DK165729B - SULPIRIDE PREPARATION ORAL SUBMITTED GALENIC FORM AND PROCEDURE FOR PREPARING THEREOF - Google Patents
SULPIRIDE PREPARATION ORAL SUBMITTED GALENIC FORM AND PROCEDURE FOR PREPARING THEREOF Download PDFInfo
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- DK165729B DK165729B DK180784A DK180784A DK165729B DK 165729 B DK165729 B DK 165729B DK 180784 A DK180784 A DK 180784A DK 180784 A DK180784 A DK 180784A DK 165729 B DK165729 B DK 165729B
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- 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
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- 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
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- 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
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Description
iin
DK 165729BDK 165729B
Den foreliggende opfindelse angår et sulpiridpræparat på oralt indgivelig galenisk form og en fremgangsmåde til fremstilling deraf.The present invention relates to a sulpiride composition in orally administrable galenic form and to a process for its preparation.
5 Præparatet ifølge opfindelsen er ejendommeligt ved det i krav l's kendetegnende del anførte, og fremgangsmåden er ejendommelig ved det i krav 3's kendetegnende del anførte.The composition of the invention is peculiar to the characterizing part of claim 1 and the method is peculiar to the characterizing part of claim 3.
10 Sulpirid, der også kaldes N-(l-ethyl-2-pyrrolidinyl)-me-thyl-2-methoxy-5-sulfamoylbenzamid, er velkendt som værende et fremragende neuroleptikum, der som terapeutisk hovedindikation har behandlingen af akutte og kroniske psykoser, og dets karakteristika og egenskaber er nærmere 15 beskrevet især i fransk patentskrift nr. 1 472 025, 4879 M og 5916 M.Sulpiride, also called N- (1-ethyl-2-pyrrolidinyl) -methyl-2-methoxy-5-sulfamoylbenzamide, is well known as being an excellent neuroleptic which has as its main therapeutic indication the treatment of acute and chronic psychoses. and its characteristics and properties are described in particular in French Patent Nos. 1 472 025, 4879 M and 5916 M.
Lægemidler til anvendelse peroralt og indeholdende sulpirid foreligger for tiden i form af tabletter, kapsler el-20 l©r drikkelige vandige opløsninger; men, som det ligeledes fremgår af det efterfølgende, kræver disse for tiden tilgængelige former et større antal daglige doser, og de udviser somme tider en reduceret procentvis absorption i organismen.Oral and sulpiride-containing drugs are currently available in the form of tablets, capsules or 20 liters of potable aqueous solutions; but, as will also be apparent from the following, these currently available forms require a greater number of daily doses, and sometimes exhibit a reduced percentage absorption in the organism.
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Man har som følge heraf forsøgt at modificere den gale-niske form, således at man i væsentlig grad forøger patienternes accept deraf, medens man reducerer det nødvendige antal daglige doser.As a result, attempts have been made to modify the Galician form so as to substantially increase the patients' acceptance thereof while reducing the required number of daily doses.
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Eftersom halveringstiden for den aktive bestanddel sulpirid i plasma er ca. 8 1/2 time, skulle det a priori synes muligt at fremstille produktet i en galenisk form, hvorved man kunne reducere den gennemsnitlige daglige dosis 35 til 2 kapsler eller tabletter pr. dag med et indhold af 100 mg sulpirid pr. kapsel eller pr. tablet, således at én skal tages om morgenen og den anden tages om aftenen,Since the half-life of the active ingredient sulpiride in plasma is approx. For 8 1/2 hours, it should, in a priori, seem possible to prepare the product in a galenic form, thereby reducing the average daily dose of 35 to 2 capsules or tablets per day. per day with a content of 100 mg of sulpiride per day. capsule or per. tablet so that one should be taken in the morning and the other taken in the evening,
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2 eller endog kun én kapsel eller tablet pr. dag med et indhold af 200 mg sulpirid.2 or even only one capsule or tablet per day. day with a content of 200 mg of sulpiride.
