(223e) The Role of Solubility Modelling and Crystallisation in the Design of Active Pharmaceutical Ingredients

The crystalline solid state (polymorphic form) of an Active Pharmaceutical Ingredient (API) is important in controlling the drug release profile in the patient, and is a key aspect in the design of API products. The polymorphic form also affects unit operations in the manufacturing process like filtration, washing and drying, which are critical for controlling the impurity profile of the drug. An introduction to the science of crystallisation is presented, together with a step by step procedure for the design of API crystallisation processes, using Cimetidine as a case study. The method is based on recent advances in predictive solubility modelling techniques: Chen, C.-C., Song, Y., 2004, Solubility Modeling with a Non-Random Two-Liquid Segment Activity Coefficient Model, Ind. Eng. Chem. Res., 43, 8354-8362; SoluCALC manual, CAPEC, Department of Chemical Engineering, Technical University of Denmark (www.capec.kt.dtu.dk).