Directed polymorphism may lead to better treatments
In the field of pharmaceuticals, the term 'polymorphism' refers to the existence of a single substance in two or more crystalline forms. These different forms can vary widely in their efficacy, bioavailability and even toxicity. An EU-funded project is working to develop a method for directing polymorphism in pharmaceutical compounds, thus promising better drug treatments for patients everywhere.
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The study of polymorphism is very important in the pharmaceutical industry. Scientists have learned, for instance, that specific crystalline forms can exhibit unique properties that might not be exhibited by other forms of the same substance.
Different polymorphic forms vary not only in terms of their clinical properties but also in their physicochemical properties, including dissolution and solubility, chemical and physical stability, flowability and hygroscopicity.
The aim of the EU-funded MAGNAPHARM project is to synthesise in a controlled way the most desirable polymorphic forms of any pharmaceutical. Initially, this project is targeting 12 of the most high-profile and high-value generic drugs on the market, together representing EUR 18 billion in sales per year worldwide.
Specifically, MAGNAPHARM researchers are working to synthesise the lowest-energy polymorphs and/or the most easily processed forms with desired properties, through applying strong magnetic fields during the crystallisation process. The work is underpinned by a profound theoretical understanding of the effects of magnetic fields on organic crystal growth, drawing on the results of cutting-edge spectroscopic and crystallographic studies.
Until now, the development of new pharmaceuticals has often been hampered by polymorphism-related issues. The EU has previously funded major international efforts to direct polymorphism in pharmaceutical compounds, notably under the FETOPEN initiative. Thus, European researchers have already established that it is possible to synthesise specific polymorphs of pharmaceutical substances such as carbamazepine, indomethacin and paracetamol.
Exerting effective control over the production of the most pharmaceutically desirable crystal polymorphs is a paradigm-shifting prospect. The ability to direct polymorphism through the application of strong magnetic fields is expected to have a transformative effect on the production of almost all pharmaceutical compounds, and hence on all medical practice.