Development and Optimization of Self-Nanoemulsifying tablet dosage form of Nateglinide using Box–Behnken design

The current study was aimed to investigate the potential of solid self-nanoemulsifying drug delivery system (SSNEDDS) composed of Capmul MCM C8 (oil), Cremophor RH40 (surfactant) and transcutol P (co-surfactant) in improving the dissolution and oral bioavailability of Nateglinide (NTG). Liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) were developed by using rational blends of components with good solubilizing ability for NTG which were selected based on solubility studies, further ternary phase diagram was constructed to determine the selfemulsifying region. The prepared L-SNEDDS formulations were evaluated to determine the effect of composition on physicochemical parameters like rate of emulsification, clarity, phase separation, thermodynamic stability, cloud point temperature, globule size and zeta potential. In vitro drug release studies of optimized L-SNEDDS showed almost 96.76±1.4% within 45 min. The globule size analysis revealed the formation of nanoemulsion (130 ± 1.6nm) from the optimized L-SNEDDS formulation. Optimized L-SNEDDS was incorporated into tabletting excipients to make optimized self-nanoemulsified tablet formulation. A three factor, three-level Box–Behnken design was used for the optimization procedure, with the amounts of X1 (maltodextrin), X2 (Kollidon VA 64), and microcrystalline cellulose (X3) as the independent variables, while Flowability index (Y1), Friability (%) (Y2), Disintegration time (min) (Y3) and Cumulative % of NTG released after 45 min (%) (Y4) as responses. The optimization model predicted 99.48% % release with X1, X2 and X3 levels of 224, 100 and 111, respectively. A new formulation was prepared according to these levels. The observed responses were in close agreement with the predicted values of the optimized formulation.