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    • 5. 发明申请
    • PHARMACEUTICAL FORMULATION WITH ENHANCED SOLUBILITY FOR THE DELIVERY OF CORTICOSTEROIDS
    • 具有增强溶解性的药用配方用于输送角质素
    • US20080081070A1
    • 2008-04-03
    • US11680276
    • 2007-02-28
    • Glynn WilsonGerhard RennerHema RavishankarPreeti Patil
    • Glynn WilsonGerhard RennerHema RavishankarPreeti Patil
    • A61K9/32A61K31/56A61P1/00
    • A61K9/5073A61K9/5078A61K31/56
    • Formulations have been developed to improve the solubility of corticosteroids such as fluticasone proprionate in a composition designed to achieve localized release of the drug in the small intestine and/or colon. In one embodiment, solid dispersions of fluticasone are prepared wherein the drug is blended with or coated onto a highly water soluble substrate such as nonpareil (sugar beads) then coated with a layer of polymer soluble in small intestinal fluid, then coated with an enteric coating. The inner polymer layer controls release of the drug, and the enteric coating, a pH sensitive polymer that is broken down in the ileum and colon, controls localized release of drug at various sites within the gastrointestinal tract. The multilayer pharmaceutical composition can be in the form of pellets, tablets compressed from pellets or pellets packed into capsules. The release profile of the drug can be manipulated by (1) altering size or shape (i.e., surface area) and solubility of the inert substrate; (2) the ratio of drug to polymer, the polymer composition and solubility, the porosity of the polymer; (3) the drug form (i.e., free base or salt, or which salt); and the thickness and/or surface area of the drug/polymer and/or enteric coating. In a preferred embodiment, the composition is administered orally. This may also be packaged to provide for an escalating or tapering dosage.
    • 已经开发了用于改善皮质类固醇(例如丙酸氟替卡松)在旨在实现药物在小肠和/或结肠中的局部释放的组合物中的溶解度的制剂。 在一个实施方案中,制备氟替卡松的固体分散体,其中将药物与高水溶性底物如非乳糖(糖珠)混合或涂覆在其上,然后用可溶于小肠液的聚合物层涂覆,然后用肠溶衣 。 内部聚合物层控制药物的释放,并且肠溶衣(在回肠和结肠中分解的pH敏感聚合物)控制药物在胃肠道内各处的局部释放。 该多层药物组合物可以是丸粒形式,从颗粒或丸剂包装的胶囊中压制的片剂。 可通过(1)改变惰性底物的尺寸或形状(即表面积)和溶解度来操纵药物的释放曲线; (2)药物与聚合物的比例,聚合物组成和溶解度,聚合物的孔隙率; (3)药物形式(即游离碱或盐,或其盐); 以及药物/聚合物和/或肠溶衣的厚度和/或表面积。 在优选的实施方案中,组合物经口施用。 这也可以被包装以提供逐渐升高或渐细的剂量。