylene 20 
sorbitan monostearate), Tween 80 (polyoxyethylene 20 sorbitan tristerate, 
polysorbate 65) and Myrj 52 (polyoxyl 40 stearate), manufactured by ICI 
Americas, Inc. 
The average HLB of all emulsifiers incorporated in the present compositions 
is preferably at least about 8, more preferably at least about 10. As used 
herein, the term "average HLB" refers to the weighed average of the HLB of 
all emulsifiers in the composition; i.e., 
##EQU1## 
wherein the composition contains "n" number of emulsifiers. The use of 
such high HLB emulsifiers to increase the efficacy of lipid-containing 
compositions is described in U.S. patent application Ser. No. 916,065, 
filed Oct. 6, 1986 (incorporated by reference herein). 
Pharmaceutical Active Material: 
The present compositions also contains a "pharmaceutical active material", 
i.e., a material which is intended to have a physiologic effect on the 
human or lower animal to whom the composition is administered. 
Pharmaceutical active materials particularly useful in the chewable tablet 
formulations of this invention include those actives which become 
bioavailable and/or have their site of action in the mouth or stomach. The 
rapid dispersion of such active materials in the saliva, as afforded by 
the present chewable tablets, is particularly advantageous. Among such 
active materials are the analgesics, such as aspirin and acetaminophen, 
and materials useful in the treatment of gastrointestinal disorders. 
Among the pharmaceutical active materials particularly useful in the 
compositions of this invention are the bismuth salts and the metallic 
antacid salts. Such bismuth salts include, for example, bismuth aluminate, 
bismuth citrate, bismuth nitrate, bismuth subcarbonate, bismuth subgalate, 
bismuth subsalicylate, and mixtures thereof. A particularly preferred 
bismuth salt is bismuth subsalicylate. Metallic antacid salts useful 
herein include, for example, aluminum carbonate, aluminum hydroxide, 
aluminum phosphate, aluminum hydroxycarbonate, dihydroxy aluminum sodium 
carbonate, aluminum magnesium glycinate, dihydroxy aluminum amino acetate, 
dihydroxy aluminum aminoacetic acid, calcium carbonate, calcium phosphate, 
aluminum magnesium hydrated sulfates, magnesium aluminate, magnesium 
alumino silicates, magnesium carbonate, magnesium glycinate, magnesium 
hydroxide, magnesium oxide, magnesium trisilicate, and mixtures thereof. 
Aluminum magnesium hydroxide sulfate (also known as magaldrate) is a 
preferred metallic antacid salt useful herein. 
Optional Components 
The compositions of this invention may also contain 
pharmaceutically-acceptable optional components which modify the physical 
and/or therapeutic effects of the composition. Such optional components 
may include, for example, emulsifiers, binders, lubricants, glidants, 
colorants, flavors and sweeteners. Such components are generally described 
in Marshall, "Solid Oral Dosage Forms", Modern Pharmaceutics, Volume 7, 
(Banker and Rhodes, editors), 359-427 (1979), incorporated by reference 
herein, and W. Gunsel, et al., "Tablets", The Theory and Practice of 
Industrial Pharmacy (L. Lachman, et al., editors, 2 ed.), 321-358 (1976), 
incorporated by reference herein. 
Pharmaceutically-acceptable oils may be included to obtain a desired 
measured viscosity (as discussed below), preferably at levels of from 
about 0.1% to about 2%, more preferably from about 0.1% to about 1%. Such 
materials include, for example, vegetable oils, mineral oils and mixtures 
thereof. Certain emulsification materials, discussed above, may also be 
oils. However, as also discussed below, it is preferred that the levels of 
oils and other liquid materials in these compositions be minimized. 
As will be appreciated by those skilled in the art, the lipid base material 
of the present composition may be present in any of a number of crystal 
forms, or polymorphs, depending upon the particular lipid material used. 
For compositions wherein POP fat is utilized as the lipid base material, 
it is preferred that the fat be present in the beta-prime-2 or beta-3 
polymorph state. The crystal structure of the lipid base material useful 
herein may be affected by a variety of factors, as can be ascertained by 
one of skill in the art. Such factors include the presence of solids in 
the composition, the presence of emulsifiers, the processing conditions 
(particularly cooling temperatures and rates), and the particular lipid 
base material employed. 
A preferred optional component in molded tablets of this invention (i.e., 
compositions that are formed upon solidification of a heated liquid 
composition after pouring into a suitable mold) is a "tempering aid". Such 
materials aid in the formation of a desired crystal structure for the 
lipid components of the present composition, such that the composition has 
a desired uniform, smooth, non-gritty texture and appearance. Tempering 
aids are preferably included at a level of from about 0.2% to about 2%. 
