Release Kinetics of Hydroxypropyl Methylcellulose Governing DrugRelease and Hydrodynamic Changes of Matrix Tablet

Background: Hydrophilic Hydroxypropyl Methylcellulose (HPMC) matrix tablets arethe standard role model of the oral controlled-release formulation. Nevertheless, the HPMC kineticsfor the mechanistic understanding of drug release and hydrodynamic behaviors are rarely investigated.This study aims to investigate the release behaviors of both HPMC and paracetamol(model drug) from the hydrophilic matrix tablet. Methods: Two different viscosity grades of HPMC were used (Low viscosity: 6 cps, High viscosity:4,000 cps). Three different ratios of drug/HPMC (H:38.08%, M:22.85%, and L:15.23% (w/w)of HPMC amounts in total weight) matrix tablets were prepared by wet granulation technique. Therelease profiles of the drug and HPMC in a matrix tablet were quantitatively analyzed by HPLCand 1H-Nuclear Magnetic Resonance (NMR) spectroscopy. The hydrodynamic changes of HPMCwere determined by the gravimetric behaviors such as swelling and erosion rates, gel layer thickness,front movement data,and distributive Near-Infrared (NIR) chemical imaging of HPMC in amatrix tablet during the dissolution process. Results: High viscosity HPMC tablets showed slower release of HPMC than the release rate ofdrug, suggesting that drug release preceded polymer release.Different hydration phenomenon wasqualitatively identified and corresponded to the release profiles. The release behaviors of HPMCand drug in the tablet could be distinguished with the significant difference with fitted dissolutionkinetics model (Low viscosity HPMC 6cps; Korsmeyer-Peppas model, High viscosity HPMC4000cps; Hopfenberg model, Paracetamol; Weibull model) according to the weight of ingredientsand types of HPMC. Conclusion: The determination of HPMC polymer release correlating with drug release, hydrodynamicbehavior, and NIR chemical imaging of HPMC can provide new insights into the drug release-modulating mechanism in the hydrophilic matrix system.