My tablet shows increase in dissolution rate when stored at 25/60 for 15 days. There was no change in hardness or porosity . DT has lowered by 5 mins. API is insoluble in water and is slightly hygroscopic. Content of API is around 50% in the tablet.
Please share your views and relevant articles.
First you need to check if you have degradation products that might induce cracks in the solid state. Second, repeat dissolution to rule out experimental error. Third, examine the possible polymorph transformations and/or water of crystallization loss (DSC, TGA, XRD).
Hi
Can you please mention the excipients and the drug added.
Dear Andrei,
Thank you for the answer. we have encountered no degradation products and XRD also showed no crystallization. Do you recommend confirming with DSC?Dissolution was repeated , but the same results were observed as before.
The answers to the first question ”why do formulations age” are numerous depending on the type of formulation, raw materials (chemical and physical properties), manufacturing process, process parameters, packaging and environmental (e.g., storage) conditions. Often, the solution to this type of problem requires more experiments to isolate the possible cause(s). Without a detailed description of the composition of your tablet and the manufacturing process it is difficult to point to suggestions.
However, here are some examples of factors to consider (presuming this is an un-coated, immediate-release conventional tablet and the issue is not related to tablet variability):
1) Raw material stability – chemical and physical (e.g., polymorphic stability)
2) Elastic recovery of the compact
3) Drug-excipient interactions
4) Drug-container interactions
5) Changes in moisture content
Also consider, monitoring the product (per your specification and characterization tests) at different time points (e.g., within the 15 day time range) to determine whether any trends can be established.
The following paper may provide additional suggestions.
Murthy, K.S. and Ghebre-Sellassie, I. (1993), Current perspectives on the dissolution stability of solid oral dosage forms. J. Pharm. Sci., 82: 113-126. https://doi.org/10.1002/jps.2600820202
As API is insoluble in water, I would assume that your tablet contained amorphous solid dispersion intermediates. It is also slightly hygroyscopic, so the first impact should be the moisture uptaken by your tablet.
XRD data cannot be used as indication of no crystalline because of its low sensitivity. In general, it can only detect above 5 to 10% crystallinity. Although it is the golden rule by the regulatory authority and QA, it is the last technique to find the root cause in most if not all cases in practice.
STA can tell thermal events that can tell the differences between the t0 and stability samples, such as initual Wt loss, etc. Its sensitivity is also not high.
Raman Micro-Analysis is the best technique to find out the root cause. It can provide you more information about your stability and t0 samples too.
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