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Release kinetics of hydroxypropyl methylcellulose governing drug release and hydrodynamic changes of matrix tablet

Author(s):

Chulhun Park, Jong Hoon Lee, Gang Jin, Hai Van Ngo, Jun-Bom Park, Thao T.D. Tran, Phuong H.L. Tran and Beom-Jin Lee*  

Abstract:


Background: Hydrophilic hydroxypropyl methylcellulose (HPMC) matrix tablets are the standard role model of the oral controlled-release formulation. Nevertheless, the HPMC kinetics for 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. The release profiles of the drug and HPMC in a matrix tablet were quantitatively analyzed by HPLC and 1H-nuclear magnetic resonance (NMR) spectroscopy. The hydrodynamic changes of HPMC were 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 a matrix tablet during the dissolution process.

Results: High viscosity HPMC tablets showed slower release of HPMC than the release rate of drug, suggesting that drug release preceded polymer release.Different hydration phenomenon was qualitatively identified and corresponded to the release profiles. The release behaviors of HPMC and drug in the tablet could be distinguished with the significant difference with fitted dissolution kinetics model (Low viscosity HPMC 6cps; Korsmeyer-Peppas model, High viscosity HPMC 4000cps; Hopfenberg model, Paracetamol; Weibull model) according to the weight of ingredients and types of HPMC.

Conclusion: The determination of HPMC polymer release correlating with drug release, hydrodynamic behavior, and NIR chemical imaging of HPMC can provide new insights into the drug release-modulating mechanism in the hydrophilic matrix system.

Keywords:

Hydroxypropyl methylcellulose, Polymer release, Drug release, Hydrodynamic behaviors, Distributive imaging of polymer, Quantitative and qualitative analysis of HPMC.

Affiliation:

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton T6G 2E1, Alberta, College of Pharmacy, Ajou University, Suwon 16499, College of Pharmacy, Ajou University, Suwon 16499, College of Pharmacy, Ajou University, Suwon 16499, College of Pharmacy, Sahmyook University, Seoul 01795, Faculty of Pharmacy, Duy Tan University, Danang 550000, Deakin University, Geelong Australia, School of Medicine, College of Pharmacy, Ajou University, Suwon 16499



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