Continuous mixing technology: Validation of a DEM model

Toson, Peter; Doshi, Pankaj; Matic, Marko; Siegmann, Eva; Blackwood, Daniel O.; Jain, Ashwinkumar C.; Brandon, Jenna K.; Lee, Kai; Wilsdon, David; Kimber, James A.; Verrier, Hugh; Khinast, Johannes; Jajčević, Dalibor

doi:10.1016/j.ijpharm.2021.121065

Cited by 13 publications

(3 citation statements)

References 36 publications

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“…Common contact models applied for tablet compaction simulation include the Luding elasto-plastic model [ 22 ], Storkers model [ 23 ], and Hertz–Mindlin theorem [ 24 ]. Recent studies from [ 14 , 25 ] showed that the Luding model is suitable for pharmaceutical materials.…”

Section: Introductionmentioning

confidence: 99%

Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

et al. 2023

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Pharmaceutical tablet disintegration is a critical process for dissolving and enabling the absorption of the drug substance into the blood stream. The tablet disintegration process consists of multiple connected and interdependent mechanisms: liquid penetration, swelling, dissolution, and break-up. One key dependence is the dynamic change of the pore space in a tablet caused by the swelling of particles while the tablet takes up liquid. This study analysed the changes in the pore structure during disintegration by coupling the discrete element method (DEM) with a single-particle swelling model and experimental liquid penetration data from terahertz-pulsed imaging (TPI). The coupled model is demonstrated and validated for pure microcrystalline cellulose (MCC) tablets across three porosities (10, 15, and 22%) and MCC with three different concentrations of croscarmellose sodium (CCS) (2, 5, and 8% w/w). The model was validated using experimental tablet swelling from TPI. The model captured the difference in the swelling behaviour of tablets with different porosities and formulations well. Both the experimental and modelling results showed that the swelling was lowest (i.e., time to reach the maximum normalised swelling capacity) for tablets with the highest CCS concentration, cCCS = 8%. The simulations revealed that this was caused by the closure of the pores in both the wetted volume and dry volume of the tablet. The closure of the pores hinders the liquid from accessing other particles and slows down the overall swelling process. This study provides new insights into the changes in the pore space during disintegration, which is crucial to better understand the impact of porosity and formulations on the performance of tablets.

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Section: Introductionmentioning

confidence: 99%

Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

et al. 2023

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“…The CMT features two rotating impellers stacked on top of each other in a cylindrical vessel with a conical section at the bottom . Powder material flows vertically through the CMT, wherein the top impeller breaks up agglomerates, and subsequently, the bottom impeller ensures mixing . This ensures homogeneous mixing of the active ingredient and excipients under an atmosphere of nitrogen.…”

Section: Introductionmentioning

confidence: 99%

“…9 Powder material flows vertically through the CMT, wherein the top impeller breaks up agglomerates, and subsequently, the bottom impeller ensures mixing. 10 This ensures homogeneous mixing of the active ingredient and excipients under an atmosphere of nitrogen. The purpose of nitrogen (inert gas) purge is to mitigate the risk of hazardous dust explosion.…”

Section: Introductionmentioning

confidence: 99%

Drug Phase Transformation and Water Redistribution during Continuous Tablet Manufacturing: A Case Study of Carbamazepine Dihydrate

et al. 2023

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In recent years, continuous tablet manufacturing technology has been used to obtain regulatory approval of several new drug products. While a significant fraction of active pharmaceutical ingredients exists as hydrates (wherein water is incorporated stoichiometrically in the crystal lattice), the impact of processing conditions and formulation composition on the dehydration behavior of hydrates during continuous manufacturing has not been investigated. Using powder X-ray diffractometry, we monitored the dehydration kinetics of carbamazepine dihydrate in formulations containing dibasic calcium phosphate, anhydrous (DCPA), mannitol, or microcrystalline cellulose. The combined effect of nitrogen flow and vigorous mixing during the continuous mixing stage of tablet manufacture facilitated API dehydration. Dehydration was rapid and most pronounced in the presence of DCPA. The dehydration product, amorphous anhydrous carbamazepine, sorbed a significant fraction of the water released by dehydration. Thus, the dehydration process resulted in a redistribution of water in the powder blend. The unintended formation of an amorphous dehydrated phase, which tends to be much more reactive than its crystalline counterparts, is of concern and warrants further investigation.

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Numerical study of wall normal stress and discharging characteristics for gravity blending silo

Zhou

Chong

Jiang³

et al. 2023

Comp. Part. Mech.

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Continuous mixing technology: Validation of a DEM model

Cited by 13 publications

References 36 publications

Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

Drug Phase Transformation and Water Redistribution during Continuous Tablet Manufacturing: A Case Study of Carbamazepine Dihydrate

Numerical study of wall normal stress and discharging characteristics for gravity blending silo

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