Grant: Virtual Formulation Laboratory for prediction and optimisation of manufacturability of advanced solids based formulations
PI: Dr Csaba Sinka, University of Leicester

Presentation: Virtual Formulation Laboratory for prediction and optimisation of manufacturability of advanced solids based formulations - pdf
Csaba Sinka, Ruslan Davidchack & Ben Edmans, University of Leicester; Vikram Karde, Imperial College, London; Hamed Salehi, University of Greenwich; Mehrdad Pasha, University of Leeds

Virtual Formulation Laboratory (VFL) is a software tool for prediction and optimisation of manufacturability and stability of advanced solids-based formulations. Four processes are considered: powder flow, mixing, compaction and storage. VFL predicts manufacturability problems quantified by suitable manufacturability indicators and accounts for a range of material types, particle structures and blend systems to enable the formulator to test the effects of formulation changes in virtual space and check for potential problems covering manufacturing difficulties experienced in production plants. In this overview the science base for understanding of surfaces, particulate structures and bulk behaviour to address physical, chemical and mechanical stability during processing and storage is introduced. The manufacturability indicators are predicted from bulk properties which are linked to particle properties and molecular information. Demonstration case studies are presented for the four manufacturing processes and problems. The talk will be followed by a more detailed presentation of the VFL approach to powder compaction.

Q&A

Question (Umair Zafar): Which silanized coating were used. Normally silanization process increases the surface energies.

Answer (Jerry Heng): Hi Umair, the silane we used introduced CH3 moieties which resulted in a reduction in their surface energies, also confirmed by liquid sessile drop contact angle measurements.

Response (Umair Zafar): That's interesting Jerry as we see opposite trend in drop test technique which was also confirmed by AFM.

Response (Jerry Heng): @umair - I think this would depend on the chemistry of the silane used. Happy to follow up separately if of interest to you.

Response (Umair Zafar): @Jerry: Thanks, yes definitely worth discussing further separately for understanding i.e. chemical vs Quasi vs Dynamic

Question (Simon Gibbon): Vikram did you investigate the role of surface roughness in the surface energies you measured?

Answer (Vikram Karde): @Simon: Thank you for the question. From IGC measuremnts we have not considered the roughness effects for the particlate solids considered here. But we can anlyse that using the sessile drop contact angle technique.

Follow-up question (Simon Gibbon): @Vikram liquid contact angles on powders are challenging too, we did a lot of work sticking particles to plates, as forming tablets often damages the particles.  I saw some interesting work using different size molecules in IGC to investigate surface roughness effects, I will send you a link if you haven't seen it.

Follow up comment (Vikram Karde): @ Simon. I agree with you. Alternatively, we have also done measurements using macroscopic single crystal of crystalline materials like Mannitol, Paracetamol etc, which can discern the surface roughness effects without damaging the particle surface. Also, I believe there's some work with reference to the roughness effect using DVS technique. Happy to look into the work in detail if you could send me the link. Thanks

Question (Tim Akerman): Hi Ruslan, in the numbers you quoted, there were some very small effects. Did you measure the reproducibility and repeatability of the test methods and the level of variation in the results?

Answer (Ruslan): @Tim Akerman.  We are still in the process of verifying the results, trying different parametrisations of the thermodynamic integration path to ensure that we don't have any systematic errors.  We are planning to have finalised results within a couple of months.

Question (Jin Sun): @Ben and Csaba: how does the particle material constitutive model change the unloading behaviour?

Answer (Ben Edmans): @Jin Sun The ratio E/sigma_y is most important, it is a measure of the particle's plasticity, so increasing this ratio increases the unloading stiffness.  However the displacement attained before unloading is also important; these two factors interact in a nonlinear way to give the unloading stiffness.  One conclusion is that a single synthetic measure of deformation is not sufficient to predict unloading stiffness at large displacements

Question (Xizhong Chen): @Ben, will the adhesion also affect the unloading behaviour?

Answer (Ben Edmans)@: @Xizhong Yes, it will, but this was not included in the simulations.  Unfortunately, this is rather difficult to implement in FEM

Question (Jin Sun): @Mehrdad, how about the stress ratio versus inertial number?

Answer (Mehrdad Pasha): @Jin, we have investigate that and we have developed a rhelogical model and now we are running CFD to confirm that

Follow-up (Mehrdad Pasha): @Jin we have run two CFD and DEM simulations calculating the flow rate out of a screw convayor and the results are promissing. 

Question (Peter Collins): To Csaba &Co, can we relate the energy to Hansen solubility parameters, as there is a lot of practically useful data surrounding them?

Answer (Jerry Heng): @Peter - yes, we are able to do this with surface energy and Hansen solubility parameters

Answer (Csaba): @Peter Collins, Hi Peter, this is an excellent suggestion, thank you. As you say, if we could make the link, or at least develop some sensible functional relationships then we could link in to a large complementary database.

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