Med henblik herpå fremstillede man mikrogranulater i 5 overensstemmelse med konventionelle fremgangsmåder, som især er beskrevet i fransk patentskrift nr. 2 313 915 (Comeille) eller fransk patentskrift nr. 2 453 642 (Labaz). Man anvendte konventionelle neutrale korn, hvis størrelse var ca. 0,50 mm i diameter, og som bestod af 25 10 vægt% stivelse og 75 vægt% saccharose, på hvilke man påførte sulpirid i en turbineproces under anvendelse af en alkoholisk opløsning af polyvinylpyrrolidon, hvorpå man påførte konventionelle overtræk baseret på en polymer af shellaktypen, methacrylattypen eller ethylcellulosetypen, 15 således at man opnåede en forud fastlagt standardkinetik for frigivelsen af den aktive bestanddel, sulpirid, in vitro i gastriske medier og intestinale medier i overensstemmelse med følgende specifikation: 20 - første time: frigivelse mindre end 40 vægt% - fjerde time: frigivelse mindre end 75 vægt% - ottende time: frigivelse mere end 75 vægt%.To this end, microgranules were prepared in accordance with conventional methods, particularly described in French Patent No. 2,313,915 (Comeille) or French Patent No. 2,453,642 (Labaz). Conventional neutral grains were used, the size of which was approx. 0.50 mm in diameter, which consisted of 10% by weight of starch and 75% by weight of sucrose applied to sulpiride in a turbine process using an alcoholic solution of polyvinylpyrrolidone, to which conventional coatings based on a shellac polymer were applied , methacrylate type or ethyl cellulose type, so as to obtain a predetermined standard kinetics of the release of the active ingredient, sulpiride, in vitro in gastric and intestinal media according to the following specification: 20 - first hour: release less than 40 wt% - fourth hour: release less than 75 wt% - eighth hour: release more than 75 wt%.
Frigivelsen i den første time gennemførtes i en kunstig 25 mavesaft med en pH-vær di på 1,3, og frigivelsen ved den fjerde time og ved den ottende time i kunstige intestinale safter med pH-værdier på henholdsvis 4,5 og 7. Forsøgsbetingelserne ved undersøgelsen af frigivelsen af den aktive bestanddel er velkendte og beskrevet i ovennævnte 30 patentskrifter.The first hour release was performed in an artificial gastric juice with a pH value of 1.3, and the release at the fourth hour and at the eighth hour in artificial intestinal juices with pH values of 4.5 and 7. respectively. upon examination of the release of the active ingredient are well known and described in the above 30 patents.
Disse mikrogranulater blev derpå anvendt til fremstilling af kapsler og tabletter med en dosering på 100 mg, og absorptionen åf sulpiridet blev undersøgt ved analyse af 35 plasmaindholdet af sulpirid ved anvendelse af radioimmu nologi, hvorpå man sammenlignende de således opnåede resultater med resultater opnået ud fra en kommerciel til-These microgranules were then used to prepare capsules and tablets at a dosage of 100 mg and absorption of the sulpiride was investigated by analyzing the plasma content of sulpiride using radioimmunology, comparing the results thus obtained with results obtained from a commercial
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3 gængelig kapselform.3 common capsule form.
De opnåede resultater er anført i efterfølgende tabel A og viser, at tabet ved de to anvendte formuleringer af 5 mikrogranulater (form I og form II) i mængden af den aktive bestanddel er for stort i sammenligning med tabene ved den normale form for kapsler (form IV) til, at det er muligt at tilvejebringe et effektivt lægemiddel med forlænget virkning.The results obtained are given in Table A below and show that the loss in the two formulations of 5 microgranules (Form I and Form II) in the amount of the active ingredient is too large in comparison with the losses in the normal form of capsules (Form IV) that it is possible to provide an effective drug with a prolonged effect.
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Form I og II blev fremstillet ifølge ovennævnte franske patentskrifter ved overtrækning af neutrale korn med et lag bestående af aktiv bestanddel efterfulgt af et lag bestående af en blanding af polymere som defineret i 15 fransk patentskrift nr. 2 313 915 og nr. 2 453 642. Forholdene mellem de forskellige lag er valgt efter FR 2 453 642. Form I og II er således sammensat af neutrale korn af 25 vægt% stivelse og 75 vægt% saccharose udgørende 47,5 vægt% af præparatet, og et lag af 85 % sulpirid og 20 15 vægt% polyvinylpyrrolidon udgørende 51,5 vægt% af præ paratet, mens det ydre overtræk udgør 1 vægt% af præparatet og for form 11 s vedkommende består af shellak og ethylcellulose og for form II's vedkommende af en blanding af methacrylpolymere som defineret i FR 2 453 642.Forms I and II were prepared according to the aforementioned French Patents by coating neutral grains with a layer of active ingredient followed by a layer consisting of a mixture of polymers as defined in French Patent Nos. 2,313,915 and 2,453,642. The ratios of the various layers are selected according to FR 2,453,642. Forms I and II are thus composed of neutral grains of 25 wt% starch and 75 wt% sucrose, comprising 47.5 wt% of the composition, and a layer of 85% sulpiride and 20 15% by weight polyvinylpyrrolidone constituting 51.5% by weight of the composition, while the outer coating constitutes 1% by weight of the composition and for form 11 s consists of shellac and ethyl cellulose and for form II a mixture of methacrylic polymers as defined in FR 2 453 642.
