Paper of the Month — December

  Metacetamol. Optical image of the characteristic needles of Form-I (circled in red), and polycrystalline Form-II (circled in blue). Image from McGregor et al., 2015.

 

Metacetamol. Optical image of the characteristic needles of Form-I (circled in red), and polycrystalline Form-II (circled in blue). Image from McGregor et al., 2015.

A New Polymorph of Metacetamol (McGregor et al., 2015)

December’s 'Paper of the Month' [L.McGregor, D.A. Rychkov, P.L. Coster, S. Day, V.A. Drebushchak, A.F. Achkasov, G.S. Nichol, C.R. Pulham, E.V. Boldyreva, A New Polymorph of Metacetamol, CrystEngComm., 2015, 17, 6183-6192; DO: 10.1039/C5CE00910C.] opens the story of metacetamol polymorphism.   

Polymorphism of drugs is a hot topic that has widespread implications for the pharmaceutical industry. New drugs can be produced not only from new substances, but also from previously known compounds that can be crystallised to give a new crystal structure, i.e. a new polymorph.

Because they have different crystal structures, polymorphs of a compound very often differ in properties — new polymorphs can have better bioavailability, or be better for technological processing. At the same time, the unexpected appearance of a new polymorph of a drug during production or storage can result in huge financial losses for a pharmaceutical company.

The Food and Drug Administration (FDA) requires that every pharmaceutical substance is fully characterised, and that particular attention is paid to the identification and characterisation of its polymorphs. Furthermore, the conditions for the crystallization of these polymorphs should be described.

However, it is often not easy to obtain new polymorphs, and it is even more difficult to rationalise the conditions under which they were formed and to ensure that their production is consistently reproducible.

Paracetamol is a well-known drug which has been around for over a century; several polymorphs of paracetamol have been obtained and studied in detail. A structural isomer of paracetamol —metacetamol— is also reported to have pharmaceutical activity, but until recently no polymorphs had been described for this compound. Metacetamol is being considered as a promising alternative to paracetamol due to its lower toxicity.

In this paper, a second new polymorph of metacetamol has been crystallised and extensively characterised using a range of instrumental techniques, including infrared spectroscopy using a Linkam FTIR600 stage. A procedure for the reliable and reproducible preparation of the new polymorph is described.

The Linkam instrumentation played a crucial role in the research. Not only was it used to measure IR-spectra at variable temperatures, but also the transformations between the previously known polymorph and the new polymorph could be followed in situ by heating and cooling the samples directly in the chamber of a Linkam FTIR600 stage.

The identification of this new form will lead to further investigation of solubilities, dissolution rates and bioavailabilities, and could potentially result in the appearance of a new pharmaceutical product on pharmacy shelves. The use of modern experimental equipment and techniques allows researchers to improve our understanding of drugs and ultimately improve medical care for patients.