Controlled absorption water-soluble pharmaceutically active organic compound formulation for once-daily administration
Inventors
Counts, David F. • Cox, Donald P. • Dam, Anup K. • Stalhamer, Michael E.
Assignees
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Publication Number
US-10463611-B2
Publication Date
2019-11-05
Expiration Date
Abstract
The present disclosure provides a once-daily water-soluble pharmaceutically active formulation for oral administration. In certain embodiments, the composition comprises a water-soluble pharmaceutically active organic compound incorporated into a small particulate, each particulate having a core of the water-soluble pharmaceutically active organic compound or an acceptable salt thereof in reversible association with a pharmaceutically acceptable drug-binding polymer. The core of the composition being surrounded by an insoluble water permeable membrane that is capable of delaying the dissolution of the pharmaceutically active compound therewithin and providing for extended release of the pharmaceutically active compound. In some embodiments, the formulation of the invention are designed to extend release of the pharmaceutically active organic compound for about 3 hours to about 8 hours, thereby enabling preparation of an extended release formulation for any pharmaceutically active compound with a half-life of from about 16 hours to about 21 hours.
Core Innovation
The invention relates to a particulate composition having a biologically active core comprising naproxen, a pharmaceutically acceptable salt of naproxen, or a combination thereof. The biologically active core further comprises a drug binding polymer in which the naproxen component is in reversible association with the drug binding polymer, with a defined weight ratio of from about 20:1 to about 1:2. The particulate composition also includes microparticles/microparticulates having an average diameter of from about 100 μm to about 900 μm.
The biologically active core is surrounded by a coat comprising a membrane-forming polymer comprising ethylcellulose. This coat surrounds the biologically active core to provide a particulate composition with a defined dissolution rate. The dissolution behavior is specified by measurements in a type 1 dissolution basket apparatus according to U.S. Pharmacopoeia XXII in phosphate buffer at pH 7.2 and at 75 r.p.m.
The particulate composition has a dissolution pattern defined in terms of percent release of the total amount of naproxen, the pharmaceutically acceptable salt of naproxen, or the combination. Specifically, from 15 to 50% is released after 0.5 hours, from 25 to 75% is released after 1 hour, and not less than 65% is released after 4 hours in the stated apparatus and conditions. The drug binding polymer is silicified high density microcrystalline cellulose composed of 98% microcrystalline cellulose and 2% colloidal silicon dioxide.
Claims Coverage
The document provides three independent claims, each covering a particulate composition with a naproxen-containing reversible association core and an ethylcellulose membrane-forming coat, together with a defined USP type 1 dissolution pattern. The independent claims additionally differ in how strictly the drug binding polymer and/or the biologically active core are defined.
Reversibly associated naproxen core with silicified high density microcrystalline cellulose drug binding polymer and defined core weight ratio
A biologically active core comprising naproxen, a pharmaceutically acceptable salt of said naproxen, or a combination thereof; and a drug binding polymer comprising silicified high density microcrystalline cellulose composed of 98% microcrystalline cellulose and 2% colloidal silicon dioxide, wherein the naproxen component is in reversible association with the drug binding polymer and in a weight ratio therewith of from about 20:1 to about 1:2.
Ethylcellulose membrane-forming coat surrounding the biologically active core for microparticles in a defined diameter range
A coat comprising a membrane-forming polymer comprising ethylcellulose surrounding the biologically active core, wherein the particulate composition comprises microparticles/microparticulates having average diameter of from about 100 μm to about 900 μm.
USP type 1 phosphate buffer dissolution pattern with defined percent release at 0.5, 1, and 4 hours
A particulate composition having a dissolution rate measured in a type 1 dissolution basket apparatus according to U.S. Pharmacopoeia XXII in phosphate buffer at pH 7.2 and at 75 r.p.m. corresponding to: 15 to 50% released after 0.5 hours; 25 to 75% released after 1 hour; and not less than 65% released after 4 hours.
Across the independent claims, the main inventive elements are a naproxen-containing biologically active core with a reversible association to silicified high density microcrystalline cellulose drug binding polymer in a defined weight ratio range, an ethylcellulose membrane-forming coat surrounding the core, microparticles/microparticulates having an average diameter of about 100 μm to about 900 μm, and a defined USP XXII type 1 phosphate buffer dissolution pattern with specified percent release at 0.5, 1, and 4 hours.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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