PRODRUGS OF GESTODENE FOR MATRIX-TYPE TRANSDERMAL DRUG-DELIVERY SYSTEMS

Purpose. The aim of this study was to enhance the transdermal absorpti on of the highly active progestin gestodene from matrix type transderm al delivery systems (TDDS) by formation of prodrugs with improved matr ix solubility. Methods. Gestodene esters were synthesized via acylatio n of the drug with the respective carboxylic anhydrides. Subsequently TDDS were produced using the solvent cast method. Selected formulation s were examined with in vitro diffusion experiments using skin of nude mice. Results. One prodrug. gestodene caproate proved to be an oil at ambient temperature and showed a very high solubility of over 10.5% i n the TDDS matrix. Within in vitro penetration studies using those sys tems the prodrug exhibited a significantly higher transdermal penetrat ion rate than gestodene from reference systems. Furthermore, the prodr ug was hydrolyzed to the parent drug to a high extent during the passa ge of the skin. Conclusions. Designing prodrugs to the requirements of matrix TDDS is an efficient way of enhancing the transdermal drug flu x rate.