I've been trying to develop Metformin 500 mg SR + Sitagliptin 50 mg IR bilayer tablets but the assay of sitagliptin drops by almost 10% in 1 month accelerated stability. Metformin is quite stable but the problem is only with the sitagliptin layer. Please give your valuable suggestions.
whats the PK curves AUC of Met and Sitag (IR and SR ) the t1/2 is also important.
for answer the question.
First of all, you have to do excipient-API compatibility studies at the beginning of your formulation studies to avoid use of incompatible excipients in your formulation and not to face stability problems. Now, the question is "what did you use in sitagliptin layer as excipient". For example, if you used lactose or similar sugar(s) in your formulation, there is a possibility of Maillard reaction with sitagliptin which would reduce your assay during stability studies and this reaction would definitely occur stonger at high temperature and humidity conditions.
the maillard reaction is a non enzymatic slow chemical reaction most mentioned with fructose, in vivo the surrounding area in whichever stay for a time it more important only if is saturated with your compounts at this point the importance of miallard plays a role .
Hi! Esen,
Thanks a lot for your information. I've not used lactose in my formulation. The sitagliptin layer in my formulation contains MCC, DCP anhydrous, Crospovidone, PVP K30, Iron oxide yellow, SLS, SSF, Aerosil and water. I've done wet granulation for these tablets.
Dear Abhishek, sitagliptin shows degradation under stress testing conditions according to the literature. Main degradation products form due to hydrolysis of amide bond, which occur strongly at basic conditions but also observed at acidic and neutral (water) conditions. The effect of degradation in all three conditions increases at high temperatures. Please see attached related articles regrading this topic. If no any incompatibility was observed between sitagliptin and the used excipients, then it is probably due to aqueous hydrolysis. So, water content of granules is important and should be kept at very low level, and tablets should be stored in Al/Al blisters to avoid moisture.
Dear Esen,
Thanks a lot for sending me the related articles. They are really very helpful.
Dear Dhakshna,
Thanks a lot for your answer. I've developed this product now which is stable.
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