Microemulsion based nasal spray: A systemic approach for non-CNS drug, its optimization, characterization and statistical modelling using QbD principles

The present study was investigated to design and characterize Domperidone (DM) loaded mucoadhesive microemulsion for enhanced systemic absorption through nasal delivery. Domperidone is a dopamine antagonist non-CNS drug, possessing high log P and extensive hepatic metabolism. The different microemulsion compositions were prepared by water titration method and optimized by D-Optimal mixture design. The screening criteria for optimization of formulation were drug loading, globule size, spray angle, spray pattern, mucoadhesion time, in-vitropermeation and in-vivopharmacokinetic profile. A microemulsion formulation comprising of oleic acid (8%), labrasol (32.5%), propylene glycol (32.5%) and water (27%) was found optimum. The spray droplets were rendered mucoadhesive by optimum quantity of PEO P7 (0.5% w/w). The globule size, mucoadhesion time and cumulative amount of drug permeated (after 240 min) of optimized formulation were 25 nm, 17 ± 2.0 min, and 80.14 ± 13.47 μg cm−2, respectively. Pharmacokinetic study of developed formulation revealed significant difference (p < 0.05) in Cmax(48.34 ng/mL) and AUC0→∞(6204 ng*h*mL−1) compared to DM solution and Domstal®, indicating enhanced bioavailability through nasal route. Safe and non-irritant nature of the formulation was proven by no severe histological changes reported in nasal irritation study. Biodistribution study exhibited least amount (2.12 ± 0.4%) of brain uptake confirming systemic absorption of drug.