Effect of Permeation Enhancers on Permeation Kinetics of Idebenone through the Bovine Buccal Mucosa

Abstract:

The buccal administration of drugs is attracting considerable attention since it has many advantages like to obtain high levels of drug in blood, circumvent extensive first-pass metabolism and avoid degradation in the gastrointestinal tract by enzymes and bacteria. This system serves as the better solution for the administration of drugs having low bioavailability like idebenone. Idebenone is synthetic analogue of coenzyme Q10 (CoQ10), a vital cell membrane antioxidant administered in friedreich's ataxia, duchenne muscular dystrophy, becker muscular dystrophy, alzheimer's disease, leber's hereditary optic neuropathy, MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis with stroke-like episodes), parkinson's disease mitochondrial myopathies etc.. The drug is practically water insoluble and shows limited bioavailability after oral administration due to a significant degree of first pass metabolism (99%). The low bioavailability of drug demands frequent dosing, hence the aim of the study was to demonstrate in vitro enhancement of drug penetration using Keshary – Chien diffusion cell. For demonstration varying concentrations of penetration enhancers and drug were prepared. Different penetration enhancers used were sodium lauryl sulphate, disodium ethylene diamine tetraacetic acid, urea, sorbitol, oleic acid, dimethylsulphoxide, physical mixtures with beta cyclodextrin, hydroxypropyl beta cyclodextrin, and complex of drug with hydroxypropyl beta cyclodextrin through buccal drug delivery system and tested for highest penetration. Drug complex with hydroxyl propyl cyclodextrin showed maximum enhancement ratio of 45.93 when compared with the enhancement ratio of other penetration enhances which ranged from 1.08 to 13.52. Hence, when compared with different penetration enhancers, this inclusion complex of idebenone with HPßCD can itself act as a best penetration enhancer for buccal drug delivery of idebenone. Overall, we can say that Idebenone Inclusion complex with HPßCD is the best way of enhancing the permeation of drug through buccal mucosa.

Keywords: Buccal drug delivery, idebenone, Penetration enhancer, idebenone complex.