IE57164B1 - Oral compositions containing sulpiride - Google Patents
Oral compositions containing sulpirideInfo
- Publication number
- IE57164B1 IE57164B1 IE817/84A IE81784A IE57164B1 IE 57164 B1 IE57164 B1 IE 57164B1 IE 817/84 A IE817/84 A IE 817/84A IE 81784 A IE81784 A IE 81784A IE 57164 B1 IE57164 B1 IE 57164B1
- Authority
- IE
- Ireland
- Prior art keywords
- sulpiride
- copolymer
- weight
- composition
- parts
- Prior art date
Links
- BGRJTUBHPOOWDU-NSHDSACASA-N (S)-(-)-sulpiride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-NSHDSACASA-N 0.000 title claims abstract description 33
- 229960004940 sulpiride Drugs 0.000 title claims abstract description 33
- 239000000203 mixture Substances 0.000 title claims abstract description 15
- 230000007935 neutral effect Effects 0.000 claims abstract description 10
- 230000002496 gastric effect Effects 0.000 claims abstract description 7
- 230000000968 intestinal effect Effects 0.000 claims abstract description 7
- 229920000642 polymer Polymers 0.000 claims abstract description 7
- 229920001577 copolymer Polymers 0.000 claims description 16
- 238000000338 in vitro Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 5
- 230000001476 alcoholic effect Effects 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- 235000013681 dietary sucrose Nutrition 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 229960004793 sucrose Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000454 talc Substances 0.000 claims description 3
- 229910052623 talc Inorganic materials 0.000 claims description 3
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 2
- 150000002734 metacrylic acid derivatives Chemical class 0.000 claims 2
- NTASFODDPBHBAM-UHFFFAOYSA-N 1-hydroxyethylazanium;chloride Chemical compound [Cl-].CC([NH3+])O NTASFODDPBHBAM-UHFFFAOYSA-N 0.000 claims 1
- 125000005395 methacrylic acid group Chemical group 0.000 claims 1
- 239000002775 capsule Substances 0.000 abstract description 12
- 238000010521 absorption reaction Methods 0.000 abstract description 8
- 239000000463 material Substances 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 4
- 229920003155 Eudragit® RL 100 Polymers 0.000 description 3
- 239000007891 compressed tablet Substances 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 229920003139 Eudragit® L 100 Polymers 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- -1 2-methyl-l-oxo-2-propenyl Chemical group 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
Orally administrable compositions containing sulpiride in microgranules formed by a neutral grain material and having an outer layer of a microporous polymer. The use of such compositions, which are made by projecting a solution of sulpiride onto the neutral grains and then applying the polymer, makes it possible to achieve absorption of sulpiride double that which is obtained with conventional capsules, while retaining a slightly greater period of action and considerably reducing the differences in absorption from one subject to another. The rate of liberation of sulpiride in artificial gastric and intestinal media is specified.
Description
SOCIETE D*ETUDES SCIENTIFIQDES ET INDDSTRIELLES DE L*ILE-DE-FRANCE, A COMPANY ORGANISED UNDER THE LANS OF FRANCE, OF 46, BOULEVARD DE LATODR-MADBODRG, 75340 PARIS CEDEX 07, FRANCE.
Price OOp The present invention concerns orally administrate pharmaceutical forms of Sulpiride and their preparation.
Sulpiride, viz. N-(l-ethyl-2-pyrroIidinyI)methyl-2-methoxy-5sulphamoylbenzamide, is known as an excellent neuroleptic disinhibitor, having as its main therapeutic indication the treatment of acute and chronic psychoses. Its characteristics and properties are described in particular in French Patents Nos. 1 472 025, 4879 M and 5916 M.
Available orally active medicaments containing Sulpiride include compressed tablets, capsules and drinkable aqueous solutions, but as set out below these forms require a plurality of daily doses and sometimes are incompletely absorbed by the organism. Consequently, attempts have been made to modify the form of composition to substantially enhance acceptance by patients while reducing the number of daily doses required.
The plasmatic half-life of the active ingredient Sulpiride is about eight and a half hours. It therefore seems possible to produce a form of the product enabling the average daily dose to be reduced to two capsules or tablets each containing 100 mg of Sulpiride, one being taken in the morning and. one in the evening, or even to one capsule or one tablet containing 200 mg of Sulpiride.
