title: Optimized self-nanoemulsifying drug delivery system of atazanavir with enhanced oral bioavailability: in vitro/in vivo characterization.
abstract: BACKGROUND
  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 and rapid first-pass metabolism in liver by CYP3A5, which result in low and erratic bioavailability.
  
  
  OBJECTIVE
  The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides of ATV in an attempt to circumvent such obstacles.
  
  
  METHODS
  Equilibrium solubility studies indicated the choice of Maisine 35-1 as lipid, and of Transcutol P and Span 20 as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X1) and surfactant (X2) as the critical factor variables. The SNEDDS were optimized (OPT) using 3(2) central composite design and the OPT formulation located using overlay plot. The pharmacokinetics and in situ single-pass intestinal perfusion studies of OPT formulation were investigated in Wistar rats.
  
  
  RESULTS
  OPT formulation indicated marked improvement in drug release profile vis-à-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT formulation. Augmentation in the values of Ka (1.96-fold) and AUC (2.57-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 Level A substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions.
  
  
  CONCLUSIONS
  The studies, therefore, indicate the successful formulation development of SNEDDS with distinctly improved bioavailability of ATV.
authors.affiliation: Al-Ameen College of Pharmacy, Department of Pharmaceutics , Bangalore, Karnataka , India roopaspai@yahoo.com.
authors.forename: Gurinder
authors.initials: G
authors.lastname: Singh
authors.forename: Roopa S
authors.initials: RS
authors.lastname: Pai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000069446:Atazanavir Sulfate; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004655:Emulsions; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006207:Half-Life; D008297:Male; D053758:Nanoparticles; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D004655:Emulsions; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate
keywords: bioavailability; central composite design; in vitro/in vivo correlation; pharmacokinetic study; self-nanoemulsifying drug-delivery system