Patent US4844910A successfully refreshed from Google Patents.
US4844910A
Expired / Lapsed
US
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Spheroids
Assignee: Euro Celtique SA
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Filing: 1987-11-19
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Granted: 1989-07-04
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Expires: 2007-11-19
Abstract
Abstract A controlled release pharmaceutical composition comprising a plurality of film coated spheroids, the film coated spheroids comprising a 3-alkylxanthine, a non-water soluble spheronising agent and between 4% and 9% (by weight) water, wherein the in-vitro dissolution rate of the 3-alkylxanthine from the film coated spheroids, when measured by the USP Paddle Method at 100 rpm in 900 ml aqueous buffer (pH 6.5 at 37° C.) is between 7.5% and 25.0% (by wt) release after 1 hour, between 22.5% and 45.0% (by wt) release after 2 hours, between 40.0% and 60.0% (by wt) release after 3 hours, between 50.0% and 75.0% (by wt) release after 4 hours, between 70.0% and 92.5% (by wt) release after 6 hours, and between 80.0% and 100.0% (by wt) release after 8 hours. Preferably the water content is between 4% and 8%, especially between 4% and 7% (by wt) of the film coated spheroid formulation. The preferred 3-alkylxanthine is theophylline (anhydrous or hydrate), whilst the preferred spheronising agent is microcrystalline cellulose.
Inventors
- 👤 Stewart T. Leslie
- 👤 Sandra T. A. Malkowska
- 👤 Joanne Marchant
- 👤 Philip J. Neale
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 06:21
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1652; A61K31/00; A61K31/33; A61K31/395; A61K31/495; A61K31/505; A61K31/519; A61K31/52; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5036; A61K9/5042; A61K9/5047
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
141 words
A controlled release pharmaceutical composition comprising a plurality of film coated spheroids, the film coated spheroids comprising a 3-alkylxanthine the alkyl group of which is up to three carbon atoms, microcrystalline cellulose as a non-water soluble spheronising agent and between 4% and 9% (by weight) water, wherein the in-vitro dissolution rate of the 3-alkylxanthine from the film coated spheroids, when measured by the USP Paddle Method at 100 rpm in 900 ml aqueous buffer (pH 6.5) at 37° C. is between 7.5% and 25.0% (by wt) release after 1 hour, between 22.5% and 45.0% (by wt) release after 2 hours, between 40.0% and 60.0% (by wt) release after 3 hours, between 50.0% and 75.0% (by wt) release after 4 hours, between 70.0% and 92.5% (by wt) release after 6 hours, and between 80.0% and 100.0% (by wt) release after 8 hours.
Claim 2
Dependent Claim
141 words
A controlled release pharmaceutical composition comprising a plurality of film coated spheroids, the film coated spheroids comprising a 3-alkylxanthine the alkyl group of which is up to three carbon atoms, microcrystalline cellulose as a non-water soluble spheronising agent and between 4% and 9% (by weight) water, wherein the in-vitro dissolution rate of the 3-alkylxanthine from the film coated spheroids, when measured by the USP Paddle Method at 100 rpm in 900 ml aqueous buffer (pH 6.5) at 37° C. is between 7.5% and 25.0% (by wt) release after 1 hour, between 22.5% and 45.0% (by wt) release after 2 hours, between 40.0% and 60.0% (by wt) release after 3 hours, between 50.0% and 75.0% (by wt) release after 4 hours, between 70.0% and 92.5% (by wt) release after 6 hours, and between 80.0% and 100.0% (by wt) release after 8 hours.
Claim 3
Dependent Claim
90 words
A composition according to claim 1 wherein the film coated spheroids contain between 4% and 8% (by weight) water and the in vitro dissolution rate of the 3-alkylxanthine is between 8.0% and 22.5% (by wt) release after 1 hour, between 25% and 42.5% (by wt) release after 2 hours, between 42.5% and 60% (by wt) release after 3 hours, between 52.5% and 72.5% (by wt) release after 4 hours, between 72.5% and 92.5% (by wt) release after 6 hours, and between 82.5% and 100% (by wt) release after 8 hours.
Claim 4
Dependent Claim
90 words
A composition according to claim 2 wherein the film coated spheroids contain between 4% and 7% (by weight) water and the in vitro dissolution rate of the 3-alkylxanthine is between 8% and 20% (by wt) release after 1 hour, between 25% and 40% (by wt) release after 2 hours, between 42.5% and 57.5% (by wt) release after 3 hours, between 55% and 70% (by wt) release after 4 hours, between 75% and 90% (by wt) release after 6 hours, and between 82.5% and 100% (by wt) release after 8 hours.
