Formulation and Characterization of Amisulpride Microemulsions for Brain Targeting via Intranasal Route-Pharmacodynamic Evaluation in Rat Model

Abstract

Amisulpride is an atypical antipsychotic drug with dopamine (D2/D3) receptor blocker activity. The oral bioavailability of amisulpride was below 48% due to first pass metabolism and poor aqueous solubility. In order to improve bioavailability and targeting to brain, amisulpride microemulsions for intranasal delivery were developed and evaluated. The amisulpride microemulsions were prepared by water titration method and optimized. The optimized formulation ME10 was composed of 5% Oleic acid, 65% of Smix (Tween 80 and PEG 400 in 2:1 ratio) and 30% of water and showed mean globule size of 117.6 nm, PDI 0.259, zeta potential -23.8 mV, steady state flux of 217.16 μg/cm2/hr and was selected as optimized formulation. The influence of Chitosan on permeability was studied and formulation MME1 containing 0.1% Chitosan showed mean zeta size of 112.5 nm, PDI 0.210, zeta potential +15.2mV, pH 6.1, steady state flux of 245.77 μg/cm2/hr. The steady state flux of optimized formulation MME1 was 1.17 times of ME 10 formulation and 3.88 times of Drug solution. The optimized formulation MME1 did not showed significant toxicity in histopathological evaluation on porcine nasal mucosa treated for 1hr. Locomotor activity was evaluated on psychosis induced male Wistar rats using +MK-801 by Photoactometer. The antipsychotic activity of MME1 treated group was 93.85%, nasal drug solution treated group was 65.07% and in oral drug Solution treated group was 41.47% measured in terms of reduction of counts in comparison to positive control. The intranasal MME1 showed significantly high efficiency (P Key words: Amisulpride, Brain targeting, Chitosan, Intranasal delivery, Microemulsion, Schizophrenia.