Quality by Design (QbD) based Formulation Optimization of Artemether Loaded Mucoadhesive Nanoemulsion for Intranasal Delivery

Abstract

Artemether is a first choice of drug used in the treatment of cerebral malaria and often used in combination.The objective of this work was to precisely design a nanoemulsion formulation for controlled release effect. The brain uptake of the drugcan be increased throughintranasal drug delivery and enhances the bioavailability by preventing the hepatic first-pass metabolism. Oleic acid was used as an oily phase as the drug exhibited maximum solubility in it.The tween 80, propylene glycol 400 were finalizedas surfactants and co-surfactants respectively based on the miscibility study. The optimization was carried out for various dependent and independent variables using Design Expert software. The optimized formulation was evaluated by various evaluation parameters. The polydispersity index (PDI) and zeta potential (ZP) were determined as 0.484±0.026 and +21±1.44mV respectively. The optimized formulation consisted of entrapment efficiency of 91.5%, globule size of 14.49nm, viscosity of 29cPas, and pH of 6.4. It showed a drug release of 93.17% in 24 hours representing the controlled drug release effect as it showed greatest R2 value for Korsmeyer-Peppas (R2 = 0.998) model. A controlled release nano emulsion formulation was successfully formulated thatcould be a smart way for effective intranasal delivery of artemether to enhance the bioavailability by avoiding the hepatic first-pass metabolism.