화학공학소재연구정보센터
Powder Technology, Vol.294, 93-104, 2016
Solid self-nanoemulsifying systems of olmesartan medoxomil: Formulation development, micromeritic characterization, in vitro and in vivo evaluation
The current studies entail development and evaluation of solid self-nanoemulsifying drug delivery systems (S-SNEDDS) employing porous carriers for enhancing the oral bioavailability of olmesartan medoxomil. Equilibrium solubility studies and pseudoternary phase diagrams revealed suitability of oleic acid, Tween 40 and Transcutol HP as the lipid, surfactant and cosolvent for formulation of the liquid SNEDDS (L-SNEDDS). The L-SNEDDS were systematically optimized using optimal mixture design, evaluated for emulsification time, globule size and in vitro drug release. S-SNEDDS formulations were prepared by adsorbing L-SNEDDS onto the porous carriers, viz. Aerosil 200, Aeroperl 300, Sylysia 550, Neusilin US2 and Fujicalin SG, and evaluated for oil adsorption tendency, micrometric behavior, flow properties and compaction characteristics using Kawakita, Heckel and Leuenberger plots for identifying the suitable solid carrier for formulation of S-SNEDDS tablet. In vitro dissolution studies were performed for comparative analysis of the drug release behavior from the S-SNEDDS formulation. Among the various solid carriers employed, Neusilin US2 exhibited superior oil adsorbing capacity, micrometric properties, excellent flowability and compactibility. Nearly 2.6-fold improvement in the drug release rate was observed from the optimized S-SNEDDS, followed by no significant difference in the drug release rate as compared to the L-SNEDDS (p > 0.05). In vivo pharmacokinetic studies in Wistar rats revealed 232 and 3.27-fold enhancement in C-max and AUC of the drug from the optimized S-SNEDDS vis-a-vis the pure drug solution. Also, high degree of prognostic ability of in vitro dissolution performance with in vivo performance was revealed from level A in vitro/in vivo correlations (IVIVC). In a nutshell, the present studies report successful development of S-SNEDDS of olmesartan medoxomil as one of the promising formulation strategies with distinctly improved biopharmaceutical attributes. (C) 2016 Elsevier B.V. All rights reserved.