UK materials scientists have found that polymers in solution can block the formation of the technologically favourable crystal form of paracetamol. The discovery gives clues to the poorly understood crystallisation process.

In an attempt to understand how the most drug-friendly form of paracetamol crystallises, Jacqueline Capes and Ruth Cameron from the University of Cambridge found that the use of polymers in solution can suppress its formation. They found that polymers affected the evaporation process of the solution, and disrupted solvent flows at sites on the edge of drops, where the metastable crystals would normally form. These results are in contrast to previous reports of polymers acting as templates to encourage the formation of metastable paracetamol.

Pharmaceutical solids can exist in different in different molecular arrangements in the crystal lattice - called polymorphic forms. Polymorphs can have different chemical and physical properties such as solubility and compressibility, and therefore can directly affect a drug's performance and processability. A metastable polymorph of paracetamol gives the best chemical and physical properties. However, as it is metastable it can transform rapidly to another more stable form.

'Little is known about why metastable forms occur under certain conditions, or how the crystallisation process can be controlled to prevent or encourage the formation of a particular polymorph,' said Capes.

Mino Caira, of the University of Cape Town, South Africa, said 'This work serves to remind us of both the unpredictability of crystallisation outcome and the need for careful, systematic experimentation to assess the possible effects of additives on the process.'

According to Capes, it will be important to study a range of different polymorphic systems to get a greater understanding of the effects of additives and template materials on forming a particular polymorph, and to establish if the same approach to selective crystallisation can be applied to many systems.

Katherine Vickers