Improved acitretin delivery through hairless mouse skin by cyclodextrin complexation

The effects of four cyclodextrins, i.e., 2-hydroxypropyl-β-cyclodextrin, randomly methylated β-cyclodextrin (MβCD), γ-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin, on the aqueous solubility of acitretin were investigated. Of the four cyclodextrins tested MβCD displayed the largest effect. The aqueous solubility of the drug could be increased even further by pH adjustment. Thus, the solubility of acitretin in an aqueous pH 7.5 buffer solution containing 23% (w/v) MβCD was determined to be 1.96 mg/ml. Acitretin is insoluble in water. The flux of acitretin through hairless mouse skin was determined to be 0.032 mg h⁻¹ cm⁻² from a pure propylene glycol vehicle but 0.201 mg h⁻¹ cm⁻² from an aqueous MβCD containing vehicle.