DEVELOPMENT OF MESOPOROUS SILICA NANOPARTICLES OF RITONAVIR WITH ENHANCED BIOAVAILABILITY POTENTIAL: FORMULATION OPTIMIZATION, IN-VITRO AND IN-VIVO EVALUATIONAbstract
The objective of the study was to develop mesoporous silica nanoparticles for the poorly water soluble drug ritonavir (RTV) for enhancement of in-vitro dissolution and corresponding in-vivo bioavailability. A comparative assessment between 2D-hexagonal silica nano-structured MCM -41NPs and 3D cubic pore system MCM -48NPs on drug release rate was also investigated. RTV (BCS class II drug), was loaded in the synthesized MCM-41NPs and MCM-48NPs by the solvent evaporation technique. The obtained MCM-41NPs, MCM-48NPs and RTV loaded mesoporous nanoparticles were characterized by different analytical techniques like UV spectrophotometry, differential scanning calorimetry, thermogravimetric analysis, FTIR, N2 adsorption-desorption technique, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and powder-XRD. The in-vitro release profile of RTV was studied in 900 mL 0.1N hydrochloric acid (HCl) medium using USP apparatus-II at 50 rpm. Further; In-vivo studies were performed in Wistar rats where drug loaded mesoporous nanoparticles were compared with pure RTV. In dissolution study MCM-48NPs showed better and fast release of RTV than the MCM-41NPs. In pharmacokinetics study, the maximum peak plasma concentrations of RTV, R- MCM-41NPs and R- MCM-48NPs reached 3.8 ± 0.85 µg/ml, 5.5 ± 0.72 µg/ml and 9.2 ± 0.77 µg/ml by 1 h. The AUC0–t values of the R- MCM-41NPs and R- MCM-48NPs were found 1.34-fold and 1.94-fold higher respectively, as compared with pure RTV. The results demonstrated superiority of MCM-48NPs against MCM-41NPs in enhancing dissolution and improving the bioavailability of RTV.
M. Mahajan and S. Rajput *
Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Kalabhavan Campus, Vadodara, Gujarat, India.
15 January, 2018
02 June, 2018
13 July, 2018
01 October, 2018