NO318227B1 - Stabilized lipophilic matrix for controlled release of active principles, pharmaceutical composition containing the same and methods for their preparation. - Google Patents
Stabilized lipophilic matrix for controlled release of active principles, pharmaceutical composition containing the same and methods for their preparation. Download PDFInfo
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- NO318227B1 NO318227B1 NO19972068A NO972068A NO318227B1 NO 318227 B1 NO318227 B1 NO 318227B1 NO 19972068 A NO19972068 A NO 19972068A NO 972068 A NO972068 A NO 972068A NO 318227 B1 NO318227 B1 NO 318227B1
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- 239000011159 matrix material Substances 0.000 title claims abstract description 26
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
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- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 3
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- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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
- A61K9/4841—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
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- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Child & Adolescent Psychology (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Foreliggende oppfinnelse vedrører en ny stabilisert lipofil matrise for kontrollert frigiving av aktive prinsipper, hvis lipofile evne tilveiebringes ved anvendelse av fettsubstanser avledet fra triglyserider av fett eller polyglykolsylerte syrer, farmasøytiske sammensetninger inneholdende det samme og fremgangsmåter for fremstilling av disse. The present invention relates to a new stabilized lipophilic matrix for the controlled release of active principles, whose lipophilic ability is provided by the use of fatty substances derived from triglycerides of fat or polyglycolsylated acids, pharmaceutical compositions containing the same and methods for their production.
Produksjonen av farmasøytiske sammensetninger som muliggjør kontrollert frigiving av aktive prinsipper, har i hovedsak som mål å erholde en uniform konsentrasjon av det aktive prinsipp i et menneskes blod ved å jevne ut toppen som normalt erholdes i blodet med øyeblikkelige frigivelsesformer, og derved ikke bare unngå uønskede effekter grunnet disse topper i blodet, men også redusert antall daglige doser av det medisinske produkt, hvilket gjør det lettere for pasienten å overholde behandlingen. The production of pharmaceutical compositions that enable the controlled release of active principles essentially aims to obtain a uniform concentration of the active principle in a person's blood by smoothing out the peak normally obtained in the blood with immediate release forms, thereby not only avoiding unwanted effects due to these peaks in the blood, but also a reduced number of daily doses of the medical product, which makes it easier for the patient to comply with the treatment.
Blant de ulike kjente typer av midler med vedvarende fri-givinger er lipofile matriser blitt beskrevet i littera-turen. Imidlertid er den største ulempen ved disse lipofile matriser en endring i frigjøringskinetikken for det aktive prinsipp ved aldring. Studier av stabilitet av former basert på lipofile matriser viser en akselerasjon av frigjøringskinetikk av det aktive prinsipp, hvilket inne-bærer at det er umulig å erholde en bestemt utløpsdato for de aktuelle farmasøytiske former. Denne endring i oppløs-ningskinetikk av det aktive prinsipp uttrykkes ved modi-fiseringen av den interne tilstand av matrisen. Denne transformasjon av fetteksipiens finner sted ved romtempe-ratur og kan gå over flere måneder. Among the various known types of agents with sustained releases, lipophilic matrices have been described in the literature. However, the major disadvantage of these lipophilic matrices is a change in the release kinetics of the active principle upon aging. Studies of the stability of forms based on lipophilic matrices show an acceleration of the release kinetics of the active principle, which means that it is impossible to obtain a specific expiry date for the relevant pharmaceutical forms. This change in dissolution kinetics of the active principle is expressed by the modification of the internal state of the matrix. This transformation of the fat excipient takes place at room temperature and can last for several months.
I tillegg til det faktum at den er ny gjør den lipofile matrise ifølge foreliggende oppfinnelse det mulig å løse stabilitetsproblemer en støter på ved andre matriser beskrevet tidligere. Den kombinerer på originalt vis to ulike typer kjemiske familier og gjør det mulig å erholde fullstendig stabilitet av den farmasøytiske form under lagringsperioden av det medisinske produkt, samt fullstendig kontrollert frigiving av det aktive prinsipp. In addition to the fact that it is new, the lipophilic matrix according to the present invention makes it possible to solve stability problems encountered with other matrices described earlier. It combines in an original way two different types of chemical families and makes it possible to obtain complete stability of the pharmaceutical form during the storage period of the medicinal product, as well as completely controlled release of the active principle.
