Controlled-release topical polymeric formulations of anthralin

Five topical polymeric formulations of anthralin were fabricated with two types of silicone elastomers and various additives, containing 5% (W/W) of anthralin. The objectives were to provide a transdermal controlled-release mechanism with which the rate limiting step of percutaneous penetration was built into the polymeric device rather than stratum corneum as with conventional dosage forms, and to overcome the problems of chemical instability and irritation to normal skin, inherent to conventional dosage forms. Product asscessments were conducted, including (1) weight, thickness and anthralin content uniformities, (2) in vitro anthralin release kinetics from the polymer and (3) in vitro anthralin penetration through and disposition in hairless mouse skin after 48 hours of application. The results provided guidelines for future product development and refinement. An HPLC assay was developed with reversed-phase octyl column, mobile phase of acetonitrile/water mixture, capable of measuring amount as low as 5 ng of anthralin. The assay was employed in all studies of content uniformity, stability, drug release, and drug penetration. The release process of anthralin from formulated polymer followed the first-order kinetics which is the characteristic of matrix-type of controlled-release device. Anthralin had a larger diffusion coefficient through the 382 silicone elastomer than through MDX-4-4210 silicone polymer. The glycerol, azone, and propylene glycol incorporated in various polymeric formulations did not affect the diffusion coefficient of anthralin in test silicone elastomer. The extent of anthralin penetration from 382 silicone elastomer into hairless mouse skin was significantly higher than that from MDX-4-4210 silicone elastomer. The incorporation of Azone and glycerol in 382 silicone polymer did not improve percutaneous penetration of anthralin from the polymer, while propylene glycol increased anthralin penetration from MDX-4-4210 silicone elastomer significantly. Anthralin degradation might not be a simple first-order process where oxygen might play a role. Azone facilitated anthralin oxidation, and Vitamin C significantly stabilized anthralin in conventional vehicle. However, when anthralin was incorporated in polymeric formulations, the degradation process was further slowed down. All formulated polymers served the purpose of preventing anthralin from decomposition.