title: Atazanavir-loaded Eudragit RL 100 nanoparticles to improve oral bioavailability: optimization and in vitro/in vivo appraisal.
abstract: Atazanavir (ATV) is a HIV protease inhibitor. Due to its intense lipophilicity, the oral delivery of ATV encounters several problems such as poor aqueous solubility, pH-dependent dissolution, rapid first-pass metabolism in liver by CYP3A5, which result in low bioavailability. To overcome afore mentioned limitations, ATV-loaded Eudragit RL100 nanoparticles (ATV NPs) were prepared to enhance oral bioavailability. ATV NPs were prepared by nanoprecipitation method. The ATV NPs were systematically optimized (OPT) using 3(2) central composite design (CCD) and the OPT formulation located using overlay plot. The pharmacokinetic study of OPT formulation was investigated in male Wistar rats, and in-vitro/in-vivo correlation level was established. Intestinal permeability of OPT formulation was determined using in situ single pass perfusion (SPIP) technique. Transmission electron microscopy studies on OPT formulation demonstrated uniform shape and size of particles. Augmentation in the values of Ka (2.35-fold) and AUC0-24 (2.91-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT formulation compared to pure drug. Successful establishment of in vitro/in vivo correlation (IVIVC) Level A substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. In situ SPIP studies ascribed the significant enhancement in absorptivity and permeability parameters of OPT formulation transport through the Peyer's patches. The studies, therefore, indicate the successful formulation development of NPs with distinctly improved bioavailability potential and can be used as drug carrier for sustained or prolonged drug release.
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Al-Ameen College of Pharmacy , Bangalore , Karnataka , India.
authors: Gurinder
authors: G
authors: Singh
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Al-Ameen College of Pharmacy , Bangalore , Karnataka , India.
authors: Roopa S
authors: RS
authors: Pai
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000284:Administration, Oral; D000818:Animals; D000069446:Atazanavir Sulfate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D016014:Linear Models; D008297:Male; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D053758:Nanoparticles; D036103:Nanotechnology; D017711:Nonlinear Dynamics; D010316:Particle Size; D010539:Permeability; D010581:Peyer's Patches / Q000378:metabolism*; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D017320:HIV Protease Inhibitors; C050528:Eudragit RS; D000069446:Atazanavir Sulfate
keywords: Bioavailability; central composite design; in situ single pass perfusion studies; in vitro/in vivo correlation; nanoparticles; pharmacokinetic study