Polymeric oral fast dissolving films of metformin: fabrication, optimization, in vitro, and in vivo evaluation

Metformin is gold standard for polycystic ovary syndrome (PCOS), but associated with gastrointestinal side effects, leading to poor patient adherence. Present oral fast-dissolving films (OFDFs) offer rapid disintegration, improving drug delivery, therapeutic outcomes, and patient compliance.

This project aimed to fabricate metformin-loaded OFDFs to enhance patient compliance and drug efficacy in treatment of PCOS.

Metformin-loaded OFDFs were prepared using solvent casting method with hydroxypropyl methylcellulose (HPMC) and gelatin as film-forming polymers and propylene glycol as a plasticizer. The Box-Behnken experimental design was utilized for optimization. Various physico-chemical characterization tests, including thickness, weight, folding endurance, percent elongation, water content, and moisture uptake, were conducted. In vitro drug release, disintegration time, and mechanical strength were analyzed. Additionally, a pharmacokinetic study in rats was conducted to compare plasma concentrations of optimized formulation with those of metformin intragastric solution.

A stable drug-loaded formulations with a uniform surface and an amorphous nature of drug were prepared in OFDFs. The optimized formulation demonstrated significant drug release at 5 min (98.9%), a rapid disintegration time (19.2 sec), and good mechanical strength (7.4 MPa) (ANOVA, p < .05). Furthermore, increased values of C_max as well as AUC_0-t were also observed in plasma of rats treated with optimized formulation (MF7) as compared to those administered with metformin intragastric solution (Student t-test, p < .05).

Results cemented a very rapid disintegration and dissolution of OFDF, suggesting a promising substitute to enhance patient adherence and reduce metformin onset time in treating PCOS.