I try to formulate a tablet dosage form of Azilsartan Medoxomil and Chlorthalidone. I face a number of challenges, mainly for Azilsartan Medoxomi, in Assay, Dissolution and Stability. Obviously, it's easily decomposed and dissociated into Azilsartan and Medoxomi (two separate peaks in HPLC). I tried many techniques and strategies, but I couldn't reach to a stable formulation.
Formula Composition
Each tablet contains the following inactive ingredients: mannitol, microcrystalline cellulose, fumaric acid, sodium hydroxide, hydroxypropyl cellulose, crospovidone, and magnesium stearate.
I am looking forward to your help!
The compound is prone to hydrolysis of the ester bond. The formulation should be in the acidic region. The sodium hydroxide in the formulation may be needed to adjust the pH. I suggest a buffer at the pH of maximum stability. Prepare a fumarate buffer at pH 3 or 4, formulate and put on stability. If you already know the pH of maximum stability. chose that pH. You may use another buffer as well.
Thank u for ur answer, Dr Andrei! Indeed, Azilsartan Medoxomil is stable in pH ranging from 3-5. I formulated the physical mixture in this pH range, using Fumaric acid (acidic microenvironment). I checked the pH of the powder form after granulation, before compression and it was in the range. It's also decomposed and dissociated into Azilsartan and Medoxomil.
Is it decomposing in the formulation, or is it decomposing during the analysis? Have you checked the pure API with the analytical method you are using for the DP?
I suggest checking the analytical method first. If you are sure that it is working properly, and no decomposition of the API is showing, then (and only then) should you start working on your formulation.
Thank u for ur answer, Dr Adam! There's no problem in the method of analysis of Azilsartan.
It is required to use a suitable surfactants to improve dissolution and also use stabilizer. To avoid decomposition use organic solvent rather than water
Follow Adam and then Blasko but do not forget, the cause of degradation. Infact, it is due to hydrolysis of ester bond. To prevent hydrolysis, you need to consider vacuum drying of tablets until moisture comes down to less than 0.5% and packaging must be in Alu/Alu with Dessicant.
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