AU8440091A - Process for formulating a solid oral dosage form of loperamide compounds - Google Patents
Process for formulating a solid oral dosage form of loperamide compoundsInfo
- Publication number
- AU8440091A AU8440091A AU84400/91A AU8440091A AU8440091A AU 8440091 A AU8440091 A AU 8440091A AU 84400/91 A AU84400/91 A AU 84400/91A AU 8440091 A AU8440091 A AU 8440091A AU 8440091 A AU8440091 A AU 8440091A
- Authority
- AU
- Australia
- Prior art keywords
- loperamide
- compound
- alcoholic solution
- solid oral
- dosage form
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
PROCESS FOR FORMULATING A SOLID ORAL DOSAGE FORM OF LOPERAMIDE COMPOUNDS
BACKGROUND OF THE INVENTION This invention relates to a process for manufacturing a solid oral dosage forms, preferably compressed unit dose forms, of a loperamide compound, preferably loperamide hydrochloride, which provides a uniform and effective dissolution profile when ingested by patients in need of its antidiarrheal effect.
Loperamide hydrochloride (4-(p-chlorophenyl)-4-hydroxy-N, N-dimethyl-alpha, alpha-diphenyl-1-piperidinebutyramide mono- hydrochloride) is the active ingredient of the antidiarrheal product Imodium A-D* (sold by McNeil Pharmaceutics), which is marketed in both a liquid and solid dose forms. Loperamide is indicated for the treatment and control of acute non-specific and chronic diarrhea associated with inflammatory bowel disease. (Physicians Desk Reference. Forty Fourth Edition, page 1028, 1990). In addition, loperamide is a recommended drug for the treatment of mild cases of travelers' diarrhea, according to the article "Travelers' Diarrhea - Consensus Conference" (JAMA. May 10, 1985, 235(18), pages 2700-4)
The process used in manufacturing a pharmaceutical solid dosage form can be an important factor in obtaining an effective therapeutic level of the active ingredient (drug component). In particular, the processing method can determine the efficiency of the release of the drug component from the solid dose form into the dissolution medium. This release is also stated in terms of its dissolution rate, and, in part, impacts the effectiveness of the active ingredient following ingestion by a patient being treated.
Manufacturing processes for certain drug components are described in: (1) Pharmaceutical Dosage Forms: Tablets. Volume 1. Chapter 2, Pages 61-107, 1980, discloses a method for formulating a pharmaceutical solid dosage form by direct compression. This
method consists of two steps. The first step is accomplished by mixing the active ingredient with an appropriate selection of pharmaceutically acceptable carrier materials, and is followed by the step of compressing the dry material into a solid dose form. (2) Johansen et al., Journal of Pharmaceutical Sciences. 67 (1), 134-136 (1978), discloses research on the use of a solvent deposition technique with phenylbutazone deposited on lactose, starch, and silicon dioxide, as well as norethindrone and digoxin deposited on lactose. (3) Law et al . , Drug Development and Industrial Pharmacy. 16 (1), 137-147 (1990), discloses the effect on the dissolution rate when griseofulvin is deposited on the disintegrants Primojel, Mobile Starch, and Ny cel using the solvent deposition system.
(4) Gholmy et al ., Drug Development and Industrial Pharmacy. 1_4 (11), 1587-1603 (1988), discloses research on the uniformity and dissolution rate of digoxin tablets made by simple blending and solvent deposition.
