AU720146B2 - Pharmaceutical composition based on stabilized lipophilic matrices for the controlled release of active principles - Google Patents
Pharmaceutical composition based on stabilized lipophilic matrices for the controlled release of active principles Download PDFInfo
- Publication number
- AU720146B2 AU720146B2 AU19991/97A AU1999197A AU720146B2 AU 720146 B2 AU720146 B2 AU 720146B2 AU 19991/97 A AU19991/97 A AU 19991/97A AU 1999197 A AU1999197 A AU 1999197A AU 720146 B2 AU720146 B2 AU 720146B2
- Authority
- AU
- Australia
- Prior art keywords
- agents
- matrix
- pharmaceutical composition
- lipophilic
- stabilized
- 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.)
- Ceased
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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Abstract
Stabilised lipophilic matrix for controlled release of active agents. Also claimed is a pharmaceutical composition containing the matrix, preferably in the form of a capsule.
Description
I/UU/U 1 28/5/91 Regulation 3.2(2)
AUSTRALIA
Patents Act 1990
ORIGINAL
COMPLETE SPECIFICATION STANDARD PATENT Application Number: Lodged: Invention Title: PHARMACEUTICAL COMPOSITION BASED ON STABILIZED LIPOPHILIC MATRICES FOR THE CONTROLLED RELEASE OF ACTIVE
PRINCIPLES
The following statement is a full description of this invention, including the best method of performing it known to us The present invention relates to a novel lipophilic matrix for producing pharmaceutical compositions which allow the controlled release of active principles.
This novel composition includes a stabilised lipophilic matrix for the controlled release of active principles, in which the lipophilic power of the matrix is obtained by the use of fatty substances derived from polyglycosylated or fatty acid triglycerides, and the stabilisation of the lipophilic matrix is obtained by the use of cellulose ethers, the stabilising amount of the cellulose ether not exceeding 10% of the total mass of the formulation.
The production of pharmaceutical compositions which allow the controlled release of active principles has the essential aim of obtaining in man a uniform concentration of the active principle in the blood by levelling out of the peak generally obtained in the blood with immediate-release forms, and thereby not only of avoiding undesirable effects due to these peaks in the blood but also 15 of decreasing the number of daily intakes of the medicinal product, which makes it easier for the patient to adhere to the treatment.
Among the various sustained-release forms know, lipophilic matrices have been described in the literature. However, the main drawback of these lipophilic matrices is a change in the release kinetics of the active principle during ageing. Studies of stability of forms based on lipophilic matrices show an acceleration of the release kinetics of the active principle, thereby implying that it Si is impossible to obtain a determined expiry date for the pharmaceutical form under consideration. This change in the dissolution kinetics of the active principle is expressed by the modification of the internal state of the matrix. This transformation of the fatty excipient takes place at room temperature and may extend over several months.
Besides the fact that it is novel, the lipophilic matrix according to the invention makes it possible to solve the stability problem encountered with the other matrices described in the prior art. It combines, in an original manner, two different types of chemical families, making it possible to obtain complete stability of the pharmaceutical form throughout the period of storage of the medicinal product, as well as entirely controlled release of the active principle.
la The first family of compounds consists of fatty acid mono-, or di- or triglycerides or of saturated polyglycosylated mono-or di- or triglycerides obtained from hydrogenated plant oils and consisting of polyehtylene glycol esters and glycerides. One part of this family is known as G6lucire®. This family of excipients is usually used for the production of lipophilic matrices. These excipients are characterised by their melting point and by their HLB value (hydrophilic-lipophilic balance). The excipients used in the present invention are those for which the lipophilic power is large, that is to say those for which the HLB value is less than
S
SS
The second chemical family which allows stabilization of the dissolution kinetics consists of cellulose ethers such as methylhydroxypropylcellulose, methylcellulose, hydroxymethylcellulose and hydroxypropylcellulose. Stabilization of this matrix should moreover be obtained while retaining the lipophilic properties of the matrix. Accordingly, in the matrices according to the invention, it has been demonstrated that the percentage of cellulose derivative which allows the matrix to be stabilized should not exceed 15 of the total mass of the formulation. Thus, this matrix made lipophilic by the use of a triglyceride derivative is stabilized, surprisingly, by the addition of a cellulose derivative.
