Surface stabilized efavirenz nanoparticles for oral bioavailability enhancement.
The aim of the present study was to prepare surface stabilized nanoparticles for oral bioavailability enhancement of efavirenz (EFZ). EFZ nanoparticles (EFZ-NPs) were prepared by combination of anti-solvent precipitation and high pressure homogenization technique, using hydroxy propyl methyl cellulose as stabilizer which resulted in formation of EFZ-NPs of average particle size -350 nm with excellent particles size distribution (< 0.2). EFZ-NPs were freeze dried using trehalose as cryoprotectant and found to be quite stable against storage at 25 +/- 2 degrees C/60 +/- 5% RH and 40 +/- 2 degrees C/75 +/- 5% RH as evidenced from particle size, particle size distribution and drug content. EFZ-NPs demonstrated an increase in saturation solubility by 5.16 folds in comparison with free EFZ. In vitro dissolution studies established advantage of EFZ-NPs over free EFZ as more than 75% drug was dissolved within 5 min in case of EFZ-NPs while it was approx 20% in case of free EFZ. In vivo pharmacokinetic studies further confirmed the potential of EFZ-NPs as 2.02 folds increase in peak plasma concentration and 2.29 folds increase in AUC(0-infinity) were observed in comparison to free EFZ. The In vitro-In vivo relationship of the formulations further suggested higher correlation coefficient of 0.9995 for EFZ-NPs in Levys plot as compared to 0.8726 for free EFZ.
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India. sanyogjain@niper.ac.in
Sanyog
S
Jain
Jagadish M
JM
Sharma
Ashish K
AK
Agrawal
Rahul R
RR
Mahajan
D000284:Administration, Oral; D000480:Alkynes; D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D003521:Cyclopropanes; D004058:Diffusion; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D005079:Excipients; D053769:Nanocapsules; C098320:efavirenz