Novel Mucoadhesive Wafers for Treating Local Vaginal Infections

Abstract

Current vaginal formulations, such as gels and pessaries, have limitations, including poor retention. Therefore, the use of mucoadhesive formulations that adhere to the vaginal wall would allow prolonged retention and controlled drug release while reducing the required dose and the potential toxicity associated with high drug loading. The aim of the current research was to develop, characterize, and optimize freeze-dried wafers loaded with metronidazole (MTz) to treat vaginal bacterial infections. Blank (BLK) composite wafers comprising carrageenan (CARR) and sodium alginate (SA) were initially formulated; however, due to poor physico-chemical properties, Carbopol (CARB), hydroxypropylmethylcellulose (HPMC), and polyethylene glycol 200 (PEG) were included. The MTz-loaded formulations were obtained by loading optimized composite CARB:CARR- or CARB:SA-based gels (modified with HPMC and/or PEG) with 0.75% of MTz prior to freeze-drying. The physico-chemical properties were investigated using texture analysis (resistance to compressive deformation and adhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. Functional properties were investigated by examining the swelling, porosity, drug release, and in vitro antimicrobial activity using E. coli as a model infection-causative agent. The results showed that HPMC and PEG generally improved the wafer’s appearance, with smoother surfaces for easy insertion. From the physico-chemical characterization studies, only two composite wafers prepared from 8% CARB:SA 1:4 and 8% CARB:SA 1:9 gels were deemed optimal and loaded with MTz. Both formulations showed sustained drug release and achieved almost 100% cumulative release within 72 h in simulated vaginal fluid. The data obtained from the drug dissolution (release) experiments were fitted to various mathematical equations and showed the highest correlation coefficient with the Higuchi equation, suggesting a drug release based on diffusion from a swollen matrix; this was confirmed by the Korsmeyer–Peppas equation. The released MTz inhibited the growth of the E. coli used as a model bacterial organism.