Factors affecting the production of nanostructure lipid carriers of valproic acid.

The objective of this study was to optimize a nano-lipid carrier (NLCs) of valproic acid for nasal delivery using statistical methods. NLCs were prepared by solvent diffusion method followed by ultrasonication. After a preliminary screening study using Taguchi design, the Box-Behnken statistical model using desirability function was applied to evaluate variables affecting key specifications (minimum particle size, maximum drug loading and optimum release) of nano-lipid carriers of valproic acid. Each variable was assessed at three levels of surfactant concentration, acetone/ethanol volume ratio and organic/aqueous phase volume ratio. The best predicted model for particle size and drug release was quadratic model, while for drug loading, 2 factor interaction model fitted better. The measured results for the optimized formulation were a mean size of 154 nm, 47% payload and 75% of drug content released within 21 days. The optimum formulation was obtained using 1% of Poloxamer-188 as surfactant, organic/aqueous phase volume ratio of 1/5 and acetone/ethanol volume ratio of 3/1. Overall, the results show that entrapment of valproic acid in nano-lipid carriers was achieved. Such carriers might be a promising delivery system in the treatment of seizures via the nasal route of administration.