Enhancement of Solubility and Bioavailability of BCS II Poorly Aqueous Soluble drugs Invitro and Invivo studies

Abstract

The present thesis is entitled as Enhancement of Solubility and Bioavailability of BCS II Poorly Aqueous Soluble Drugs: In Vitro and In Vivo Studies. In the present study, an attempt has been made to enhance the solubility and bioavailability of selected poorly water soluble drugs like ambrisentan and bosentan. Both are BCS class II drug use in the treatment of pulmonary arterial hypertension. Solid dispersion and Melt sonocrystallization technique is employed for the purpose of solubility enhancement of drugs. Solid dispersion of both the drug was prepared using carrier Gelucire 50/13 and Soluplus in different drug to carrier ratio utilizing kneading technique. Melt sonocrystallization of both the drug was performed by applying the ultra sound energy using probe sonicator at fixed amplitude of 80% for different time period. Obtained solid dispersions and Melt sonocrystallized form of drug ware evaluated for solubility, percentage yield, drug content and in vitro dissolution study. Powder characterization was performed by infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Scanning electron microscopy (SEM). Solubility study conducted on resultant SDs and MSC form of drug showed multifold increase in aqueous solubility of drugs as compare to is pure form. FTIR study of prepared formulations showed no interaction between drug and carrier and no change in drug symmetry. DSC and XRD study suggest the reduction in crystallinity and amorphous conversion of both drug by both process. SEM study demonstrate the complete encapsulation drug in carrier in SD and reduction in crystalline state of drug in MSC. In vitro dissolution study showed the faster rate of drug release for both process as compare to pure drugs. Among the two drugs and two methods, on the basis of solubility and dissolution rate of drug, Solid dispersion of ambrisentan prepared with Gelucire 50/13 at 1:4 drug to polymer ratio (ASD4) was considered as optimized formulation and selected for In vivo study.