EP0325843A2
Expired / Lapsed
EP
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Pharmaceutical formulations for preventing drug tolerance
Assignee: Elan Corp PLC
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Filing: 1988-11-18
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Granted: —
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Expires: 2008-11-18
Abstract
Abstract Pharmaceutical formulations for once-daily administration of a drug to inhibit the development of drug tolerance in humans being treated with the drug which can achieve therapeutically effective levels of said drug in the plasma over a period of not more than 20 hours of the day and then cause said blood levels to fall significantiy below the therapeutic levels throughout the remainder of the 24 hour period. The formulations are adapted for either oral or percutaneous administration.
Inventors
- 👤 Mary Margaret Foynes
- 👤 Edward James Geoghegan
- 👤 Seamus Mulligan
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-03 18:05
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/70; A61K9/7023; A61K9/703; A61K9/7038; A61K9/7046; A61K9/7069; A61K31/00; A61K31/33; A61K31/335; A61K31/34; A61K9/48; A61K9/50; A61K9/5073; A61K9/5078; A61P; A61P9/00; A61P9/08
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
225 words
A controlled absorption ISMN containing pellet formulation for oral administration, said pellet comprising: i) a core of (a) a powder mixture containing an ISMN or a pharmaceutically acceptable salt thereof and optionally one or more excipients selected from an organic acid or base and a pharmaceutically acceptable diluent, and (b) a polymeric material containing a major proportion of a pharmaceutically acceptable water soluble polymer and optionally a minor proportion of a pharmaceutically acceptable water insoluble polymer, said core comprising layers of said powder mixture and said polymeric material superimposed one upon the other and said polymeric material being present in an amount effective to ensure that all of said powder mixture is coated into said core; and (ii) a multi-layer membrane surrounding said core and containing a major proportion of a pharmaceutically acceptable film-forming, water- insoluble polymer and optionally a minor proportion of a pharmaceutically acceptable film-forming, water soluble polymer, the number of layers in said membrane and the ratio of said water-soluble polymers to said water-insoluble polymers being effective to permit release of said ISMN from said pellet at a rate allowing controlled absorption thereof over a 24 hour period following oral administration, said rate being measured in vivo and having a Tmax between 2 and 10 hours and achieving minimum effective blood levels from 12 to 20 hours over a 24 hour period.
Claim 2
Dependent Claim
12 words
A pellet formulation according to Claim 1, wherein the ISMN is isosorbide-5-mononitrate.
Claim 3
Dependent Claim
36 words
A pellet formulation according to Claim 1 or 2, wherein the ISMN or pharmaceutically acceptable salt thereof and organic acid or base and/or pharmaceutically acceptable diluent are present in a ratio of from 1:4 to 50:1.
Claim 4
Dependent Claim
45 words
A pellet formulation according to any preceding claim, wherein the polymeric material of the core includes a major proportion of a polymer which is freely permeable to ISMN and water and a minor proportion of a polymer which is slightly permeable to ISMN and water.
Claim 5
Dependent Claim
49 words
A pellet formulation according to any one of Claims 1 to 4, wherein the multi-layer membrane is composed of a major proportion of a polymer which is slightly permeable to ISMN and water and optionally a minor proportion of a polymer which is freely permeable to ISMN and water.
Claim 6
Dependent Claim
35 words
A pellet formulation according to any one of Claims 1 to 5, wherein the multi-layer membrane is composed of a major proportion of a non-porous polymer and optionally a minor proportion of a porous polymer.
Claim 7
Dependent Claim
67 words
A process for the production of a controlled absorption ISMN-containing pellet according to any one of Claims 1-6, which comprises forming said core as set forth in Claim 1 and enclosing the core in a membrane of a film-forming polymer or mixture thereof as defined in Claim 1 which permits release of the ISMN or pharmaceutically acceptable salt thereof in the manner set out in Claim 1.
Claim 8
Dependent Claim
55 words
A controlled absorption ISMN formulation for oral administration comprising a blend of pellets as defined in any one of Claims 1 to 6 in admixture with a rapidly releasing form of ISMN or a pharmaceutically acceptable salt thereof to ensure a rapid attainment of effective therapeutic blood levels of ISMN within 3 hours following administration.
Claim 9
Dependent Claim
32 words
A controlled absorption ISMN formulation according to Claim 8, wherein the rapidly releasing form of ISMN comprises pellets as defined in any one of Claims 1 to 6 without said multi-layer membrane.
Claim 10
Dependent Claim
21 words
A capsule or tablet comprising a formulation of pellets according to any one of Claims 1 to 6, 8 and 9.
Claim 11
Dependent Claim
106 words
A preparation for the once-daily, percutaneous administration of ISMN or a pharmaceutically acceptable salt thereof which comprises ISMN or a pharmaceutically acceptable salt thereof uniformly distributed in a solid, semi-solid or mucilaginous medium which can be placed in intimate contact with the skin, the release of said ISMN or pharmaceutically acceptable salt thereof from said preparation being at a rate allowing controlled absorption thereof over a 24 hour period following topical application of said preparation, said rate being measured in vivo and having a Tmax between 2 and 16 hours and achieving minimum effective blood levels from 12 to 20 hours over a 24 hour period.
Claim 12
Dependent Claim
34 words
A preparation according to Claim 11, wherein the solidifying or gel-forming agent is a gum selected from guar gum, acacia gum, ghatti gum, karaya gum, tragacanth gum and xanthan gum or a mixture thereof.
Claim 13
Dependent Claim
40 words
A preparation according to Claim 11, wherein the solidifying or gel-forming agent is a synthetic or natural polysaccharide selected from alkylcelluloses, hydroxyalkylcelluloses, cellulose ethers, cellulose esters, nitrocelluloses, dextrin, agar, carrageenan, pectin, furcellaran and starch or starch derivatives and mixtures thereof.
Claim 14
Dependent Claim
14 words
A preparation according to any one of Claims 11-13 which contains a penetration enhancer.
Claim 15
Dependent Claim
67 words
A process for the manufacture of a preparation according to any one of Claims 11-14, which comprises adding a given amount of ISMN or a pharmaceutically acceptable salt thereof to a solution of a solidifying or gel-forming agent or mixture thereof in a suitable solvent or mixture of solvents and mixing or heating the mixture thereby obtained so as to form said solid, semi-solid or mucilaginous medium.
Claim 16
Dependent Claim
90 words
Use of a drug for the manufacture of a pharmaceutical formulation for use in the once-daily administration of said drug in a method to inhibit the development of drug tolerance in humans being treated with said drug in which the once-daily formulation is adapted to achieve therapeutically effective levels of said drug in the blood over a period of not more than 20 hours of the day and further adapted to cause said blood levels to fall significantly below said therapeutic levels throughout the remainder of the 24 hour period.
Claim 17
Dependent Claim
37 words
Use according to Claim 14, wherein the pharmaceutical formulation is in the form of a pellet formulation according to any one of Claims 1-6, 8 and 9 or a preparation according to any one of Claims 11-14.
References Cited (Backward Citations)
No citation records indexed.
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