Molecular Docking-guided Coformer Selection and Cocrystallization for Enhanced Biopharmaceutical Performance of Tolvaptan
Year: 2026
Type: article
Abstract: Tolvaptan (TLN), a vasopressin V2 receptor antagonist, is limited by poor aqueous solubility and low oral bioavailability. Cocrystallization with suitable coformers offers a promising strategy to enhance its solubility and dissolution. This study aimed to design, characterize, and evaluate TLN cocrystals with GRAS listed coformers to improve solubility, dissolution, and immediate-release tablet performance. Tolvaptan (TLN) cocrystals were prepared via solvent-drop grinding and characterized using melting point analysis, DSC, and PXRD. Molecular docking guided the selection of nicotinic acid as a suitable coformer. The synthesized cocrystals were subjected to solubility and dissolution studies, and the nicotinic acid cocrystal was formulated into tablets with various disintegrants. The formulations were evaluated through pre- and post-compression studies, while the dissolution profile of the optimized formulation was analyzed in terms similarity factor (f2) in comparison with the marketed tablet. DSC and PXRD analyses confirmed the formation of new crystalline phases. The optimized tablet formulation (F4, 2:3 TLN-to-nicotinic acid ratio with crospovidone as the disintegrant) exhibited rapid disintegration (
Institution: Osmania University
Language: Turkish
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W7204808590