Small-scale batches and a scale-up batch of the API were submitted for analysis. The API for these samples were crystalline and designed to directly produce particles with a particle median size of approximately 50 micron which is suitable for intranasal formulations. On receipt of the samples, analysts immediately identified that there were significantly different physical differences between the two materials, as seen below in Figure 1.
Figure 1 - Physical comparison of the small scale and scale-up batch API
All batches analysed were similar in particle size and polymorphic form. However, analysis demonstrated that the current scale-up resulted in a different morphology (plate-like) to that of the initial small-scale batch, creating highly agglomerated API. This highlighted that the current scale-up of manufacture may not be suitable for future development.