Den første familie av forbindelser omfatter fettsyre mono-, eller di- eller triglyserider eller mettede polyglykosylerte mono- eller di- eller triglyserider erholdt fra hydrogenerte planteoljer omfattende polyetylenglykolestre og glyserider. En del av denne familie er kjent som Gé-lucire<7>. Denne familie av eksipienser anvendes normalt ved produksjon av lipofile matriser. Disse eksipienser er karakterisert ved deres smeltepunkt og ved deres HLB-verdi {hydrofil-lipofil balanse). Eksipiensene anvendt i foreliggende oppfinnelse er de med stor lipofil evne, dvs. de som har HLB-verdier på mindre enn 10. The first family of compounds comprises fatty acid mono-, or di- or triglycerides or saturated polyglycosylated mono- or di- or triglycerides obtained from hydrogenated vegetable oils comprising polyethylene glycol esters and glycerides. A part of this family is known as Gé-lucire<7>. This family of excipients is normally used in the production of lipophilic matrices. These excipients are characterized by their melting point and by their HLB value (hydrophilic-lipophilic balance). The excipients used in the present invention are those with high lipophilic ability, i.e. those with HLB values of less than 10.
Den andre kjemiske familie som tillater stabilisering av oppløsningskinetikk omfatter cellulose-etere så som metylhydroksypropylcellulose, metylcellulose, hydroksy-metylcellulose og hydroksypropylcellulose. Stabilisering av denne matrise skal ytterligere erholdes mens de lipofile egenskaper av matrisen bibeholdes. I henhold til dette har det i matriser ifølge foreliggende oppfinnelse blitt vist at prosenten av cellulosederivater som tillater stabilisering av matrisen ikke bør overskride 15 % av sammensetningens totale masse. Følgelig stabiliseres denne matrise som er gjort lipofil ved anvendelse av triglyserid-derivater, overraskende ved tilsetning av The other chemical family that allows stabilization of dissolution kinetics includes cellulose ethers such as methylhydroxypropylcellulose, methylcellulose, hydroxymethylcellulose and hydroxypropylcellulose. Stabilization of this matrix is to be further obtained while the lipophilic properties of the matrix are maintained. Accordingly, in matrices according to the present invention, it has been shown that the percentage of cellulose derivatives which allow stabilization of the matrix should not exceed 15% of the total mass of the composition. Consequently, this matrix, which has been rendered lipophilic by the use of triglyceride derivatives, is surprisingly stabilized by the addition of
cellulosederivater. cellulose derivatives.
Den lipofile matrise ifølge foreliggende oppfinnelse omfatter som følger: - en eller flere polyglykosylerte eller fettsyretrigly-seridderivater (fettsubstanser) The lipophilic matrix according to the present invention comprises as follows: - one or more polyglycosylated or fatty acid triglyceride derivatives (fatty substances)
- en eller flere cellulosederivater (stabilisatorer) - one or more cellulose derivatives (stabilizers)
- ett eller flere aktive prinsipper - one or more active principles
- og, eventuelt, en eller flere eksipienser som kan virke som plastifiseringsmidler, smakstilsetninger eller søtningsmidler. - and, possibly, one or more excipients that can act as plasticizers, flavorings or sweeteners.
Nærmere bestemt omfatter foreliggende oppfinnelse en stabilisert lipofil matrise for kontrollert frigiving av aktive prinsipper hvis lipofile evne tilveiebringes ved anvendelse av fettsubstanser avledet fra triglyserider av fett eller polyglykolsylerte syrer, karakterisert ved at matrisen er stabilisert ved anvendelse av cellulosederivater i et forhold som ikke overskrider 15% av sammensetningens totale vekt; og disse fettsubstansene har en HLB-koeffisient på mindre enn 10. More specifically, the present invention comprises a stabilized lipophilic matrix for the controlled release of active principles whose lipophilic ability is provided by the use of fatty substances derived from triglycerides of fat or polyglycolsylated acids, characterized in that the matrix is stabilized by the use of cellulose derivatives in a ratio that does not exceed 15% of the total weight of the composition; and these fatty substances have an HLB coefficient of less than 10.
