Process intermediates: Opportunities for improvements
Attention is rightly directed to establishing the desired attributes of the final material or drug substance which have been determined from the solid state investigations and the crystallisation process to enable development.
As larger quantities of material are required to support further investigations, initial processes that were suitable often become inappropriate in terms of costs of materials and number of batches required. This can have implications on time to the availability of material and hamper the progress of the development programme.
On scale up, pilot plant and production, the isolation of solid intermediates can become a rate determining step, as the filtration and drying activities require longer to complete in processing assets. This might be acceptable in the short term, but with rising demand, availability of production assets might also restrict throughput.
Whilst addressing improvements in the intermediate synthetic process, the isolation of solids should be considered in terms of the crystallisation process, filtration and drying.
Poor filtration and drying of solids during isolation is often a consequence of particle morphology, that is shape and size. The selected solvent can also have a detrimental impact upon drying. These are governed by the crystallisation process to generate the solid. The crystallised solid should not have too small a particle size. Avoiding this will minimise the ‘clogging’ or ‘blinding’ of the filtration media during isolation and drying. Also, the shape or habit of the particles should be such that suspensions of material flow freely.
Consequently, improving the crystallisation of intermediates can have a manifest impact upon throughput. This does not necessarily mean that all intermediate solid isolations have to be developed to the same extent as for the final material attributes, but sufficiently to be reliable in affording the intermediates in terms of characteristics and throughput time.
MorphCryst Consulting can assist with the assessment of processes and how they might be improved to address your requirements.
