Development, Characterization and Comparative Phar-macokinetic Evaluation of Ritonavir Nanosuspension, with a Model Nanoemulsion and Coarse Suspension for Improved Oral Delivery

Abstract

Ritonavir (RV) is an antiretroviral drug, classified as BCS class II pharmaceutical active.It has limited bioavailability due to poor aqueous solubility and first pass metabolism. The purpose of this investigation was to develop optimal nanosuspension and to compare with a model nanoemulsion of RV for improved oral delivery. DSC studies showed good compatibility of excipients with drug. Nanosuspension was prepared by high pressure homogenization, while nanoemulsion was prepared by hot homogenization followed by ultrasonication. All prepared RV formulations were characterized and optimal system was selected and in vivo evaluated. Nanosuspension (F1) formulation containing 0.5% SLS showed homogeneity with least particle size was optimized and compared with coarse (powder) suspension. SEM studies on lyophilized nanosuspension revealed the absence of needle shaped drug crystals, indicating the loss of crystallinity. Prepared a model lipid nanoemulsion. It was having the size, PDI, ZP, EE and assay of 193.14 ± 12.66nm, 0.311 ± 0.04, -27.6 ± 1.184mV, 90.79 ± 0.319% and 99.57 ± 1.25% respectively. Next, a comparative pharmacokinetic study of RV nanosuspenison with respect to lipid nanoemulsion and coarse suspension was performed in male wistar rats. The Cmax of nanosuspension was significantly more when compared to that of NE or coarse drug suspension. The tmax was similar in case of both nanodelivery systems and significantly less when compared to that of coarse suspension. About 1.36 and 1.27 fold improvements in relative bioavailability (BA) of ritonavir via lipid nanoemulsion and nanosuspension were found when compared to coarse suspension. The study results revealed nominal but nonsignificant difference in oral bioavailability for the two nanodelivery systems. Taken together, this study confirmed the potential of nanosuspension and nanoemulsion systems in improving the bioavailability of ritonavir.