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Polymorph, Salt & Cocrystal Screening

 Selecting the optimal solid form of an API during early drug development can mitigate the risk of failure later in development. This can be achieved through polymorph, salt and cocrystal screening.

  • Polymorph screening aims to identify all relevant forms of an API, investigate their properties and choose the optimal crystalline form. Polymorphism control is exceptionally important and conducting these screens can help prevent the appearance of new forms in the latter stages of development. We focus on establishing the interconversions between forms, the relative stability of forms and understanding the monotropic or enantiotropic relationship between polymorphs when required. Polymorph screening is a regulatory requirement whether a salt, cocrystal or free form compound is chosen for development.
  • Salt screening is an approach to quickly identify and assess the salt forms of an API. This allows drug developers to modify the physical properties of an API while preserving the benefits of a crystalline solid form. Salts of an API, often improve the APIs solubility, stability, crystallinity and can grow the solid-state portfolio of the API.
  • Cocrystal screening can identify and assess the potential cocrystal forms of an API. It provides an alternative approach to modify the physical properties of an API where salts do not achieve the desired performance or are not an option.

The Verapharma solid form and particle engineering team is capable of assessing controlled substances and has the appropriate licence and additional protocols in place to handle these compounds.

Structure of polymorphs, salts and cocrystals

Our general approach to screening is underpinned by three sequential phases:

  • Phase 1: Comprehensive solid-state characterization and understanding of the material supplied
  • Phase 2: Generation of solids polymorphs/salts/cocrystals followed by basic characterization and evaluation of the ‘hits’
  • Phase 3: Scale-up of the relevant hits followed by full characterization and recommendations regarding the most suitable form for further development.

Diagram to show pKa increasing from salt to cocrystal


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