Process for preparing a crystalline form of halobetasol propionate
Inventors
Gutman, Daniella • Chernyak, Shimon
Assignees
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Publication Number
US-9365609-B2
Publication Date
2016-06-14
Expiration Date
Abstract
The present invention provides a process for preparing a crystalline form of halobetasol propionate, comprising the step of crystallizing halobetasol propionate from absolute ethanol or a mixture of ethanol and water, wherein the crystalline form of halobetasol propionate is characterized by an x-ray powder diffraction pattern having peaks at 10.0, 11.6, 12.9, 13.4, 14.5, 16.4, 17.6, and 23.5±0.2 degrees 2θ.
Core Innovation
The invention relates to a process for preparing a crystalline form of halobetasol propionate by crystallizing a single batch of at least about 100 grams. The process involves heating halobetasol propionate in absolute ethanol or in a mixture of between about 80:20 and about 100:0 ethanol:water to a reflux temperature and then cooling the solution to induce precipitation.
The crystalline form is characterized by an x-ray powder diffraction pattern having peaks at 10.0, 11.6, 12.9, 13.4, 14.5, 16.4, 17.6, and 23.5±0.2 degrees 2-theta. The crystallization is based on the selected ethanol and ethanol:water system and on cooling to induce precipitation of the crystalline form.
Characterization further defines the crystalline form by an infrared spectrum having absorption peaks at 1741, 1709, 1665, 1627, and 1611±0.4 cm−1. The process may include isolating the crystallized halobetasol propionate from the ethanol solution, and the crystallized product may be subjected to a second crystallization from a second ethanol solution.
Claims Coverage
The independent claims cover two process variants, each centered on preparing a crystalline form of halobetasol propionate and characterizing that crystalline form by a specified XRPD peak pattern. The independent claims share the same core XRPD characterization and differ in whether a second crystallization and isolation step is included.
Single-batch crystallization defined by XRPD peaks
A process for preparing a crystalline form of halobetasol propionate comprising crystallizing a single batch of at least about 100 grams by heating to a reflux temperature in absolute ethanol or a mixture of between about 80:20 and about 100:0 ethanol:water, and cooling to induce precipitation, wherein the crystalline form is characterized by an x-ray powder diffraction pattern having peaks at 10.0, 11.6, 12.9, 13.4, 14.5, 16.4, 17.6, and 23.5±0.2 degrees 2-theta.
Two-step crystallization with isolation defined by XRPD peaks
A process for preparing a crystalline form of halobetasol propionate comprising crystallizing a first single batch of at least about 100 grams from a first ethanol solution to reflux and cooling to induce precipitation, isolating crystallized halobetasol propionate from the first ethanol solution, crystallizing the isolated halobetasol propionate from a second ethanol solution to reflux and cooling to induce precipitation, and isolating the crystallized halobetasol propionate from the second ethanol solution, wherein the crystalline form is characterized by an x-ray powder diffraction pattern having peaks at 10.0, 11.6, 12.9, 13.4, 14.5, 16.4, 17.6, and 23.5±0.2 degrees 2-theta.
Across both independent claims, the central inventive concept is preparing a crystalline form of halobetasol propionate by crystallization from absolute ethanol or an ethanol:water mixture followed by cooling to induce precipitation, with the resulting crystalline form defined by a specified XRPD peak pattern at 10.0, 11.6, 12.9, 13.4, 14.5, 16.4, 17.6, and 23.5±0.2 degrees 2-theta. The second independent claim additionally requires isolating crystals after a first crystallization and repeating crystallization from a second ethanol solution.
Stated Advantages
Not explicitly described in patent.
Documented Applications
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