Den lipofile matrise ifølge foreliggende oppfinnelse kan fordelaktig anvendes for å produsere mikrosfærene eller mikrogranulene som skal anvendes ved fremstilling av gelatinkapsler, tabletter, implantater, geler, kremer, trans-dermale eller transmukøse systemer eller drikkelige eller injiserbare løsninger. En foretrukket form er produksjon av gelatinkapsler. The lipophilic matrix according to the present invention can advantageously be used to produce the microspheres or microgranules to be used in the production of gelatin capsules, tablets, implants, gels, creams, transdermal or transmucosal systems or drinkable or injectable solutions. A preferred form is the production of gelatin capsules.
Blant de aktive prinsipper som anvendes i de farmasøytiske sammensetninger ifølge foreliggende oppfinnelse, kan det på ubegrensende vis nevnes: antiinfektøse midler så som penicilliner, kefalosporiner, sykliner, beta-laktamase-inhibitorer, aminosider, kinoloner, nitroimidazoler, sulfamider eller antibakterielle midler, antihistaminer, antiallergiske midler, anestetika, steroidale eller ikke-steroidale antiinflammatoriske midler, analgetika med lokal eller systemisk virkning, antispasmodiske midler, anticancermidler, diuretika, beta-blokkere, antihypertensive midler, antianginamidler, antiarrytmiske midler, vasodilatorer, bradykardiske midler, kalsiuminhibitorer, sedativer, kardiotoniske midler, antifungale midler, antiulcerøse midler, veinotoniske midler, vaskulobeskyttende midler, antiiskemiske midler, antiemetika, antikoagulanter, antitrombotiske midler, immunosuppressanter, immunomodulatorer, antivirale midler, antidiabetika, hypolipidemiske midler, antifedmemidler, antikonvulsive midler, hypnotiske midler, antiparkinsonsmidler, antimigrenemidler, nevroleptiske midler, anxiolytika midler, antidepressiva, psykostimulater, hukommelsesfremmende midler, bronkodilatorer, antitussiva, antiosteoporotiske midler, peptidhormoner, steroider, enzymer, enzyminhibitorer og melatoninerge agonister og antagonister. Among the active principles used in the pharmaceutical compositions according to the present invention, the following can be mentioned without limitation: anti-infectives such as penicillins, cephalosporins, cyclins, beta-lactamase inhibitors, aminosides, quinolones, nitroimidazoles, sulfamides or antibacterial agents, antihistamines, antiallergic agents, anaesthetics, steroidal or non-steroidal anti-inflammatory agents, analgesics with local or systemic action, antispasmodic agents, anticancer agents, diuretics, beta-blockers, antihypertensive agents, antianginal agents, antiarrhythmic agents, vasodilators, bradycardic agents, calcium inhibitors, sedatives, cardiotonic agents , antifungal agents, antiulcer agents, venotonic agents, vasculoprotective agents, antiischemic agents, antiemetics, anticoagulants, antithrombotic agents, immunosuppressants, immunomodulators, antiviral agents, antidiabetics, hypolipidemic agents, antiobesity agents, anticonvulsants m idlers, hypnotic agents, antiparkinson agents, antimigraine agents, neuroleptic agents, anxiolytic agents, antidepressants, psychostimulants, memory enhancers, bronchodilators, antitussives, antiosteoporotic agents, peptide hormones, steroids, enzymes, enzyme inhibitors and melatoninergic agonists and antagonists.
Resultatene erholdt med disse lipofile matriser viser: The results obtained with these lipophilic matrices show:
- på den ene side at det ikke er noen konversjon av fetteksipiensen som en funksjon av temperatur (varmebehandling) - på den annen side at denne stabilisering er langvarig. Ingen modifikasjon ble observert etter flere måneders lagring under standard lagringsbetingelser definert ved de internasj onale standarder. - on the one hand, that there is no conversion of the fat excipient as a function of temperature (heat treatment) - on the other hand, that this stabilization is long-lasting. No modification was observed after several months of storage under standard storage conditions defined by the international standards.
Følgelig er ingen behandling nødvendig for å erholde en stabil matrise, og dette er en viktig fordel på industri-nivå, og det gir også en svært markant reduksjon i produksj onskostnader. Consequently, no treatment is necessary to obtain a stable matrix, and this is an important advantage at industrial level, and it also provides a very marked reduction in production costs.