(5) Monkhouse et al., Journal of Pharmaceutical Sciences. 61 (9), 1430-1435 (1972), discloses an approach for increasing the dissolution rates of indo ethacin, aspirin, sulfaethidole, griseo¬ fulvin, reserpine, chloramphenicol, oxolinic acid, probucol , and hydrochlorothiazide by equilibration of the. drug in an organic solvent on an insoluble excipient with an extensive surface (an adsorbent). An object of the present invention is to provide a method for formulating solid oral dosage forms of loperamide compounds which will have a desirable dissolution profile. A further object is to provide processes for preparing a solid dosage form of loperamide compound-containing compositions having an improved dissolution profile to afford a faster release of loperamide compound from the solid oral dosage form, and/or to enhance the ability to consistently obtain a safe and therapeutically effective level of loperamide compound in vivo. An additional object is to provide a solid unit dosage form of loperamide compound-containing compositions, having loperamide compound dispersed uniformly therein, having a fast and effective dissolution profile, and/or consistently supplying a uniform, safe, and effective therapeutic
dose of loperamide compound. A further object is to provide a process for manufacturing compressed lopera ide-containing unit dosage forms which consistently contain the desired level of loperamide per unit dose and consistently deliver within a short period of time a safe and effective amount of loperamide to the patient being treated.
These and other objects of the present invention will become readily apparent from the detailed description which follows.
All percentages and ratios used herein are by weight, and all measurements made at 25* C, unless otherwise specified.
SUMMARY OF THE INVENTION The present invention involves a process for manufacturing a solid oral dosage form of loperamide compound comprising the steps of: (a) dissolving a loperamide compound in an alcoholic solution comprising at least about 50% by volume of short chain alcohol selected from the group consisting of methanol, ethanol, propanol , and mixtures thereof;
(b) combining pharmaceutically acceptable carrier materials with the loperamide compound-containing alcoholic solution; and
(c) drying the combination of the loperamide compound and pharmaceutically acceptable carrier materials.
The present invention also relates to loperamide-containing solid oral dosage compositions prepared by the present process. Such compositions comprise:
(a) from about 0.1% to about 5% of loperamide; and
(b) from about 95% to about 99.9% pharmaceutically accept¬ able carrier, and wherein further the compositions are prepared by a process according to the present invention. DETAILED DESCRIPTION OF THE INVENTION
The process of the present invention employs two essential components: a loperamide compound and certain short chain alcohols suitable for dissolving the loperamide compound. Furthermore, the present invention process involves manufacturing a solid oral dosage form of loperamide compound by the steps of: (a) dissolving the loperamide compound in an alcoholic solution comprising the short chain alcohol; (b) combining pharmaceutically
acceptable carrier materials with the loperamide compound- containing alcoholic solution; and (c) drying said combination of the loperamide compound and pharmaceutically acceptable carrier materials. These and other agents optionally and preferably used in the process and compositions according to the present invention, as well as the levels and amounts preferred therefor, are described in greater detail hereinafter, (a) Loperamide Compounds
The term "loperamide compounds", as used herein, means compounds which are members of the class of 2,2-diaryl-4-(4'- aryl-4'-hydroxy-piperidino) butyramides, active metabolites thereof, the pharmaceutically acceptable salts thereof, and mixtures thereof, having antidiarrheal and analgesic activities, which are disclosed and described in detail in U.S. Patent 3,714,159, issued January 30, 1973 and U.S. Patent 3,884,916, issued May 20, 1975, both to Janssen et al., and U.S. Patent
4,824,853, issued April 25, 1989 to Wals et al . , the disclosures of all these patents being incorporated by reference herein in their entirety. The preferred loperamide compound is loperamide per se and the hydrochloride salt of loperamide, as described in
The Merck Index. 11th Ed., No. 5450, 1989, incorporated by reference in its entirety herein.
