Metformin HCl Controlled-Release Microparticles: DoE-Based Formulation Development and In-Vivo Proof of Concept Study

Conventional drug delivery systems deal with side effects caused by fluctuating plasma levels. However, controlled drug delivery systems face another challenge since big dosing results in voluminous dosage forms. The drug delivery system is only suitable for some patients. A sustained-release drug delivery system in microparticles is proposed to conquer the problems. This research proposed to develop and optimize sustained-release microparticles consisting of metformin HCl as a drug model and a mixture of Eudragit RS and Kollidon SR as a polymeric matrix using a Box-Behnken design. The evaluation was conducted regarding drug loading, entrapment efficiency, and particle size to determine the optimal formulation. Metformin HCl concentration and drug-polymer ratio were dominant increased particle size, drug loading, entrapment efficiency, and particle size distribution. Particle size testing showed that the optimized formulation had a microparticle size of 1.363 ± 0.03 µm with a particle size distribution of 1.131 ± 0.028. In vitro evaluation showed that the release of metformin HCl microparticles followed Weibull kinetics within 24 hours. In contrast, in vivo evaluation confirmed the ability of microparticles to control blood glucose levels in mice for up to 24 hours with a 59% reduction. The microparticle effectively controlled drug release and reduced blood glucose levels in the rats.