title: Role of lipid-based excipients and their composition on the bioavailability of antiretroviral self-emulsifying formulations.
abstract: The objective of this study was to develop self-emulsifying drug delivery system (SEDDS) to improve solubility and enhance the oral absorption of the poorly water-soluble drug, nevirapine. This lipid-based formulation may help to target the drug to lymphoid organs where HIV-1 virus resides mainly. The influence of the oil, surfactant and co-surfactant types on the drug solubility and their ratios on forming efficient and stable SEDDS were investigated in detail. Two SEDDS (F1 and F2) were prepared and characterized by morphological observation, droplet size and zeta potential determination, cloud point measurement and in vitro diffusion study. The influence of droplet size on the absorption from formulations with varying concentration of oil and surfactant was also evaluated from two self-emulsifying formulations. Oral bioavailability of nevirapine SEDDS was checked by using rat model. Results of diffusion rate and oral bioavailability of nevirapine SEDDS were compared with marketed suspension. The absorption of nevirapine from F1 and F2 showed 1.92 and 1.98-fold increase (p < 0.05) in relative bioavailability, respectively, compared with that of the suspension. There was no statistical significant difference (p < 0.05) between F1 and F2 in their AUC and C(max). This indicated that there was apparent poor correlation between the droplet size and in vivo absorption. However, nevirapine in SEDDS showed higher ex vivo stomach and intestinal permeability and in vivo absorption than the marketed suspension, suggesting that the SEDDS may be a useful delivery system for targeting nevirapine to lymphoid organs.
authors.affiliation: Department of Pharmaceutics .
authors.forename: Arpan
authors.initials: A
authors.lastname: Chudasama
authors.forename: Vineetkumar
authors.initials: V
authors.lastname: Patel
authors.forename: Manish
authors.initials: M
authors.lastname: Nivsarkar
authors.forename: Kamala
authors.initials: K
authors.lastname: Vasu
authors.forename: Chamanlal
authors.initials: C
authors.lastname: Shishoo
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry*; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013535:Suspensions
chemical_list: D019380:Anti-HIV Agents; D004655:Emulsions; D005079:Excipients; D008055:Lipids; D013501:Surface-Active Agents; D013535:Suspensions; D019829:Nevirapine
keywords: Anti-HIV; lipid-based formulation; nevirapine; pseudo-ternary phase diagrams; triglycerides