Dear Atdhe Kycyku ,

The experiment has two variables by the setup: the wt% of the excipient and the remaining wt% of the API. The relative area is related to both variations.

In any pharmaceutical formulation, the API concentration is fixed to the therapeutic dose. So, the variable is the remaining additions to the pill, capsule, whatever.

Nevertheless, to use XRD for the determination, both must be crystalline, the API and the excipient; if one component has low crystallinity, an error is already introduced in the area determination. The origin of the error would be the background considered for subtraction for area determination.

The API concentration fixed to the therapeutic dose, the remaining probe component may vary inside some pre-defined range, and the relative area determination may work.

Remember, the excipient of your choice needs to have no interaction with any other component in the probed sample; otherwise, the effect will vary from each mixture.

In case other components are present, the concentration must be fixed as well; the only varying parameter is the increased amount of the probed excipient.

Good luck,

WNM

Hi Wagner Da Nova Mussel ,

Thank you so much for the information! Both the API and excipient are indeed crystalline and there is no interaction of the excipient with anything else in the mixture.

I do have one question that I'm hoping you could clarify: If you are loading a set quantity onto the XRD for all 8 data points of the calibration curve (e.g. 10mg), and the wt% of the excipient is increasing along these samples, then how do you fix the API concentration given these are the only two components of the mixture? (i.e. at a set loading weight with an increasing wt% increase of excipient, then the API % must decrease).

The only way I see this being done is if an additional component was added as a filler that would vary with wt% of the excipient whilst the API is fixed?

If you could provide some insight that would be greatly appreciated!

Dear Atdhe Kycyku ,

You answer the question. The API has no meaning in have the wt% changed; otherwise, the calibration curve would be useful only for your specific mixture.

Use the total amount of the pill, for instance, like 100%. If the probed phase increase by 1%, the API is fixed, and the remaining components decrease 1%.

As you mention, there are no interactions; it is the only dilution.

The intention is to check the API's behaviour with the probed phase; if you increase the phase and the API by the same amounts simultaneously, supposing no interaction of any order is observed, the effect would be null. Even in the dilution point of view, increasing probed phase and API simultaneously by the same amount, the dilution is unchanged.

I am not considering the final mixture density in the last observation, just in case probed phase and API have quite different densities, only a physical solid mixture.

Best regards,

WNM