Design of industrial crystallization of interferon gamma: Phase diagrams and solubility curves

Phase diagrams and solubility curves for engineering of crystallization for interferon gamma have been developed by small scale precipitation and crystallization experiments. A scale up was carried out to proof the accuracy and the suitability of the created phase diagram with sodium sulfate for bulk crystallization. To provide nucleation and a high yield the operating point was chosen at a protein concentration of 6 mg/mL and a sodium sulfate concentration of 25% [w/v]. Crystallization was completed within 5 h with a yield of>95%. The double logarithmic plot of crystallized fraction versus time yielded in an overall kinetic crystallization constant of 5.79×10−2 min−1. Regular cubic crystals can be observed which contradicts the low Avrami coefficient. The Avrami coefficient of 1 is interpreted that nucleation takes place throughout the entire crystallization process and larger crystals are formed by Ostwald ripening instead of growth out of the liquid phase. The established process with its conditions is suited for industrial protein crystallization.