Solid Form Screening and Selection

The majority of drugs are administered as solids. It infers that apart from the molecular structure of the active ingredient, solid-state properties can significantly influence the performance of the final product. Often new substances with pharmaceutical activity are weak acids or bases or may have suboptimal solid-state properties. In such cases it may be preferable to develop the drug as a salt or co-crystal form. When only amorphous form is known, specially designed crystallization screenings can help to find crystalline candidates, often improving the chemical purity and stability. General solid form screening (polymorph screening, salt screening, cocrystal screening, crystallization screening, and selection of a desired solid form) strategies that we use at Seven Star are depicted in Scheme-1.

Scheme 1. Solid form screening strategies and selection of a desired form for a given API.

Selection of the best available crystalline candidate should be based on the following physical and chemical parameters:

Stability (chemical and physical)
Solubility/dissolution/bioavailability
Hygroscopicity
Melting point
Polymorph landscape complexity and polymorphic transformations
Number of polymorphs
Processability
Ease of preparation

In addition to its impact on chemical and physical properties, salt and co-crystal formation is also relevant for intellectual property considerations because solids with superior properties can be patent protected.

For the best overall results, Seven Star provides an integrated and comprehensive approach to solid-state development - from systematic salt, co-crystal, and polymorph screening to controlled scale-up of the crystallization process, all complemented with the full range of physicochemical studies performed at Seven Star.