Salt Screening and Selection

We have developed a systematic high throughput salt screening protocol that enables rapid identification of a range of pharmaceutically acceptable salts. This is also applicable to intermediates and fine chemicals, where isolation or purification issues may benefit from salt formation.

At the beginning of any study, a comprehensive understanding of both the physical and chemical properties of the study candidate is essential. This enables an efficient coverage of the relevant chemical space during experimental design and salt selection. Generally, following quantification of the pKa values of any ionisable groups, the pharmaceutical application counter ions that are generally regarded as safe (GRAS) are selected, with preference for those which have high incidence in marketed salt forms of drugs.

The experimentation protocol consists of an automated crystallisation platform with the capability to perform many experiments in parallel, in 96 well plates, with only milligram amounts of sample. During a salt screen, the first step is to create a solid crystalline material. After crystallisation and filtration, all solid products are then characterised using high-throughput X-ray powder diffraction as the primary analytical technique. Any crystalline samples are then moved forward to a more experimentally comprehensive study, including scale-up of the selected relevant salt versions. Further characterisation involves: thermal analysis (DSC and TGA), Hot Stage Microscopy imaging, spectroscopy (Raman, NMR and FTIR), solubility, purity profile and Dynamic Vapour Sorption.

Single crystal X-ray diffraction can be out sourced upon customer's request. On the basis of these data the solid form(s) identified are ranked, for example, in order of stability and crystallinity and also on the basis of a viable production process. Once the optimal solid form has been chosen, our wealth of experience in process development then allows us to generate protocols, in the form of a subsequent development proposal, for reliably producing the desired final form at scale.

  Solid State Services

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