Optimization and In Vitro Evaluation of Raloxifene Hydrochloride-Loaded Calcium Phosphate Microparticles for Sustained Drug Delivery

Abstract

Objective: Raloxifene hydrochloride (RH) is a commonly applied drug for osteoporosis, but it has inadequate bioavailability and rapid release of the drug, which diminishes its therapeutic effects. The study aimed to design and optimize a sustained-release drug delivery system based on calcium phosphate microparticles, which possess biocompatibility and have an intrinsic property to attach to bone tissue. Methods: Calcium phosphate (CaP) microparticles were prepared through a co-precipitation method. A 32 factorial design was used to optimize formulations, with the drug-carrier ratio (X1) and stirring time (X2) as independent variables. The dependent responses were entrapment efficiency (EE, Y1) and cumulative drug release at 6 h (CDR, Y2) and 8 h (CDR, Y3). The optimized batch was further profiled for particle size, in vitro drug release versus a commercially available formulation, and osteogenic potential on the basis of alkaline phosphatase (ALP) in MG-63 cell lines. Results: The optimized formulation according to desirability criteria was found to be batch F6. It had a particle size of 1.12 µm, high entrapment efficiency, and released the drug for up to 12 h, following a zero-order kinetic model (R² = 0.9864). Furthermore, the optimized formulation showed a 1.26-fold increase in osteogenic activity compared to the pure drug (one-way ANOVA, p<0.001). Conclusion: The study confirms that CaP microparticles can be effectively used as a biodegradable and biocompatible carrier in the long-term delivery of drugs. The optimized formula enhances the characteristics of drug release and increases osteogenic potential, which indicates the potential of the formulation to be used in bone-targeted therapies.