Integrated Quality by Design Approach for Developing Nanolipidic Drug Delivery Systems of Olmesartan Medoxomil with Enhanced Antihypertensive Action

The present work endeavors to report a systematic approach of developing the lipidic self-nanoemulsifying formulation of olmesartan medoxomil (OMT) on the principles of Quality by Design (QbD).

For preparing the self-nanoemulsifying formulation, a mixture of oil, surfactant and cosurfactant were used as vehicles. The excipients were selected after screening by solubility as well as pseudoternary phase titration studies. Mixture design was adopted for systematic optimization of the composition of nanolipidic formulations, which were evaluated for smaller globule size, stable zeta potential and lower values of polydispersity index. The optimized liquid self-nanoemulsifying formulation was identified using numerical and graphical optimization techniques, followed by validation of the experimental model. Solidification of self-nanoemulsifying formulation was carried out using porous carriers, and then optimized on the basis of oil adsorption potential, powder flow property and drug release performance. Pharmacokinetic study was performed in male Wistar rats for evaluating the drug absorption parameters. All the experimental data obtained were subjected to statistical analysis using oneway ANOVA followed by post hoc analysis using Student’s t test.

The optimized liquid self-nanoemulsifying formulation showed globule size <100 nm, emulsification efficiency <5 minutes and in vitro drug release >85% within in 30 minutes. Further, the solid SNEDDS formulation was effectively formulated using Neusilin US2 with maximum oil adsorption capacity and good micromeritic properties. Pharmacokinetic evaluation indicated 4 to 5-folds increase (P<0.05) in the values of Cmax, AUC, and reduction in Tmax from the nanoformulations vis-à-vis the marketed formulation.

Overall, the developed nanolipidic formulation of olmesartan indicated superior efficacy in augmenting the drug dissolution and absorption performance.