Kinetic Parameters Estimation & Population Balanced Modelling (gFormulated) of Micro-Scale Mefenamic Acid in Ethyl Acetate Crystallisation

Abstract

Mefenamic acid is an analgesic anti-inflammatory drug. It is commonly used for pain associated with menstruation. The crystallisation kinetics of mefenamic acid in ethyl acetate solvent was investigated. The experiments were carried out at small scales, using 1-5 ml vessels. These experiments were conducted in a high throughput reactor system (Crystalline instrument from Technobis). The experimental data was then used as the input for estimating the kinetic parameters. This methodology aims to obtain the sequential parameter estimation which is validated for the determination of the kinetic parameters of mefenamic acid in ethyl acetate. Another aim is to estimate the parameters of the following; primary, secondary nucleation, growth and agglomeration kinetics. Population balanced modelling (PBM) in the gFormulated products program (gPROMS) was used to predict the optimum parameters of kinetic growth and nucleation. The resulting crystallisation model has been able to obtain the quantiles d25, d50, d75 of particle size distribution, although, some errors and deviation in prediction might have arisen due to inaccurate measurements used. In this work, the comprehensive methodology proposed is intended to be an efficient estimation strategy for modelling mefenamic acid of crystallisation processes.