The loperamide compound, for purposes of the process of the present invention, is dissolved in an alcoholic solution (as described hereinafter) at a level from about 0.001% to about 5% by weight of the short chain alcohol present in the alcoholic solution. Preferably the loperamide compound comprises about 2.5% by weight of said alcohol in the alcoholic solution. Also the solid dosage forms of the present invention typically comprise a level of loperamide compound from about 0.1% to about 25%, and preferably at a level from about 0.1% to about 5%. Most preferred is loperamide hydrochloride in solid unit dose form compositions (e.g., compressed tablets) at levels from about 0.5% to about 1%. (b) Alcoholic Solutions
In the process of the present invention, the loperamide compound is dissolved in an alcoholic solution prior to combining
the loperamide compound with the pharmaceutically acceptable carrier materials useful for formulating the desired solid dose form. The alcohols useful herein for these alcoholic solutions are short chain alcohols selected from the group consisting of methanol, ethanol, propranol, and mixtures thereof. Preferred are ethanol and propanol , with ethanol being the most preferred.
The alcohol is present in the alcoholic solution at a level of from about 50% to about 100% by volume of the alcoholic solution, with the remaining portion of the solution preferably comprising water at a level from about 0% to about 50% by volume of the alcoholic solution. Preferrably, alcohol is present in the alcoholic solution at a level from about 95% to about 100% by volume of said solution, and water is present at a level from about 0% to about 5% by volume of alcoholic solutions. The final solid oral compositions of the present invention contain very little, and preferably none, of these short chain alcohols which are used in the processing of the compositions, (c) Pharmaceutically Acceptable Carrier Materials
In addition, the components of the manufacturing process and compositions of the present invention include certain pharmaceu¬ tically acceptable carrier materials. The term "pharmaceutically acceptable carrier materials", as used herein, means one or more solid or liquid ingredients, suitable for use with humans and/or other animals without undue adverse side effects (such as toxi- city, irritation and allergic response), within a reasonable benefit/risk ratio, and which ingredients provide the integrity of a solid dosage form of a pharmaceutical composition, causing it to bind, and increasing the ease of administration.
A variety of pharmaceutically acceptable carrier materials may be used in a solid dose pharmaceutical composition. The class of possible pharmaceutically acceptable carrier materials includes disintegrants, fillers or diluents, and binders. Some examples of substances whch can serve as pharmaceutically acceptable carrier materials are sugars such as lactose, dextrose, mannitol, glucose, and sucrose; starches such as corn starch, sodium starch glyco- late, and potato starch; cellulose and its derivatives such as sodium carboxymethylcellulose, icrocrystalline cellulose, ethyl-
cellulose, cellulose acetate; powdered tragacanth; malt; gelatin; acacia; talc; calcium sulfate; polyvinylpyrrolidone; polyacryl- a ides; clays; ion-exchange resins; and certain algins.
Lubricants can also be used in the present invention to enhance the compression of the loperamide containing composition into a solid oral unit dose form. Some examples of lubricants are stearic acid, magnesium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyethylene glycol 4000, polyethylene glycol 6000, sodium lauryl sulfate, or light mineral oil. In addition, coloring agents, anti-oxidants, and preservatives can also be present. Compositions for manufacturing solid oral unit dosage forms useful herein are described in the following references, incorporated herein in their entirety, Lieberman, et al., Pharmaceutical Dosage Forms; Tablets (1981), and Remington's Pharmaceutical Sciences. Seventh Edition. Chapter 90, pages 1603-1632, 1985.
The pharmaceutically acceptable carrier materials utilized in the present invention are collectively present in the final solid oral composition at a level from about 75% to about 99.9% by weight of the composition. Preferrably the pharmaceutically acceptable carrier materials are present at a level from about 95% to about 99.9%, and most preferred level is from about 99% to about 99.5%. (d) Processing Method The present process for formulating a solid oral dosage form, preferably a unit dose form, of loperamide compounds first employs the above described alcoholic solution to dissolve the loperamide compound at levels as indicated. If a more economic method of manufacturing is desired, the loperamide co pound- containing alcoholic solution (once the loperamide compound is completely dissolved) may be diluted such that the short chain alcohol concentration is reduced, typically being at least about 25% by volume of the alcoholic solution. Dilution should not cause precipitation of the loperamide compound from the alcoholic solution.
