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.
['Stavropoulos|Kathy|K|', 'Johnston|Steven C|SC|', 'Zhang|Yuegang|Y|', 'Rao|Bhisetti Govinda|BG|', 'Hurrey|Michael|M|', 'Hurter|Patricia|P|', 'Topp|Elizabeth M|EM|', 'Kadiyala|Irina|I|']
D010131:Aminosalicylic Acid D000818:Animals D000998:Antiviral Agents D001682:Biological Availability D002152:Calorimetry, Differential Scanning D002626:Chemistry, Pharmaceutical D003460:Crystallization D003890:Desiccation D008297:Male D008958:Models, Molecular D008968:Molecular Conformation D009842:Oligopeptides D033362:Powder Diffraction D051381:Rats D017207:Rats, Sprague-Dawley D012995:Solubility D017361:Viral Nonstructural Proteins
telaprevir coformer solubility cocrystal formulation anti-viral crystal engineering solid state