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Identifying polymorphisms to progress drug formulation development

A polymorphism is the existence of more than one crystal structure for a certain material. Most pharmaceuticals are produced in solid form, but can vary significantly in their efficacy due to the presence of polymorphic forms. This existence of multiple structures can occur for a number of reasons, such as differences in formulation or storage. For example, if the solid-state form of the active pharmaceutical ingredient (API) is a crystalline material, an amorphous solid or a solvate can impact the drug’s properties, such as the dissolution rate, solubility and bioavailability.

The solid-state properties of drug formulations must be properly understood in order to reliably produce the optimal form of a drug during the clinical trials phase of drug development. Further research to advance knowledge of pharmaceutical polymorphs can lead to improved drug properties, making polymorph screening technology an important area for development.

Studying polymorphs in solid-state pharmaceuticals presents a challenge in drug development. Characterising all of the components within a formulation is not possible with traditional techniques, and many polymorphs cannot be obtained as a single crystal suitable for solving their crystal structure. 

Raman spectrometers are used to identify the crystals by monitoring polymorph transitions in formulation development. Raman spectroscopy can provide fundamental insights with comparatively little time and effort, and Raman scattering is an efficient method in polymorphic investigations due to its high sensitivity to the crystalline structure of molecular compounds.

More recently, solid-state NMR has also been used in the study of solid pharmaceutical form properties and now represents a crucial tool for polymorphism investigations in drug development. As a highly sensitive technique, solid-state NMR is able to identify crystalline and amorphous forms of drugs and excipients, as well as solvates and hydrates. 

Solid-state NMR can also be used to investigate the interactions between drugs and excipients and changes that can occur during formulation, such as crystallisation. An additional benefit of this technique is its non-destructive nature, allowing the samples to be re-analysed using alternative techniques.