Tolvaptan is a selective, competitive vasopressin receptor 2 antagonist used to treat of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium < 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone. Tolvaptan belongs to BCS class IV with low solubility and low permeability, which results into poor bioavailability after oral administration. Therefore, solid dispersions (SDs) of Tolvaptan were prepared to enhance the solubility and bioavailability by two methods, Hot-melt extrusion (HME) and Spray drying technique (SDT) using various carriers like Soluplus, Copovidone (Kollidon VA64), Polyvinyl pyrrolidone (Kollidon 30) and Hypromellose 2.5cPs.to increase its aqueous solubility. Higher drug release was found in the SDs prepared by hot melt extrusion (HM3) as compared with spray drying technique (SDT2). There is more than 7 fold increases in the solubility of Tolvaptan prepared by HME and SDT compared with pure drug substance. The in vitro drug release profiles in HM3 and SDT2 are found to be comparable to that of drug release profiles of corresponding Innovator product. Physical characterization of hot melt extrudes of HM3 and spray dried mixture of SDT2 by FT-IR, DSC, XRD and SEM revealed that there was a change in crystal structure toward an amorphous form of Tolvaptan. The obtained results suggested that developed Tolvaptan SDs by HME & SDT has potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of Tolvaptan.