For that purpose, microgranules having a prolonged effect were produced, in accordance with the conventional processes described in particular in French Patents Nos. 2 315 915 and 2 453 642. Neutral grains about 0.50 mm in diameter and comprising 25% of starch and 75% of saccharose were used. The Sulpiride was directed onto them in a turbine process, by means of an alcoholic solution of polyvinylpyrrolidone, and then conventional coating fibres were applied, based on polymer of the shellac, methacrylate or ethylcellulose type, so as to produce pre-established standard kinetics for liberation of the Sulpiride in vitro in gastric and intestinal media, in accordance with the following specifications: 1st liour : liberation less than 40%. 4th hour : liberation less than 75%.
Sth hour : liberation more than 75%.
Liberation at the first hour is effected in an artificial gastric juice having a pH of 1.3, and at the fourth and at eighth hours in artificial intestinal juices having pHs of 4.5 and 7 respectively. The operating conditions for studying the liberation of the active ingredient are known and described in the above-mentioned patents.
Those microgranules were then used to produce capsules and compressed tablets giving a dosage of 100 mg; the absorption of the Sulpiride was studied by determining the plasmatic amounts of Sulpiride in circulation by means of radio-immunology; and the results obtained were compared with those obtained from the capsule form at present on the market.
The results are set out in Table A below and show that, with the two formulations of microgranules used (form I and form ID, the loss in the amount of active ingredient circulating is too substantial with respect to that with the normal form of capsules (form IV) to make it possible to provide an effective prolonged-effect medicament.
Forms I and II used had the following kinetics in respect of liberation in vitro in artificial media: Liberation at the first hour form I form II in a medium of pH 1J Liberation at the fourth hour 20.0% 29.2% in a medium of pH 4.5 Liberation at the eighth hour 68.6% 58.4% in a medium of pH 7 90.8% 98.2% After studying a series of prolonged-effect formulations which all gave results incompatible with producing a good properly absorbed oral form, the idea was conceived of retaining the microgranule form (substantially spherical grains of a diameter of between 0.2 and 2 mm), which in practice should permit of better absorption of the active ingredient than a conventional powder of the capsule or the tablet, while having kinetics in respect of liberation in vitro much closer to those forms, that is to say, liberating substantially 90% of the active ingredient after one hour in an artificial gastric medium having a pH of 1.3.
Surprisingly, the results of tlie microgranules using those in vitro kinetics showed that, in dependence on the comparative plasmatic proportions, the form ΠΙ formed by microgranuies put into capsule form with a dosage of 100 mg makes it possible to achieve a degree of absorption double that obtained with the conventional capsules of Sulpiride (form IV), while retaining a slightly greater period of action and substantially reducing the differences in absorption from one subject to another. The aboveindicated improvement in the absorption of Sulpiride, both in the quantitative respect and in respect of its regularity, permits of a reduction in the doses used and the number of daily doses to be taken.
Those results are set out in Table A, and also in Figure 1, showing the 10 variation in the plasmatic proportions in circulation between 0 and 32 hours, expressed in ng/ml of Sulpiride, by comparison between form ΠΪ and form IV.
Complementary experiments, in the course of which the external coatings of the microogranules according to the invention are varied, made it possible to acertain that the preferential form with improved absorption of the Sulpiride should substantially correspond to the following analytical conditions in respect of liberation in vitro: minutes : 30 minutes : liberation between 35 and gastric medium of pH 1.3 liberation between 60 and 50% in an artificial artificial 75% in an 20 60 minutes : gastric medium of pH 1.3 liberation between 80 and intestinal medium of pH 4.5. 95% in an artificial Moreover, an overall liberation rate of higher than 90% is noted in an artificial intestinal medium of pH 6.9.
In accordance with the present invention, there are provided pharmaceutical compositions for oral administration containing Sulpiride and in the form of microgranuies having a diameter of from 0.2 to 2 mm, constituted by a neutral core comprising a mixture of saccharose and starch, a layer of Sulpiride and polyvinylpyrrolidone, and an outer layer comprising a copolymer A of methacrylic acid and methyl methacrylate with a copolymer B of ethyl acrylate, methyl methacrylate and Ν,Ν,Ν-trimethyi 2[(2-methyl-l-oxo-2-propenyl) oxy] ethanaminium chloride, coated with a layer of the said copolymer B, in which the liberation in vitro of the Sulpiride in artificial gastric and intestinal media is substantially as set forth immediately above. Copolymers A and B are preferably those sold under the trade marks Eudragit L - 100 and Eudragit RL - 100, respectively.
The production formula for 2500 capsules with a dosage of 100 mg, of form ΙΠ, and the process for* their manufacture is set out below by way of example. 250 g of Sulpiride in a 20% ethanolic solution of polyvinylpyrrolidone 5 is applied by a turbine process to 50 g of neutral grains substantially 0.50 mm in diameter and comprising about 25% of starch and 75% of saccharose.
