(492d) Investigation into the Effects of Roller Compaction on Granule and API Properties

Solid oral dosage forms are the most popular drug delivery system. The pharmaceutical industry is a very highly regulated one and as such the processes involved in the manufacture should be carefully controlled. One key aspect to control is the particle size and shape of the Active Pharmaceutical Ingredient (API), as this has been shown to have significant effects on prcoessibility (e.g. punch sticking) and the performance of the final product (e.g. dissolution rate) (Leane et al. 2015).

However, this can prove challenging as the API is subjected to harsh environments in various unit operations, such as roller compaction, which can cause attrition of the particles (Gamble et al. 2014). For control purposes it is important to understand what is occurring to the API within these processing steps, however, tracking changes in the API’s properties once it has been incorporated into a blend is challenging. Consequently the performance of the end product are often related to the input properties, which are likely to have changed during processing.

A modern approach combining static image analysis (SIA) and Raman Spectroscopy can be utilised to measure the particle size and shape of a single component within a multi-component system (Gamble et al. 2015) thus enabling changes in API particle size during processing to be measured. This approach has been applied to investigate the effects of roller compaction process parameters on API properties. The results of this study provide an insight into the dry granulation processing route and the effects of processing conditions on the properties of API particles and the subsequent granule. The presentation will also address topics including the nature of the API within granulate, both in terms of size and location, and the possible impact on to downstream processing such as tabletting.

References:

Gamble, J. F., Hoffmann, M., Hughes, H., Hutchins, P. and Tobyn, M. (2014). "Monitoring process induced attrition of drug substance particles within formulated blends." International Journal of Pharmaceutics 470(1): 77-87.

Gamble, J. F., Tobyn, M. and Hamey, R. (2015). "Application of Image-Based Particle Size and Shape Characterization Systems in the Development of Small Molecule Pharmaceuticals." Journal of Pharmaceutical Sciences 104(5): 1563-1574.

Leane, M., Pitt, K. and Reynolds, G. (2015). "A proposal for a drug product Manufacturing Classification System (MCS) for oral solid dosage forms." Pharmaceutical Development & Technology 20(1): 12-21.