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Monitoring of particle growth at a low concentration of a poorly water soluble drug using the NanoSight LM20

Gillespie, Cheska and Halling, Peter and Edwards, Darren (2011) Monitoring of particle growth at a low concentration of a poorly water soluble drug using the NanoSight LM20. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 384 (1-3). pp. 233-239. ISSN 0927-7757

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Abstract

The purpose of this work was to investigate the precipitation of a poorly water soluble drug (tolnaftate) from low, mu M concentration solutions. This was to test the applicability of nanoparticle tracking analysis (NTA; the NanoSight instrument), with comparison to results from dynamic light scattering (DLS). Samples containing 30 mu M of tolnaftate, 1% dimethylsulfoxide (DMSO) (by volume) were prepared by mixing a concentrated DMSO stock solution and an aqueous buffer. The samples were then analysed over time either using the NanoSight instrument or by DLS. Obtaining meaningful results from the former required careful attention to instrument settings. From NTA there was initially a fairly narrow size distribution around 200 nm, with concentration of around 4 x 10(8) nanoparticles/mL. Over 3 h, the particles grew, with increasing polydispersity, and skewed distribution up to 800 nm, whilst the concentration fell to around 1 x 10(8) particles/mL. DLS was consistent in showing the size increase, but could not detect the remaining smaller particles and polydispersity. Conclusions: The growth of particles of a poorly water soluble drug was successfully monitored using NTA, which gives additional information not offered by DLS. Nanoparticle precipitation at the concentrations used here is of relevance to high throughput screening in early drug discovery. (C) 2011 Elsevier B.V. All rights reserved.