Equilibrium Solubility of Biapenem in Different Neat and Binary Solvents: Experimental Determination and Model Correlation

The equilibrium solubility is the basis of purification and further theoretical studies of biapenem. In this work, the solubility of biapenem in 10 pure solvents (methanol, ethanol n-propanol, isopropanol, acetone, N,N-dimethylformamide (DMF), acetonitrile, dimethyl sulfoxide (DMSO), N-methyl pyrrolidone (NMP), and ethyl acetate) and solvent mixtures (ethyl acetate + methanol) was measured by using a static equilibrium method at temperatures from 283.15 to 323.15 K, at p = 101.2 kPa. To sum up, the solubility was highest in NMP and lowest in acetone. The solubility from high to low is NMP (0.9663 X 10(-4), 298.15 K) > DMSO (0.8655 x 10(-4), 298.15 K) > DMF (0.7796 X 10(-4), 298.15 > ethyl acetate (0.7161 x 10(-4), 298.15 K) > acetonitrile (0.5169 X 10(-4), 298.15 K) > methanol (0.3068 X 10(-4), 298.15 K) > ethanol (0.2455 X 10(-4), 298.15 K) > n-propanol (0.1966 X 10(-4), 298.15 K) > isopropanol (0.1205 X 10(-4), 298.15 K) > acetone (0.04576 X 10(-4), 298.15 K). The experiment values in monosolvents were associated with the modified Apelblat equation. The experiment values in mixed solvents were associated with the Jouyban-Acree model, Apelblat-Jouyban-Acree model, and CNIBS/R-K model. From the correlation results, the largest RAD values of the above three models are 0.83%, 0.98%, and 0.60%, respectively. These models can all fit the experiment values very well. Accordingly, in values of solubility in the pure solvent correlation process, the maximum values of root-mean-square deviation (RMSD) and relative average deviation (RAD) are 0.42 x 10(-6) and 0.80%, respectively. Furthermore, solute-solvent interactions have been studied in monosolvents. The hydrogen bonds play an important role in the dissolution process of biapenem. Especially, the experimental values have influences on purification, recrystallization, and formulation development of biapenem in production.