dr Anna Hoser
Towards new methods of extracting thermodynamic properties from X-ray diffraction data of model polymorphic systems
Financing amount: 638 461 PLN
Polymorphism is the occurrence of a compound in several crystal forms which have different conformation of molecules or different packing of molecules in crystal lattice. Polymorphism is a very important phenomenon because polymorphs of the same substance exhibit different physicochemical properties (melting point, solubility etc.) and different biological activity, which is important for the pharmaceutical industry. Around 30% of drugs exhibit more than one polymorphic form, and it is important to be sure before drug is released for the market, that all polymorphic forms are known, characterized and the one which is active is a stable one. Recently, it was shown that even aspirin exist in two polymorphic forms.
A famous example of lack of control of polymorphism is the disastrous billion dollar market withdrawal — the story of the HIV drug Ritonavir. Ritonavir was first released to the market by Abbot in 1996 and withdrew two years later because it appeared that the drug does not exhibit the expected activity. The explanation was surprising – the form I which exhibits drug activity converts into form II which has lower solubility and lower activity than the form I.
A new approach, being developed by us, shall allow estimating the relative stability of polymorphs in wide temperature and pressure ranges on the basis of a combination of theoretical ab-initio calculations and X-ray diffraction experiments. Therefore, it could be used during the process of production of new drugs.
Moreover, we have been focused on polymorphs as they are excellent test cases to verify our approach. This is due to small stability differences they exhibit. In general our approach can be applied to any other ordered crystalline material, thus our project is important for material sciences as well.