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

Clinsmart LLC

Abstract

The present disclosure provides a once-daily water-soluble pharmaceutically active formulation for oral administration. In certain embodiments, the composition comprises a watersoluble 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 once-daily oral extended-release particulate formulation in which a water-soluble pharmaceutically active is reversibly associated with a drug-binding polymer within a small core and surrounded by an insoluble water-permeable membrane-forming polymer to delay dissolution and extend drug release. The formulation is described as a particulate composition for oral administration comprising a biologically active core and a coat, where the biologically active core includes naproxen, a pharmaceutically acceptable salt of naproxen, or combinations thereof in reversible association with a drug binding polymer.

In the described particulate composition, the drug binding polymer comprises silicified high density microcrystalline cellulose composed of 98% microcrystalline cellulose and 2% colloidal silicon dioxide, with naproxen, the pharmaceutically acceptable salt, or combinations thereof in reversible association with the drug binding polymer at a weight ratio from about 20:1 to about 1:2. The core is surrounded by a coat comprising a membrane-forming polymer comprising ethylcellulose, where the particulate composition comprises microparticles having average diameter from about 100 µm to about 900 µm.

The invention further defines a dissolution rate behavior measured in a type 1 dissolution basket apparatus according to U.S. Pharmacopoeia XXII in phosphate buffer at pH 7.2 and 75 r.p.m. The dissolution pattern requires staged release such that from 15 to 50% of the total amount 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. The described formulation is presented as achieving controlled absorption for once-daily treatment.

Claims Coverage

The provided material includes three independent claims, each covering a method of treating pain using a particulate composition with a specific naproxen core reversibly associated with a specified drug-binding polymer and surrounded by an ethylcellulose membrane-forming polymer coat, with microparticle size and a defined dissolution rate pattern in a USP type 1 basket apparatus. Across the independent claims, the number of inventive features is driven by five features: the core composition and reversible association, the specified drug-binding polymer identity and weight ratio, the ethylcellulose membrane coat, the microparticle size, and the dissolution-release pattern with specific timepoint ranges.

Across the independent claims, the covered inventive aspects are a naproxen, or salt or combination thereof, biologically active core reversibly associated with silicified high density microcrystalline cellulose at a specified weight ratio, an ethylcellulose membrane-forming polymer coat surrounding the core, microparticles sized to an average diameter of about 100 µm to about 900 µm, and a USP type 1 phosphate buffer dissolution pattern defined by timepoint release ranges at 0.5, 1, and 4 hours.

Stated Advantages

Documented Applications