Sustained drug release and improved product stability using non-covalent particle coating methods
Inventors
Assignees
ITL PHARMA, INC. • JEROME STEVENS PHARMACEUTICALS, INC. • Latham Keith
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Publication Number
US-9526701-B2
Publication Date
2016-12-27
Expiration Date
Abstract
The present invention relates to improved methods of making compositions and compositions made by these methods having improved stability and/or extended release of an active agent or drug upon administration. These compositions may generally comprise an active agent or drug non-covalently immobilized or bound to an excipient substrate. The active agent or drug may include a wide variety of drugs. Binding of the active agent or drug to the substrate may be achieved by evaporating a solvent containing the active agent dissolved therein or by triggering co-precipitation by addition of a precipitating solvent. Additional steps of vacuum removal of surrounding atmosphere and replacement with inert gas may provide additional stability. Present methods and compositions also facilitate manufacturing of drug products and may make these processes safer in some cases. The present invention further provides improved methods of treatment or administration, which may take advantage of improvements with present compositions.
Core Innovation
The invention stabilizes an active agent or drug by starting with an active agent or drug hydrate having bound water, where the active agent or drug degrades in the presence of water. The bound water is removed by dissolving the hydrate in one or more independent solvents comprising 0.05% water by volume or less, wherein the solvent is capable of forming an azeotrope with the dissolved previously bound water. The dissolving forms a solution comprising the dissolved active agent or drug and an azeotrope of the solvent and the dissolved previously bound water.
A substrate that is a pharmaceutically suitable excipient is added to form a suspension with the solution, and the dissolved previously bound water is sequestered from the active agent or drug. Sequestering includes depositing an anhydrous active agent or drug of the active agent or drug hydrate onto the substrate. The azeotrope is then evaporated until a substrate powder is formed, wherein at least one molecule of the anhydrous active agent or drug is non-covalently bound to the substrate.
For thyroid hormone congener stabilization, the invention forms an azeotropic solution by dissolving a thyroid hormone congener hydrate in a solvent such that the azeotropic solution comprises the thyroid hormone congener dissolved in an azeotrope, with the azeotrope comprising the solvent and previously bound water from the thyroid hormone congener hydrate. A pharmaceutically suitable excipient substrate is added to form an azeotropic suspension, and the azeotrope is evaporated until a substrate powder is formed. The substrate powder comprises at least one molecule of anhydrous thyroid hormone congener dehydrated during evaporating, where the anhydrous thyroid hormone congener is non-covalently bound to the substrate.
Claims Coverage
The partial content includes two independent claims that cover two inventive features.
Azeotrope-based bound-water removal and deposition onto a pharmaceutically suitable excipient substrate
The method provides an active agent or drug hydrate having bound water where the active agent or drug degrades in the presence of water, removes the bound water by dissolving the hydrate in one or more independent solvents comprising 0.05% water by volume or less that can form an azeotrope with the previously bound water, adds a pharmaceutically suitable excipient substrate to form a suspension, sequesters the dissolved previously bound water by depositing an anhydrous active agent or drug onto the substrate, and evaporates the azeotrope until a substrate powder is formed with at least one molecule of the anhydrous active agent or drug non-covalently bound to the substrate.
Thyroid hormone congener stabilization via azeotropic solution, azeotropic suspension, and non-covalent deposition onto excipient substrate powder
The method forms an azeotropic solution by dissolving a thyroid hormone congener hydrate in a solvent such that the azeotrope comprises the solvent and previously bound water from the hydrate, where the solvent comprises 0.05% water by volume or less before forming the azeotrope; forms an azeotropic suspension by adding a substrate that comprises a pharmaceutically suitable excipient; and deposits an anhydrous thyroid hormone congener onto the substrate by evaporating the azeotrope until a substrate powder is formed, wherein the substrate powder comprises at least one molecule of anhydrous thyroid hormone congener dehydrated during evaporating and the anhydrous thyroid hormone congener is non-covalently bound to the substrate.
Across the independent claims, stabilization is achieved by dissolving a hydrate in a low-water, azeotrope-forming solvent, adding a pharmaceutically suitable excipient substrate to sequester previously bound water, and evaporating the azeotrope to form a substrate powder where the anhydrous active agent or drug, including anhydrous thyroid hormone congener, is non-covalently bound to the substrate.
Stated Advantages
Improved stabilization of an active agent or drug by removing bound water, where degradation occurs in the presence of water.
Produces a substrate powder in which anhydrous active agent or drug molecules are non-covalently bound to the substrate.
Documented Applications
Sustained-release composition including a substrate powder prepared by the method of claim 1.
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