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De anvendte former I og II havde følgende kinetiske egenskaber med hensyn til frigivelsen in vitro i kunstige medier:Forms I and II used had the following kinetic properties in vitro release in artificial media:
5 Form I Form II5 Form I Form II
Frigivelse i den første time i et medium med pH-værdien 1,3 20,0 vægt% 29,2 vægt%Release in the first hour in a medium of pH 1.3 20.0 wt% 29.2 wt%
Frigivelse ved den fjerde 10 time i et medium med pH- værdien 4,5 68,6 vægt% 58,4 vægt%Release at the fourth 10 hours in a medium of pH 4.5 68.6% by weight 58.4% by weight
Frigivelse ved den ottende time i et medium med pH- 15 værdien 7 90,8 vægt% 98,2 vægt%Release at the eighth hour in a medium of pH 7 90.8 wt% 98.2 wt%
Man fik efter at have undersøgt en serie af formuleringer med forlænget virkning, der alle førte til resultater, der ikke var forenelige med fremstillingen af en god, 20 passende absorberbar oralt indgivelig form, den ide, at man skulle bevare mikrogranulatformen (stort set kugleformede korn med en diameter på mellem 0,2 og 2 mm), hvilket i praksis skulle føre til en bedre absorption af den aktive bestanddel end af et konventionelt pulver i en 25 kapsel eller i tabletten, medens den skulle have kinetiske egenskaber med hensyn til frigivelsen in vitro, som var meget nærmere ved egenskaberne for de umiddelbart absorberbare former, dvs., som frigav stort set 90 vægt% af den aktive bestanddel efter 1 time i et kunstigt gastrisk 30 medium med en pH-værdi på 1,3.After examining a series of extended-action formulations, all of which resulted in incompatible results with the preparation of a good, suitably absorbable orally-administered form, the idea of maintaining the microgranulate form (largely spherical grains) was obtained. with a diameter of between 0.2 and 2 mm), which should in practice result in better absorption of the active ingredient than that of a conventional powder in a capsule or in the tablet, while having kinetic properties with respect to its release. in vitro, which was much closer to the properties of the readily absorbable forms, i.e., which released about 90% by weight of the active ingredient after 1 hour in an artificial gastric medium having a pH of 1.3.
Nu viste det sig overraskende ud fra resultaterne af mi-krogranulaterne under anvendelse af denne in vitro kinetik, at i afhængighed af de sammenlignelige plasmamængde-35 forhold gjorde formen III, som blev fremstillet af mikro-granulater bragt på kapselform med et indhold på 100 mg, det muligt at opnå en dobbelt så stor absorption, som 6Now, surprisingly, from the results of the microgranules using this in vitro kinetics, it was found that, depending on the comparable plasma volume ratios, the Form III, made from microgranules, was delivered in capsule form with a content of 100 mg. , it is possible to achieve twice as much absorption as 6
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den, der opnås med konventionelle kapsler indeholdende sulpirid (form IV), samtidig med at man bibeholder en virkningsperiode, som er lidt længere, og samtidig med at man i stor udstrækning reducerer forskellene i absorption 5 fra én patient til en anden. Den ovenfor angivne forbedring i absorptionen af sulpirid såvel i kvantitativ henseende som i henseende til regelmæssighed gør det muligt at foretage en reduktion både af de doser, der skal anvendes, og af antallet af daglige doser.that obtained with conventional capsules containing sulpiride (Form IV), while retaining a slightly longer duration of action and to a large extent reducing the differences in absorption 5 from one patient to another. The improvement noted above in the absorption of sulpiride both in quantitative and in terms of regularity makes it possible to reduce both the doses to be used and the number of daily doses.
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Disse resultater er vist i tabel A og ligeledes på figuren, hvor der vises variationen i mængdeforholdene i plasma udtrykt som ng/ml sulpirid til tidspunkterne mellem 0 og 32 timer i sammenligning mellem formen III og 15 formen IV.These results are shown in Table A and also in the figure, showing the variation in the plasma volume ratios expressed as ng / ml sulpiride at the times between 0 and 32 hours, in comparison between Form III and Form IV.
