Nucleation and crystal growth in supersaturated solutions of a model drug
2008 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 325, no 2, 404-413 p.Article in journal (Refereed) Published
The crystallization process in aqueous solutions of the drug bicalutamide and the effect of the polymer polyvinylpyrrolidone (PVP) have been studied. Results show that PVP decreased the crystallization rate significantly in a system with PVP concentrations as low as 0.01% (w/w), without changing the polymorph formed. The crystal habit was changed 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 adsorbes 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.
Place, publisher, year, edition, pages
2008. Vol. 325, no 2, 404-413 p.
Crystal nucleation, Crystal growth, Poorly soluble drugs, Classical nucleation theory
Research subject Biopharmaceutics
IdentifiersURN: urn:nbn:se:uu:diva-178050DOI: 10.1016/j.jcis.2008.05.034OAI: oai:DiVA.org:uu-178050DiVA: diva2:541904