Effects of Direct Tabletting Agents on Drug Release Kinetics and Swelling Behavior of Hydrophilic Matrix Tablets


Abstract: Aims: This work focused on the effects of direct tabletting agents (DC-agents) (Microcel PH101^®, Cellactose 80^®, Ludipress LCE^®, Pharmatose DCL11^®) and hydroxypropyl-methylcellulose (HPMC) types (Methocel^® K100LV, K15M, K100M) on release of Verapamil HCl from hydrophilic matrix tablets and swelling behaviors of these tablets. Material and Methods: Tablets were prepared by direct compression method. In vitro dissolution and swelling degree tests were performed on the tablets. The release mechanisms of drug were evaluated by using Korsmeyer-Peppas model. Results: While the increase in cellulose content of DC-agents contributed to the swelling of matrices and decreased the release rate of drug from the matrices, in contrast the increase in lactose content of DC-agents caused a faster hydration and erosion of the matrices and accelerated the release of drug. The increase in viscosity grade of HPMC resulted as a decrease in release rate of drug and Methocel K15M and K100M delayed the release of drug to the same extent. Drug release was mainly fitted to the non-Fickian transport mechanism and became diffusive by decreasing the R/F values of the matrices. Tablets containing Cellactose^® 80 showed an equal contribution of diffusion and swelling with 3 types of HPMCs, according to their n values and R/F profiles. The FM1 formulation containing Microcel PH101® with Methocel K100LV and the reference product Isoptin^®-KKH both showed a non-Fickian transport mechanism and they were found to be similar depending on the values of difference factor (f_1 = 9.4) and similarity factor (f_2 = 56.8). Conclusions: An extended release tablet formulation can be prepared as a matrix tablet by using a cellulose based DC-agent and a low viscosity grade HPMC polymer as an alternative to film coated tablets.

Keywords: Hydroxypropyl-methylcellulose, Direct tabletting agents, Matrix tablet, Swelling degree, Verapamil hydrochloride

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