Development of cyclodextrin hydrogels for vaginal delivery of dehydroepiandrosterone

ObjectiveTo develop a new vaginal delivery system for a sustained release of dehydroepiandrosterone (DHEA) in the treatment of postmenopausal symptoms, aimed to overcome the problems of poor bioavailability of the drug related to its very low water solubility. MethodsCyclodextrin (CD)-containing hydrogels were developed, combining in a single device the hydrogel controlled release and mucoadhesion properties, and the CD solubilizing power towards DHEA. The effect of different CDs, alone or in mixtures, on the hydrogel technological and mucoadhesion characteristics was investigated. The best formulations were loaded with DHEA and character-ized for loading efficiency and release properties. Key findingsHydrogels based on HPbCD/cCD (15/10%w/w) or HPbCD/HP cCD (30/20%w/w) combinations proved to be the most effective, giving ovules with the desired mechanical and mucoadhesive properties. Both formulations showed high drug loading efficiency, due to the solubilizing effect of CDs, and provided a sustained in-situ release, with a rate suitably tunable by varying the drug loaded amount and/or the CD combination. ConclusionsThe proposed formulative strategy allowed to develop an intravagi-nal device with right consistency and elasticity, easy to apply, able to be retained in situ over 8 h, and to provide an effective DHEA loading and a tunable release rate