Dasabuvir is a non-nucleoside polymerase inhibitor for the treatment of hepatitis C virus (HCV) infection. It is an extremely weak diacidic drug (p = 8.2 and 9.
View Article and Find Full Text PDFSmall molecule developability challenges have been well documented over the last two decades. One of these critical developability parameters is aqueous solubility. In general, more soluble compounds have improved oral absorption.
View Article and Find Full Text PDFA principal advantage of magic angle spinning (MAS) NMR spectroscopy lies in its ability to determine molecular structure in a noninvasive and quantitative manner. Accordingly, MAS should be widely applicable to studies of the structure of active pharmaceutical ingredients (API) and formulations. However, the low sensitivity encountered in spectroscopy of natural abundance APIs present at low concentration has limited the success of MAS experiments.
View Article and Find Full Text PDFThis work examines cocrystal solubility in biorelevant media (FeSSIF, fed-state simulated intestinal fluid), and develops a theoretical framework that allows for the simple and quantitative prediction of cocrystal solubilization from drug solubilization. The solubilities of four hydrophobic drugs and seven cocrystals containing these drugs were measured in FeSSIF and in acetate buffer at pH 5.00.
View Article and Find Full Text PDFIn this manuscript we bring together concepts that are relevant to the solubilization and thermodynamic stability of cocrystals in the presence of drug solubilizing agents. Simple equations are derived that allow calculation of cocrystal solubilization and transition point solubility. Analysis of 10 cocrystals in 6 different solubilizing agents shows that cocrystal solubilization is quantitatively predicted from drug solubilization.
View Article and Find Full Text PDFIn recent years cocrystal formation has emerged as a viable strategy towards improving the solubility and bioavailability of poorly soluble drugs. In this review the success of numerous pharmaceutical cocrystals for the improvement of the solubility and dissolution rates of poorly soluble drugs is demonstrated using various examples taken from the literature. The role of crystal engineering principles in the selection of appropriate coformers and the nature of the supramolecular synthons present within the crystals are described.
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