Cocrystalline Solids of Telaprevir with Enhanced Oral Absorption.

Autor: Stavropoulos K; Vertex Pharmaceuticals, Incorporated, Boston, Massachusetts., Johnston SC; (Vertex Pharmaceuticals, Incorporated) Currently at SycnovAte, Inc., Litchfield, New Hampshire., Zhang Y; Vertex Pharmaceuticals, Incorporated, Boston, Massachusetts., Rao BG; Vertex Pharmaceuticals, Incorporated, Boston, Massachusetts., Hurrey M; (Vertex Pharmaceuticals, Incorporated) Currently at Gilead Sciences, Incorporated, Foster City, California., Hurter P; Vertex Pharmaceuticals, Incorporated, Boston, Massachusetts., Topp EM; (Vertex Pharmaceuticals, Incorporated) Currently at Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana., Kadiyala I; Vertex Pharmaceuticals, Incorporated, Boston, Massachusetts.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical sciences [J Pharm Sci] 2015 Oct; Vol. 104 (10), pp. 3343-50. Date of Electronic Publication: 2015 Jun 11.
DOI: 10.1002/jps.24534
Abstrakt: 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.)
Databáze: MEDLINE
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