Among tempering aids useful herein are mixtures of mono- and diglycerides, 
such as Dur-Em 127 (manufactured by Durkee Foods, Division of SCM 
Corporation) and triglyceride mixtures, such as Cessa 60 (manufactured by 
Friwessa). 
Also preferably, the compositions of this invention contain less than about 
1% of materials that are liquid at ambient conditions in addition to any 
liquid components of the lipid material. It has been found that the level 
of such liquid materials may affect the storage stability of these 
compositions. More preferably these compositions contain less than about 
0.5% of such additional liquid materials. 
Other preferred optional components useful herein include flavorants and 
sweeteners, at levels of from about 0.01% to about 1.0%. Colorants may be 
included at typical levels of from about 0.01% to about 0.5%. 
As stated above, the present compositions may be coated, to provide a 
coated unit dosage form. The coated compositions of the invention comprise 
a lipid-containing composition of this invention, covered with from about 
10% to about 50%, preferably from about 10% to about 30%, (by weight of 
final coated composition) of a solid, water-soluble coating material 
having a melting point greater than about 45.degree. C. Such coated 
compositions preferably are in unit-dosage form, i.e., containing an 
amount of pharmaceutical active material suitable for administration to a 
human subject, in one dose, according to good medical practice. The coated 
compositions of this invention preferably contain from about 0.5 to about 
2.5 grams, preferably from about 1.0 to about 2.0 grams, of the 
lipid-containing composition of this invention. 
Coating materials, and methods, among those useful herein are well known in 
the pharmaceutical arts. See, for example, W. Gunsel, et al., "Tablets", 
The Theory and Practice of Industrial Pharmacy (L. Lachman, et al., 
editors, 2d ed.) 321-358 (1976), incorporated by reference herein. 
Preferred coatings and materials are described in U.S. patent application 
Ser. No. 916,066, filed Oct. 6, 1986, incorporated by reference herein. 
Methods 
The chewable tablet compositions of this invention may be made by molding 
techniques. Molding techniques generally involve admixture of components 
in an essentially liquid form, followed by pouring into a desired tablet 
mold and cooling to a solid, or semi-solid form. The compositions of this 
invention are preferably in molded form. 
The lipid base material used in molded compositions of the present 
invention is preferably in a stable crystal form, such that the 
composition is comprised of stable crystals less than about 5 microns, 
preferably from about 1 to about 2 microns, in size, and the composition 
has a uniform, smooth, non-gritty appearance and rheology. Such 
parameters, and the factors which influence them, are analagous to 
parameters that are well known in the chocolate confectionery arts. As 
discussed above, materials may be added to the present compositions which 
aid in obtaining a preferred, stable crystal structure, or "temper". 
Processing conditions for making molded compositions are also critical, 
and are preferably controlled to yield a preferred tempered composition. 
Such "tempering", for compositions utilizing POP fat as a lipid base 
material, typically involves cooling of the product in liquid form, to a 
temperature of approximately 22.degree. C. This cooling induces formation 
of a variety of crystals of different melting points. The composition is 
then heated, with stirring, to approximately 29.5.degree. C., melting the 
undesired lower-melting crystals. (The fluid product at this point is 
thereby "seeded" with higher-melting crystals.) The fluid product is then 
poured into molds, vibrated to remove air bubbles, and slowly cooled to 
solidify the composition into a product having the desired crystal form. 
The molded, uncoated compositions of this invention preferably have a 
viscosity (herein "measured viscosity") of less than about 10,000 
centipoises (cps), while in liquid mixture (melted) at approximately 
40.degree. C. More preferably, the measured viscosity is less than about 
8,000 cps, more preferably less than about 5,000 cps. This measured 
viscosity may be measured using a Brookfield Viscometer, Model RVT/2 with 
Helipath (Spindle C, at 10 rpm). The uncoated product is first melted, 
using a water bath, at a temperature of approximately 50.degree. C. The 
product is then mixed for approximately one hour, using a paddle mixer 
(such as a Model K4553 Kitchen Aid Mixer, at speed setting #2). The 
product mixture is cooled slowly (over a period of approximately 30 
minutes), while mixing, to a temperature of approximately 40.degree. C. 
The mixing is stopped, and the viscometer spindle is then inserted into 
the product mass. The viscosity reading is taken at equilibrium, or after 
lapse of 30 seconds, whichever comes first. 