Det var muligt ud fra kompletterende eksperimenter, under hvilke de ydre overtræk for mikrogranulaterne i sulpirid-præparatet ifølge opfindelsen blev varieret, at fastlæg-20 g©/ ©t den foretrukne form med forbedret absorption af sulpiridet stort set skulle svare til følgende analytiske forhold med hensyn til frigivelsen in vitro: - 15 minutter: frigivelse mellem 35 og 50 vægt% i et kun- 25 stigt gastrisk medium med pH-værdien 1,3, - 30 minutter: frigivelse mellem 60 og 75 vægt% i et kun stigt gastrisk medium med pH-værdien 1,3, - 60 minutter: frigivelse mellem 80 og 95 vægt% i et kun stigt intestinalt medium med pH-værdien 30 4,5.It was possible from complementary experiments during which the outer coatings of the microgranules in the sulpiride composition of the invention were varied that determining 20 g / µl the preferred form with improved absorption of the sulpiride should largely correspond to the following analytical conditions with in vitro release: - 15 minutes: release between 35 and 50% by weight in an artificial gastric medium having a pH of 1.3, - 30 minutes: release between 60 and 75% by weight in a strictly gastric medium with pH 1.3, - 60 minutes: release between 80 and 95% by weight in only a rigid intestinal medium with pH 30 4.5.
Derudover iagttog man en total frigivelsesandel på over 90 vægt% i et kunstigt intestinalt medium med pH-værdien 6,9.In addition, a total release rate of over 90% by weight in an artificial intestinal medium having a pH of 6.9 was observed.
Som et eksempel skal her anføres produktion af 2500 kapsler med en dosis på 100 mg af formen III samt fremgangs- 35As an example, production of 2500 capsules at a dose of 100 mg of Form III and
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7 måden til fremstilling deraf.7 the way of making them.
Ved fremgangsmåden anvendtes 50 g neutrale korn bestående af ca. 25 vægt% stivelse og 75 vægt% saccharose i en 5 kornstørrelse, som stort set svarer til 0,50 mm i diameter, hvortil man ved en turbineproces påførte 250 g sulpirid inkorporeret i en 20 vægt%'s ethanolisk opløsning af polyvinylpyrrolidon.In the process, 50 g of neutral grains consisting of approx. 25% by weight of starch and 75% by weight of sucrose in a 5 grain size which is roughly equivalent to 0.50 mm in diameter, to which, in a turbine process, 250 g of sulpiride incorporated in a 20% by weight ethanolic solution of polyvinylpyrrolidone is applied.
10 Derpå påførte man efter tørring og sigtning ydre lag bestående af 20 g af en blanding af methacrylpolymere, som markedsføres af firmaet Rohm og Haas under navnet "Eudragit®". Blandingen består af 80 vægt% polymer "Eudragit®" type L og af 20 vægt% polymer "Eudragit®" 15 type RL og anvendes i form af en alkoholisk opløsning.10 After drying and sieving, outer layers consisting of 20 g of a mixture of methacrylic polymers marketed by the company Rohm and Haas under the name "Eudragit®" were applied. The mixture consists of 80% by weight polymer "Eudragit®" type L and 20% by weight polymer "Eudragit®" type RL and is used in the form of an alcoholic solution.
Derefter gennemførte man en tørring med talkum i små mængder, indtil der blev dannet mikrogranulater, som frigiver stort set 100 % sulpirid i løbet af 1 time ved de 20 analytiske betingelser, som er defineret ovenfor.Subsequently, a small amount of talcum drying was carried out until microgranules were formed which release substantially 100% sulpiride over 1 hour at the 20 analytical conditions defined above.
Dernæst gennemførte man en tørring i en tørringsovn ved 37 eC i ca. 2 dage, hvorpå det ydre lag blev afsluttet med et overtræk bestående af 5,4 g polymer "Eudragit®" 25 type RL påført ved påsprøjtning af 40 g af en 13,5 %'s ethanolisk opløsning af denne polymere. Analyseresultatet viste nu ca. 730 mg aktiv bestanddel pr. g mikrogranulat.Next, drying was performed in a drying oven at 37 ° C for approx. 2 days after which the outer layer was completed with a coating of 5.4 g of polymer "Eudragit®" type RL applied by spraying 40 g of a 13.5% ethanolic solution of this polymer. The analysis result now showed approx. 730 mg of active ingredient per day. g of microgranules.
