Mechanistic time scales in adhesive mixing investigated by dry particle sizing

Nguyen, Duy; Rasmuson, Anders; Björn, Ingela Niklasson; Thalberg, Kyrre

doi:10.1016/j.ejps.2014.12.016

Cited by 24 publications

(6 citation statements)

References 25 publications

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“…Important events during DPI formulation blending include random blending, deagglomeration, adhesion, and redistribution. 58 In many cases, simply increasing the blending time cannot improve inadequate blending. Instead, mixer selection, rotation fill level, speed, and capacity should be considered for optimization to improve blending homogeneity (Table 1).…”

Section: Overview For Modeling Inhalable Dry Powder Blending Processesmentioning

confidence: 99%

“…Important events during DPI formulation blending include random blending, deagglomeration, adhesion, and redistribution . In many cases, simply increasing the blending time cannot improve inadequate blending.…”

Section: Overview For Modeling Inhalable Dry Powder Blending Processesmentioning

confidence: 99%

“…For example, it is necessary for lowconcentration (drug−carrier ratio) blends to have initial geometric dilutions to improve final blending homogeneity. 58 To ensure the desired dose of the drug is delivered to the lung, a preblending process may be needed if inadequate drug/ carrier separation happens during aerosolization due to the strong adhesion force between drugs and carriers. Ideally, the adhesion force must be strong enough to prevent demixing but small enough to allow detachment during aerosolization.…”

Section: Overview For Modeling Inhalable Dry Powder Blending Processesmentioning

confidence: 99%

“… Different drug powders may exhibit specific blending requirements due to the distinctive presence of interactive forces within that specific system. For example, it is necessary for low-concentration (drug–carrier ratio) blends to have initial geometric dilutions to improve final blending homogeneity . To ensure the desired dose of the drug is delivered to the lung, a preblending process may be needed if inadequate drug/carrier separation happens during aerosolization due to the strong adhesion force between drugs and carriers.…”

Section: Overview For Modeling Inhalable Dry Powder Blending Processesmentioning

confidence: 99%

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Emerging Process Modeling Capabilities for Dry Powder Operations for Inhaled Formulations

Lou,

Ding,

et al. 2023

Mol. Pharmaceutics

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Dry powder inhaler (DPI) products are commonly formulated as a mixture of micronized drug particles and large carrier particles, with or without additional fine particle excipients, followed by final powder filling into dose containment systems such as capsules, blisters, or reservoirs. DPI product manufacturing consists of a series of unit operations, including particle size reduction, blending, and filling. This review provides an overview of the relevant critical process parameters used for jet milling, highshear blending, and dosator/drum capsule filling operations across commonly utilized instruments. Further, this review describes the recent achievements regarding the application of empirical and mechanistic models, especially discrete element method (DEM) simulation, in DPI process development. Although to date only limited modeling/simulation work has been accomplished, in the authors' perspective, process design and development are destined to be more modeling/simulation driven with the emphasis on evaluating the impact of material attributes/process parameters on process performance. The advancement of computational power is expected to enable modeling/simulation approaches to tackle more complex problems with better accuracy when dealing with real-world DPI process operations.

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Section: Overview For Modeling Inhalable Dry Powder Blending Processesmentioning

confidence: 99%

Section: Overview For Modeling Inhalable Dry Powder Blending Processesmentioning

confidence: 99%

Section: Overview For Modeling Inhalable Dry Powder Blending Processesmentioning

confidence: 99%

Section: Overview For Modeling Inhalable Dry Powder Blending Processesmentioning

confidence: 99%

See 2 more Smart Citations

Emerging Process Modeling Capabilities for Dry Powder Operations for Inhaled Formulations

Lou,

Ding,

et al. 2023

Mol. Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…This is not easy given the dynamic interplay of process and material variables. The mixing process for producing adhesive mixtures can be summarized to consist of 4 mechanistic processes, 6 which are envisaged to be sequential but often occur with significant overlap during dynamic mixing. These rate processes are as follows:…”

Section: Introductionmentioning

confidence: 99%

Development of a Rational Design Space for Optimizing Mixing Conditions for Formation of Adhesive Mixtures for Dry-Powder Inhaler Formulations

Sarkar

Minatovicz

Thalberg

et al. 2017

Journal of Pharmaceutical Sciences

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The purpose of the present study was to develop guidance toward rational choice of blenders and processing conditions to make robust and high performing adhesive mixtures for dry-powder inhalers and to develop quantitative experimental approaches for optimizing the process. Mixing behavior of carrier (LH100) and AstraZeneca fine lactose in high-shear and low-shear double cone blenders was systematically investigated. Process variables impacting the mixing performance were evaluated for both blenders. The performance of the blenders with respect to the mixing time, press-on forces, static charging, and abrasion of carrier fines was monitored, and for some of the parameters, distinct differences could be detected. A comparison table is presented, which can be used as a guidance to enable rational choice of blender and process parameters based on the user requirements. Segregation of adhesive mixtures during hopper discharge was also investigated.

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Numerical modeling of adhesive particle mixing

et al. 2017

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The discrete element method is used to investigate adhesive particle mixing in a system that includes large carrier particles and fine particle agglomerates in a Couette mixer. The simulation starts with 200 carriers and 10 agglomerates with 1000 fine particles each. During mixing, the agglomerates are broken, fractions adhere to the carriers, and there is continuous redistribution of fines between carriers. The focus is to obtain information on the quantity and quality of fine particles adhered to carriers by postprocessing the simulation data. Variation in the structure of agglomerates due to shearing is studied over mixing time. Findings indicate that major fraction of fine particles are dispersed evenly onto the surface of carriers and the rest are in form of free debris. A time‐dependent index is introduced to predict the degree of mixing. Finally, the adhesion force between carriers and coated layers is observed to have a peak at 1 nN. © 2017 American Institute of Chemical Engineers AIChE J, 63: 2599–2609, 2017

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Mechanistic time scales in adhesive mixing investigated by dry particle sizing

Cited by 24 publications

References 25 publications

Emerging Process Modeling Capabilities for Dry Powder Operations for Inhaled Formulations

Emerging Process Modeling Capabilities for Dry Powder Operations for Inhaled Formulations

Development of a Rational Design Space for Optimizing Mixing Conditions for Formation of Adhesive Mixtures for Dry-Powder Inhaler Formulations

Numerical modeling of adhesive particle mixing

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