Metformin hydrochloride-loaded biodegradable microspheres employing the Box Behnken design for local delivery in periodontitis: design, optimization, and characterization

Abstract

In the current research, periodontitis was treated by filling periodontal pockets with metformin hydrochlorideloaded microspheres, either with or without grafts. In order to do this, chitosan was selected as the polymer and used in various drug/polymer ratios during the emulsion cross-linking process to create microspheres. Utilizing a three-factor, three-level Box–Behnken architecture allowed for optimization. Regression analysis was used to create mathematical models for the responses of particle size (PS) and entrapment efficiency (EE). The experimental design considered the economical reduction of chemical usage and formulation time to develop an optimized formulation with highest %EE and minimal PS under optimal process conditions for the microsphere formulation. Based on the desirability function, the optimal formulation was chosen, and it was then assessed in terms of particle size, entrapment efficiency, drug release in vitro, differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, and surface morphology investigations. Kinetic and statistical analyses were performed on the release study findings. The chosen batch's particle size and entrapment effectiveness were determined to be between 40.2 and 59.6 μm and 85 and 95%, respectively. The drug's molecular dispersion and transformation into an amorphous state were shown by the DSC investigations. By using scanning electron microscopy (SEM) to examine the surface morphology of the microspheres, it was discovered that they had a smooth, spherical surface