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Nucleation and crystal growth in supersaturated solutions of a model drug

Lindfors, Lennart; Forssen, Sara; Westergren, Jan and Olsson, Ulf LU (2008) In Journal of Colloid and Interface Science 325(2). p.404-413
Abstract
The crystallization Process in aqueous solutions of the drug bicalutamide and the effect of the polymer polyvinylpyrrolidone (PVP) have been studied. Results showed that PVP decreased the crystallization Fate significantly in a system with PVP concentrations as low as 0.01% (w/w), without changing the polymorph formed. The crystal habit was altered already at PVP concentrations as low as 0.001% (w/w). Measurements made with self-diffusion NMR indicated that the decrease in crystallization rate was not because of a reduced supersaturation due to bicalutamide binding to PVP in solution. Furthermore, in experiments designed to specifically study crystal nucleation, the same nucleation rate was found in the absence and presence of PVP.... (More)
The crystallization Process in aqueous solutions of the drug bicalutamide and the effect of the polymer polyvinylpyrrolidone (PVP) have been studied. Results showed that PVP decreased the crystallization Fate significantly in a system with PVP concentrations as low as 0.01% (w/w), without changing the polymorph formed. The crystal habit was altered already at PVP concentrations as low as 0.001% (w/w). Measurements made with self-diffusion NMR indicated that the decrease in crystallization rate was not because of a reduced supersaturation due to bicalutamide binding to PVP in solution. Furthermore, in experiments designed to specifically study crystal nucleation, the same nucleation rate was found in the absence and presence of PVP. Instead, PVP adsorbs to the crystals formed in solution and by doing so, the crystal growth rate is reduced. This was confirmed in separate experiments using bicalutamide nanocrystals. By combining theories describing classical nucleation and crystal growth, with some modifications, a consistent description of several independent experiments performed in polymer-free systems was obtained. From these experiments a crystal-water interfacial tension of 22.1 mN/m was extracted. We also analyze the interfacial tension of other crystalline organic solids and find that it varies approximately as the logarithm of the solubility. This finding is discussed within the framework of the Bragg-Williams regular solution theory where we also compare with the tension of liquid alkanes. (c) 2008 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
poorly soluble drugs, crystal nucleation, crystal growth, classical, nucleation theory
in
Journal of Colloid and Interface Science
volume
325
issue
2
pages
404 - 413
publisher
Elsevier
external identifiers
  • wos:000258553900016
  • scopus:49049117501
ISSN
1095-7103
DOI
10.1016/j.jcis.2008.05.034
language
English
LU publication?
yes
id
304e99ff-5619-4533-b133-0fb64842b650 (old id 1251885)
date added to LUP
2008-11-18 15:33:35
date last changed
2017-09-24 03:46:12
@article{304e99ff-5619-4533-b133-0fb64842b650,
  abstract     = {The crystallization Process in aqueous solutions of the drug bicalutamide and the effect of the polymer polyvinylpyrrolidone (PVP) have been studied. Results showed that PVP decreased the crystallization Fate significantly in a system with PVP concentrations as low as 0.01% (w/w), without changing the polymorph formed. The crystal habit was altered already at PVP concentrations as low as 0.001% (w/w). Measurements made with self-diffusion NMR indicated that the decrease in crystallization rate was not because of a reduced supersaturation due to bicalutamide binding to PVP in solution. Furthermore, in experiments designed to specifically study crystal nucleation, the same nucleation rate was found in the absence and presence of PVP. Instead, PVP adsorbs to the crystals formed in solution and by doing so, the crystal growth rate is reduced. This was confirmed in separate experiments using bicalutamide nanocrystals. By combining theories describing classical nucleation and crystal growth, with some modifications, a consistent description of several independent experiments performed in polymer-free systems was obtained. From these experiments a crystal-water interfacial tension of 22.1 mN/m was extracted. We also analyze the interfacial tension of other crystalline organic solids and find that it varies approximately as the logarithm of the solubility. This finding is discussed within the framework of the Bragg-Williams regular solution theory where we also compare with the tension of liquid alkanes. (c) 2008 Elsevier Inc. All rights reserved.},
  author       = {Lindfors, Lennart and Forssen, Sara and Westergren, Jan and Olsson, Ulf},
  issn         = {1095-7103},
  keyword      = {poorly soluble drugs,crystal nucleation,crystal growth,classical,nucleation theory},
  language     = {eng},
  number       = {2},
  pages        = {404--413},
  publisher    = {Elsevier},
  series       = {Journal of Colloid and Interface Science},
  title        = {Nucleation and crystal growth in supersaturated solutions of a model drug},
  url          = {http://dx.doi.org/10.1016/j.jcis.2008.05.034},
  volume       = {325},
  year         = {2008},
}