An Enthalpy-Balance Model for Timewise Evolution of Temperature during Wet Stirred Media Milling of Drug Suspensions

Guner, Gulenay; Elashri, Sherif; Mehaj, Mirsad; Seetharaman, Natasha; Yao, Helen; Clancy, Donald J.; Bilgili, Ecevit

doi:10.1007/s11095-022-03346-3

Cited by 8 publications

(7 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have seen in this dataset that an increase in tip speed (or rotation speed for a given mill) and bead loading both led to higher T avg. This finding is in line with earlier heat transfer–generation studies [ 65 , 66 , 67 ], which demonstrated that a higher power consumption was observed at the higher rotation speed, and that higher bead loading was the origin of higher heat generation and ensuing temperature rise.…”

Section: Resultssupporting

confidence: 91%

“…Bead size can be an important process parameter as it may provide combined advantages of faster breakage [ 21 , 50 , 64 ], lower heat generation rate [ 65 , 66 , 67 ], and lower media wear [ 21 , 64 ]. However, its impact on the breakage rate may be more subtle because it has counteracting microhydrodynamic trends where smaller beads capture drug particles more frequently but apply less stress upon contact [ 20 , 60 ].…”

Section: Resultsmentioning

confidence: 99%

“…4.1.5. Impact of Temperature Temperature during milling varies over time and is influenced by the process parameters [65][66][67], which may have an impact on the particle size evolution. To investigate this hypothesis, we proposed an Arrhenius function for the j th size quantile that accounts for the temperature dependency, i.e., Kt j (see Section 3.2.2).…”

Section: Impact Of Bead Sizementioning

confidence: 99%

See 2 more Smart Citations

Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions

Clancy,

Guner,

Chattoraj

et al. 2024

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

This study aimed to develop a practical semi-mechanistic modeling framework to predict particle size evolution during wet bead milling of pharmaceutical nanosuspensions over a wide range of process conditions and milling scales. The model incorporates process parameters, formulation parameters, and equipment-specific parameters such as rotor speed, bead type, bead size, bead loading, active pharmaceutical ingredient (API) mass, temperature, API loading, maximum bead volume, blade diameter, distance between blade and wall, and an efficiency parameter. The characteristic particle size quantiles, i.e., x10, x50, and x90, were transformed to obtain a linear relationship with time, while the general functional form of the apparent breakage rate constant of this relationship was derived based on three models with different complexity levels. Model A, the most complex and general model, was derived directly from microhydrodynamics. Model B is a simpler model based on a power-law function of process parameters. Model C is the simplest model, which is the pre-calibrated version of Model B based on data collected from different mills across scales, formulations, and drug products. Being simple and computationally convenient, Model C is expected to reduce the amount of experimentation needed to develop and optimize the wet bead milling process and streamline scale-up and/or scale-out.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Impact Of Bead Sizementioning

confidence: 99%

See 1 more Smart Citation

Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions

Clancy,

Guner,

Chattoraj

et al. 2024

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Other challenges related to processing and manufacturing operations include long cycle times, high power and energy consumption, media wear, and ensuing product contamination [ 12 , 13 ]. To resolve these issues, the impacts of process conditions such as stirrer speed, bead loading, bead type, bead size, flow rate, and drug loading on breakage rate and cycle time [ 2 , 14 , 15 ], media wear [ 16 , 17 ], heat dissipation and temperature rise [ 18 , 19 ], power consumption, and operational costs [ 20 , 21 ] were investigated.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, increasing stirrer speed and bead loading led to faster breakage of the particles and, therefore, shorter cycle times [ 14 ]. However, these conditions require higher power and energy consumption [ 14 , 21 ], which increases the cost of production [ 21 ] and bead wear/contamination [ 16 , 22 ], as well as heat generation and temperature rise as mechanical power is converted to heat [ 18 , 19 ]. Based on these findings, the existence of an optimal stirrer speed and bead loading combination is obvious.…”

Section: Introductionmentioning

confidence: 99%

Do Mixtures of Beads with Different Sizes Improve Wet Stirred Media Milling of Drug Suspensions?

Guner,

Mehaj,

Seetharaman

et al. 2023

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

The impacts of bead sizes and bead mixtures on breakage kinetics, the number of milling cycles applied to prevent overheating, and power consumption during the nanomilling of drug (griseofulvin) suspensions were investigated from both an experimental and theoretical perspective. Narrowly sized zirconia beads with nominal sizes of 100, 200, and 400 µm and their half-and-half binary mixtures were used at 3000 and 4000 rpm with two bead loadings of 0.35 and 0.50. Particle size evolution was measured during the 3 h milling experiments using laser diffraction. An nth-order breakage model was fitted to the experimental median particle size evolution, and various microhydrodynamic parameters were calculated. In general, the beads and their mixtures with smaller median sizes achieved faster breakage. While the microhydrodynamic model explained the impacts of process parameters, it was limited in describing bead mixtures. For additional test runs performed, the kinetics model augmented with a decision tree model using process parameters outperformed that augmented with an elastic-net regression model using the microhydrodynamic parameters. The evaluation of the process merit scores suggests that the use of bead mixtures did not lead to notable process improvement; 100 µm beads generally outperformed bead mixtures and coarser beads in terms of fast breakage, low power consumption and heat generation, and low intermittent milling cycles.

show abstract

Elaborating the crystal transformation referenced microhydrodynamic model and fracture mechanism combined molecular modelling of irbesartan nanosuspensions formation in wet media milling

Meng

et al. 2023

International Journal of Pharmaceutics

View full text Add to dashboard Cite

An Enthalpy-Balance Model for Timewise Evolution of Temperature during Wet Stirred Media Milling of Drug Suspensions

Cited by 8 publications

References 53 publications

Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions

Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions

Do Mixtures of Beads with Different Sizes Improve Wet Stirred Media Milling of Drug Suspensions?

Elaborating the crystal transformation referenced microhydrodynamic model and fracture mechanism combined molecular modelling of irbesartan nanosuspensions formation in wet media milling

Contact Info

Product

Resources

About