Preparation, Pharmaceutical Properties and Stability of Lesinurad Co-crystals and Solvate

Lesinurad is a BCS class 2, low solubility drug, indicated for hyperglycemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone. Co-crystallization and solvate formation with pharmaceutically acceptable coformers and solvents are one of the best ways to improve solubility of BCS class 2 drugs. Lesinurad DMSO (dimethyl sulphoxide) solvate (1: 1 mole ratio), urea and 4-Hydroxy benzoic acid co-crystals (1:1 mole ratio) prepared and scaled up to 100g and characterized using PXRD, FTIR, DSC, TGA, solid state C-13 NMR and H-1 NMR. Unique PXRD pattern, red shift in acid carbonyl stretching of Lesinurad in DMSO solvent, Urea co-crystal and parahydroxybenzoic acid co-crystals are the evidence of solvate and co-crystal formation. Urea co-crystal is further characterized using C-13 solid state NMR. Deshielding of acid carbonyl carbon from delta(ppm) of 168.98 to 173.12 and shielding of urea carbonyl carbon from delta(ppm) of 169 to 164.56 indicates co-crystal formation between lesinurad and urea. DMSO solvate has shown 1.26 fold increase in Intrinsic dissolution rate measurement (IDR) over marketed Form-II and urea co-crystal. DMSO solvate, urea and 4-Hydroxy benzoic acid cocrystals of lesinurad are stable for six months at 40 degrees C and 75% RH. (C) 2019 Elsevier Ltd. All rights reserved.