De lipofile matriser ifølge foreliggende oppfinnelse erholdes ifølge de teknikker som innbefatter smelting, spraying med varm eller kald luft ("spray-tørking" eller "spray-størkning"), varm eller kald ekstrusjon, sfæronifi-sering eller teknikker som omfatter det å ejisere en væske gjennom en dyse utstyrt med en rekke hull som det utføres en vibrasjonsoperasjon på ("prilling"). The lipophilic matrices according to the present invention are obtained according to the techniques which include melting, spraying with hot or cold air ("spray drying" or "spray solidification"), hot or cold extrusion, spheronification or techniques which include ejizing a liquid through a nozzle equipped with a series of holes on which a vibration operation is performed ("prilling").
En foretrukket prosess for fremstilling av gelatinkapsler er som følger: Trinn 1: Smelting av fettsubstansen(e) i en smeltedigel. Trinn 2; Inkorporering av en eller flere celluloseetere i den smeltede masse av fettsubstans(er). Deretter homogenisering av blandingen ved anvendelse av et egnet system. A preferred process for making gelatin capsules is as follows: Step 1: Melting the fatty substance(s) in a crucible. Step 2; Incorporation of one or more cellulose ethers into the molten mass of fatty substance(s). Then homogenization of the mixture using a suitable system.
Trinn 3: Inkorporering av det aktive prinsipp og av de andre eksipienser om nødvendig. Deretter homogenisering av blandingen ved anvendelse av et egnet system. Step 3: Incorporation of the active principle and of the other excipients if necessary. Then homogenization of the mixture using a suitable system.
Trinn 4: Fylling av gelatinkapsler med blandingen erholdt i trinn 3, holdt ved temperatur og kontinuerlig homogensiert for å sikre total reproduserbarhet av den farmasøytiske form. Step 4: Filling gelatin capsules with the mixture obtained in step 3, kept at temperature and continuously homogenized to ensure total reproducibility of the pharmaceutical form.
Gelatinkapslene som ble erholdt på denne måte, underkastes alternativt varmebehandling. The gelatin capsules obtained in this way are alternatively subjected to heat treatment.
Eksemplene under illustrerer oppfinnelsen, men begrenser den ikke på noen som helst måte. The examples below illustrate the invention, but do not limit it in any way.
EKSEMPEL 1: EXAMPLE 1:
- uten tilsetning av den stabiliserende forbindelse - without the addition of the stabilizing compound
En gelatinkapsel med vedvarende frigiving fremstilles ved anvendelse av formelen gitt i den følgende tabell og ifølge produksjonsprosessen beskrevet i trinn 1, 3 og 4 over uten tilsetning av stabilisatoren hydroksypropylmetylcellulose A sustained-release gelatin capsule is prepared using the formula given in the following table and according to the manufacturing process described in steps 1, 3 and 4 above without the addition of the stabilizer hydroxypropylmethylcellulose
(HPMC). (HPMC).
Kurvene for in vitro oppløsning før og etter varmebehandling er presentert i figur 1 i vedlegg. Det observeres en økning i frigivingskinetikken av det aktive prinsipp i løpet av varmebehandlingen. The curves for in vitro dissolution before and after heat treatment are presented in figure 1 in the appendix. An increase in the release kinetics of the active principle is observed during the heat treatment.
- Med tilsetning av den stabiliserende forbindelse - With the addition of the stabilizing compound
En gelatinkapsel med vedvarende frigiving fremstilles ved anvendelse av formel identisk til den tidligere, men med tilsetning av stabilisatoren, HPMC. Den eksakte formel er gitt i tabellen under. Fremstillingsprosessen er den som er beskrevet i trinn 1-4 over. A sustained release gelatin capsule is prepared using a formula identical to the previous one, but with the addition of the stabilizer, HPMC. The exact formula is given in the table below. The manufacturing process is that described in steps 1-4 above.
Kurvene for in vitro oppløsning før og etter varmebehandling er gitt i figur 2 i vedlegg. Det observeres ingen modifikasjon i frigivingskinetikker for det aktive prinsipp under varmebehandlingen. The curves for in vitro dissolution before and after heat treatment are given in figure 2 in the appendix. No modification in release kinetics for the active principle is observed during the heat treatment.
