Introducing novel hybridization technique for solubility enhancement of Bosentan formulation

Abstract

Bosentan is choice of drug for pulmonary arterial hypertension. It belongs to BCS class-II category. Due to poor solubility in aqueous media, treatment leads to frequent dosing & increasing cost of therapy subsequently. One cannot unseen the shortcomings of commonly existing solubility enhancement techniques such as physical and chemical modifications of the drug, salt formation, solid dispersion, complexation because of the need for sophisticated equipment, decreased yield, incomplete removal of organic solvents, etc. The novel hybridization technique is a fusion of complexation and liquisolid technique. In this research work, Bosentan was complexed with captisol in the first step. In the second step, the complex was dispersed in non-volatile solvent & mixed with the carrier using mortar-pestle followed by the addition of coating material to form a free-flowing powder. It was then compressed into tablets by mixing with other excipients. The formulation was characterized by phase solubility study, DSC, FTIR, and XRD to confirm drug-excipients compatibility, crystallinity etc. The phase solubility study showed ∼28.85 fold increase in solubility. From screening, Avicel PH101 & Parteck SLC 500 as carrier and coating material respectively & PEG-600 as non-volatile solvent were selected. Explotab as super-disintegrant and Pearlitol 100SD as direct compressible excipient were used. Optimization by 32 factorial design gave Bosentan tablet with disintegrate in time of 7–8 min and showed 87.264±0.823% drug release in 30 min higher than marketed tablet i.e. 61.750±1.226%. From the stability study, the Novel hybridization technique was proved as a choice for solubility enhancement.

Keywords

• Bosentan
• Liquisolid
• Complexation
• Captisol (Sulfobutylether β-cyclodextrin)
• Mesoporous silica