Formulation and Evaluation of Berberine-Loaded Hydrogel Microspheres for Gut Microbiota Modulation

Background: Berberine hydrochloride is an isoquinoline alkaloid with pronounced pharmacological activity, including reported effects on the gut microbial community. Its therapeutic utility following oral administration is constrained by pH-dependent solubility and by premature absorption and release in the upper gastrointestinal tract. A pH-responsive, polysaccharide-based hydrogel carrier may allow controlled delivery of the drug along the gastrointestinal tract. Objective: To formulate and evaluate berberine hydrochloride-loaded sodium alginatepectin hydrogel microspheres intended for modulation of the gut microbiota. Methods: Six formulations (F1–F6) were prepared by ionic cross-linking with calcium chloride, using varying levels of sodium alginate, pectin and cross-linker. Preformulation studies comprised solubility, melting point, Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The microspheres were characterised for particle size, polydispersity index (PDI), surface morphology, entrapment efficiency, drug loading and swelling behaviour. The optimised formulation (F5) was further evaluated by FTIR, DSC, in-vitro release under sequential simulated gastrointestinal conditions, release kinetics and a three-month stability study.