Processability, stability, and uniformity of content are a few of the factors influenced by particle size of drug substances. To avoid undesirable effects, adequate analytical methods should be used. Once these methods and specifications have been set, variability in analyses and manufacturing should be also considered. Manufacturing processes determine the particle size characteristics, so it is a challenging task to control variability. The reproducibility of particle size analysis is also determined by manufacturing processes, so this subject is of great importance due to the order of magnitude of variability in particle size as determined by processes instead of, for instance, analyses for purity.
It is interesting to look at typical manufacturing and analytical variability and how they affect the results of laser diffraction analyses. Milling, quality of unmilled product, different instrument vendors, homogeneity, reference materials – are all examples of factors that can account for variability. By some estimates, the deviations of the characteristic values of the particle size distributions were in the 20% range. Due to this, it is evident that quality cannot be guaranteed within a smaller range than that given by the compound variability of these factors.
These points all contribute to the challenge of publishing adequate specifications and specification documents that help assure the quality of pharmaceutical products, especially when it comes to particle size.
Pharmaceutical consultancy firms are often contracted to help sort out these problems due to their knowledge of several benchmarked and in-house testing methodologies and techniques, through their work with many firms in the pharmaceutical manufacturing industry.
Particle size is a very important factor both when talking about an intermediate product and a consumer-ready product.