The pharmaceutically acceptable carrier materials (preferably excepting the lubricant) are also prepared for the manufacturing
process (preferably a granulation process). These pharmaceu¬ tically acceptable carrier materials are combined with the loperamide compound-containing alcoholic solution by utilizing an acceptable apparatus for combining these compounds (typically equipment for mixing or granulating solid compositions). Some examples of apparatuses useful herein are the Planetary mixers, such as the Hobart mixer or the Glen mixer which have served this purpose in the pharmaceutical industry for many years. Additional types of mixing equipment are the Patterson-Kelly twin-shell blender, and the Fluid-bed granulator, which will be described in more detail hereinafter. A preferred mixer, because of its ease of production, is the Hobart mixer, e.g. model number N-50. The Hobart mixer resembles a common household freestanding mixer with rotating blades that provide a uniform mix of ingredients. Another preferred apparatus is the Patterson-Kelly twin-shell blender, because this blender allows precision blending of large quantities of powder. The preferred method herein involves granulation, performed by adding the loperamide compound- containing alcoholic solution to the mixing apparatus where the pharmaceutical carrier materials were initially prepared, and then by mixing until complete granulation is achieved.
Finally, after the combining of the loperamide compound and pharmaceutically acceptable carrier materials is complete, the loperamide compound-containing composition is dried, typically to a level of less than about 2% of alcoholic solution. Drying said loperamide compound-containing composition may be accomplished several ways. The loperamide composition may be dried by placing said composition on trays and allowing them to air-dry, oven dry, or drying under a vacuum. It is also possible to dry the loperamide compound-containing composition in a fluid bed dryer. In the fluid bed dryer, the particles of the composition are tumbled and dried by the force of an upward stream of heated air. (Remington's Pharmaceutical Sciences. Seventeenth Edition, pages 1610-1613, 1985, incorporated herein in its entirety.)
The fluid bed dryer may also be employed to granulate the pharmaceutically acceptable carrier materials with the loperamide compound-containing alcoholic solution and drying the loperamide
composition in a singular process. This method is accomplished by placing the pharmaceutical carriers in the fluid bed dryer and simultaneously granulating them with a spray consisting of the loperamide compound-containing alcoholic solution. Once the desired dryness level is obtained, preferably such that there is essentially no short chain alcohol remaining in the solid composition, the loperamide composition is screened to achieve a reduced and more uniform particle size. Preferably said loperamide composition is screened through a 40-mesh screen.
A desired pharmaceutically acceptable lubricant is preferably then introduced into the loperamide composition. The addition of a lubricant assists in preparing the said loperamide composition for compression into a solid unit dosage form. The preferred lubri¬ cant is magnesium stearate. Once the lubricant is added to the dried pharmaceutical composition of loperamide compound, the oral solid dose form is preferably compressed, using an acceptable tableting process, into a unit dose form to a hardness level typically from about 5sc (Strong-Cobb unit, herein referred to as "sc") to about 20sc. The final unit dose form of the loperamide compound is preferably compressed to a hardness level of about 7sc to about 15sc, and wherein the loperamide is present in the composition at a level of about O.l g to about 5mg, and preferably at a level of about 2mg.
The following examples further describe and demonstrate the referred embodiments within the scope of the present invention. The examples are given solely for the purpose of illustration, and are not to be construed as limitations of the present invention since many variations thereof are possible withut departing from its spirit and scope.
EXAMPLE 1 Solid Unit Dose Form of Loperamide Hydrochloride A solid oral unit dosage form of loperamide hydrochloride, prepared by the method set forth in the present invention, contains the following components.
