Combined Raft Formation-Interpenetrating Complex Approach to Reconstitutable Sustained-Release Suspension Development

Background: The foundation of this work is the use of raft formation and Interpenetrating Polymeric Network (IPN) complexation techniques to create a reconstitutable sustained-release suspension of Diltiazem Hydrochloride (DZH) for elderly patients. Materials and Methods: Xanthan gum and chitosan were used in combination to prepare IPN complexes of DZH. A central composite design was used to optimize the raft-forming in situ gelling system. The concentrations of HPMC K4M and sodium alginate were the independent variables. Results: In vitro dissolution, X-ray powder diffraction, and differential scanning calorimetric studies were conducted to examine the IPN complexes. The optimized batch (ratio of sodium alginate to HPMC K4M, 1500:100) exhibited gelation properties for an extended time period, as well as the desirable floating duration (>12 hr). A desirable drug release of 97.39±0.97% in up to 12 hr was achieved. The release kinetics of the DZH obeyed the Higuchi order of release following the Fickian diffusion mechanism with an n value of 0.366. Conclusion: The in vitro study suggested that a reconstitutable sustained-release suspension was successfully prepared using the raft forming formulation approach and the IPN complex of DZH. The optimized formulation exhibited sustained release of the water-soluble drug over 12 hr due to the combined effect of the RFGS and the IPN complex.