Design and optimization of antisolvent crystallization of L-aspartic acid using response surface model: Focused beam reflectance measurements

Abstract

In the present study, optimization of antisolvent crystallization of L-aspartic acid (L-ASP) was performed using response surface methodology (RSM) and a focused beam reflectance measurement (FBRM) tool. The main process parameters such as storage temperate, stirrer velocity, storage time and solvent ratio influencing the crystallization process were identified by RSM to achieve significant improvement in the yield and quality of the product while chord length distribution (CLD) data was obtained from FBRM. From the studies, it can be observed that 2-propanol was more effective antisolvent than methanol for L-aspartic acid crystallization. The temperature was found to have a critical effect on crystal formation. Crystals were formed between 298.15 and 303.15 K, whereas cohesion, disintegration, and conglomeration were noticed at other temperatures. ANOVA results revealed that all the studied variables have a significant impact on the yield and CLD. The optimum crystallization was obtained at 18 h, stirrer velocity of 200 rpm, distilled water-formic acid/IPA of 1:3(v/v), and storage temperature of 298.15 K. A quadratic response surface model described the crystallization of L-ASP satisfactorily with R2 of 0.99 and a deviation of 1.2%.