Lipid-Polymer Hybrid Nanocarriers to Overcome Intestinal Permeability Barriers in Oral Delivery of Risedronate for Osteoporosis Therapy: Preformulation and Analytical Studies

Osteoporosis remains a major global health concern, and risedronate sodium is a first-line bisphosphonate for its treatment. However, its oral bioavailability is limited to approximately 0.65% due to poor intestinal permeability despite high aqueous solubility (BCS Class III). The present study aimed to develop and optimize risedronate sodium-loaded lipid-polymer hybrid nanoparticles using a double-emulsion solvent evaporation technique to enhance intestinal permeation. A systematic approach involving preformulation studies, analytical method and formulation development was employed. Drug authentication was performed using physical characterization, Fourier-transform infrared spectroscopy, differential scanning calorimetry, melting point determination, and equilibrium solubility studies. A UV-visible spectrophotometric method was developed and validated at 262 nm in distilled water, 0.1 N HCl, and phosphate buffer pH 6.8. The drug exhibited a melting point of 262.86°C with characteristic FTIR peaks confirming structural integrity. Calibration curves showed excellent linearity over the concentration range of 10–50 µg/mL, while solubility studies confirmed high aqueous solubility (62.7 ± 0.05 mg/mL in distilled water) and negligible solubility in organic solvents, supporting the selection of the W₁/O/W₂ double-emulsion solvent evaporation technique for LPHN preparation. These findings provide a robust foundation for formulation optimization and the subsequent development of LPHNs to improve intestinal permeability of risedronate sodium.