Development and Characterization of Intravaginal Inserts for Targeting of Therapeutics for the Treatment of Uterine Fibroids

Abstract

The most common benign tumor in women is uterine fibroids (UFs). UFs are commonly newlinelinked with heavy or extended menstrual flow, atypical uterine hemorrhage, anemia, and newlinepelvic discomfort. Surgical therapies are preferred in progressive UFs however medicinal treatments are used to avoid surgery in the initial stages of UFs. Conventional treatments involve oral and parenteral routes, which may cause dose-related side effects due to nonspecific targeting. Therefore, there is a need to develop a formulation that give site-specific and prolonged drug release which reduces systemic side effects and enhances therapy newlineefficacy. Mifepristone (MFP) belongs to BCS Class-IV, a selective progesterone receptor newlinemodulator, and Raloxifene hydrochloride (RLH) belongs to BCS Class-II, a selective estrogen receptor modulator, are chosen as the drugs of choice. Currently, MFP and RLX are used in the termination of pregnancy and treatment of osteoporosis respectively. So far newlinethere has been no commercial use of these drugs in the treatment of UFs. However, clinical trials made on these drugs are highly effective in the treatment of UFs. For that reason, newlinecurrent investigation both the drug was investigated in detail with the support of some animal experiment to generate the proof of concept. The repurposing of MFP and RLH was investigated using drug-eluting intrauterine insert (DE-IUI) and 3D Printed-intrauterine insert (3DP-IUI) approaches via the intravaginal route to intrauterine targeting for the treatment of UFs. Enhance formulation approach quality by desing was employed for both newlinethe formualtions. newlineFor MFP, DE-IUI was prepared using a combination of PCL and solubilizers. The solid newlinedispersion (SD) approach via melt granulation was found to be appropriate for achieving newlinesolubility of drug. Subsequently, the SD of drug was included in a poly-and#949;-caprolactone-based newlinecapsular-shaped in situ porous DE-IUI using molding method. The drug was solubilized newlineusing the modified liquid-solid compact (MLSC) technique in the preparation of 3DP-IUI. newline3D p