Solid self-nanoemulsifying systems of olmesartan medoxomil: Formulation development, micromeritic characterization, in vitro and in vivo evaluation

• Published in: Powder technology 2016-06, Vol.294, p.93-104
• Main Authors: Beg, Sarwar, Katare, O.P., Saini, Sumant, Garg, Babita, Khurana, Rajneet Kaur, Singh, Bhupinder
• Format: Article
• Language: English
• Subjects: Bioavailability; Design of Experiments; Dissolution; Lipids; Porous carriers; Solubility
• ISSN: 0032-5910; 1873-328X
• DOI: 10.1016/j.powtec.2016.02.023

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 andin vitrodrug 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 vitrodissolution 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 vivopharmacokinetic studies in Wistar rats revealed 2.32 and 3.27-fold enhancement in Cmaxand AUC of the drug from the optimized S-SNEDDSvis-à-visthe pure drug solution. Also, high degree of prognostic ability ofin vitrodissolution performance within vivoperformance was revealed from level Ain vitro/in vivocorrelations (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. [Display omitted] •Development of oil adsorbed solid self-nanoemulsifying formulations•Porous carriers provide excellent adsorption capacity and formulation ability.•Micromeritic studies and mathematical modeling show good flow and compactibility.•In vitrorelease andin vivopharmacokinetic show superior oral bioavailability.