Components Weight % loperamide hydrochloride 0.80 polyvinylpyrrolidone 4.00 sodium starch glycolate 4.00 icrocrystalline cellulose* 90.95 magnesium stearate 0.25 ethanol2 (32.00)
1 Microcrystalline cellulose is manufactured under the tradename Avicel® by FMC Corporation.
2 Ethanol (100% by volume) is used in the process and removed prior to tableting.
This composition is prepared by first dissolving the loper¬ amide hydrochloride in ethanol to obtain a clear solution. Next, a mixture of polyvinylpyrrolidone, sodium starch glycolate, and Avicel® is granulated with the alcoholic solution of loperamide hydrochloride. This composition is then dried" in a fluid bed dryer and screened through a 40-mesh screen. Finally, the mag¬ nesium stearate is added and the composition compressed to a hardness level of Use.
Ingestion of two of the tablets, after each unformed stool, by a human in need of treatment for diarrhea provides rapid, safe, and effective relief.
EXAMPLE 2 Solid Unit Dose Form of Loperamide Hydrochloride A solid oral unit dosage form of loperamide hydrochloride, prepared by the method set forth in Example 1 hereinbefore, contains the following components.
Components Weight % loperamide hydrochloride 0.80 polyvinylpyrrolidone 4.00 sodium starch glycolate 4.00 microcrystalline cellulose 90.20 talc 1.00 ethanol1 (32.00)
- Removed prior to tableting.
Ingestion of two of these tablets after each unformed stool by humans in need of treatment for diarrhea provides rapid, safe, and effective relief.
WHAT IS CLAIMED IS:
Claims (10)
1. A process for formulating a solid oral dosage form of loperamide compound, said process comprising the steps of:
(a) dissolving a loperamide compound in an alcoholic solution, wherein said alcoholic solution comprises at least 50% by volume of short chain alcohol selected from the group consisting of methanol, ethanol, propanol , and mixtures thereof;
(b) combining pharmaceutically acceptable carrier materials with the loperamide compound-containing alcoholic solution; and
(c) drying said combination of loperamide compound and pharmaceutically acceptable carrier materials.
2. A process for formulating a solid oral dosage form of loperamide compound, according to Claim 1, wherein the loperamide compound is selected from the group consisting of loperamide, the pharmaceutically acceptable salts thereof, and mixtures thereof.
3. A process for formulating a solid oral dosage form of loperamide compound, according to either of Claims 1 or 2, wherein said alcoholic solution contains ethanol as the short chain alcohol.
4. A process for formulating a solid oral dosage form of loperamide compound, according to any of Claims 1-3, wherein said alcoholic solution comprises from 50% to 100% of ethanol and from 50% to 0% of water.
5. A process for formulating a solid oral dosage form of loperamide compound, according to any of Claims 1-4, wherein said loperamide compound is dissolved in said alcoholic solution at a level from 0.001% to 5% by weight of said short chain alcohol present in the alcoholic solution.
6. A process for formulating a solid oral dosage form of loperamide compound, according to any of Claims 1-5, wherein said combination of loperamide compound and pharmaceutically acceptable carrier materials is dried to less than 2% of alcoholic solution, and wherein further the dried composition of loperamide compound and pharmaceutically acceptable carrier materials is screened through a 40 mesh screen.
7. A process for formulating a solid oral dosage form of loperamide compound, according to any of Claims 1-6, wherein after the screening step a pharmaceutically acceptable lubricant is added.
8. A process for formulating a solid oral dosage form of loperamide compound, according to any of Claims 1-7, wherein said composition is compressed into a unit dose form comprising from O.lmg to 5mg of loperamide hydrochloride and the composition is compressed to a level of hardness from 5sc to 20sc.
9. A process for formulating a solid oral unit dose form of loperamide hydrochloride, said process comprising the steps of:
(a) dissolving loperamide hydrochloride in an alcoholic solution comprising from 50% to 100% ethanol and from 50% to 0% water, and wherein further the loperamide hydrochloride is dissolved in said alcoholic solution at a level of from 0.001% to 5% by weight of the ethanol present in the alcoholic solution;
(b) granulating pharmaceutically acceptable carrier materials with the loperamide hydrochloride-containing alcoholic solution;
(c) drying the loperamide hydrochloride-containing granulates to remove essentially all of the ethanol; and
(d) compressing the dried granules into a unit dose form to a level of hardness of from 5sc to 20sc.