The lipophilic matrix according to the invention is thus composed as follows: one or more polyglycosylated or fatty acid triglyceride derivatives (fatty substances), one or more cellulose derivatives (stabilizers), one or more active principles, and, optionally, one or more excipients which may act as plasticizers, flavorings or sweeteners.
15 The lipophilic matrix according to the invention may advantageously be used to produce microspheres or microgranules which will be used for the manufacture of gelatin capsules, tablets, implants, gels, creams, transdermal or transmucous systems, or drinkable or injectable solutions. A preferred form is the production of gelatin capsules.
SAmong the active principles used in this pharmaceutical composition according to the 20 invention, mention may be made, in a non-limiting manner, of: antiinfectious agents such as penicillins, cephalosporins, cyclines, beta-lactamase inhibitors, aminosides, chinolones, nitroimidazoles, sulfamides or antibacterial agents, antihistamines, antiallergic agents, anesthetics, steroidal or non-steroidal antiinflammatory agents, analgesics of local or systemic action, antispasmodic agents, anticancer agents, diuretics, beta-blockers, antihypertensive agents, antiangina agents, antiarrhythmic agents, vasodilators, bradycardiac agents, calcium inhibitors, sedatives, cardiotonics, antifungal agents, antiulcer agents, veinotonic agents, vasculoprotective agents, antiischemic agents, antiemetic agents, anticoagulants, antithrombotic agents, immunosuppressants, immunomodulators, antiviral agents, antidiabetic agents, hypolipidemiating agents, antiobesity agents, anticonvulsive agents, hypnotic agents, antiparkinsonian agents, antimigraine agents, neuroleptic agents, anxiolytic agents, antidepressants, psychostimulants, memory enhancers, bronchodilators, antitussive agents, antisteoporotic agents, peptide hormones, steroids, enzymes, enzyme inhibitors, and melatoninergic agonists and antagonists.
The results obtained with these lipophilic matrices show that: on the one hand, there is no conversion of the fatty excipient as a function of the temperature (heat treatment), on the other hand, this stabilization is long-lasting. No modification was observed after several months of storage under the standard storage conditions defined by the international standards.
Thus, no treatment is necessary in order to obtain a stable matrix, this being an essential advantage at the industrial level and, likewise, a very considerable decrease in the production costs.
The lipophilic matrices according to the invention are obtained according to techniques which involve melting, spraying with hot or cold air ("spray-drying" or "spray-congealing"), hot or cold extrusion, spheronization or the technique which consists in ejecting a liquid through a nozzle provided with a number of orifices on which a vibration operation is applied ("prilling").
15 A preferred process for producing gelatin capsules is as follows: Sta-e I Melting of the fatty substance(s) in a melting pot.
Stage 2 Incorporation of one or more cellulose ethers into the molten mass of the fatty substance(s). Next, homogenization of the mixture using a suitable system.
Stage 3 Incorporation of the active principle and of the other excipients if need be.Next, homogenization of the mixture using a suitable system.
Stage 4 Filling of the gelatin capsules with the mixture obtained in Stage 3, maintained at temperature and homogenized continuously in order to ensure total reproducibility of the pharmaceutical form.
The gelatin capsules thus obtained are optionally subjected to a heat treatment.
The examples which follow illustrate the invention but do not limit it in any way.
EXAMPLE 1: Without addition of the stabilizing compound A sustained-release gelatin capsule is prepared using the formula given in the following table, according to the manufacturing process described in Stages 1, 3 and 4 above without addition of hydroxypropylmethylcellulose (HPMC), the stabilizer.
Name of the constituents Amounts (mg) Indapamide G61ucire® 50-02 295 Finished gelatin capulse containing 300 a The curves of in vitro dissolution before and after heat treatment are presented in the annex in Figure 1. An increase in the release kinetics of the active principle during the heat treatment is observed.
