Experimental determination and modelling of the co-solvent and antisolvent behaviour of binary systems on the dissolution of pharma drug; L-aspartic acid and thermodynamic correlations

Abstract

Solid-liquid equilibrium (SLE) data and thermodynamic properties play an important role to understand the crystallization phenomenon as it became an important step for purification and separation to get a required specific product. In this study, solubility of L-aspartic acid (L-ASP) in different binary mixtures (formic acid/trimethylamine(TMA)/methanol/iso-propylalcohol(IPA) + water) were carried out at temperatures from 283.15 to 328.15 K. The experimental data was generated using the gravimetric and titrimetric method. For a binary system, the solubility of L-ASP increased with increasing temperature. The effect of solvent on mole fraction solubility of L-ASP decreased with increasing methanol/IPA mole fraction in mixture, whereas solubility increased with increased formic acid/TMA fractions in mixture. The order of solubility for binary solvents systems as follows: TMA + water > formic acid + water > methanol + water > IPA + water. Different thermodynamic models like Apelblat equation, Apelblat-Jouyban-Acree model, NRTL model, and general single model were applied to correlate the experimental data. It was found that Apelblat equation and general single model was the best-fit for correlating solubility of L-ASP in binary mixtures with average relative deviation (ARD) less than 2% and root mean square deviation (RMSD) are below 5.3E-04. It can also be concluded that formic acid and TMA act as co-solvent in dissolution of L-ASP in their respective binaries, wheras methanol and IPA exhibited anti-solvent effect in the aqueous solution. The generated SLE data would be helpful in technological research for production of drugs in purification and separation process.