I have been making Tenofovir disoproxil fumarate (TDF) tablet based on wet granulation method.
The assay test is not good, it's dropped by 5% in accelarated storage condition in 3 months. TDF is difficult to formulated by direct compression due to its flowability.
How could stability of TDF tablet be improved?
Thanks in advanced.
First, you have to address the structure activity relationships of Tenofovir disoproxil fumarate to find relationships between chemical structure (or structural-related properties) and biological or physicochemical activity. Then you will identify what exactly do you need in your formula?, either a stabilising agent, antioxidant, or a blend of antioxidants.
First you check out the reasons for Stability problems. Then you can go for addition of suitable stabilizing agent. Even though if you are getting the same problem then you can go for another dosage form development or you can mention in label as store in cool place.
There are couple of patents related to the formulation of Tenofovir disoproxil fumarate, may be useful (links below):
https://www.google.com/patents/WO2015085976A1?cl=en
https://www.google.com/patents/EP2365798A2?cl=en
I would study, first of all, products of degradation of disoproxil fumarate to take a decision about its stabilisation. probably its necessary to reduce the content of water in the granulation, if products of degradation of disoproxil fumarate are product of its hydrolysis
I agree with some suggestions pointed above. Before you design the experiments to improve the stability, you will need first to investigate all factors causing instability of your drug/drug product.
Possible degradation pathway of Tenofovir disoproxil fumarate is hydrolysis and oxidation. water presence in formulation cause stability problem.
My suggestion,
1. Try DC granulation method:- Use MCC PH 200(For Better flow):MCC PH 112(Low Moisture diluent and binder):Lactose anhydrous(Flowlac)
2. Try Dry Granulation method:- Roll compactor process
3. Try Wet granulation method with IPA
4. Seal coat tablet for moisture barrier during self life
5. Protect formulation by using suitable packing material
6. Manufacturing the batch in low RH area, you can use nitrogen pusing during mfg, primary packing.
- Badges
- Science topic
- Similar topics
- Engineering
- Petroleum Engineering
- Oil