Formulation and Evaluation of Idebenone Microemulsion as a Potential Approach for the Transmucosal Drug Delivery Systems

Abstract

Idebenone, a synthetic analogue of ubiquinone (Co-Q10), is used for the treatment of Leiber’s hereditary optic neuropathy. Although it is almost completely absorbed from GIT, its extensive rate of metabolism makes its oral bioavailability less than 1%. This study aims to formulate the poorly water-soluble drug as nanoemulsion (NE) to increase drug solubility as well as transmucosal permeation and circumventing hepatic biodegradation by using transmucosal routes of administration such as intranasal rout to enhance drug bioavailability. Nanoemulsion components were selected through screening of the preferential solubility of IDB in several oils and emulsifying agents and subsequent formulation optimization through screening for their best miscibility through phase study. Lemongrass oil showed superior characteristics to represent the oil phase in which the drug was dissolved while Cremophor EL® and Transcutol-P® represented the surfactant system. The method of spontaneous-emulsification was used to prepare twelve NE formulas (F1-F12) which were subjected to several characterization tests. Out of four successful formulas, F-11 showed the best globule size (45.6nm), PDI (0.19) zeta-potential (-2.8 mV), low viscosity and suitable pH (5.9). Using sheep nasal mucosa as model, (F-11) was subjected to ex-vivo transmucosal permeation study against plain drug oil dispersion with pronounced enhanced permeation due to formulation as NEs. Permeation kinetic parameters were obtained such as permeation rate 40.9 µg/h/cm2, lag time 15min, permeability coefficient 40.9x10-4 cm/h and enhancement ratio 39. The outcome of this study indicates the possibility of incorporation of this formula into a suitable carrier for finalizing its formulation as non-enteral dosage form with enhanced IDB bioavailability.

Keywords

• Bioavailability, Idebenone, Microemulsion, Permeation, Solubility