Summary of the pitfalls and opportunities, which are related to the size analysis of submicron particles [16,17,22].


parts of the performance of size analysis   parameters which might influence the size result   pitfalls   opportunities   references

prior to the measurement   selection of measuring medium   Measuring in a medium, which is able to dissolve the particles, can lead to incorrect results due to the dissolution of the particles.   A fast dissolution test could be performed using a suitable dissolution medium as measuring medium.   [17, 22]
  preparation of sample for the measurement   Larger particles, i.e. agglomerates might be destroyed during the shaking prior to sampling.   A possible instability of a sample could be detected early by analysis of samples collected from different positions of non-shaken samples.   cf. Section 3.1
  selection of the sampling device   Depending on sampling device, particles might lead to agglomeration or to de-agglomeration of particles and consequently incorrect results.   A possible instability of a sample could be detected early, e.g. by using a sampling instrument which possesses some shear forces and consequently promotes agglomeration of instable samples.   cf. Section 3.2

measurement   sampling   Sampling from different positions of non-shaken samples can lead to different size results and thus to non-reproducible measurements.   A possible instability of a sample could be detected early by analysis of samples collected from different positions of non-shaken samples.   cf. Section 3.1
  stirring speed/ ultra sound   Depending on stirring speed and application of sonication particles might lead to agglomerations or de-agglomerations of particles.   A discrimination between more and less instable samples and the determination of the tightness of agglomerates is possible by applying different stirring speeds and/or sonication.   cf. Section 3.3
  additional technique   With using the additional technique the detection of larger particles beside small sized main population could failure.   Using the additional technique extents the measuring range. Thus, the measuring of submicron particles is possible.   [16]

analysis of results   optical parameters   Using incorrect optical parameters can lead to incorrect particle size and distribution results.   -   [16, 22]

M Keck et al.Journal of Pharmaceutical Technology and Drug Research  2013 2:17DOI : 10.7243/2050-120X-2-17