Glass鈥揕iquid Phase Separation in Highly Supersaturated Aqueous Solutions of Telaprevir

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• 作者：Laura I. Mosquera-Giraldo ; Lynne S. Taylor
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：February 2, 2015
• 年：2015
• 卷：12
• 期：2
• 页码：496-503
• 全文大小：417K
• ISSN：1543-8392

文摘

Amorphous solid dispersions are of great current interest because they can improve the delivery of poorly water-soluble compounds. It has been recently noted that the highly supersaturated solutions generated by dissolution of some ASDs can undergo a phase transition to a colloidal, disordered, drug-rich phase when the concentration exceeds the 鈥渁morphous solubility鈥?of the drug. The purpose of this study was to investigate the phase behavior of supersaturated solutions of telaprevir, which is formulated as an amorphous solid dispersion in the commercial product. Different analytical techniques including proton nuclear magnetic resonance spectroscopy (NMR), ultraviolet spectroscopy (UV), fluorescence spectroscopy and flux measurements were used to evaluate the properties of aqueous supersaturated solutions of telaprevir. It was found that highly supersaturated solutions of telaprevir underwent glass鈥搇iquid phase separation (GLPS) when the concentration exceeded 90 渭g/mL, forming a water-saturated colloidal, amorphous drug-rich phase with a glass transition temperature of 52 掳C. From flux measurements, it was observed that the 鈥渇ree鈥?drug concentration reached a maximum at the concentration where GLPS occurred, and did not increase further as the concentration was increased. This phase behavior, which results in a precipitate and a metastable equilibrium between a supersaturated solution and a drug-rich phase, is obviously important in the context of evaluating amorphous solid dispersion formulations and their crystallization routes.