Understanding Polymorphism & Crystallisation Issues in the Pharmaceutical Industry

Crystallisation has been described as one of the most difficult unit operations to control. This is partly because the primary nucleation event, particularly in batch crystallisers, is difficult to control reproducibly without seeding, partly because secondary nucleation processes which result are highly scale and process dependent and partly because of the delicate balance between thermodynamic and kinetic factors in crystallisation processes which operate far from equilibrium.

The consequence of these features can be poor reproducibility of purity, particle size distribution, morphology and crystal structure. The latter phenomenon, known as polymorphism, is a subject which has been and remains an important issue across the pharmaceutical, pigment, agrochemical, explosive and fine chemical industries, where the physical form of the product affects the properties (stability, colour, dissolution rate etc) of the finished product.

It is important, therefore, for chemists who are developing crystallisation operations to understand in detail the key physical processes which occur and which need to be under control - irrespective of whether the process utilises cooling, evaporative, or drown-out crystallisation. This course will teach chemists and engineers some fundamental aspects of crystal chemistry, nucleation and crystal growth, the operation of batch crystallisers and methodologies of characterisations. Because polymorphism is such an important issue the course will cover this in some detail, particularly addressing the case of disappearing (or appearing) polymorphs, when a new form of a product in development (or even worse, in manufacture) suddenly appears. Case studies will be used to illustrate important issues.