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Crystallisation screening is a critical phase of any drug development programme. This can entail two aims, the first to achieve the requisite purity and the second to achieve the desired form.
Our experience in producing scalable crystallisations, to deliver a preferred form (either process intermediates or GMP material to ICH specified guidelines), is ideally suited to the demands of
this phase. The investigation generally involves a systematic scale-up of a process obtained during one of our crystallisation screens, with a combination of parameters being varied, as described
below:
- Solvent choice and volumes
- Concentration (saturation point vs temperature)
- Counter solvent choice and concentration (including temperature variance)
- Heating/cooling rates/isothermal periods
- Agitation rate during heating/cooling/isothermal periods
- Seeding experiments
- Rates of addition
- Wash solvent volume/composition
- Slurry experiments
- Polishing filtrations
- Product drying conditions
In crystallisation screening, all of the considerations above can be essential in controlling crystallisation factors such as nucleation and crystal growth, which in turn can affect the efficiency
of filtration and product purity. Also, variation of the parameters above can provide vital data for the determination of metastable zones, the manipulation of which, for example by varying cooling
rates, can be used in turn to control polymorphism.
A combination of analytical techniques would then be used to identify the optimum conditions, with the aim of delivering, after the appropriate process development, a controllable process that
achieves not simply form and purity, but also efficiency in terms of yield, throughput and safety.
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Lead optimisation
Solid State
Chemistry