10. A solid oral dosage form of loperamide compound prepared according to the process of any of Claims 1-9 comprising:
(a) from 0.1% to 5% loperamide hydrochloride; and
(b) from 95% to 99.9% pharmaceutically acceptable carrier materials; and wherein further said composition comprises less than 2% of ethanol.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US565010 | 1983-12-20 | ||
US56501090A | 1990-08-09 | 1990-08-09 | |
PCT/US1991/005291 WO1992002223A1 (en) | 1990-08-09 | 1991-07-29 | Process for formulating a solid oral dosage form of loperamide compounds |
Publications (2)
Publication Number | Publication Date |
---|---|
AU8440091A true AU8440091A (en) | 1992-03-02 |
AU661972B2 AU661972B2 (en) | 1995-08-17 |
Family
ID=24256836
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU84400/91A Ceased AU661972B2 (en) | 1990-08-09 | 1991-07-29 | Process for formulating a solid oral dosage form of loperamide compounds |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP0542879A1 (en) |
JP (1) | JPH06500104A (en) |
AU (1) | AU661972B2 (en) |
CA (1) | CA2088273C (en) |
FI (1) | FI930536A (en) |
IE (1) | IE912815A1 (en) |
NZ (1) | NZ239308A (en) |
PT (1) | PT98612A (en) |
WO (1) | WO1992002223A1 (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005117834A1 (en) * | 2004-05-27 | 2005-12-15 | Janssen Pharmaceutica N.V. | Solid dispersions of a basic drug compound and a polymer containing acidic groups |
US10508373B2 (en) | 2016-05-13 | 2019-12-17 | Nike, Inc. | Embroidered article |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1332236C (en) * | 1985-10-11 | 1994-10-04 | Lourens Wals | ,--diaryl-4-aryl-4-hydroxy-1-piperidinebutanamide, n-oxides |
DE3906779A1 (en) * | 1989-03-03 | 1990-09-06 | Hoechst Ag | Compositions against animal parasites (parasites of animals) |
GB8908361D0 (en) * | 1989-04-13 | 1989-06-01 | Beecham Group Plc | Composition |
NZ233403A (en) * | 1989-04-28 | 1992-09-25 | Mcneil Ppc Inc | Simulated capsule-like medicament |
-
1991
- 1991-07-29 EP EP91915390A patent/EP0542879A1/en not_active Withdrawn
- 1991-07-29 CA CA002088273A patent/CA2088273C/en not_active Expired - Fee Related
- 1991-07-29 JP JP3514470A patent/JPH06500104A/en active Pending
- 1991-07-29 AU AU84400/91A patent/AU661972B2/en not_active Ceased
- 1991-07-29 WO PCT/US1991/005291 patent/WO1992002223A1/en not_active Application Discontinuation
- 1991-08-08 PT PT98612A patent/PT98612A/en not_active Application Discontinuation
- 1991-08-08 NZ NZ239308A patent/NZ239308A/en unknown
- 1991-08-08 IE IE281591A patent/IE912815A1/en unknown
-
1993
- 1993-02-08 FI FI930536A patent/FI930536A/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
PT98612A (en) | 1992-06-30 |
JPH06500104A (en) | 1994-01-06 |
WO1992002223A1 (en) | 1992-02-20 |
EP0542879A1 (en) | 1993-05-26 |
CA2088273C (en) | 1996-05-14 |
IE912815A1 (en) | 1992-02-12 |
FI930536A0 (en) | 1993-02-08 |
FI930536A (en) | 1993-02-08 |
AU661972B2 (en) | 1995-08-17 |
CA2088273A1 (en) | 1992-02-10 |
NZ239308A (en) | 1994-04-27 |
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