Salt Synthesis: selecting the best salt form for pharmaceutical development.

In order to produce a desirable drug dosage form of an active pharmaceutical ingredient (API), developmental chemists often start by considering the possible formation of various salt forms of the API.

By formulating salts with different specific counter ion functionalities, it is possible to alter the physical properties of the drug active, such as improve its aqueous solubility, degree of crystallinity, hygroscopic nature and solid-state stability. Such factors also contribute directly to the drugs effectiveness and safety, as well as improving commercial suitability such as shelf life and manufacturing process simplification etc.

Our individually designed studies enable us to rationally select suitable counter-ions for salt formation and is restricted to acids/bases and solvents suitable for pharmaceutical manufacturing. Such studies are designed to explore a range of stoichiometries and to optimise crystallisation conditions for a particular crystalline form.

For companies with limited sample quantities, crystallisation experiments are performed in specially designed micro-titre plates that are individually sealed. After crystallisation and solid-liquid separation, the solid samples are then characterised using

• high-throughput Raman spectroscopy (96 well plate),
• Pharmaterials outstanding 96 well plate reading transmission X-ray diffraction system and
• state-of-the-art chemometric software to speed up hit identification, with the resulting spectra grouped and assigned.

Once evaluated, the most suitable formulated salts are scaled up and physically screened using the following techniques:

X-ray crystallography

Thermal Analysis - DSC, TGA, hot-stage microscopy

Spectroscopy - NMR and FTIR

Solubility, intrinsic dissolution and purity by HPLC.

Such studies are carried for each of the solid forms, allowing us to rank order the salts with respect to suitability and functionality. This then allows our clients to move forward with confidence on their drug compound selection program.

As well as identifying suitable salt forms to alter the physicochemical properties of the API, our technologies may also be used for increased patent protection. For more information please contact a representative.  

Pharmaterials - we don't just measure we understand. 

We provide the information and advice you need to make the decision on the best salt to develop.