With addition of the stabilizing compound A sustained-release gelatin capsule is prepared using a formula identical to the previous one but with addition of the stabilizer, HPMC. The exact formula is given in the table below. The manufacturing process is that described in Stages 1 to 4 above.
Name of the constituents Amounts (mg) Indapamide G61ucire® 50/02 295 Hydroxypropylmethylcellulose Finished gelatin capsule containing 330 The curves of in vitro dissolution before and after heat treatment are presented in the annex in Figure 2. No modification in the release kinetics of the active principle during the heat treatment is observed.
EXAMPLE 2: Without addition of the stabilizing compound A sustained-release gelatin capsule is prepared using the formula given in the following table, according to the manufacturing process described in Stages 1, 3 and 4 above without addition of hydroxypropylmethylcellulose (HPMC), the stabilizer.
Name of the constituents Amounts (mg) Fenspiride 200 G6lucire® 63-03 47 G61ucire® 63-05 188 Finished gelatin capsule containing 435 oo 1* o o* *o The curves of in vitro dissolution before and after heat treatment are presented in the annex in Figure 3. An increase in the release kinetics of the active principle during the heat treatment is observed.
With addition of the stabilizing compound A sustained-release gelatin capsule is prepared using a formula identical to the previous one but with addition of the stabilizer, HPMC. The exact formula is given in the table below. The manufacturing process is that described in Stages 1 to 4 above.
Name of the constituents Amounts (mg) Fenspiride 200 G61ucire® 63-03 47 G6lucire® 63-05 188 Hydroxypropylmethylcellulose Finished gelatin capsule containing 480 The curves of in vitro dissolution before and after heat treatment are presented in the annex in Figure 4. No modification in the release kinetics of the active principle during the heat treatment is observed.
-6- EXAMPLE 3 9 EXAMPLE 4 EXAMPLE 5 EXAMPLE 6 Name of the constituents Amounts (mg) Gliclazide G6lucire® 50-02 220 Hydroxypropylmethylcellulose Finished gelatin capsule containing 330 Name of the constituents Amounts (mg) Tianeptine Akoline MCM Akomed R 180 Hydroxypropylcellulose Finished gelatin capsule containing 245 Name of the constituents Amounts (mg) Amineptine 200 G61ucire® 50-02 200 Hydroxypropylmethylcellulose Finished gelatin capsule containing 440 Name of the constituents Amounts (mg) Dexfenfluramine chlorhydrate G61ucire® 50-02 120 Hydroxypropylmethylcellulose Finished gelatin capsule containing 165 EXAMPLE 7 Study of the stability of the matrices under the storage conditions defined by ICH (International Conference on Harmonization) international standards.
The formulations used for this study are those described in Example 2. The curves of in vitro dissolution of gelatin capsules containing or not containing hydroxypropylmethylcellulose (HPMC), obtained after storage for one month under three different conditions, are presented in the annex in Figures 5 and 6. They show that without HPMC, the matrix is unstable, whereas, when these matrices contain HPMC, they are stable for one month under the three temperature and relative humidity conditions tested.
EXAMPLE 8 Study of long-term stability of the matrices according to the invention The formulations used are those described in Example 2. The curves of in vitro dissolution of the gelatin capsules tested, obtained after storage for three months at 30 0 C under 60 relative humidity, are presented in the annex in Figures 7 and 8. These curves shown that after three months, the gelatin capsules containing the matrices according to the invention are entirely stable, whereas those not containing HPMC are highly unstable and are therefore unusable and unsuitable for marketing.
°oo .5 *o*oo
Claims (9)
1- A stabilized lipophilic matrix for the controlled release of active principles, in which the lipophilic power of the matrix is obtained by the use of fatty substances derived from polyglycosylated or fatty acid triglycerides which fatty substances have an HLB coefficient of less than 10, and the stabilization of the lipophilic matrix is obtained by the use of cellulose ethers, the stabilizing amount of the cellulose ether not exceeding 10 of the total mass of the formulation.
