Solid-State Characterization of Novel Propylene Glycol Ester Solvates Isolated from Lipid Formulations

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• 作者：Paroma Chakravarty ; Sanjeev Kothari ; Alan Deese ; Joseph W. Lubach
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：July 6, 2015
• 年：2015
• 卷：12
• 期：7
• 页码：2551-2557
• 全文大小：363K
• ISSN：1543-8392

文摘

The purpose of this study was to identify and characterize precipitates obtained from a liquid formulation of GNE068.HCl, a Genentech developmental compound, and lipophilic excipients, such as propylene glycol monocaprylate, and monolaurate. Precipitates were characterized using powder X-ray diffractometry (PXRD), differential scanning calorimetry, thermogravimetry, microscopy, nuclear magnetic resonance spectroscopy (NMR; solution and solid-state) and water sorption analysis. PXRD and NMR revealed the precipitates to be crystalline solvates of propylene glycol esters. The solvates (capryolate and lauroglycolate) were isomorphic and stable up to 70 掳C, beyond which melting of the lattice occurred with subsequent dissolution of the active ingredient in the melt (microscopy and variable temperature PXRD). They were found to be mechanically stable (no change in PXRD pattern upon compression) and were nonhygroscopic up to 鈭?0% RH (25 掳C). Our results highlight the outcome of inadvertent drug-excipient interactions in two separate lipid solution formulations with good solid-state properties and, thus, potential for further development.