NOVEL TECHNIQUES TO PREPARE SOLID DISPERSIONS TO IMPROVE SOLUBILITY OF BOSENTAN

ABSTRACT

Objective: Bosentan presents challenges with regard to low and variable oral bioavailability due to its poor aqueous solubility and poor dissolution in gastric fluid. Solid dispersion has been used as the solubility enhancement technique due to its ability to develop suitable system with improved solubility and dissolution rate. Methods: Solid dispersions of bosentan were prepared by using novel techniques like solvent controlled coprecipitation, fusion and nanoprecipitation. Polymers with different ionic characteristics like Eudragit^® EPO (cationic), Eudragit^® L 100 55 (anionic) and Povidone K 30 (non-ionic) were employed at three different ratios of 1:1, 1:2 and 1:3 to prepare the solid dispersions of weakly basic bosentan. Dissolution study in buffers corresponding to different physiologically relevant pH was performed to understand the effectiveness of the technique and effect of the polymer. Additionally, samples were subjected for X-ray powder diffraction study to understand the nature of the drug in solid state in the solid dispersion systems. Results: It was observed that irrespective of the pH of the dissolution media, the dissolution rate of the solid dispersions of BOS prepared with Eudragit^® L 100 55 are higher than that of pure drug and the solid dispersions prepared with the other polymers i.e. Eudragit^® EPO and Povidone K 30, which is attributed to the weakly basic nature of bosentan. The diffractograms show decrease in the crystallinity of bosentan in the solid dispersions. Conclusion: The combination of solid dispersion technology with supersaturable systems appears to hold promise for improving dissolution and bioavailability of poorly soluble drugs. The selection of polymers that can inhibit crystallization of the drug in a supersaturated state becomes the key factor for an effective formulation. The present work is an attempt in this direction.

KEYWORDS: Solid Dispersion, Super Saturable systems, Insoluble drugs.