Impact of Insoluble Separation Layer Mechanical Properties on Disintegration and Dissolution Kinetics of Multilayer Tablets.

Dissolution and disintegration of solid dosage forms such as multiple-layer tablet with different active ingredients depend on formulation and properties used in the formulations, and it may sometimes result in counterintuitive release kinetics. In this manuscript, we investigate the behavior of combined acetylsalicylic acid and mefenamic acid bi- and triple-layer formulations. We show that the simulation model with a cellular automata predicted the impact of the inert layer between the different active ingredients on each drug release and provide a good agreement with the experimental results. Also, it is shown that the analysis based on the Noyes-Whitney equation in combination with a cellular automata-supported dissolution and disintegration numerical solutions explain the nature of the unexpected effects. We conclude that the proposed simulation approach is valuable to predict the influence of material attributes and process parameters on drug release from multicomponent and multiple-layer pharmaceutical tablets and to help us develop the drug product formulation.