Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485803 | Journal of Pharmaceutical Sciences | 2011 | 11 Pages |
Abstract
Three new forms of the osteoporosis drug sodium risedronate, sodium [1-hydroxy-2-(3-pyridinyl)ethylidene]bisphosphonate, were identified and designated as the J, K, and M phases. Form J is an acetic acid disolvate with the chemical composition Na+ [C7H10NO7P2]â · 2CH3COOH, as determined by single-crystal structure analysis. This novel solvate is easily formed by the recrystallization of sodium risedronate from acetic acid. Dissolution of the new disolvate was characterized in distilled water, a compendial buffer, simulated gastric fluid sine pepsin (pH 1.2), and a biorelevant buffer system FaSSIF-V2 (pH 6.8). It was demonstrated that solubility of the disolvate in physiological buffers differed significantly from that of the original molecule, with delayed dissolution under simulated esophageal and gastric conditions, but rapid and complete dissolution under simulated intestinal conditions. These studies suggest that through the generation of novel solvates, the biopharmaceutical properties of poorly soluble drug candidates can be improved.
Keywords
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Authors
Jürgen Brüning, Anna Christine Petereit, Edith Alig, Michael Bolte, Jennifer B. Dressman, Martin U. Schmidt,