2- The stabilized lipophilic matrix as claimed in claim 1, in which the fatty substances consist essentially of one or more saturated polyglycosylated mono-, di- or triglycerides obtained from hydrogenated plant oils and consisting of polyethylene glycol esters and glycerides.
3- The stabilized lipophilic matrix as claimed in claim 1, in which matrix the stabilizer is hydroxypropylmethylcellulose.
4-The stabilized lipophilic matrix as claimed in any one of claims 1 to 3, which matrix S. contains one or more active principles and pharmaceutically acceptable excipients.
5- The stabilized lipophilic matrix as claimed in claim 4, in which matrix the active principle or principles are chosen from antiinfectious agents such as penicillins, cephalosporins, cyclines, beta-lactamase inhibitors, aminosides, chinolones, nitroimidazoles, sulfamides or antibacterial agents, antihistamines, antiallergic agents, anesthetics, steroidal or non- steroidal antiinflammatory agents, analgesics of local or systemic action, antispasmodic '2C agents, anticancer agents, diuretics, beta-blockers, antihypertensive agents, antiangina agents, antiarrhythmic agents, vasodilators, bradycardiac agents, calcium inhibitors, sedatives, cardiotonics, antifungal agents, antiulcer agents, veinotonic agents, vasculoprotective agents, antiischemic agents, antiemetic agents, anticoagulants, antithrombotic agents, immunosuppressants, immunomodulators, antiviral agents, antidiabetic agents, hypolipidemiating agents, antiobesity agents, anticonvulsive agents, hypnotic agents, antiparkinsonian agents, antimigraine agents, neuroleptic agents, anxiolytic agents, antidepressants, psychostimulants, memory enhancers, bronchodilators, -9- antitussive agents, antisteoporotic agents, peptide hormones, steroids, enzymes, enzyme inhibitors, and melatoninergic agonists and antagonists.
6- A pharmaceutical composition containing a lipophilic matrix as claimed in any one of claims 1 to
7- The pharmaceutical composition as claimed in claim 6, which is in the form of gelatin capsules.
8- A process for obtaining the lipophilic matrix as claimed in any one of claims 4 or 5, which process involves the following steps: Stage A: melting of one or more fatty substance(s) in a melting pot, Stage B incorporation of the stabilizer into the molten mass obtained in the above stage, followed by homogenization, Stage C incorporation of one or more active principle(s) and the excipients, followed by homogenization.
9- The process for producing the pharmaceutical composition as claimed in claim 7, in which process the gelatin capsules are filled with the aid of the stabilized lipophilic matrix obtained as claimed in claim 8, while maintaining the temperature and homogenizing in order to obtain total reproducibility of the pharmaceutical composition. DATED this 30th day of March, 2000 ADIR ET COMPAGNIE WATERMARK PATENT TRADE MARK ATTORNEYS 290 BURWOOD ROAD HAWTHORN VICTORIA 3122 AUSTRALIA P2926AU00 IAS/CLR/SIG
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR96/05606 | 1996-05-06 | ||
FR9605606A FR2748209B1 (en) | 1996-05-06 | 1996-05-06 | PHARMACEUTICAL COMPOSITION BASED ON STABILIZED LIPOPHILIC MATRICES FOR THE CONTROLLED RELEASE OF ACTIVE INGREDIENTS |
Publications (2)
Publication Number | Publication Date |
---|---|
AU1999197A AU1999197A (en) | 1997-11-13 |
AU720146B2 true AU720146B2 (en) | 2000-05-25 |
Family
ID=9491845
