Enhancement of Bioavailability Performance using Solid-self Microemulsifying Drug Delivery System for High Molecular Weight Drug

Bosentan Hydrochloride (BOS) is poorly water soluble, high molecular weight and eleven hydrogen bond acceptors. Thus, it exhibits poor bioavailability. A new Solid-Self Emulsifying Drug Delivery System (S-SMEDDS) of BOS has been successfully developed to enhance its oral bioavailability by improving its solubility and facilitating high molecular weight of BOS absorption. The primary composition of SMEDDS formulation was selected from solubility, pseudoternary phase diagram, emulsifying efficiency and compatibility test confirmed the suitability of Capmul MCM as oil, Tween 20 as surfactant and Propylene glycol as a co-surfactant for preparation of Liquid-Self Emulsifying Drug Delivery System (L-SMEDDS). The formulation of the BOS loaded L-SMEDDS were prepared in different concentration of oil, surfactant/co-surfactant and optimized by various evolutionary parameter such as robustness to dilution, drug content, ultrasonic interferometer, ease of emulsification, droplet size and in vitro diffusion study. The optimized L-SMEDDS converted into free flowing granules by spray drying technique. S-SMEDDS powder undergoes for characterization and confirmed the no interaction between drug and excipients. The S-SMEDDS powder compressed with variable concentration of directly compressible excipients. S-SMEDDS formulations were employing for both pre-compression and post-compression parameters. In vitro drug release study indicated that significant increased dissolution rate of the drug by all S-SMEDDS tablets versus the marketed formulation. In vivo studies in Sprague-Dowley rat for the optimized formulation was performed and compared to Marketed formulation observe significant increase the Cmax and AUC of BOS compared to Marketed formulation (P>0.05). Thus, the present investigation improved the oral bioavailability of BOS.