Applying the Taguchi method and Response Surface design for optimized fabrication of nasalnano lipid carriers of valproic acid

摘要

Valproic acid (VPA) is the drug of choice for a range ofgeneralized epilepsies. The need for high daily VPAdosage requirement is due to its relatively inefficientdelivery to the brain. The objective of this study wasproduction a nasal formulation of VPA for its directdelivery to the brain to reduce the systemic side effectsespecially hepatotoxicity of this drug caused by high oraltherapeutic doses. Nano lipid carriers (NLC) wereprepared by solvent diffusion method followed byultrasonication. Seven processing variables each at twolevels were studied by a Taguchi design for screening themost effective variables on the preparation the NLC. Thestudied variables included: lipid type, surfactant type,surfactant percentage, lipid/drug weight ratio, organicphase/aqueous phase, acetone/ethanol volume ratio, andsonicating time. The studied responses were particle size,zeta potential, loading efficiency and release efficiency(RE %). Results showed that three factors (surfactantconcentration, organic/ aqueous volume ratio and acetone/alcohol volume ratio) were the most effective variables onthe studied responses. These variables each in 3 levelswere then used for process optimization by a surfaceresponse methodology based on the Box-Behnkenanalysis. The range of size (Y1) for all batches was 128.3-758 nm. The range of other responses, Y2 ( zeta, mV), Y3( % release after 16 days) and Y3 ( % Drug loading), were-12.5 to -3.5, 37.3-66% and 41.7-48.4%, respectively.