Diffusion controlled formation of microparticles

Boraey, Mohammed A.; Vehring, Reinhard

doi:10.1016/j.jaerosci.2013.10.002

Cited by 57 publications

(60 citation statements)

References 48 publications

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“…As a result, in the last two decades, several studies have been conducted to investigate the particle formation process theoretically and experimentally 13,[36][37][38] . These studies focused mainly on the first part of the process which can be modeled as evaporation of a solution droplet.…”

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Analysis of the Particle Formation Process of Structured Microparticles

et al. 2015

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The particle formation process for microparticles of cellulose acetate butyrate dried from an acetone solution was investigated experimentally and theoretically. A monodisperse droplet chain was used to produce solution microdroplets in a size range of 55-70 μm with solution concentrations of 0.37 and 10 mg/mL. As the droplets dried in a laminar air flow with a temperature of 30, 40, or 55 °C, the particle formation process was recorded by two independent optical methods. Dried particles in a size range of 10-30 μm were collected for morphology analysis, showing hollow, elongated particles whose structure was dependent on the drying gas temperature and initial solution concentration. The setup allowed comprehensive measurements of the particle formation process to be made, including the period after initial shell formation. The early particle formation process for this system was controlled by the diffusion of cellulose acetate butyrate in the liquid phase, whereas later stages of the process were dominated by shell buckling and folding.

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Analysis of the Particle Formation Process of Structured Microparticles

et al. 2015

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“…First, as water is removed from the droplet surface, the high surface concentration of the solutes generates a concentration gradient towards the interior of the droplet. 16,21,31 Nevertheless, during drying, the viscosity of the semi-dried particles could quickly reach a high level in a short period of time (usually tens of seconds in the spray drying process), which may impede possible solute diffusion caused by the concentration difference. Second, after the formation of the incipient 20 shell, the water interface continues to recede within the formed shell; solids with high mobility or high solubility may continue to equilibrate with the receding water phase, constituting a de facto inwards flow.…”

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“…3 and 4), which forces dissolved/suspended solids adjacent to the droplet surface to move inwards. 16 Prior to the formation of an initial shell, droplet shrinkage is mainly governed by the loss of water mass. 41 Once the surface shell is completely formed, the composition is unlikely to undergo substantial change due to the high viscosity, 15 which may restrict further outgoing solute flow.…”

Section: Applicability Of the Proposed Mechanism In Other Drying Procmentioning

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“…Vehring and co-workers related the final particle morphology after spray drying to the Péclet number, Pe i , defined as the ratio between the evaporation rate of the droplet and the diffusivity of the solute component, i, in the droplet. 16,44 Pe i in the SDD and spray drying processes would be different due to the difference in heat transfer rate and evaporation flux, while the solute diffusivity would remain the same. Nevertheless, the similar particle core-shell structure formed from the two processes suggests that the difference in Pe i is relatively insignificant in terms of altering the particle morphology.…”

Section: Applicability Of the Proposed Mechanism In Other Drying Procmentioning

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Formation process of core‐shell microparticles by solute migration during drying of homogenous composite droplets

et al. 2017

AIChE Journal

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Abstract:Particle formation process during spray drying profoundly impacts particle morphology and microstructure. This study experimentally investigated the formation of core-shell-structured microparticles by one-step drying of composite droplets made of Eudragit ® RS (a polycationic acrylic polymer in nanoparticle form) and silica sol. The formation of an incipient surface shell was monitored using single droplet drying technique, and the freshly formed shell was recovered for subsequent analyses. Adding silica to RS precursor increased the shell formation time and altered the properties of the incipient shell from waterdispersible to non-dispersible. The incipient shell formed from RS/silica droplets with mass ratios of 1.5%:1.5% and 0.5%:2.5% showed ingredient segregation with a preferential accumulation of RS, similar to the shell region of dried microparticles. After shell formation, excess silica sol in the liquid phase could flow inwards, producing a dense core. This mobility-governed solute migration would be useful for constructing core-shell microparticles using other precursor systems.

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“…In the case of relatively high solubility of both components in the spray solution, the differential diffusion rates of polymer and drug may lead to a polymer skin forming at the surface of the drying droplet and lead to a particle with a relatively polymer-enriched surface. If the API or the polymer has a relatively poor solubility in the spray solution relative to the other component, then the lower solubility component would be expected to precipitate initially and concentrate on the surface due to the slow diffusion coefficient of the larger precipitated material (Boraey and Vehring 2014). It may be preferable to obtain a particle with a polymer-rich surface.…”

Section: Process and Solubility Induced Concentration Gradients Acrosmentioning

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Practical Considerations for Spray Dried Formulation and Process Development

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Baumann

Vodak

et al. 2014

Discovering and Developing Molecules With Optimal Drug-Like Properties

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Spray drying is a broadly applicable process for the manufacture of many products in the food, chemical, and pharmaceutical areas. Powders are produced in a continuous process during the drying of liquid feed stocks through an atomization and drying process. The ability to control the final product attributes to maintain the desired physical state, performance, and bulk powder attributes for downstream processing has made spray drying an important unit operation for the manufacture of amorphous solid dispersions. It can enable progression of compounds with poor aqueous solubility throughout the drug development lifecycle from discovery through commercial production.Efficient development of the process for spray dried amorphous solid dispersions has been demonstrated to ensure the critical quality attributes are maintained during development and scale-up, for example with Vertex Pharmaceuticals' Incivek. To successfully achieve these goals, it is necessary to have a deep understanding of the process and the key formulation attributes along with their potential interaction. By developing this understanding, it is possible to achieve a robust process and formulation that have both been designed to maximize the success during drug development and to achieve the target performance and stability goals.

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Diffusion controlled formation of microparticles

Cited by 57 publications

References 48 publications

Analysis of the Particle Formation Process of Structured Microparticles

Analysis of the Particle Formation Process of Structured Microparticles

Formation process of core‐shell microparticles by solute migration during drying of homogenous composite droplets

Practical Considerations for Spray Dried Formulation and Process Development

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