Determination of Particle Size inside a Tablet
Suddenly the question will occur: What is the actual particle size of your drug component inside the formulated tablet, after all processing steps?
To measure particle sizes of the individual ingoing components separately before formulation is a fairly straightforward process. Once entered into the manufacturing process and mixed with all necessary excipients, the challenges increases dramatically. It is far from trivial to deduce the modified (from different applied processing steps) particle sizes – not to mention to be able to separate the contribution from the other ingoing components.
The standard approach would presumably be to try to identify a dissolving medium in which the API of interest is basically insoluble while all other ingredients are significantly more soluble and consequently dissolve while leaving the API particles intact. This strategy has however serious flaws e.g.:
- It will, to start with, generally be very hard to identify such a solvent (if it even exists).
- Even the slightest solubility of the API will make the inevitable present amorphous regions (from processing steps) gradually dissolving, due to higher solubility, and then precipitating out onto the crystalline solids and consequently changing the observed particle size.
The Adroit approach was instead to investigate the situation directly in-situ, in the internal of the tablet, without changing anything that could influence the situation.
By carefully evaluating different sample preparation methodologies, and optimizing the experimental conditions, it was possible to explore the exposed internal tablet surface and identifying the desired API particles. Once identified, it was possible to successfully estimate the particle size in-situ, as desired, and even evaluate the actual distribution/homogeneity of the API within the excipient matrix.