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU19991/97A Ceased AU720146B2 (en) | 1996-05-06 | 1997-05-05 | Pharmaceutical composition based on stabilized lipophilic matrices for the controlled release of active principles |
Country Status (16)
Country | Link |
---|---|
EP (1) | EP0806202B1 (en) |
JP (1) | JP3983339B2 (en) |
CN (1) | CN1171270A (en) |
AT (1) | ATE212543T1 (en) |
AU (1) | AU720146B2 (en) |
CA (1) | CA2204475C (en) |
DE (1) | DE69710121T2 (en) |
DK (1) | DK0806202T3 (en) |
ES (1) | ES2170922T3 (en) |
FR (1) | FR2748209B1 (en) |
HU (1) | HU222045B1 (en) |
NO (1) | NO318227B1 (en) |
NZ (1) | NZ314740A (en) |
PL (1) | PL190562B1 (en) |
PT (1) | PT806202E (en) |
ZA (1) | ZA973836B (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE1011363A3 (en) * | 1997-09-11 | 1999-08-03 | Smb Technology | Capsules semi-solid matrix autoemulsionnables a prolonged action. |
FR2782006B1 (en) | 1998-08-07 | 2002-04-19 | Gattefosse Ets Sa | SUSTAINED RELEASE COMPOSITION CAPABLE OF FORMING MICRO-EMULSION |
DE10161078A1 (en) * | 2001-12-12 | 2003-08-28 | Achim Goepferich | Matrices for the stabilization and controlled release of problem drugs |
EP1660047B1 (en) | 2003-08-13 | 2013-11-27 | Biocon Limited | Micro-particle fatty acid salt solid dosage formulations for therapeutic agents |
GB0324574D0 (en) * | 2003-10-21 | 2003-11-26 | Glaxo Group Ltd | Novel compositions |
US8333989B2 (en) | 2005-10-26 | 2012-12-18 | Banner Pharmacaps, Inc. | Hydrophilic vehicle-based dual controlled release matrix system |
CA2627351C (en) * | 2005-10-26 | 2012-05-01 | Banner Pharmacaps, Inc. | Lipophilic vehicle-based dual controlled release matrix system |
US8198268B2 (en) | 2008-10-31 | 2012-06-12 | Janssen Biotech, Inc. | Tianeptine sulfate salt forms and methods of making and using the same |
JP2013119540A (en) * | 2011-12-08 | 2013-06-17 | Nipro Corp | Solid pharmaceutical composition and method for producing the same |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0222614A2 (en) * | 1985-11-12 | 1987-05-20 | Eli Lilly And Company | Orally administerable sustained release pharmaceutical formulations |
AU2256495A (en) * | 1994-04-18 | 1995-11-10 | Basf Aktiengesellschaft | Sustained-release matrix pellets and method for preparing them |
AU4380896A (en) * | 1995-01-10 | 1996-07-31 | Galephar P.R. Inc. | Pharmaceutical composition containing fenofibrate and polyglycolized glycerides |
-
1996
- 1996-05-06 FR FR9605606A patent/FR2748209B1/en not_active Expired - Fee Related
-
1997
- 1997-05-02 AT AT97400990T patent/ATE212543T1/en active
- 1997-05-02 DE DE69710121T patent/DE69710121T2/en not_active Expired - Lifetime
- 1997-05-02 EP EP97400990A patent/EP0806202B1/en not_active Expired - Lifetime
- 1997-05-02 PT PT97400990T patent/PT806202E/en unknown
- 1997-05-02 ES ES97400990T patent/ES2170922T3/en not_active Expired - Lifetime
- 1997-05-02 DK DK97400990T patent/DK0806202T3/en active
- 1997-05-05 NZ NZ314740A patent/NZ314740A/en not_active IP Right Cessation
- 1997-05-05 PL PL97319808A patent/PL190562B1/en not_active IP Right Cessation
- 1997-05-05 CA CA002204475A patent/CA2204475C/en not_active Expired - Fee Related
- 1997-05-05 NO NO19972068A patent/NO318227B1/en not_active IP Right Cessation
- 1997-05-05 HU HU9700842A patent/HU222045B1/en not_active IP Right Cessation
- 1997-05-05 AU AU19991/97A patent/AU720146B2/en not_active Ceased
- 1997-05-05 ZA ZA9703836A patent/ZA973836B/en unknown
- 1997-05-05 CN CN97109780A patent/CN1171270A/en active Pending
