Two polymorphs of biclotymol

Crystal of tienoxolol

Maître de Conférences - HDR (associate professor)

Laboratoire SMS, University of Rouen

Faculty of Pharmacy

University de Paris

Polymorphism in Pharmacy

Active pharmaceutical ingredients (API) or more simply drug molecules need to be administered to patients in a controlled way. The activity and toxicity of an API require a specific concentration range in the body for optimal pharmaceutical activity and minimal toxicity. Different crystal forms of the same molecule can have different solubilities and different dissolution profiles, affecting drug activity. Furthermore phase changes (the change of one crystal form into another) of API’s in tablets during storage may cause the tablet to fall apart, destroying the entire dose form and making the tablet as a drug effectively useless.

Evidently, drug development requires the study of API polymorphism.

Our work involves the mapping of the stability hierarchy of API crystalline forms in the pressure - temperature domain. We make use of calorimetry, high resolution X-ray diffraction and thermodynamics to construct topological phase diagrams. Measurements of transition temperatures under hydrostatic pressure are used to corroborate and reinforce the topological result.

Essentially, the methodology leads to a pressure - temperature diagram with the different phase boundaries and the stability hierarchy. These phase diagrams can be used to determine the stable API form at room temperature and to evaluate the possibility whether the API will transform into another crystal form depending on the conditions to which it is subjected.