Predicting the Temperature Evolution during Nanomilling of Drug Suspensions via a Semi-Theoretical Lumped-Parameter Model

Guner, Gulenay; Yilmaz, Dogacan; Yao, Helen; Clancy, Donald J.; Bilgili, Ecevit

doi:10.3390/pharmaceutics14122840

Cited by 6 publications

(6 citation statements)

References 70 publications

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“…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%

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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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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Impact Of Bead Sizementioning

confidence: 99%

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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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“…In recent years, one of the most challenging issues encountered in both the pharmaceutical industry and pharmaceutical studies has been drug candidates with low water solubility [ 1 ]. The main challenges are that the dose-response linearity of drugs with low water solubility may decrease, and unexpected collapse of the drug may be encountered after administration, leading to decreased patient compliance and decreased bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Formulation Strategies of Nanosuspensions for Various Administration Routes

et al. 2023

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Nanosuspensions (NSs), which are nanosized colloidal particle systems, have recently become one of the most interesting substances in nanopharmaceuticals. NSs have high commercial potential because they provide the enhanced solubility and dissolution of low-water-soluble drugs by means of their small particle sizes and large surface areas. In addition, they can alter the pharmacokinetics of the drug and, thus, improve its efficacy and safety. These advantages can be used to enhance the bioavailability of poorly soluble drugs in oral, dermal, parenteral, pulmonary, ocular, or nasal routes for systemic or local effects. Although NSs often consist mainly of pure drugs in aqueous media, they can also contain stabilizers, organic solvents, surfactants, co-surfactants, cryoprotectants, osmogents, and other components. The selection of stabilizer types, such as surfactants or/and polymers, and their ratio are the most critical factors in NS formulations. NSs can be prepared both with top-down methods (wet milling, dry milling, high-pressure homogenization, and co-grinding) and with bottom-up methods (anti-solvent precipitation, liquid emulsion, and sono-precipitation) by research laboratories and pharmaceutical professionals. Nowadays, techniques combining these two technologies are also frequently encountered. NSs can be presented to patients in liquid dosage forms, or post-production processes (freeze drying, spray drying, or spray freezing) can also be applied to transform the liquid state into the solid state for the preparation of different dosage forms such as powders, pellets, tablets, capsules, films, or gels. Thus, in the development of NS formulations, the components/amounts, preparation methods, process parameters/levels, administration routes, and dosage forms must be defined. Moreover, those factors that are the most effective for the intended use should be determined and optimized. This review discusses the effect of the formulation and process parameters on the properties of NSs and highlights the recent advances, novel strategies, and practical considerations relevant to the application of NSs to various administration routes.

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“…Modeling the processes in wet stirred and ball mills is challenging. It requires simultaneous modeling of the complex physics of interactions between the grinding media, the moving mixing elements, and the grinding materials [20,21]. According to Esteves et al [22], in fine grinding applications, the energy efficiency of gravity-induced stirred mills is higher than that of traditional ball mills.…”

Section: Introductionmentioning

confidence: 99%

Relation between Scale-Up and Life Cycle Assessment for Wet Grinding Process of Pumice

Mannheim

Kruszelnicka

2023

Energies

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This study examines the grinding process of pumice based on the dry and wet laboratory measurements, scale-up method, and life cycle assessment. This research’s main goal was to set up the relation between scale-up and life cycle assessment results for the wet grinding process with the help of mathematical equations. Within the first research works, basic grinding testing in a laboratory dry Bond mill was accomplished. This step allowed the description of the estimated particle size distribution, median particle size, specific grinding work, and grindability index number of pumice. The second step was the determination of power consumption and scale-up in a laboratory stirred media mill, and it involved the assessment of resources, primary energies, and environmental impacts of wet grinding using GaBi 8.0 software. According to the results, we obtain life cycle emission factors by introducing five coefficients for grinding in laboratory and industrial conditions. These constants depend on the external dimensions of the mill and can be expressed by a derived scale constant from the scale-up. Research results enable the industry to make a prognosis for industrial plants based on the integration between life cycle assessment and scale-up of the pilot grinding processes.

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Predicting the Temperature Evolution during Nanomilling of Drug Suspensions via a Semi-Theoretical Lumped-Parameter Model

Cited by 6 publications

References 70 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

Formulation Strategies of Nanosuspensions for Various Administration Routes

Relation between Scale-Up and Life Cycle Assessment for Wet Grinding Process of Pumice

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