Modelling and understanding powder flow properties and compactability of selected active pharmaceutical ingredients, excipients and physical mixtures from critical material properties

Worku, Zelalem Ayenew; Kumar, Dinesh; Gomes, João Victor; He, Yunliang; Glennon, Brian; Ramisetty, Kiran A.; Rasmuson, Åke C.; O’Connell, P.; Gallagher, K.; Woods, Trevor; Shastri, Nalini R.; Healy, Anne Marie

doi:10.1016/j.ijpharm.2017.08.063

Cited by 35 publications

(7 citation statements)

References 36 publications

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“…The flow property of solids is affected by the amount of moisture ( Figure 7 A) [ 48 , 49 ]. The storage (particularly the RH) conditions decide the thickness of the adsorbed liquid layer on the particles and the strength of the liquid bridges formed between the particles and moisture.…”

Section: Impact Of Moisture-sensitive Materials On a Process And The ...mentioning

confidence: 99%

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

et al. 2023

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Stability is an essential quality attribute of any pharmaceutical formulation. Poor stability can change the color and physical appearance of a drug, directly impacting the patient’s perception. Unstable drug products may also face loss of active pharmaceutical ingredients (APIs) and degradation, making the medicine ineffective and toxic. Moisture content is known to be the leading cause of the degradation of nearly 50% of medicinal products, leading to impurities in solid dose formulations. The polarity of the atoms in an API and the surface chemistry of API particles majorly influence the affinity towards water molecules. Moisture induces chemical reactions, including free water that has also been identified as an important factor in determining drug product stability. Among the various approaches, crystal engineering and specifically co-crystals, have a proven ability to increase the stability of moisture-sensitive APIs. Other approaches, such as changing the salt form, can lead to solubility issues, thus making the co-crystal approach more suited to enhancing hygroscopic stability. There are many reported studies where co-crystals have exhibited reduced hygroscopicity compared to pure API, thereby improving the product’s stability. In this review, the authors focus on recent updates and trends in these studies related to improving the hygroscopic stability of compounds, discuss the reasons behind the enhanced stability, and briefly discuss the screening of co-formers for moisture-sensitive drugs.

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Section: Impact Of Moisture-sensitive Materials On a Process And The ...mentioning

confidence: 99%

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

et al. 2023

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“…Category 2A and 2B powders require fine compression pressure adjustment. Category 2C and Category 3 powders may be directly compressed, but compact mechanical properties may be impaired as the percolation threshold is approached (39).…”

Section: Compression Behavior Classification Systemmentioning

confidence: 99%

Mathematical approaches for powders and multiparticulate units processability characterization in pharmaceutical development

Vasiljević¹,

Turković²,

Aleksić³

et al. 2022

Arhiv za farmaciju

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An understanding of material properties and processing effects on solid dosage forms performance is required within the Quality-by-design approach to pharmaceutical development. Several research groups have developed mathematical approaches aiming to facilitate the selection of formulation composition and the manufacturing technology. These approaches are based on material particulate, bulk and compression-related properties. This paper provides theoretical assumptions and a critical review of different mathematical approaches for processability characterization of powders and multiparticulate units. Mathematical approaches have mainly been developed for directly compressible materials, but sometimes other manufacturing technologies, such as roller compaction and wet granulation, are also considered. The obtained compact tensile strength has been implemented in the majority of approaches, as an important characteristic describing compact mechanical properties. Flowability should be also evaluated, since it affects sample processability. Additionally, particle size and shape, material density and compressibility, compactibility and tabletability profiles have been also distinguished as relevant properties for solid dosage form development. The application of mathematical approaches may contribute to the mechanistic understanding of critical material attributes and facilitate dosage form development and optimization. However, it is essential to select the appropriate one, based on the intended dosage form characteristics, in order to ensure that all relevant powder/multiparticulate units characteristics are implemented and critically evaluated.

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“…In addition, the cohesion value is identified by the shear cell test [63]. This value is the shear stress at which the normal stress is equal to zero for the best fit of the shear and applied normal stress plot [64]. Generally, a cohesive powder will have higher values for cohesion and UYS and consequently a low ff c .…”

Section: Cohesion and Flow Function Coefficientmentioning

confidence: 99%

A multivariate regression parametric study on DEM input parameters of free-flowing and cohesive powders with experimental data-based validation

et al. 2020

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One of the key challenges in the implementation of discrete element method (DEM) to model powder's flow is the appropriate selection of material parameters, where empirical approaches are mostly applied. The aim of this study is to develop an alternative systematic numerical approach that can efficiently and accurately predict the influence of different DEM parameters on various sought macroscopic responses, where, accordingly, model validation based on experimental data is applied. Therefore, design of experiment and multivariate regression analysis, using an optimized quadratic D-optimal design model and new analysis tools, i.e., adjusted response and Pareto graphs, are applied. A special focus is laid on the impact of six DEM microscopic input parameters (i.e., coefficients of static and rolling friction, coefficient of restitution, particle size, Young's modulus and cohesion energy density) on five macroscopic output responses (i.e., angle of repose, porosity, mass flow rate, translational kinetic energy and computation time) using angle of repose tests applied to free-flowing and cohesive powders. The underlying analyses and tests show, for instance, the substantial impact of the rolling friction coefficient and the minor role of the static friction coefficient or the particle size on the angle of repose in cohesive powders. In addition, in both powders, the porosity parameter is highly influenced by the static and rolling friction coefficients.

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Modelling and understanding powder flow properties and compactability of selected active pharmaceutical ingredients, excipients and physical mixtures from critical material properties

Cited by 35 publications

References 36 publications

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

Mathematical approaches for powders and multiparticulate units processability characterization in pharmaceutical development

A multivariate regression parametric study on DEM input parameters of free-flowing and cohesive powders with experimental data-based validation

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