Improvement of vaginal implant systems by hot melt extrusion method

Vaginitis is one of the most frequent gynecological diseases. It has been reported that of three fourths of all women experience acute episodes of vaginal candidiasis at least once during their life time. For treatment of vaginitis, topical antifungal therapy has been favored owing to the toxicity of antifungal drugs after systemic administration. For vaginal delivery systems of antifungal agents to be more effective, they need to reside at the sites of infection for a prolonged period. With commercial dosage forms for vaginal delivery are used one or two times in a day for a period between 3 to 14 days. However, the treatment with available dosage forms makes difficulties for the patients and causes incomplete treatment and consequently relapse risk of disease shows up. In this study it was aimed to develop sustained release vaginal implants to solve these problems. In the literature there are no studies on vaginal implants prepared using chosen antifungal drug and method. Thereby a biodegradable vaginal implant which is planned todevelop in this study has an important place in the treatment of vaginal candidiasis. Hence, vaginal implants were prepared using poly-lactic-co-glycolic acid 50:50 (PLGA) as biodegradable polymer and different mucoadhesive polymers such as hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), sodiumcarboxymethyl cellulose (NaCMC), chitosan and sodium alginate. Tioconazole was used as model drug. For the characterization of the vaginal implants, FTIR, DSC, TGA, SEM, GPC, X-ray diffraction analyses, determination of melt viscosity, determination of drug content, in vitro drug release, determination of mechanical properties, water uptake study, in vitro and in vivo antifungal activity and histopathological studies were performed. It's suggested that the sustained release vaginal implants which were aimed to develop within the study will solve the problems about the usage of available commercial products and have a promising place in the treatment of vaginal candidiasis. Sustained release implant formulation of tioconazole using hot melt extrusion was developed for the first time with this study and the formulation was applied for both national (2017/10102) and international (2017/15422) patent. This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) with the number of 115S476. Keywords: Hot Melt Extrusion, Vaginal Implant, Vaginal Candidiasis, Tioconazole