Surface Adsorbed Templates for Directing the Crystal Growth of Entacapone as Monitored Using Process Analytical Techniques

Abstract

Crystallisation of Entacapone (E-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl) propenamide) in acetone solution at 500 mL scale using a self-assembled layer of the host material on Au(111) as a seeding template was studied and monitored using ATR-UVvis spectroscopy and FBRM. The data reveal that the template promotes crystal growth at lower supersaturations and at an increased rate when compared to experiments carried out without the template. The resulting crystals prepared are also found to have superior properties with respect of those produced without the template, notably having a much narrower crystal size distribution, a greatly superior perfection and a more equant crystal morphology. These observations are rationalised by the template providing a sympathetic surface for the promotion of crystallisation in an analogous mechanism to that associated with conventional seeding, but with the added advantage of conferring a well-ordered, easily reproducible and more robust process.2

Precision measurement of the growth rate and mechanism of ibuprofen {001} and {011} as a function of crystallization environment

“…Nowadays, in-process data mostly uses FBRM instrumentation [19][20][21] which measures only the chord length distribution which can be challenging to extract 'first-principles' face-specific kinetics [45].…”

“…Nowadays, in-process data mostly uses FBRM instrumentation [19][20][21] which measures only the chord length distribution from which it can be challenging to extract 'first-principles' face-specific kinetics. 45 Measurements of the growth rates of crystal populations, usually involve seeding within the metastable zone. However, the process can itself provide variability in the measured growth rates [46][47][48] depending on the seed preparation techniques adopted and/or the size fraction selected and/or the seed concentration.…”

Direction of the polymorphic form of entacapone using an electrochemical tuneable surface template

“…Although preliminary in nature, this work suggests the potential to apply the underpinning ideas of electrochemicaldirected crystallisation more widely, particularly with a view to tailoring the molecular and supramolecular structure of the condensed interfacial template for wider applications to other systems. Previous work 46,47 has also shown the utility of the generic approach underpinning this work, particularly its potential for process scale-up and through its utility as an alternative technology for the seeding of batch reactors.…”

“…Previous work 46,47 has also shown the utility of the generic approach underpinning the approach, particularly its potential for process scale up and through its utility as an alternative technology for the seeding of batch reactors. For the pharmaceutical industry, the high quality of the materials produced through this technology confers an ability not only to engineer polymorphic selection but also to ensure high uniformity and low variability, in terms of the particle size and shape of the resultant product form.…”

“…Similarly, low dc electric fields have been used to control the spatial and temporal localisation of nucleation, decrease the number of surface nuclei and increase the size and quality of protein crystals. [43][44][45] Recent research 46,47 by this group have demonstrated that under quiescent conditions Au(100) and Au(111) surface template can direct the formation of form A at its surface with the concomitant crystallisation of form D in the bulk solution. In 100% of the cases form D crystallise spontaneously from that particular solution and supersaturation in the absence of the template.…”