EKSEMPEL 2 i EXAMPLE 2 i
- Uten tilsetning av den stabiliserende forbindelse - Without the addition of the stabilizing compound
En gelatinkapsel med vedvarende frigiving fremstilles ved anvendelse av formlene gitt i den følgende tabell og ifølge produksjonsprosessen beskrevet i trinn 1, 3 og 4 over uten tilsetning av stabilisatoren hydroksypropylmetylcellulose A sustained-release gelatin capsule is prepared using the formulas given in the following table and according to the manufacturing process described in steps 1, 3 and 4 above without the addition of the stabilizer hydroxypropylmethylcellulose
(HPMC). (HPMC).
Kurvene for in vitro oppløsning før og etter varmebehandling er gitt i figur 3 i bilag. Det observeres en økning i frigivingskinetikk for det aktive prinsipp under varmebehandlingen. The curves for in vitro dissolution before and after heat treatment are given in figure 3 in the appendix. An increase in release kinetics for the active principle is observed during the heat treatment.
- Med tilsetning av den stabiliserende forbindelse - With the addition of the stabilizing compound
En gelatinkapsel med vedvarende frigiving fremstilles identisk med den over, men med tilsetning av stabilisatoren, HPMC. Den eksakte formel er gitt i tabellen under. Produksjonsprosessen er den beskrevet i trinn 1-4 over. Kurvene for in vitro oppløsning før og etter varmebehandling er gitt i figur 4 vedlagt. Det observeres ingen modifikasjon i frigivingskinetikk for det aktive prinsipp under varmebehandlingen. A sustained-release gelatin capsule is manufactured identically to the one above, but with the addition of the stabilizer, HPMC. The exact formula is given in the table below. The production process is as described in steps 1-4 above. The curves for in vitro dissolution before and after heat treatment are given in figure 4 attached. No modification in the release kinetics of the active principle is observed during the heat treatment.
EKSEMPEL 3: EXAMPLE 3:
EKSEMPEL 7i Studie av matrisenes stabilitet ved lagringsbetingelser definert ved internasjonale ICH(International Conference on Harmoni-zation)-standarder EXAMPLE 7i Study of matrix stability under storage conditions defined by international ICH (International Conference on Harmonization) standards
Formuleringene anvendt i dette studie er de beskrevet i eksempel 2. Kurvene for in vitro oppløsning av gelatinkapsler inneholdende eller ikke inneholdende hydroksypropyl-meylcellulose (HPMC), erholdt etter lagring i en måned under tre ulike betingelser, er gitt i figur 5 og 6 i bilag. De viser at matrisen er ustabil uten HPMC mens matrisene inneholdende HPMC er stabile i 1-3 måneder under de testede betingelser for temperatur og relativ fuktighet. The formulations used in this study are those described in example 2. The curves for in vitro dissolution of gelatin capsules containing or not containing hydroxypropyl meylcellulose (HPMC), obtained after storage for one month under three different conditions, are given in figures 5 and 6 in the appendix . They show that the matrix is unstable without HPMC while the matrices containing HPMC are stable for 1-3 months under the tested conditions of temperature and relative humidity.
EKSEMPEL 8t Studie av langvarig stabilitet av matriser EXAMPLE 8t Study of long-term stability of matrices
ifølge oppfinnelsen according to the invention
De anvendte formuleringer er de beskrevet i eksempel 2. Kurvene for in vitro oppløsning av de testede gelatinkapsler erholdt etter tre måneders lagring ved 30EC under 60 % relativ fuktighet er gitt i figur 7 og 8. Disse kurvene viser at gelatinkapsler som inneholder matriser ifølge foreliggende oppfinnelse, er fullstendig stabile etter tre måneder, mens de som ikke inneholder HPMC er svært ustabile og derfor ubrukelige og uegnede for salg. The formulations used are those described in example 2. The curves for in vitro dissolution of the tested gelatin capsules obtained after three months of storage at 30EC under 60% relative humidity are given in Figures 7 and 8. These curves show that gelatin capsules containing matrices according to the present invention , are completely stable after three months, while those that do not contain HPMC are highly unstable and therefore unusable and unfit for sale.