De mikrogranulater, der blev fremstillet på denne måde, 30 er i overensstemmelse med de standarder med hensyn til frigivelsen in vitro, der er beskrevet ovenfor, og de er repræsentative for de hidtil ukendte galeniske former for sulpirid ifølge den foreliggende opfindelse.The microgranules prepared in this manner are in accordance with the in vitro release standards described above and are representative of the novel galenic forms of sulpiride of the present invention.
35 Man fandt såvel deres accelererede som naturlige stabiliteter som værende fremragende uden forekomsten af poten-tialiseret toxicitet.35 Both their accelerated and natural stabilities were found to be excellent without the occurrence of potential toxicity.
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Produkterne kan anvendes i form af kapsler, tabletter eller suspension i neutrale medier.The products can be used in the form of capsules, tablets or suspension in neutral media.
Det er klart, at man kan foretage variationer især med 5 hensyn til de indbyrdes forhold mellem excipienserne og den aktive bestanddel og til sammensætningen af de neutrale korn samt med hensyn til arten af de polymere, som udgør de ydre lag.It is clear that variations can be made especially with respect to the interrelationships between the excipients and the active ingredient and to the composition of the neutral grains as well as to the nature of the polymers constituting the outer layers.
10 15 20 25 30 3510 15 20 25 30 35
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8320635A FR2556964A1 (en) | 1983-12-23 | 1983-12-23 | NEW GALENIC FORMS OF SULPIRIDE USED ORALALLY |
| FR8320635 | 1983-12-23 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK180784D0 DK180784D0 (en) | 1984-04-06 |
| DK180784A DK180784A (en) | 1985-06-24 |
| DK165729B true DK165729B (en) | 1993-01-11 |
| DK165729C DK165729C (en) | 1993-06-07 |
Family
ID=9295477
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK180784A DK165729C (en) | 1983-12-23 | 1984-04-06 | SULPIRIDE PREPARATION ORAL SUBMITTED GALENIC FORM AND PROCEDURE FOR PREPARING THEREOF |
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 (7)
| 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 |
| PH30929A (en) * | 1992-09-03 | 1997-12-23 | Janssen Pharmaceutica Nv | Beads having a core coated with an antifungal and a polymer. |
| 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 DE DE19843412868 patent/DE3412868A1/en not_active Withdrawn
- 1984-04-05 BE BE1/10992A patent/BE899331A/en not_active IP Right Cessation
- 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 FI FI841376A patent/FI82603C/en not_active IP Right Cessation
- 1984-04-06 GR GR74337A patent/GR79584B/el unknown
- 1984-04-06 AR AR296218A patent/AR231398A1/en active
- 1984-04-06 IN IN242/MAS/84A patent/IN160415B/en unknown
- 1984-04-06 HU HU841362A patent/HU190924B/en not_active IP Right Cessation
- 1984-04-06 LU LU85290A patent/LU85290A1/en unknown
- 1984-04-06 PT PT78382A patent/PT78382B/en not_active IP Right Cessation
- 1984-04-06 GB GB08408978A patent/GB2151920B/en not_active Expired
- 1984-04-06 DK DK180784A patent/DK165729C/en not_active IP Right Cessation
- 1984-04-06 NO NO841367A patent/NO169575C/en unknown
- 1984-04-06 OA OA58273A patent/OA07700A/en unknown
- 1984-04-06 BG BG064985A patent/BG49707A3/en unknown
- 1984-04-06 DD DD84261741A patent/DD220782A5/en not_active IP Right Cessation
- 1984-04-06 YU YU640/84A patent/YU44762B/en unknown
- 1984-04-06 SU SU843728542A patent/SU1478993A3/en active
- 1984-04-06 PL PL1984247098A patent/PL144356B1/en unknown
- 1984-04-06 CH CH1755/84A patent/CH659386A5/en not_active IP Right Cessation
- 1984-04-06 IT IT48001/84A patent/IT1177655B/en active
- 1984-04-06 JP JP59069883A patent/JPS60139616A/en active Granted
- 1984-04-06 PH PH30510A patent/PH21938A/en unknown
- 1984-04-07 KR KR1019840001840A patent/KR910004570B1/en not_active Expired
- 1984-04-07 RO RO84114201A patent/RO89437A/en unknown
- 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 |
|---|---|---|---|
| PBP | Patent lapsed |