Analytical methods for dissolution testing of nanosized drugs.

OBJECTIVES: This mini-review describes the theoretical advantages of nanosizing drugs in terms of dissolution and the characterization of their behaviour with in-vitro dissolution testing. KEY
FINDINGS: It is shown that the increase in dissolution rate is not commensurate with common theories. The calculation of dissolution rate by surface area increase using the Nernst-Brunner equation is inappropriate since the diffusion layer, δ, cannot be assessed. These results highlight the importance of an appropriate experimental design to assess the dissolution rate in vitro, which will then serve as a building block for establishing in vitro-in vivo correlations. Several techniques to assess the amount of released drug in dissolution testing are discussed, some through a review of current literature (dialysis, turbidity measurement methods, fibre optics, asymmetrical flow-field-flow fractionation), some through experimental experience (ion-selective electrode and syringe filters). Further methods, such as microdialysis, ultrasonic resonance technology and centrifugal filter devices, are reviewed from literature with some additional data obtained in house. The techniques are further discussed with a view to coupling the results with simulation software tools such as STELLA© to predict the in-vivo behaviour of the drug. In doing so, it is necessary to generate experimental data on the dissolution rate, since this cannot be calculated directly from the surface increase of drug particles but rather depends on further factors such as the boundary layer thickness.
SUMMARY: It was concluded that syringe filters of appropriate pore size and the ion-selective electrode appear to be suitable for measurement of the dissolution rate of nanosized drugs.