Cocrystalline Solids of Telaprevir with Enhanced Oral Absorption

A combination of coformer screening and modeling, followed by characterization using calorimetry, structure elucidation, and solubility led to the identification of novel crystalline forms of the hepatitis C protease inhibitor, telaprevir. The lead crystalline form, a cocrystalline solid of telaprevir with 4-aminosalycilic acid, was identified among the list of possible cocrystals via modeling and confirmed by initial screening. It displayed the most significant aqueous solubility improvement over the neat crystalline form. Enhancement of in vivo performance was further demonstrated: a 10-fold increase in bioavailability was achieved for the cocrystal in comparison to the neat nanocrystalline telaprevir and it was found to be not statistically different from the lead amorphous spray-dried formulation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3343-3350, 2015

通过共形成物筛选和建模，接着使用量热法进行表征、结构解析以及溶解度研究，鉴定出了丙型肝炎蛋白酶抑制剂特拉匹韦的新型晶型。通过建模在可能的共晶列表中确定了主要晶型，即特拉匹韦与4 - 氨基水杨酸的共晶固体，并通过初步筛选得到了证实。它相较于纯晶型在水溶性方面有最显著的提高。体内性能的增强得到了进一步证明：与纯纳米晶特拉匹韦相比，该共晶的生物利用度提高了10倍，并且发现它与主要的无定形喷雾干燥制剂在统计学上没有差异。© 2015威利期刊公司和美国药剂师协会《药物科学杂志》104:3343 - 3350, 2015