IMPROVEMENT OF POMALIDOMIDE SOLUBILITY BY SOLID LIPID NANOPARTICLES BY DESIGN OF EXPERIMENT

The aim of the present work is to develop and optimize solid lipid nanoparticles (SLNs) of pomalidomide with the aid of Box-Behnken design (BBD). A design space with three formulation variables at three levels was evaluated in BBD. Amount of lipid (A), surfactant (B), and co-surfactant (C) were selected as independent variables, whereas particle size (Y1), entrapment efficiency (Y2), and percentage drug release after 12 h (Y3) as responses. Pomalidomide-SLNs were prepared by hot emulsification/ ultra-sonication method and evaluated for responses to obtain optimized formulation. The effect of different levels of factors was evaluated for the particle size, PDI, zetapotential, entrapment efficiency, and % cumulative drug released. Kinetic model fitting for all pomalidomide SLN formulations was done to interpret the release rate. Characterization for the optimized formulation was done by FTIR, SEM, and stability studies. The optimized formulation PLF15 with 6% of tricapric as lipid, 6% of poloxamer 188 as surfactant and 2% eupikuron 200 of co-surfactant used in the nanoparticles with 126.59 ± 1.17 nm of size, 0.172 ± 0.02 of polydispersity index, -25.13 ± 4.69 mV zeta potential 89.16±2.72% of entrapment efficiency, 99.53±2.18% of content uniformity and 98.74±2.46% of drug release. The release kinetics suggest that drug release followed zero-order and release was anomalous non- fickian diffusion super case II transport. FTIR studies revealed that there is no incompatibility between drug and excipients, SEM studies confirmed the spherical shape of SLN formulations. Stability studies indicated formulation was stable for 6months. The enhancement in the drug release of pomalidomide from solid lipid nano-particles, explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery of this poorly soluble drug.