Development of Bosentan Hydrochloride - Loaded Solid Self-Micro Emulsifying Drug Delivery System (SMEDDS) For the Treatment of Pulmonary Hypertension

The main purpose of this research study was to investigate the potential of self- micro-emulsifying drug delivery system (SMEDDS) in improving the bioavailability of Bosentan (BOS) and its therapeutic effect. In this study the S-SMEDDS of BOS powder was prepared by spray drying technology. It contains S-SMEDDS of BOS (59.57%), anhydrous lactose (11.4%), pregelatinized starch (3%), microcrystalline cellulose (22%), Magnesium stearate (2%) and Talc (2%) were selected and final weight of tablet was 965 mg. The S-SMEDDS consists of well separated particle with smooth surface observed from SEM. Both the DSC and XRD analysis suggest that BOS in S-SMEDDS may be in molecular dispersion state. In-vitro dissolution test shows that S-SMEDDS of BOS tablet had faster release rate. Formulation (F3) released 99.80% BOS within 30 min. The similarity factor found between F3 and marketed formulation was 18.19 therefore it confirmed F3 formulation better release pattern than the marketed formulation and pure drug. Release profile treated with different kinetic equations it indicated S-SMEDDS tablet best fit to Zero order model, non Fickian confirms the release of drug by diffusion mechanism. In-vivo Adsorption study in rat showed that S-SMEDDS tablet (F3) increased significant bioavailability of BOS compared to the pure drug. The “%”relative bioavailability of F3 formulation was found to be 159 % compared to pure drug and marketed formulation of BOS. Thus the S-SMEDDS provide a useful oral solid dosage form for poorly water soluble and higher molecular weight drug BOS. Methods: PubMed and Embase databases have been searched, and related studies are compiled and summarized. Conclusion: The study successfully developed a solid self-microemulsifying drug delivery system (S-SMEDDS) for BOS using spray-drying technology, with an optimal composition of Campul MCM (30%), Tween 20 (50%), and propylene glycol (20%) in the liquid SMEDDS (L-SMEDDS). The S-SMEDDS powder exhibited well-separated, smooth-surfaced particles while retaining self-emulsifying properties. DSC and XRD analyses indicated that BOS was molecularly dispersed within the system. When formulated into tablets (F3), the S-SMEDDS demonstrated significantly faster drug release (99.80% within 30 minutes) compared to the marketed formulation and pure drug, as evidenced by a low similarity factor (f₂ = 18.19). Drug release followed zero-order kinetics with non-Fickian diffusion, suggesting a combined diffusion-based mechanism. These findings highlight the potential of S-SMEDDS tablets to enhance the dissolution and bioavailability of BOS.