An effort to augment solubility and efficiency of the oral bosentan-bucco-adhesive drug delivery system using graft co-polymer as the carrier

Abstract

Although there are rapid developments in molecular science and synthetic chemistry for investigation of many essential drug molecules, poor solubility and bioavailability issues are major constraint in the design of more efficient formulations. This research study focuses on the enhancement of solubility and development of the bucco-adhesive drug delivery system of bosentan using Soluplus® (polyvinyl-caprolactam-polyvinyl-acetate-polyethylene glycol graft co-polymer) as a carrier. A 32-factorial design was implemented to develop bucco-adhesive tablets using hydroxypropyl methyl cellulose (HPMC) K100 LV (X1) and Carbopol 934 P (X2) as independent variables at various levels whereas t50%(Y1) (time required to release 50% of drug), Rel4h (Y2) (percentage of the drug release in 4 h) and bio-adhesive strength (Y3) were considered as set response parameters. The positive effect of the surface response quadratic model demonstrated the change in the already set dependent variables of t50%, Rel4h and bio-adhesive strength. The FT-IR study confirmed the suitability of all the components used in the design of formulation. DSC and XRD study have confirmed the encapsulation of bosentan in the Soluplus® carrier and amorphous form of bosentan, respectively. Overall, 6.832-fold increase in solubility was observed for bosentan-solid dispersion. High-water uptake and swelling of bucco-adhesive tablets (containing bosentan-solid dispersion) was observed due to presence of the highly hydrophilic-Soluplus®. Rel4hwas found to be 97.86 ± 0.57% for optimized formulation (F4) and was decreased with increasing polymer content. The values of t50% were found to be enhanced from 1.11 to 2.32 h at the lower to higher levels of both the polymers respectively.