Challenges Of Particle Characterisation - Pharmaceutical Technology

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Challenges Of Particle Characterisation
Particle characteristics can affect pharmaceutical formulations and products in a number of ways, and a variety of techniques are available that enable particle monitoring and characterisation. The author discusses some of these techniques and describes how, in some cases, it can be beneficial to combine them in a complementary way whilst being aware of the different results they may provide.


Pharmaceutical Technology Europe
Volume 4, Issue 23

Particles in practice

It is one thing to know the size, shape and appearance of particles, but one also needs to know how these parameters affect product and process performance. As noted above, small particles don't necessarily dissolve more rapidly than large particles of the same chemical.

In early phase development, it is critical to investigate how particles of the proposed new API will dissolve in the body. Using methods specified in the pharmacopoeia, one can mimic the environment of the mouth and gut, and determine where in the GI tract an API is likely to dissolve. This information can potentially justify whether the candidate molecule is worth pursuing. One might also investigate whether the particle size within the finished product has an impact on release rates.

Rheological studies are also valuable because subtle changes to particle size, distribution and shape can affect the rheology positively or negatively. With medicines that are suspensions, for example, it is important to control viscosity to prevent settling during storage, and to mitigate inconsistent dosing.

Conclusion

Many techniques are available to establish, measure and monitor particle characteristics, and there is much that can be learned about the effect of particle size and morphology on end product performance. However, when using results to set specifications or manage quality control, it is always necessary to seek out the detail of the methodology used to generate data because different methods 'see' particles in different ways.

To take an obvious example, one might have a particle size specification such as "50% of particles (by mass) must be less than 80 μm" set after sieve tests on representative batches. This would not necessarily be confirmed by analysis of the same batches using laser diffraction and reporting the d50 (diameter of the 50th percentile), even though, at first sight, the two specifications might seem to be equivalent. In the case of laser diffraction, the key parameter is particle volume rather than mass, and particle orientation and shape are not accounted for in the same manner.

Using techniques that permit the recording of visual images makes it possible to give further supporting evidence to the robustness of a particle characterisation method that generates only numeric data. In this way, it is possible to ensure that the procedure is characterising primary particles and not agglomerates, and that the method of analysis does not have a destructive effect on the distribution being recorded.

Acknowledgement

The author would like to acknowledge Malvern Instruments.

Victoria Jones Laboratory Manager, Physical Science Laboratory, RSSL

References

1. P. Kippax, Pharm. Technol. Eur., 21(4) (2009).

2. D.J. Burgess et al., AAPS J., 6(3), 23–24 (2004).

3. J. Netterwald, Pharmaceutical Formulation and Quality (December/January 2010).

4. US Pharmacopoeia

5. European Pharmacopoeia, Chapter 2.9.31, Laser Diffraction Measurement of Particle Size, Supplement 5.6 (2006).


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