Development and characterization of long-acting darifenacin intravaginal ring for managing overactive bladder in women: harnessing QbD approach

Abstract Background The oral administration of darifenacin hydrobromide (DBr) is associated with low bioavailability of 15–19% due to poor solubility and extensive first-pass metabolism. Additionally, the conventional oral formulation results in poor patient compliance due to frequent administration. By designing an intravaginal ring as a sustained release formulation for the treatment of an overactive bladder, the present investigation aims to explore an alternate method of drug administration. Methods Intravaginal ring of matrix design was prepared comprising of DBr incorporated in polyurethane as biodegradable polymer, by injection molding technique. Intravaginal rings were evaluated for dimensional analysis, tensile strength, percent compression, drug content, in vitro drug release studies and accelerated stability studies. A 3 2 factorial design was employed to optimize the formulation, by taking quantity of polymer and plasticizer concentration as the critical material attribute and tensile strength, T50% and T90% as the critical quality attributes. Numerical and graphical optimization was carried out for optimization of vaginal ring. Tolerability of IVR was assessed on vaginal tissues, and cytotoxic evaluations were made on HeLa cell line. Results The tensile strength, percent compression and drug content at the end of 21 days for the optimized IVR were found to be 5.78 ± 0.4 MPa, 86.82 ± 5.1% and 95.44 ± 2.3%, respectively, and cumulative drug release T50% and T90% was 10.33 and 20.71 days. Under storage conditions, the accelerated stability assessment revealed little-to-no changes. The developed IVR exhibited biocompatibility and absence of any significant cytotoxicity. Conclusion The study highlights the possibility of intravaginal delivery as an alternative route for DBr administration that is stable and efficacious, and provides prolonged release. The user-centric delivery system underscores the broader potential of intravaginal delivery systems for addressing unmet needs in women's health. Graphical abstract