Characterization of a new solvate of risedronate.
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(+) [C(7) H(10) NO(7) P(2)](-) · 2CH(3) COOH, 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.
Brüning
Jürgen
J
Institute of Inorganic and Analytical Chemistry, Goethe-University, Max-von-Laue-Str. 7, 60438 Frankfurt am Main, Germany.
Petereit
Anna Christine
AC
Alig
Edith
E
Bolte
Michael
M
Dressman
Jennifer B
JB
Schmidt
Martin U
MU
D050071:Bone Density Conservation Agents / Q000737:chemistry*; D002021:Buffers; D003460:Crystallization; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D033362:Powder Diffraction; D000068296:Risedronic Acid; D012995:Solubility; D044366:Transition Temperature; D014867:Water
D050071:Bone Density Conservation Agents; D002021:Buffers; D014867:Water; D000068296:Risedronic Acid; D012968:Etidronic Acid