Comparative studies of powder flow predictions using milligrams of powder for identifying powder flow issues

Developing a model-driven workflow for the digital design of small-scale batch cooling crystallisation with the antiviral lamivudine

“…21) at an elevated temperature (10 °C below boiling point) with an aspect ratio of above 0.5. 22 These physical constraints were chosen to ensure a well-suspended slurry ( i.e. , the elevated temperature concentration cannot be so high that a paste results at low temperatures), to promote a high crystallisation yield ( i.e.…”

“…, the low temperature concentration should be sufficiently low to crystallise most of the API but not so low to promote potential inclusion of impurities), 21 and, finally, to encourage powder flowability of the resulting drug product (aspect ratio >0.5). 22 At this stage of the workflow, yield and crystal shape are not optimised but, instead, used as constraints ( e.g. , only solvent systems that give crystals with an aspect ratio exceeding 0.5 are accepted) to subsequently rank possible solvent choices.…”

“…43 Additional parameter constraints were included in the kinetic parameter estimation including a D90 size distribution of 100 μm to 250 μm so that the resultant powder would be free-flowing. 22…”

“…43 Additional parameter constraints were included in the kinetic parameter estimation including a D90 size distribution of 100 μm to 250 μm so that the resultant powder would be free-flowing. 22 From a bioavailability and drug product perspective, there was no targeted preference between form I and form II as the both forms have similar oral bioavailability and are both used in commercial formulations. 44 Form I and form III exhibited needle geometry, and thus would not satisfy the aspect ratio target parameter.…”

Comparative Study on Adaptive Bayesian Optimization for Batch Cooling Crystallization for Slow and Fast Kinetic Regimes

“…This implementation of BO has the potential to translate to meaningful cost savings for materials, resource, energy utilization, and chemical waste and to accelerate development timelines. This method could also be expanded to investigate the optimization of other numerical parameter objectives such as solute concentration, aspect ratio, and yield and applied to optimization of drug substant filtration and flow …”