Solid Form Screening and Selection

The majority of pharmaceutical drugs are administered in solid form, and therefore, the solid-state properties can significantly impact the performance of the final product, in addition to the molecular structure of the active ingredient. New substances with pharmaceutical activity are often weak acids or bases or may have suboptimal solid-state properties, necessitating the development of the drug as a salt or co-crystal form. In cases where only the amorphous form is known, specifically designed crystallization screenings can assist in finding crystalline candidates, improving chemical purity and stability. The solid form screening strategies employed at Seven Star encompass polymorph screening, salt screening, cocrystal screening, crystallization screening, and the selection of a desired solid form, as depicted in Scheme-1.

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

The selection of the most suitable crystalline candidate should be based on a comprehensive evaluation of the following physical and chemical parameters:

- Stability (chemical and physical)
- Solubility, dissolution, and bioavailability
- Hygroscopicity
- Melting point
- Complexity of polymorph landscape and polymorphic transformations
- Number of polymorphs
- Processability
- Ease of preparation

Additionally, the formation of salts and co-crystals should be considered not only for their impact on chemical and physical properties but also for intellectual property considerations, as superior solid properties can be eligible for patent protection.

For a comprehensive approach to solid-state development, Seven Star offers integrated services ranging from systematic salt, co-crystal, and polymorph screening to controlled scale-up of the crystallization process. These services are complemented by a full range of physicochemical properties evaluation studies performed at Seven Star.