Mucoadhesive 3D printed vaginal ovules to treat endometriosis and fibrotic uterine diseases

Gynaecological health is a neglected field of research that includes conditions such as endometriosis, uterine fibroids, infertility, viral and bacterial infections, and cancers. There is a clinical need to develop dosage forms for gynaecological diseases that increase efficacy and reduce side effects, particularly for enigmatic pathologies like endometriosis. Vaginal drug delivery allows direct targeting of the reproductive organs via the first uterine pass effect, in which countercurrent flow of blood vessels in the vagina facilitates direct vagina-to-uterus transport, leading to elevated concentrations of the active principle in and around the uterus. A repurposed drug candidate being explored for endometriosis is pirfenidone, which was shown to be effective but unfavourable to be administered orally due to its severe adverse event profile. Vaginal administration of pirfenidone has the potential to lower the dose, reduce side effects, and reduce administration frequency compared to oral administration; however, to date no vaginal formulation for pirfenidone exists. Here, we develop vaginal dosage forms containing pirfenidone and perform comprehensive in vitro formulation characterization, including bespoke drug release, ex vivo, and cell culture assays. We show that a semisoft suppository manufactured using semisolid extrusion additive manufacturing is superior to ovules manufactured using standard excipients with respect to the release profile and to mucoadhesive properties. This work enables further preclinical and clinical studies into vaginally administered pirfenidone to assess its efficacy as a repurposed treatment for endometriosis and fibrotic uterine diseases.