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Multi-Solvent Microdroplet Evaporation: Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics

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Multi-Solvent Microdroplet Evaporation : Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics. / Ordoubadi, Mani; Gregson, Florence K.A.; Melhem, Omar; Barona, David; Miles, Rachael E.H.; D’Sa, Dexter; Gracin, Sandra; Lechuga-Ballesteros, David; Reid, Jonathan P.; Finlay, Warren H.; Vehring, Reinhard.

In: Pharmaceutical Research, Vol. 36, 100, 14.05.2019.

Research output: Contribution to journalArticle

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Ordoubadi, M, Gregson, FKA, Melhem, O, Barona, D, Miles, REH, D’Sa, D, Gracin, S, Lechuga-Ballesteros, D, Reid, JP, Finlay, WH & Vehring, R 2019, 'Multi-Solvent Microdroplet Evaporation: Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics', Pharmaceutical Research, vol. 36, 100. https://doi.org/10.1007/s11095-019-2630-7

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Ordoubadi, Mani ; Gregson, Florence K.A. ; Melhem, Omar ; Barona, David ; Miles, Rachael E.H. ; D’Sa, Dexter ; Gracin, Sandra ; Lechuga-Ballesteros, David ; Reid, Jonathan P. ; Finlay, Warren H. ; Vehring, Reinhard. / Multi-Solvent Microdroplet Evaporation : Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics. In: Pharmaceutical Research. 2019 ; Vol. 36.

Bibtex

@article{95b82e319f0d4e91acfa86429a304d3f,
title = "Multi-Solvent Microdroplet Evaporation: Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics",
abstract = "Purpose: Evaporation and particle formation from multi-solvent microdroplets containing solid excipients pertaining to spray-drying of therapeutic agents intended for lung delivery were studied. Various water and ethanol co-solvent systems containing a variety of actives and excipients (beclomethasone, budesonide, leucine, and trehalose) were considered. Methods: Numerical methods were used to predict the droplet evaporation rates and internal solute transfers, and their results verified and compared with results from two separate experimental setups. In particular, an electrodynamic balance was used to measure the evaporation rates of multicomponent droplets and a monodisperse droplet chain setup collected dried microparticles for further analytical investigations and ultramicroscopy. Results: The numerical results are used to explain the different particle morphologies dried from solutions at different co-solvent compositions. The obtained numerical data clearly show that the two parameters controlling the general morphology of a dried particle, namely the P{\'e}clet number and the degree of saturation, can change with time in a multi-solvent droplet. This fact complicates product development for such systems. However, this additional complexity vanishes at what we define as the iso-compositional point, which occurs when the solvent ratios and other composition-dependent properties of the droplet remain constant during evaporation, similar to the azeotrope of such systems during distillation. Conclusions: Numerical and experimental analysis of multi-solvent systems indicate that spray-drying near the iso-compositional ratio simplifies the design and process development of such systems.",
keywords = "co-solvents, inhaled therapeutics, microparticles, multi-solvent spray-drying, particle engineering",
author = "Mani Ordoubadi and Gregson, {Florence K.A.} and Omar Melhem and David Barona and Miles, {Rachael E.H.} and Dexter D’Sa and Sandra Gracin and David Lechuga-Ballesteros and Reid, {Jonathan P.} and Finlay, {Warren H.} and Reinhard Vehring",
year = "2019",
month = "5",
day = "14",
doi = "10.1007/s11095-019-2630-7",
language = "English",
volume = "36",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer US",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Multi-Solvent Microdroplet Evaporation

T2 - Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics

AU - Ordoubadi, Mani

AU - Gregson, Florence K.A.

AU - Melhem, Omar

AU - Barona, David

AU - Miles, Rachael E.H.

AU - D’Sa, Dexter

AU - Gracin, Sandra

AU - Lechuga-Ballesteros, David

AU - Reid, Jonathan P.

AU - Finlay, Warren H.

AU - Vehring, Reinhard

PY - 2019/5/14

Y1 - 2019/5/14

N2 - Purpose: Evaporation and particle formation from multi-solvent microdroplets containing solid excipients pertaining to spray-drying of therapeutic agents intended for lung delivery were studied. Various water and ethanol co-solvent systems containing a variety of actives and excipients (beclomethasone, budesonide, leucine, and trehalose) were considered. Methods: Numerical methods were used to predict the droplet evaporation rates and internal solute transfers, and their results verified and compared with results from two separate experimental setups. In particular, an electrodynamic balance was used to measure the evaporation rates of multicomponent droplets and a monodisperse droplet chain setup collected dried microparticles for further analytical investigations and ultramicroscopy. Results: The numerical results are used to explain the different particle morphologies dried from solutions at different co-solvent compositions. The obtained numerical data clearly show that the two parameters controlling the general morphology of a dried particle, namely the Péclet number and the degree of saturation, can change with time in a multi-solvent droplet. This fact complicates product development for such systems. However, this additional complexity vanishes at what we define as the iso-compositional point, which occurs when the solvent ratios and other composition-dependent properties of the droplet remain constant during evaporation, similar to the azeotrope of such systems during distillation. Conclusions: Numerical and experimental analysis of multi-solvent systems indicate that spray-drying near the iso-compositional ratio simplifies the design and process development of such systems.

AB - Purpose: Evaporation and particle formation from multi-solvent microdroplets containing solid excipients pertaining to spray-drying of therapeutic agents intended for lung delivery were studied. Various water and ethanol co-solvent systems containing a variety of actives and excipients (beclomethasone, budesonide, leucine, and trehalose) were considered. Methods: Numerical methods were used to predict the droplet evaporation rates and internal solute transfers, and their results verified and compared with results from two separate experimental setups. In particular, an electrodynamic balance was used to measure the evaporation rates of multicomponent droplets and a monodisperse droplet chain setup collected dried microparticles for further analytical investigations and ultramicroscopy. Results: The numerical results are used to explain the different particle morphologies dried from solutions at different co-solvent compositions. The obtained numerical data clearly show that the two parameters controlling the general morphology of a dried particle, namely the Péclet number and the degree of saturation, can change with time in a multi-solvent droplet. This fact complicates product development for such systems. However, this additional complexity vanishes at what we define as the iso-compositional point, which occurs when the solvent ratios and other composition-dependent properties of the droplet remain constant during evaporation, similar to the azeotrope of such systems during distillation. Conclusions: Numerical and experimental analysis of multi-solvent systems indicate that spray-drying near the iso-compositional ratio simplifies the design and process development of such systems.

KW - co-solvents

KW - inhaled therapeutics

KW - microparticles

KW - multi-solvent spray-drying

KW - particle engineering

UR - http://www.scopus.com/inward/record.url?scp=85065758950&partnerID=8YFLogxK

UR - https://link.springer.com/article/10.1007%2Fs11095-019-2648-x

U2 - 10.1007/s11095-019-2630-7

DO - 10.1007/s11095-019-2630-7

M3 - Article

VL - 36

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

M1 - 100

ER -