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Modeling of Disintegration and Dissolution Behavior of Mefenamic Acid Formulation Using Numeric Solution of
Reiji Yokoyama1,2, Go Kimura3, Christian M Schlepütz4
1Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, CH4056 Basel, Switzerland. reiji.yokoyama@shionogi.co.jp.
Abstract:
Manufacturing parameters may have a strong impact on the dissolution and disintegration of solid dosage forms. In line with process analytical technology (PAT) and quality by design approaches, computer-based technologies can be used to design, control, and improve the quality of pharmaceutical compacts and their performance. In view of shortcomings of computationally intensive finite-element or discrete-element methods, we propose a modeling and simulation approach based on numerical solutions of the Noyes-Whitney equation in combination with a cellular automata-supported disintegration model. The results from in vitro release studies of mefenamic acid formulations were compared to calculated release patterns. In silico simulations with our disintegration model showed a high similarity of release profile as compared to the experimental evaluation. Furthermore, algorithmically created virtual tablet structures were in good agreement with microtomography experiments. We conclude that the proposed computational model is a valuable tool to predict the influence of material attributes and process parameters on drug release from tablets.
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