Claims (9)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9605606A FR2748209B1 (en) | 1996-05-06 | 1996-05-06 | PHARMACEUTICAL COMPOSITION BASED ON STABILIZED LIPOPHILIC MATRICES FOR THE CONTROLLED RELEASE OF ACTIVE INGREDIENTS |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO972068D0 NO972068D0 (en) | 1997-05-05 |
| NO972068L NO972068L (en) | 1997-11-07 |
| NO318227B1 true NO318227B1 (en) | 2005-02-21 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19972068A NO318227B1 (en) | 1996-05-06 | 1997-05-05 | Stabilized lipophilic matrix for controlled release of active principles, pharmaceutical composition containing the same and methods for their preparation. |
Country Status (16)
| Country | Link |
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| 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) |
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| 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 |
| CN101360485B (en) | 2005-10-26 | 2013-04-17 | 班纳制药公司 | Hydrophilic vehicle-based dual controlled release matrix system |
| JP5406529B2 (en) * | 2005-10-26 | 2014-02-05 | バナー ファーマキャプス， インコーポレイテッド | Dual controlled release matrix system based on lipophilic vehicle as capsule filler |
| 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 |
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| US4797286A (en) * | 1985-11-12 | 1989-01-10 | Eli Lilly And Company | Orally administerable sustained release pharmaceutical formulations |
| DE4413350A1 (en) * | 1994-04-18 | 1995-10-19 | Basf Ag | Retard matrix pellets and process for their production |
| US5545628A (en) * | 1995-01-10 | 1996-08-13 | Galephar P.R. Inc. | Pharmaceutical composition containing fenofibrate |
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1996
- 1996-05-06 FR FR9605606A patent/FR2748209B1/en not_active Expired - Fee Related
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1997
- 1997-05-02 DK DK97400990T patent/DK0806202T3/en active
- 1997-05-02 AT AT97400990T patent/ATE212543T1/en active
- 1997-05-02 PT PT97400990T patent/PT806202E/en unknown
- 1997-05-02 ES ES97400990T patent/ES2170922T3/en not_active Expired - Lifetime
- 1997-05-02 EP EP97400990A patent/EP0806202B1/en not_active Expired - Lifetime
- 1997-05-02 DE DE69710121T patent/DE69710121T2/en not_active Expired - Lifetime
- 1997-05-05 HU HU9700842A patent/HU222045B1/en not_active IP Right Cessation
- 1997-05-05 NO NO19972068A patent/NO318227B1/en not_active IP Right Cessation
- 1997-05-05 NZ NZ314740A patent/NZ314740A/en not_active IP Right Cessation
- 1997-05-05 CA CA002204475A patent/CA2204475C/en not_active Expired - Fee Related
- 1997-05-05 CN CN97109780A patent/CN1171270A/en active Pending
- 1997-05-05 PL PL97319808A patent/PL190562B1/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
- 1997-05-06 JP JP11554897A patent/JP3983339B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| HU9700842D0 (en) | 1997-06-30 |
| PL190562B1 (en) | 2005-12-30 |
| NO972068D0 (en) | 1997-05-05 |
| NZ314740A (en) | 1998-11-25 |
| EP0806202B1 (en) | 2002-01-30 |
| DE69710121T2 (en) | 2002-11-28 |
| HU222045B1 (en) | 2003-04-28 |
| PT806202E (en) | 2002-06-28 |
| JPH1045629A (en) | 1998-02-17 |
| EP0806202A1 (en) | 1997-11-12 |
| JP3983339B2 (en) | 2007-09-26 |
| FR2748209A1 (en) | 1997-11-07 |
| AU1999197A (en) | 1997-11-13 |
| PL319808A1 (en) | 1997-11-10 |
| ATE212543T1 (en) | 2002-02-15 |
| AU720146B2 (en) | 2000-05-25 |
| NO972068L (en) | 1997-11-07 |
| HUP9700842A1 (en) | 1998-08-28 |
| FR2748209B1 (en) | 1998-06-05 |
| DE69710121D1 (en) | 2002-03-14 |
| ZA973836B (en) | 1997-12-02 |
| DK0806202T3 (en) | 2002-05-06 |
| ES2170922T3 (en) | 2002-08-16 |
| CN1171270A (en) | 1998-01-28 |
| CA2204475C (en) | 2002-12-03 |
| CA2204475A1 (en) | 1997-11-06 |
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