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What is a Suitable Dissolution Method for Drug Nanoparticles?

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Abstract

Purpose

Many existing and new drugs fail to be fully utilized because of their limited bioavailability due to poor solubility in aqueous media. Given the emerging importance of using nanoparticles as a promising way to enhance the dissolution rate of these drugs, a method must be developed to adequately reflect the rate-change due to size reduction. At present, there is little published work examining the suitability of different dissolution apparatus for nanoparticles.

Methods

Four commonly-used methods (the paddle, rotating basket and flow-through cell from the US Pharmacopia, and a dialysis method) were employed to measure the dissolution rates of cefuroxime axetil as a model for nanodrug particles.

Results

Experimental rate ratios between the nanoparticles and their unprocessed form were 6.95, 1.57 and 1.00 for the flow-through, basket and paddle apparatus respectively. In comparison, the model-predicted value was 7.97. Dissolution via dialysis was rate-limited by the membrane.

Conclusions

The data showed the flow-through cell to be unequivocally the most robust dissolution method for the nanoparticulate system. Furthermore, the dissolution profiles conform closely to the classic Noyes–Whitney model, indicating that the increase in dissolution rate as particles become smaller results from the increase in surface area and solubility of the nanoparticles.

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Acknowledgements

The authors are grateful to Lee Ford-Griffiths (Particle & Surface Sciences Pty. Ltd.) for the BET analysis and staff of the Electron Microscope Unit (The University of Sydney) for kind usage of the field emission scanning electron microscope and the X-ray powder diffractometer. This work was supported by a grant from the Australian Research Council (ARC Linkage Project LP 0561675 with Nanomaterials Technology Pty. Ltd). One of the authors (JAR) is currently at the National Science Foundation. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

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Authors and Affiliations

  1. Advanced Drug Delivery Group, Faculty of Pharmacy, A15, The University of Sydney, Sydney, NSW, 2006, Australia

    Desmond Heng, David J. Cutler & Hak-Kim Chan

  2. Department of Chemical Engineering, University of Missouri-Rolla, Rolla, Missouri, 65409, USA

    Judy A. Raper

  3. Nanomaterials Technology Pty. Ltd., 28 Ayer Rajah Crescent, #03-03, Singapore, 139959, Singapore

    Desmond Heng & Jimmy Yun

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  1. Desmond Heng
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Correspondence to Hak-Kim Chan.

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Heng, D., Cutler, D.J., Chan, HK. et al. What is a Suitable Dissolution Method for Drug Nanoparticles?. Pharm Res 25, 1696–1701 (2008). https://doi.org/10.1007/s11095-008-9560-0

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