Polymorph Study

It is estimated that 30-50% of Active Pharmaceutical Ingredients (APIs) exhibit polymorphism – defined as the ability of a compound to exhibit two or more crystalline phases. Polymorphic forms differ in internal structure (solid state) and may consist of changes in packing, kinetics, mechanical, spectroscopic, surface and thermodynamic properties. Each of these dimensions can greatly influence the bioavailability of the API. As a consequence, polymorph screening and selection play a vital role in the drug development process, not only to optimise performance but also to secure new intellectual property (IP) positions and ensure robust IP protection.

Crystec’s mSAS® supercritical fluid (SCF) technology is a highly effective tool in isolating ‘known’ stable and metastable polymorphs, as well as in identifying polymorphic forms unique to the high-pressure SCF environment. As such, mSAS® is often seen as an enhanced polymorph screening technique for both new chemical entities and currently marketed APIs. It has been used to separate complex polymorphs including:

Crystec mSAS® Case Study

The aim of this project was to discover new polymorphs of an API to strengthen an existing IP position (only one polymorph was known to exist). An enhanced mSAS® polymorph screen was carried out, identifying one new form. An analytical data package was generated in support of arising patent applications.

Product Development

Developing the product involved:

Product Analysis and Performance

A new polymorphic form of the API was identified. The new solid state form was characterised by PXRD and DSC analysis. Particle size and habit were determined using Scanning Electron Microscopy (SEM).