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Pharmaceutics
Volume 16
Issue 3
10.3390/pharmaceutics16030394
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Article

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

by
Donald J. Clancy
1,*,†,
Gulenay Guner
1,2,†,
Sayantan Chattoraj
1,
Helen Yao
1,
M. Connor Faith
1,
Zahra Salahshoor
1,
Kailey N. Martin
1 and
Ecevit Bilgili
2
1
GlaxoSmithKline R&D, Collegeville, PA 19426, USA
2
Otto H. York Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA
*
Author to whom correspondence should be addressed.
†
Primary authors contributed equally to this work.
Pharmaceutics 2024, 16(3), 394; https://doi.org/10.3390/pharmaceutics16030394
Submission received: 22 February 2024 / Revised: 8 March 2024 / Accepted: 11 March 2024 / Published: 13 March 2024
(This article belongs to the Special Issue 15th Anniversary of Pharmaceutics—Advances in Process and Formulation Modeling)
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Abstract

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.
Keywords: milling; wet bead milling; particle size prediction; modeling; semi-mechanistic modeling; microhydrodynamic model; process scale-up; process optimization milling; wet bead milling; particle size prediction; modeling; semi-mechanistic modeling; microhydrodynamic model; process scale-up; process optimization

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MDPI and ACS Style

Clancy, D.J.; Guner, G.; Chattoraj, S.; Yao, H.; Faith, M.C.; Salahshoor, Z.; Martin, K.N.; Bilgili, E. Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions. Pharmaceutics 2024, 16, 394. https://doi.org/10.3390/pharmaceutics16030394

AMA Style

Clancy DJ, Guner G, Chattoraj S, Yao H, Faith MC, Salahshoor Z, Martin KN, Bilgili E. Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions. Pharmaceutics. 2024; 16(3):394. https://doi.org/10.3390/pharmaceutics16030394

Chicago/Turabian Style

Clancy, Donald J., Gulenay Guner, Sayantan Chattoraj, Helen Yao, M. Connor Faith, Zahra Salahshoor, Kailey N. Martin, and Ecevit Bilgili. 2024. "Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions" Pharmaceutics 16, no. 3: 394. https://doi.org/10.3390/pharmaceutics16030394

APA Style

Clancy, D. J., Guner, G., Chattoraj, S., Yao, H., Faith, M. C., Salahshoor, Z., Martin, K. N., & Bilgili, E. (2024). Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions. Pharmaceutics, 16(3), 394. https://doi.org/10.3390/pharmaceutics16030394

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