D-optimal design-based optimization of etoricoxib cubogel for management of arthritis; in vitro and in vivo evaluation.

Abstract

Etoricoxib (Et) is selective COX-2 inhibitor with several drawbacks after oral administration. Current study focused on formulating targeted Et cubogel for osteoarthritis management. Interaction between formulation factors; (glyceryl-monooleate (GMO) and Poloxamer407 (Px)) concentrations and process parameters (melting/solvent-evaporation preparation methods) was investigated using D-optimal design. Considered levels were 3, 5 and 7% for GMO and 0.5,0.75 and 1% for Px. Effect of selected variables on particle size (PS) and entrapment efficiency (EE) of Et cubosomes was studied using Design Expert software. Optimized formulation was studied for zeta potential, TEM, and Et release. Optimum formula was loaded into gel formulations and subjected to physical characterization and in-vitro Et release. Selected cubogel was evaluated for ex-vivo permeation, and anti-inflammatory activity using carrageenan-induced edema model. Optimum formulation (6.5% GMO,1% Px , melting preparation method) had PS of 58.6 ± 0.51 nm, EE of 96.1 ± 1.5%, zeta potential of -26.6 ± 0.66 mV and cubic structure as indicated by TEM. Formulated cubogels had acceptable physical properties with sustained release depending on gelling agent type and concentration. Ex-vivo permeation confirmed higher permeability for Et cubogel than Etgel. Anti-inflammatory study confirmed enhanced (p < 0.05) anti-inflammatory activity of Et cubogel as compared to Et gel. Hence, the present study presents Et cubgel formulation as anti-inflammatory remedy.