- 1997-05-06 JP JP11554897A patent/JP3983339B2/en not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0222614A2 (en) * | 1985-11-12 | 1987-05-20 | Eli Lilly And Company | Orally administerable sustained release pharmaceutical formulations |
AU2256495A (en) * | 1994-04-18 | 1995-11-10 | Basf Aktiengesellschaft | Sustained-release matrix pellets and method for preparing them |
AU4380896A (en) * | 1995-01-10 | 1996-07-31 | Galephar P.R. Inc. | Pharmaceutical composition containing fenofibrate and polyglycolized glycerides |
Also Published As
Publication number | Publication date |
---|---|
AU1999197A (en) | 1997-11-13 |
HU9700842D0 (en) | 1997-06-30 |
NZ314740A (en) | 1998-11-25 |
EP0806202B1 (en) | 2002-01-30 |
NO318227B1 (en) | 2005-02-21 |
ES2170922T3 (en) | 2002-08-16 |
ZA973836B (en) | 1997-12-02 |
DK0806202T3 (en) | 2002-05-06 |
DE69710121D1 (en) | 2002-03-14 |
CA2204475A1 (en) | 1997-11-06 |
NO972068L (en) | 1997-11-07 |
PL190562B1 (en) | 2005-12-30 |
NO972068D0 (en) | 1997-05-05 |
ATE212543T1 (en) | 2002-02-15 |
CA2204475C (en) | 2002-12-03 |
PL319808A1 (en) | 1997-11-10 |
PT806202E (en) | 2002-06-28 |
DE69710121T2 (en) | 2002-11-28 |
JP3983339B2 (en) | 2007-09-26 |
HU222045B1 (en) | 2003-04-28 |
EP0806202A1 (en) | 1997-11-12 |
FR2748209A1 (en) | 1997-11-07 |
FR2748209B1 (en) | 1998-06-05 |
CN1171270A (en) | 1998-01-28 |
HUP9700842A1 (en) | 1998-08-28 |
JPH1045629A (en) | 1998-02-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0249587B1 (en) | Solid pharmaceutical preparation with extended release and process for its preparation | |
US6491950B1 (en) | Controlled release pharmaceutical composition | |
US6524615B2 (en) | Controlled release pharmaceutical composition | |
DD144667A5 (en) | PROCESS FOR PREPARING 2,6-DIMETHYL-4-PHENYL-1,4-DIHYDROPYRIDINE-3,5-DICARBONE ACID DIEDESTS | |
IL139113A0 (en) | Pharmaceutical compositions capable of being gelled | |
EP0702953A2 (en) | Dosage form comprising alpha-lipoic acid or solid salts thereof with improved bioavailability | |
AU720146B2 (en) | Pharmaceutical composition based on stabilized lipophilic matrices for the controlled release of active principles | |
GB2196852A (en) | Sustained release composition | |
JP2013189463A (en) | Formulation | |
AU637549B1 (en) | Solid formulation containing amide derivative and method of manufacturing the formulation | |
EP1885342B1 (en) | Crystallization inhibitor and its use in gelatin capsules | |
US5175002A (en) | Amantadine hydrochloride syspension with enhanced dissolution characteristics for use in soft gelatin capsules | |
SK7342000A3 (en) | Formulations comprising dissolved paroxetine | |
DE3602577A1 (en) | PHARMACEUTICAL COMPOSITIONS CONTAINING 9,10-DIHYDROGENATED ERGOTAL CALOIDS | |
EP1663160B1 (en) | Melt-formulated, multi-particulate oral dosage form | |
EP0326103B1 (en) | Pharmaceutical composition for 4-aroylimidazol-2-ones | |
RU2160107C2 (en) | Tablet, capsule, or granule containing desogestrel and method of preparation thereof | |
GB2394895A (en) | Proton pump inhibitor composition in paste form | |
JPH07228531A (en) | Nicorandil capsule | |
SI8710407A (en) | Process for obtaining solid pharmaceutical preparation with extended release of active compound | |
JPH08325148A (en) | Pharmaceutical composition containing dinoreburnamenine derivative |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FGA | Letters patent sealed or granted (standard patent) | ||
PC | Assignment registered |
Owner name: LES LABORATOIRES SERVIER Free format text: FORMER OWNER WAS: ADIR ET COMPAGNIE |