Crystallization kinetics of mefenamic acid and polymorphism

Mefenamic acid (MA) is a high-dose, anti-inflammatory, analgesic agent that is widely prescribed for pain related to menstrual disorders. It has been reported to exist in two polymorphic forms (Forms I and II), which differ in their solubility and dissolution. Apart from the high dose of MA, it has some negative properties such as a high hydrophobicity and propensity to stick to surfaces, and poses great problems during granulation and tableting. The main measures of the quality of the outcome of a crystallization process are the crystal size distribution, crystal shape, and polymorphic form. In this study, to characterize the polymorphism of mefenamic acid, Raman microscopy and X-ray patterns of crystal particles were investigated by preparing different solutions of mefenamic acid with different solvents such as N, N-dimethylformamide (DMF), acetone, N, N-dimethylacetamide (DMA), and Dimethylsulfoxide (DMS). The experiments for the measurement of crystal growth kinetics were carried out by the desupersaturation curve principle based on the measurement of the solution concentration versus time in a seeded isothermal batch experiment. To estimate the growth kinetics from the desupersaturation curve obtained, the method developed by Garside et. al. (1982) was used. The derivatives of the desupersaturation curve at time zero were also used. It was assumed in the method that the concentration change was due only to crystal growth with no nucleation occurring. Using this analysis, the power g and constant k g of the crystal growth equation were obtained as 0.99 and 1.63×10-6 Lasentec® FBRM® (Focused Beam Reflectance Measurement) were used for the measurements of the crystal size distribution. Availability of data on the kinetics of crystal growth is very important for the development and operation of industrial crystallization processes. This information can be incorporated in process models, can be used in process and crystallizer design, and can shed light on the observed behavior of the system.