After drying and sieving, outside layers are applied, comprising the * said copolymers A and B, preferably those marketed under the registered 10 trade mark Eudragit by Rohm and Haas in alcoholic solutions in proportions of 4 parts by weight of Copolymer A (preferably Eudragit L - 100) for 1 part by weight of Copolymer B (preferably Eudragit RL - 100).
Drying is then effected with small proportions of talc until microgranules are produced, which liberate substantially 100% Sulpiride in an hour in accordance with the analytical conditions defined above.
Drying is then effected in a drying oven at 37°C for about two days, and then the outside layer is completed by projecting 90 g of a 13.5% ethanolic solution of Copolymer B (preferably Eudragit RL - 100). The titre found is about 730 mg of active ingredient per gram of microgranules.
The microgranules produced in that way comply with the standards in respect of in vitro liberation as set out above, as representative of the novel forms of Sulpiride in accordance with the invention.
Their accelerated and natural stabilities are found to be excellent, without the appearance of potential toxicity.
They may be used in the form of capsules, compressed tablets or suspensions in neutral media.
It will be appreciated that variations may be introduced, in particular with regard to the proportions of the excipients and the active ingredient, the composition of the neutral grains, and the nature of the polymers forming the outer layers.
In the foregoing description, parts and percentages are by weight unless otherwise stated.
TABLE A Kinetics parameters Form 1 Form II Form XII Form IV Mean maximum concentration tOnax) in ng/ml - 40 βθ - 45 315 - 65 150 - 60 Time corresponding to mean Qnax Mean (Thax) in hours curve ί 1.50 3.90 - 1.40 3.30 - 1.30 3.20 - 1.30 Area under the 0-8 hours in ng/ml h 340 - 75 365 - 80 1280 -230 715 -320 observed (AUC) 0-24 hours in ng/ml h 720 - 190 780 i 200 2970 - 400 1565 - 430
Claims (9)
1. A pharmaceutical composition for oral administration containing Sulpiride and in the form of microgranules having a diameter of from 0.2 to 2 mm, constituted by a neutral core comprising a mixture of saccharose and
2. A composition as claimed in Claim 1, in which the mixture of methacrylate polymers comprises
3. To 4 parts by weight of methacrylates of the said Copolymer A and 0.5 to 2 parts by weight of methacrylates of the said Copolymer B. 20 A composition as claimed in Claim 1 or 2, in which the layer containing the Sulpiride applied to the neutral grain comprises from 0.5 to 5% by weight of polyvinylpyrrolidone,
4. A composition as claimed in a preceding claim, in which the layer containing the Sulpiride contains small proportions of talc. 25 5. A process for preparing a ccnpositicn as claimed in any preceding claim, comprising projecting in a turbine process about 70 parts by weight of Sulpiride in solution onto 20 parts by weight of neutral grains, drying and sifting the microgranules, ^nd applying a solution of the desired polymers to form the outer layer in quantity so as to adjust the Sulpiride in vitro 30 liberation kinetics in accordance with the said characteristic values. I
5. Is effected with talc and then in a drying oven at 37°C and the outer layer is completed by means of an alcoholic solution of the said Copolymer B. 5 starch, a layer of Sulpiride and polyvinylpyrrolidone, and an outer layer comprising a copolymer A of methacrylic acid and methyl methacrylate t with a copolymer B of ethyl acrylate, methyl methacrylate and Ν,Ν,Νtrimethyl 2- [(2-methyl-l-oxo-2-propenyI) oxyl ethanaminium chloride, . coated with a layer of the said copolymer B, in which the liberation in vitro 10 of the Sulpiride in artificial gastric and intestinal media is substantially as follows: after 15 minutes, 35 to 50% in a medium of a pH 1.3; after 30 minutes, 60 to 75% in a medium of pH 1.3; after 60 minutes, 80 to 95% in a medium of pH 4.5; 15 after more than 2 hours, more than 90% in a medium of pH 6.9.
