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Understanding the effect of API changes in pharmaceutical processing

2022-03-15 06:20   Automobiles   Salem   121 views Reference: 775

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Characterisation challenges

The use of chemical imaging to investigate the distribution of single components with a formulated sample have previously been reported2. However, due to limitations in the optical resolution of such systems, the individual particle sizes cannot be directly measured; pixels often contain more than one of the constituents. Pixels are instead colour coded to indicate the relative concentration of each constituent, thus enabling identification of ‘domains’ (areas of high component concentration). The relationship between domain size and particle size can be affected by multiple factors such as homogeneity, aggregation and morphology.

The challenge of characterising the primary particle characteristics of single components within multi-component systems has recently been addressed through the application of image-based particle characterisation with integrated Raman capability. This approach enables the characterisation of particles in terms of both size and shape. Utilising the Raman probe, the components within a blended sample can be sub-classified in terms of their chemistry, thus enabling the actual particle size distribution of individual components to be determined rather than the domain size.

Examples of this approach have recently been reported; Gamble3 demonstrated the process-induced attrition of a formulated API. It was demonstrated that blending and cone milling process steps had little impact on the primary particle size of the API, whilst a powder feed system, associated to a roller compactor, was observed to significantly reduce particle size. Such attrition could impact the processability of the material, both positively and negatively. This work highlighted that the powder feeding step, a hitherto overlooked sub-process, has a significant impact on the API/blend properties, and therefore requires consideration when selecting sources of process variation.

In addition to size, changes to the particle shape were also investigated. The combination of the two datasets provides insight into the attrition mechanisms within the unit processes. For the milling process, minor shifts in both size and shape could suggest a surface abrasion mechanism where the elongated particles undergo ‘chipping’. For the powder feed system, however, more significant shifts in both size and shape were proposed to suggest a bulk fracture mechanism where the particles undergo more complete fracture.

The work not only demonstrates that the input API size was impacted by the process, but that by characterising the API particle characteristics one could understand the mechanism of the change. This improved understanding of the intermediate API/blend characteristics could be applied to subsequent processing steps, removing the requirement to rely on the input particle characterisation data.

Subsequent work4 utilised the measured API attrition to determine the location of attrition events within the feed system. These efforts applied the understanding of the process/API interaction in order to develop a better elucidation of the unit process and to investigate the impact of varying process conditions on the extent of attrition. The study demonstrated how changes in the feed screw speed could alter the extent of attrition; increased feed rates resulted in increased levels of attrition. This raises an interesting issue; for such unit processes the feed system is often utilised as part of the automated feedback control to maintain the intermediate product characteristics, but if by changing the feed system we alter the blend characteristics, the tool used to control process variation could be a significant source of said variation.

Active pharmaceutical ingredients (APIs) refer to vital chemicals that are responsible for making the drug work. Depending on type, biotech/biological API, synthetic chemical API, high-potency API, plant extracts API, and classical fermentation API are some of the products available in the active pharmaceutical ingredients (API) market.

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