The product measured viscosity may be obtained by selection of materials 
and processing conditions. For example, the desired measured viscosity may 
be obtained by selection of the type and level of lipid material, 
emulsifiers, particulate materials (active material and dispersant 
material) and optional materials. The measured viscosity of the present 
compositions may be obtained by control of processing conditions, 
including (for example) milling of materials, order of addition of 
materials, and tempering conditions. 
In particular, the particle size of particulate materials of the present 
compositions are controlled by selection of materials and/or by selection 
of processing conditions. (As used herein "particulate materials" include 
the pharmaceutical active material, dispersant material, and any optional 
components that are not substantially soluble in the lipid material or 
other components of the composition.) The mean (by volume) particle size 
of the particulate materials is in the range of from about 4 microns to 
about 10 microns, preferably from about 6 microns to about 10 microns. 
Less than about 10% of the particulate materials have a particle size 
greater than about 30 microns. (As used herein, "particle size" of a 
particulate refers to the diameter of a sphere having a volume equal to 
that of said particulate.) 
The particle size of the uncoated compositions of this invention may be 
determined using a Malvern 2600/3600 Particle Sizer (manufactured by 
Malvern Instrument Company). The uncoated composition is melted in mineral 
oil, at approximately 40.degree. C. The mixture is then dispersed using a 
high speed mixer, for at least about 5 minutes. After mixing, several 
drops of the product mixture are placed in the Particle Sizer, using 
mineral oil as the dispersant. The product mixture is mixed in the 
apparatus at a medium speed setting.

The following non-limiting Examples illustrate the compositions, processes 
and uses of the present invention. 
EXAMPLE I 
A coated antacid composition according to this invention was made 
comprising: 
______________________________________ 
Component % Bulk Composition 
% Final Tablet 
______________________________________ 
POP fat.sup.1 
34.009 28.908 
sucrose 31.640 26.894 
magaldrate.sup.2 
31.640 26.894 
simethicone 0.991 0.842 
Span 80.sup.3 
0.478 0.406 
Tween 60.sup.4 
0.148 0.126 
sucrose monoester.sup.5 
0.487 0.414 
sodium stearoyl 
0.009 0.008 
lactylate.sup.6 
Dur-Em 127.sup.7 
0.498 0.423 
peppermint oil 
0.100 0.085 
100.000 
(Coating) 
Neosorb P100T.sup.8 8.700 
Iycasin 4.100 
mannitol 2.200 
100.000 
______________________________________ 
.sup.1 lipid base material, comprising approximately 88% SUS triglyceride 
with an St:P ratio of approximately 0.13 
.sup.2 aluminum magnesium hydroxide sulfate, antacid active material 
.sup.3 sorbitan molooleate emulsifier, HLB = 4.3, manufactured by ICI 
Americas, Inc. 
.sup.4 polyoxyethylene (20) sorbitan monooleate emulsifier, HLB = 14.9, 
manufactured by ICI Americas, Inc. 
.sup.5 emulsifier, HLB = 15.0 
.sup.6 emulsifier, HLB = 9.0 
.sup.7 tempering aid mixture of mono and diglycerides, HLB = 2.8, 
manufactured by Durkee Foods, Division of SCM Corporation. 
.sup.8 fine sorbitol powder, manufactured by The Roquette Corporation 
A composition according to this invention was made by admixing the 
magaldrate and sugar, and heating to approximately 40.degree. C. 
Separately, approximately 55% of the POP fat was melted at approximately 
40.degree. C., and approximately 10% of the Span 80 was added, and mixed. 
The POP-fat mixture was then added to the active/sugar mixture, 
maintaining the temperatures at approximately 40.degree. C., and mixed for 
approximately 45 minutes. The mixture was passed through a 4-roll roller 
mill, at approximately 300 psi, to ensure adequate contact and mixture of 
the lipid base material and the powdered materials. The 4 mill rollers 
were at temperatures of approximately 27.degree. C., 21.degree. C., 
21.degree. C. and 21.degree. C., respectively. 
Separately, the remaining portion of POP (approximately 45% of the original 
quantity) was admixed with the remaining portion of Span 80 (approximately 
90% of the original quantity), the Dur-Em, and the sodium stearyl 
lactylate emulsifier, for approximately 10 minutes, at a temperature of 
approximately 50.degree. C. The sucrose monoester and Tween 60 were 
dissolved in ethanol, and then added to the composition. The peppermint 
oil and simethicone were then added, and the compositions mixed for 
approximately 45 minutes, maintaining the temperature at approximately 
50.degree. C. The milled POP mixture was then added to this POP/emulsifier 
mixture, and mixed for approximately 15 minutes. 