6. A process as claimed in Claim 5,in which the Sulpiride is applied in an alcoholic solution of polyvinylpyrrolidone, an alcoholic solution of methacrylic polymers comprising about 4 parts by weight of the said Copolymer A and 1 part by weight of the said Copolymer B is applied, drying
7. A pharmaceutical composition according to claim 1, substantially as hereinbefore described. - s o.
8. A process according to claim 5 for preparing a )0 composition, substantially as hereinbefore described. ι
9. A composition whenever-prepared by a process f claimed in any one of claims 5, 6 or 8.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8320635A FR2556964A1 (en) | 1983-12-23 | 1983-12-23 | NEW GALENIC FORMS OF SULPIRIDE USED ORALALLY |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE840817L IE840817L (en) | 1985-06-23 |
| IE57164B1 true IE57164B1 (en) | 1992-05-20 |
Family
ID=9295477
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE817/84A IE57164B1 (en) | 1983-12-23 | 1984-04-02 | Oral compositions containing sulpiride |
Country Status (38)
| Country | Link |
|---|---|
| EP (1) | EP0147244A1 (en) |
| JP (1) | JPS60139616A (en) |
| KR (1) | KR910004570B1 (en) |
| AR (1) | AR231398A1 (en) |
| AU (1) | AU569516B2 (en) |
| BE (1) | BE899331A (en) |
| BG (1) | BG49707A3 (en) |
| CH (1) | CH659386A5 (en) |
| CZ (1) | CZ262984A3 (en) |
| DD (1) | DD220782A5 (en) |
| DE (1) | DE3412868A1 (en) |
| DK (1) | DK165729C (en) |
| ES (1) | ES8502332A1 (en) |
| FI (1) | FI82603C (en) |
| FR (1) | FR2556964A1 (en) |
| GB (1) | GB2151920B (en) |
| GR (1) | GR79584B (en) |
| HU (1) | HU190924B (en) |
| IE (1) | IE57164B1 (en) |
| IL (1) | IL71470A (en) |
| IN (1) | IN160415B (en) |
| IS (1) | IS1364B6 (en) |
| IT (1) | IT1177655B (en) |
| LU (1) | LU85290A1 (en) |
| MA (1) | MA20088A1 (en) |
| MX (1) | MX7715E (en) |
| NO (1) | NO169575C (en) |
| NZ (1) | NZ207753A (en) |
| OA (1) | OA07700A (en) |
| PH (1) | PH21938A (en) |
| PL (1) | PL144356B1 (en) |
| PT (1) | PT78382B (en) |
| RO (1) | RO89437A (en) |
| SU (1) | SU1478993A3 (en) |
| YU (1) | YU44762B (en) |
| ZA (1) | ZA842573B (en) |
| ZM (1) | ZM2084A1 (en) |
| ZW (1) | ZW6084A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8414220D0 (en) * | 1984-06-04 | 1984-07-11 | Sterwin Ag | Medicaments in unit dose form |
| DE3678643D1 (en) * | 1985-08-16 | 1991-05-16 | Procter & Gamble | PARTICLES WITH CONSTANT RELEASE OF ACTIVE SUBSTANCES. |
| US4853229A (en) * | 1987-10-26 | 1989-08-01 | Alza Corporation | Method for adminstering tiny pills |
| JPH0791184B2 (en) * | 1988-03-31 | 1995-10-04 | 田辺製薬株式会社 | Controlled release formulation and process for producing the same |
| GB8903328D0 (en) * | 1989-02-14 | 1989-04-05 | Ethical Pharma Ltd | Nifedipine-containing pharmaceutical compositions and process for the preparation thereof |
| FR2762213B1 (en) * | 1997-04-18 | 1999-05-14 | Synthelabo | PHARMACEUTICAL COMPOSITION WITH GASTRIC RETENTION |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3342826A (en) * | 1964-01-13 | 1967-09-19 | Ile De France | Heterocyclic aminoalkyl benzamides |
| FR2313915A1 (en) * | 1976-01-26 | 1977-01-07 | Corneille Gilbert | Sustained release vincamine microcapsules - with inert core, vincamine (deriv.) intermediate layer and microporous outer coating |
| US4285665A (en) * | 1978-05-08 | 1981-08-25 | Johnson, Matthey & Co., Limited | Engines |
| FR2453639A1 (en) * | 1979-04-09 | 1980-11-07 | Sanofi Sa | NAFTIDROFURYL-BASED IMMEDIATE-DELAYED RELEASE DRUG COMPOSITION |
| FR2453642A1 (en) * | 1979-04-12 | 1980-11-07 | Sanofi Sa | Controlled release of ergo-toxin methane sulphonate - from micro-granules coated with anionic and cationic methacrylic! polymers and a plasticiser |