Claim 5
Dependent Claim
20 words
A composition according to claim 1 wherein the 3-alkylxanthine comprises a 1,3-dimethylxanthine or a salt or derivative of a 1,3-dimethylxanthine.
Claim 6
Dependent Claim
19 words
A composition according to claim 4 wherein the 3-alkylxanthine comprises acepifylline, bamifylline, bufylline, diprophylline, etamiphylline, etofylline, proxyphylline or theophylline.
Claim 7
Dependent Claim
23 words
A composition according to claim 4 wherein the 3-alkylxanthine comprises theophylline, aminophylline, choline theophyllinate, theophylline monoethanolamine, theophylline sodium glycinate or theophylline calcium salicylate.
Claim 8
Dependent Claim
11 words
A composition according to claim 6 wherein the 3-alkylxanthine comprises theophylline.
Claim 9
Dependent Claim
19 words
A composition according to claim 7 wherein the film coated spheroids comprise between 40% and 75% (by weight) theophylline.
Claim 10
Dependent Claim
19 words
A composition according to claim 8 wherein the film coated spheroids comprise between 45% and 70% (by weight) theophylline.
Claim 11
Dependent Claim
22 words
A composition according to claim 1 wherein the film coated spheroids comprise between 20% and 50%, (by weight) of the spheronising agent.
Claim 12
Dependent Claim
22 words
A composition according to claim 10 wherein the film coated spheroids comprise between 25% and 45% (by weight) of the spheronising agent.
Claim 13
Dependent Claim
16 words
A composition according to claim 1 wherein the film coat comprises ethyl cellulose and hydroxypropylmethyl cellulose.
Claim 14
Dependent Claim
216 words
A process for the preparation of a controlled release pharmaceutical composition comprising a plurality of film coated spheroids comprising (a) granulating a mixture comprising a 3-alkylxanthine, the alkyl group of which is up to three carbon atoms microcrystalline cellulose as non-water soluble spheronising agent and water to form a granulated mixture, (b) extruding the thus formed granulated mixture to give an extrudate, (c) spheronising the extrudate until spheroids are formed, (d) drying the spheroids to a water content of between 4% and 9% (by weight), and coating the spheroids with a film coat that permits release of the 3-alkylxanthine at a controlled rate in an aqueous medium, to give film coated spheroids containing between 4% and 9% (by weight) water and the in-vitro underlying dissolution rate of the 3-alkylxanthine from the film coated spheroids, when measured by the USP Paddle Method at 100 rpm on 900 ml aqueous buffer (pH 6.5) at 37° C. is between 7.5% and 25.0% (by wt) release after 1 hour, between 22.5% and 45.0% (by wt) release after 2 hours, between 40.0% and 60.0% (by wt) release after 3 hours, between 50.0% and 75.0% (by wt) release after 4 hours, between 70.0% and 92.5% (by wt) release after 6 hours, and between 80.0% and 100% (by wt) release after 8 hours.
Claim 15
Dependent Claim
216 words
A process for the preparation of a controlled release pharmaceutical composition comprising a plurality of film coated spheroids comprising (a) granulating a mixture comprising a 3-alkylxanthine, the alkyl group of which is up to three carbon atoms microcrystalline cellulose as non-water soluble spheronising agent and water to form a granulated mixture, (b) extruding the thus formed granulated mixture to give an extrudate, (c) spheronising the extrudate until spheroids are formed, (d) drying the spheroids to a water content of between 4% and 9% (by weight), and coating the spheroids with a film coat that permits release of the 3-alkylxanthine at a controlled rate in an aqueous medium, to give film coated spheroids containing between 4% and 9% (by weight) water and the in-vitro underlying dissolution rate of the 3-alkylxanthine from the film coated spheroids, when measured by the USP Paddle Method at 100 rpm on 900 ml aqueous buffer (pH 6.5) at 37° C. is between 7.5% and 25.0% (by wt) release after 1 hour, between 22.5% and 45.0% (by wt) release after 2 hours, between 40.0% and 60.0% (by wt) release after 3 hours, between 50.0% and 75.0% (by wt) release after 4 hours, between 70.0% and 92.5% (by wt) release after 6 hours, and between 80.0% and 100% (by wt) release after 8 hours.
Claim 16
Dependent Claim
32 words
A process according to claim 13 wherein, after the spheroids are dried and before the spheroids are film coated, the spheroids are sieved to give spheroids having a predetermined particle size range.
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JPS56122311A
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-07-03 | 1993-01-02 | 1993-07-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-07-03 | 1997-01-02 | 1997-07-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-07-03 | 2001-01-02 | 2001-07-04 | $7700.00 | Window Closed / Lapsed |