The composition was then cooled to approximately 22.degree. C., and 
tempered by rapidly raising the temperature to approximately 29.5.degree. 
C., forming seed crystals. The composition was then poured into tablet 
molds and allowed to solidify. The average tablet weight was approximately 
2.2 g. 
The tablets were then coated by placing them in a conventional coating pan 
apparatus. A portion of the lycasin was added, and the tablets evenly 
wetted. The mannitol was then added, and the tablets mixed for 
approximately 10 minutes, and then dried for approximately one hour. The 
tablets were then coated with lycasin and Neosorb, following the same 
procedure, and dried for approximately 12 hours. 
A coated antacid tablet, comprised as above, was administered to a human 
subject experiencing heartburn, and was effective in reducing the severity 
of symptoms. The average HLB of the lipid containing core composition of 
this Example is calculated to be approximately 8.1. The measured viscosity 
of the lipid-containing core composition is found to be approximately 
6,600 cps. 
EXAMPLE II 
A coated antacid composition according to this invention is made 
comprising: 
______________________________________ 
Component % Bulk Composition 
% Final Tablet 
______________________________________ 
POP fat 28.0 23.80 
sucrose 15.0 12.75 
sorbitol 15.0 12.75 
calcium carbonate 
40.0 34.00 
sucrose monoester 
1.0 0.85 
Tween 60 0.5 0.43 
flavorant 0.5 0.42 
100.00 
(Coating) 
sorbitol 3.00 
corn syrup 1.00 
sucrose 10.50 
maltrin 0.50 
100.00 
______________________________________ 
A coated antacid composition, comprised as above, is made by a method 
analogous to that described in Example I. The tablets are formed into unit 
dosage tablets, containing approximately 2.2 grams of the lipid-containing 
composition. The average HLB of the lipid-containing core composition of 
this Example is calculated to be approximately 14.9. 
EXAMPLE III 
A coated antacid composition according to this invention was made 
comprising: 
______________________________________ 
Component % Bulk Composition 
% Final Tablet 
______________________________________ 
POP fat 35.942 30.000 
sucrose 26.119 21.800 
magaldrate 35.703 29.800 
Cessa 60.sup.1 
0.994 0.830 
Myrj 52.sup.2 
0.503 0.402 
Caprol PGE 860.sup.3 
0.395 0.330 
Polyaldo HGDS.sup.4 
0.252 0.210 
flavorant 0.092 0.077 
100.000 
(Coating) 
sorbitol solution.sup.5 10.700 
lycasin 1.060 
mannitol 4.023 
Klucel EF.sup.6 0.750 
100.000 
______________________________________ 
.sup.1 triglyceride mixture, tempering aid, manufactured by Friwessa 
.sup.2 polyoxyl (40) stearate, nonionic emulsifier, HLB = 16.9, 
manufactured by ICI Americas, Inc. 
.sup.3 decaglycerol monodioleate nonionic emulsifier, HLB = 11.0, 
manufactured by Capital City Products Co., division of StokelyVan Camp, 
Inc. 
.sup.4 hexaglycerol distearate nonionic emulsifier, HLB = 7.0, 
manufactured by Glyco, Inc. 
.sup.5 70% solution 
.sup.6 hydroxypropyl cellulose gum, manufactured by Hercules Chemical 
Company. 
A coated composition, comprised as above, was made by a method analogous to 
that described in Example I. 
EXAMPLE IV 
An uncoated composition according to this invention is made comprising: 
______________________________________ 
Component % by Weight 
______________________________________ 
Hydrokote SP1 fat* 
34.00 
vegetable oil 1.50 
sucrose 30.93 
magaldrate 30.93 
simethicone 1.00 
Caprol PGE 860 0.90 
sucrose monoester 
0.50 
Tween 60 0.10 
Span 80 0.04 
flavorant 0.10 
______________________________________ 
*lauric lipid material, manufactured by Capital City Products Co. 
EXAMPLE V 
An uncoated composition according to this invention is made comprising: 
______________________________________ 
Component % by Weight 
______________________________________ 
POP fat 35.00 
mannitol 15.76 
bismuth subsalicylate 
25.95 
calcium carbonate 20.00 
hexaglycerol distearate 
0.25 
polyoxyl (40) stearate 
0.50 
sucrose monoester 0.48 
flavorant 1.60 
sweetener 0.20 
colorant 0.26 
______________________________________ 
Unit dosage tablets, comprised as above, are made containing approximately 
1.1 grams of composition per tablet. Two tablets are administered to a 
human subject experiencing nausea, lessening the severity of symptoms. The 
average HLB of the composition of this Example is calculated to be 
approximately 14.6.