Comparison of In Vitro Dissolution and Permeation of Fluconazole from Different Suppository Bases

Abstract

Fluconazole suppositories were prepared in hydrophilic, lipophilic, and amphiphilic bases. In vitro evaluation was conducted to compare the effect of different bases on the release and permeation of fluconazole. Four types of suppository bases were evaluated: hydrophilic (polyethylene glycol, PEG), lipophilic (cocoa butter, CB; Witepsol W45® WW45), and amphiphilic (Suppocire AP® SAP, a polyglycolized glyceride). The uniformity of dosage units prepared with each base was determined by ultraviolet (UV) spectroscopy. The influence of suppository base on the release of fluconazole was studied using USP dissolution apparatus I. Rate constants for each release pattern were determined and compared using a one-way analysis of variance (ANOVA) on ranks. The order of in vitro dissolution of fluconazole from the bases was as follows: PEG > (SAP = WW45) > CB. Results suggest that in vitro release of fluconazole is greater from a hydrophilic base (PEG). Preliminary permeation studies were conducted on each type of base using Franz diffusion cells. Permeation was studied through the rat rectal membrane, and normal saline was used as the receptor medium. A modified reverse-phase high-performance liquid chromatography (HPLC) method was used and validated for analyzing fluconazole. Flux values (μg/cm2/hr) were calculated and compared using a one-way ANOVA (p <. 001). The order of permeation was as follows: SAP > (PEG = WW45) > CB. The increased permeation characteristics seen with the SAP base are probably due to an alteration of the membrane characteristics due to the surface active properties of the base.