Optimization of Process Conditions for the Separation and Purification of Erythromycin Thiocyanate Using Response Surface Methodology

A water acetone biphasic extraction system was developed for the separation and purification of erythromycin thiocyanate. Response surface methodology based on a Box-Behnken design was used to evaluate the effects of pH, liquid-to-solid ratio, extraction temperature, and acetone-to-water volume ratio on mass yield. All four variables influenced the extraction performance, and acetone-to-water volume ratio and liquid-to-solid ratio were the most significant factors. Under the optimized conditions of 50.5 °C, pH 9.2, a liquid-to-solid ratio of 3.0 mL/g, and an acetone-to-water volume ratio of 2.5 mL/mL, the mass yield reached 81.58 percent. The predicted and experimental values were in good agreement, confirming the adequacy of the model. The product obtained under the optimized conditions met the relevant requirements of the Chinese Pharmacopoeia. The proposed process is simple and effective, and provides a basis for the purification and scale up of erythromycin thiocyanate and related derivatives.