What is a Suitable Dissolution Method for Drug Nanoparticles?
- 1k Downloads
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.
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.
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.
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.
Key wordscefuroxime axetil drug nanoparticles Noyes–Whitney equation poorly water-soluble drug powder dissolution apparatus
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.
- 2.B. R. Rohrs. Dissolution method development for poorly soluble compounds. Dissolution Technologies. 8:1–5 (2001).Google Scholar
- 9.M. H. El-Shabouri. Nanoparticles for improving the dissolution and oral bioavailability of spironolactone, a poorly-soluble drug. STP Pharma Sciences. 12:97–101 (2002).Google Scholar
- 14.B. K. Johnson, and R. K. Prud’homme. Chemical processing and micromixing in confined impinging jets. Alchem. J. 49:2264–2282 (2003).Google Scholar
- 15.R. H. Muller and J. A. H. Junghanns. Drug nanocrystals/nanosuspensions for the delivery of poorly soluble drugs. In V. P. Torchilin (ed.), Nanoparticulates as Drug Carriers, Imperial College Press, London, 2006, pp. 308–309.Google Scholar
- 16.R. B. Gupta. Fundamentals of drug nanoparticles. In R. B. Gupta, and U. B. Kompella (eds.), Drugs and the Pharmaceutical Sciences: Nanoparticle Technology for Drug Delivery, Taylor and Francis, New York, 2006, pp. 6–9.Google Scholar
- 17.L. M. Katz. Nanotechnology and applications in cosmetics: general overview. American Chemical Society Symposium Series (2007). 961:193–200 (2007).Google Scholar
- 21.P. Finholt. Influence of formulation on dissolution rate. In L. J. Leeson, and J. T. Carstensen (eds.), Dissolution Technology, The Industrial Pharmaceutical Technology Section of the Academy of Pharmaceutical Science, Washington, 1974, pp. 106–146.Google Scholar
- 24.B. Wennergren, J. Lindberg, M. Nicklasson, G. Nilsson, G. Nyberg, R. Ahlgren, C. Persson, and B. Palm. A collaborative in vitro dissolution study: comparing the flow-through method with the USP paddle method using USP prednisone calibrator tablets. Int. J. Pharm. 53:35–41 (1989).CrossRefGoogle Scholar
- 25.K. Gjellan, A. B. Magnusson, R. Ahlgren, K. Callmer, D. F. Christensen, U. Espmarker, L. Jacobsen, K. Jarring, G. Lundin, G. Nilsson, and J. O. Waltersson. A collaborative study of the in vitro dissolution of acetylsalicylic acid gastro-resistant capsules comparing the flow-through cell method with the USP paddle method. Int. J. Pharm. 151:81–90 (1997).CrossRefGoogle Scholar
- 26.H. Moller. Dissolution testing of different dosage forms using the flow-through method. Pharm. Ind. 45:617–622 (1983).Google Scholar
- 27.H. Moller, and E. Wirbitzki. Special cases of dissolution testing using the flow-through system. STP Pharma Sciences. 6:657–662 (1990).Google Scholar
- 28.F. Langenbucher, D. Benz, W. Kurth, H. Moller, and M. Otz. Standardized flow-cell method as an alternative to existing pharmacopoeial dissolution testing. Pharm. Ind. 51:1276–1281 (1989).Google Scholar
- 29.A. D. Karande, and P. G. Yeole. Comparative assessment of different dissolution apparatus for floating drug delivery systems. Dissolution Technologies. 13:20–23 (2006).Google Scholar
- 30.M. C. Gohel, P. R. Mehta, R. K. Dave, and N. H. Bariya. A more relevant dissolution method for evaluation of floating drug delivery system. Dissolution Technologies. 11:22–25 (2004).Google Scholar
- 32.J. Hu, A. Kyad, V. Ku, P. Zhou, and N. Cauchon. A comparison of dissolution testing on lipid soft gelatin capsules using USP apparatus 2 and apparatus 4. Dissolution Technologies. 12:6–9 (2005).Google Scholar
- 33.E. Beyssac, and J. Lavigne. Dissolution study of active pharmaceutical ingredients using the flow through apparatus USP 4. Dissolution Technologies. 12:23–25 (2005).Google Scholar
- 39.Micromeritics. Instruction manual (Multivolume Pycnometer 1305) for determining skeletal density and volume of powders, porous materials, and irregularly shaped solid objects, Micromeritics Instrument Corporation, USA, 1992.Google Scholar