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

Meng, Tao; Li, Ye; Ma, Shanshan; Zhang, Qian; Qiao, Fangxia; Hou, Yanhui; Yang, Jianhong

doi:10.1016/j.ijpharm.2022.122562

Cited by 6 publications

(1 citation statement)

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“…Even though both bead materials have the potential for providing fast breakage kinetics through different mechanisms, the collision stress and frequency outweigh the contact circle diameter, and zirconia beads provide faster breakage overall [ 29 , 48 ]. On the other hand, according to their lower collision stress, CPS beads can provide a gentler particle breakage, which, in turn, may reduce the amorphous transformation rates for sensitive materials [ 71 ] and contamination from media wear. In addition, they provided better control over temperature increase during milling [ 49 ], making CPS a competitive alternative to YSZ.…”

Section: Resultsmentioning

confidence: 99%

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

Clancy,

Guner,

Chattoraj

et al. 2024

Pharmaceutics

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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.

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