Spherical Crystallization: Modeling of the Emulsion Solvent Diffusion Technique
Kawashima developed the spherical crystallization technique to produce shaped and sized particles with improved properties. He presented two methods: Spherical Agglomeration (SA) and Emulsion Solvent Diffusion (ESD). It was established that ES...
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Hosokawa Powder Technology Foundation
2014-05-01
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doaj-91c106fda33e4658a49c42cf6903fafc2021-02-03T01:20:12ZengHosokawa Powder Technology FoundationKONA Powder and Particle Journal0288-45342187-55372014-05-0115015916910.14356/kona.1997020konaSpherical Crystallization: Modeling of the Emulsion Solvent Diffusion TechniqueFabienne Espitalier0Béatrice Biscans1Claude Laguerie2Michel Deleuil3University of Toulouse, FranceUniversity of Toulouse, FranceUniversity of Toulouse, FranceRhone-Poulenc, FranceKawashima developed the spherical crystallization technique to produce shaped and sized particles with improved properties. He presented two methods: Spherical Agglomeration (SA) and Emulsion Solvent Diffusion (ESD). It was established that ESD proceeds from a spontaneous emulsion of the drug solution into a non-solvent liquid, whereas the solvent and the non-solvent are miscible. We investigated the general pharmaceutical case of a drug substance (DS) which is highly soluble in acetone (S), and moderately soluble in water (NS). The phase diagram DS/S/NS confirms that a concentrated DS/S solution poured into an NS will generate a biphasic liquid/ liquid system (DS/S emulsion into NS), which then moves into a triphasic liquid/liquid/solid one (DS into DS/S emulsion into NS) by counter diffusion S ↔ NS. Droplet size and mixing conditions are major determinants of where and at which speed solid growth will occur in the droplet. In large droplets, the solid growth takes place on the surface and extends in layers to the center. In small droplets, a homogeneous texture is obtained. This article presents a complete kinetic model of these mechanisms, which show how a specific texture can be selected and the whole process controlled. Two kinds of grains were produced and compared according to the micromeritic criteria required for direct tableting. The question of tablet cohesion is not critical with the drug we tested, and both grains are effective with regard to flowability whereas the powder produced from the standard crystallization technique is not suitable. With other drugs, a particular texture may be preferred, depending on cohesion and dissolution rate.https://www.jstage.jst.go.jp/article/kona/15/0/15_1997020/_pdf/-char/en |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fabienne Espitalier Béatrice Biscans Claude Laguerie Michel Deleuil |
spellingShingle |
Fabienne Espitalier Béatrice Biscans Claude Laguerie Michel Deleuil Spherical Crystallization: Modeling of the Emulsion Solvent Diffusion Technique KONA Powder and Particle Journal |
author_facet |
Fabienne Espitalier Béatrice Biscans Claude Laguerie Michel Deleuil |
author_sort |
Fabienne Espitalier |
title |
Spherical Crystallization: Modeling of the Emulsion Solvent Diffusion Technique |
title_short |
Spherical Crystallization: Modeling of the Emulsion Solvent Diffusion Technique |
title_full |
Spherical Crystallization: Modeling of the Emulsion Solvent Diffusion Technique |
title_fullStr |
Spherical Crystallization: Modeling of the Emulsion Solvent Diffusion Technique |
title_full_unstemmed |
Spherical Crystallization: Modeling of the Emulsion Solvent Diffusion Technique |
title_sort |
spherical crystallization: modeling of the emulsion solvent diffusion technique |
publisher |
Hosokawa Powder Technology Foundation |
series |
KONA Powder and Particle Journal |
issn |
0288-4534 2187-5537 |
publishDate |
2014-05-01 |
description |
Kawashima developed the spherical crystallization technique to produce shaped and sized particles with improved properties. He presented two methods: Spherical Agglomeration (SA) and Emulsion Solvent Diffusion (ESD). It was established that ESD proceeds from a spontaneous emulsion of the drug solution into a non-solvent liquid, whereas the solvent and the non-solvent are miscible. We investigated the general pharmaceutical case of a drug substance (DS) which is highly soluble in acetone (S), and moderately soluble in water (NS). The phase diagram DS/S/NS confirms that a concentrated DS/S solution poured into an NS will generate a biphasic liquid/ liquid system (DS/S emulsion into NS), which then moves into a triphasic liquid/liquid/solid one (DS into DS/S emulsion into NS) by counter diffusion S ↔ NS. Droplet size and mixing conditions are major determinants of where and at which speed solid growth will occur in the droplet. In large droplets, the solid growth takes place on the surface and extends in layers to the center. In small droplets, a homogeneous texture is obtained. This article presents a complete kinetic model of these mechanisms, which show how a specific texture can be selected and the whole process controlled. Two kinds of grains were produced and compared according to the micromeritic criteria required for direct tableting. The question of tablet cohesion is not critical with the drug we tested, and both grains are effective with regard to flowability whereas the powder produced from the standard crystallization technique is not suitable. With other drugs, a particular texture may be preferred, depending on cohesion and dissolution rate. |
url |
https://www.jstage.jst.go.jp/article/kona/15/0/15_1997020/_pdf/-char/en |
work_keys_str_mv |
AT fabienneespitalier sphericalcrystallizationmodelingoftheemulsionsolventdiffusiontechnique AT beatricebiscans sphericalcrystallizationmodelingoftheemulsionsolventdiffusiontechnique AT claudelaguerie sphericalcrystallizationmodelingoftheemulsionsolventdiffusiontechnique AT micheldeleuil sphericalcrystallizationmodelingoftheemulsionsolventdiffusiontechnique |
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