| FR2454804B1 (en) * | 1979-04-26 | 1986-11-21 | Sanofi Sa | DIHYDROERGOTOXIN-BASED MEDICINAL PRODUCT AND PROCESS FOR PREPARING THE SAME |
| FR2470599A1 (en) * | 1979-12-07 | 1981-06-12 | Panoz Donald | IMPROVEMENTS IN PROCESSES FOR THE PREPARATION OF GALENIC SHAPES WITH DELAYED ACTION AND PROGRAMMED RELEASE AND GALENIC FORMS OF MEDICAMENTS THUS OBTAINED |
| SE8003805L (en) * | 1980-05-21 | 1981-11-22 | Haessle Ab | A PHARMACEUTICAL PREPARATION WITH IMPROVED EMISSION PROPERTY |
| JPS5753326A (en) * | 1980-09-17 | 1982-03-30 | Dainippon Printing Co Ltd | Manufacture of biaxially stretching blow molded vessel of saturated polyester |
| FR2492661A1 (en) * | 1980-10-28 | 1982-04-30 | Laruelle Claude | NOVEL GALENIC FORM OF ADMINISTRATION OF METOCLOPRAMIDE, ITS PREPARATION METHOD AND MEDICINAL PRODUCT COMPRISING THIS NOVEL FORM |
| FR2494112B1 (en) * | 1980-11-19 | 1986-01-10 | Laruelle Claude | |
| FR2534139B1 (en) * | 1982-10-07 | 1986-08-29 | Laruelle Claude | NOVEL GALENIC FORM OF SULPIRIDE, METHOD FOR PREPARING SAME, AND MEDICINAL PRODUCT COMPRISING THIS NEW FORM |
-
1983
- 1983-12-23 FR FR8320635A patent/FR2556964A1/en not_active Withdrawn
-
1984
- 1984-03-30 IS IS2900A patent/IS1364B6/en unknown
- 1984-04-02 IE IE817/84A patent/IE57164B1/en not_active IP Right Cessation
- 1984-04-04 MA MA20309A patent/MA20088A1/en unknown
- 1984-04-04 EP EP84400661A patent/EP0147244A1/en not_active Withdrawn
- 1984-04-05 BE BE1/10992A patent/BE899331A/en not_active IP Right Cessation
- 1984-04-05 DE DE19843412868 patent/DE3412868A1/en not_active Withdrawn
- 1984-04-05 CZ CS842629A patent/CZ262984A3/en unknown
- 1984-04-05 NZ NZ207753A patent/NZ207753A/en unknown
- 1984-04-05 ZA ZA842573A patent/ZA842573B/en unknown
- 1984-04-06 JP JP59069883A patent/JPS60139616A/en active Granted
- 1984-04-06 LU LU85290A patent/LU85290A1/en unknown
- 1984-04-06 FI FI841376A patent/FI82603C/en not_active IP Right Cessation
- 1984-04-06 PH PH30510A patent/PH21938A/en unknown
- 1984-04-06 NO NO841367A patent/NO169575C/en unknown
- 1984-04-06 YU YU640/84A patent/YU44762B/en unknown
- 1984-04-06 OA OA58273A patent/OA07700A/en unknown
- 1984-04-06 HU HU841362A patent/HU190924B/en not_active IP Right Cessation
- 1984-04-06 DD DD84261741A patent/DD220782A5/en not_active IP Right Cessation
- 1984-04-06 AR AR296218A patent/AR231398A1/en active
- 1984-04-06 IN IN242/MAS/84A patent/IN160415B/en unknown
- 1984-04-06 GR GR74337A patent/GR79584B/el unknown
- 1984-04-06 PL PL1984247098A patent/PL144356B1/en unknown
- 1984-04-06 GB GB08408978A patent/GB2151920B/en not_active Expired
- 1984-04-06 PT PT78382A patent/PT78382B/en not_active IP Right Cessation
- 1984-04-06 BG BG064985A patent/BG49707A3/en unknown
- 1984-04-06 IT IT48001/84A patent/IT1177655B/en active
- 1984-04-06 CH CH1755/84A patent/CH659386A5/en not_active IP Right Cessation
- 1984-04-06 SU SU843728542A patent/SU1478993A3/en active
- 1984-04-06 DK DK180784A patent/DK165729C/en not_active IP Right Cessation
- 1984-04-07 RO RO84114201A patent/RO89437A/en unknown
- 1984-04-07 KR KR1019840001840A patent/KR910004570B1/en not_active IP Right Cessation
- 1984-04-08 IL IL71470A patent/IL71470A/en unknown
- 1984-04-10 ZW ZW60/84A patent/ZW6084A1/en unknown
- 1984-04-16 MX MX84101994U patent/MX7715E/en unknown
- 1984-04-24 ZM ZM20/84A patent/ZM2084A1/en unknown
- 1984-05-03 ES ES532125A patent/ES8502332A1/en not_active Expired
- 1984-05-31 AU AU28904/84A patent/AU569516B2/en not_active Ceased
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |