What is a suitable dissolution method for drug nanoparticles?
OBJECTIVE
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.
Heng
Desmond
D
Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.
Cutler
David J
DJ
Chan
Hak-Kim
HK
Yun
Jimmy
J
Raper
Judy A
JA
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry; D002444:Cefuroxime / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D011208:Powders; D012995:Solubility; D014961:X-Ray Diffraction
D000900:Anti-Bacterial Agents; D004364:Pharmaceutical Preparations; D011208:Powders; D002444:Cefuroxime; C040738:cefuroxime axetil