ASK （questions from customers）
Ask colleagues, capsule dissolution using paddle method without dissolution sinker, capsule floating on the liquid surface to do dissolution is feasible, read the dissolution guidelines, the capsule is recommended to use basket method, if you use paddle method, you need to add dissolution sinker.
If there is no settlement, is it feasible to use paddle method directly? Because the basket method dissolves slowly in the water medium, it is speculated that the capsules are relatively sticky in the water medium and are not easy to dissolve in the basket.
The use of different dissolution sinkers has an effect on dissolution, so it is not planned to add dissolution sinkers to paddle method. Please give me some advice!!
Answer 1: add the dissolution sinker or use the rotating basket method. If it doesn’t dissolve out, then it won’t dissolve out in the original research. You have to consider the solubility of API. If the solubility of API in water is low, then it’s the inherent physical property of API, so don’t worry about it.
In addition, poor dissolution means that the medium you choose may not be the key medium. If you do research, you should find the key medium with the most distinguishing power.
Capsule winding is executable
Answer 2: I have made two kinds of capsules, and the dissolution does not add a dissolution sinker. Generally speaking, gelatin capsules will break in the medium in 2-4 minutes, and the contents will slowly sink to the bottom when absorbing water.
Capsules vary in quality due to different manufacturers. Generally, the RSD of the first point is very large, and the reference preparation is also very large (which is what I encountered). Therefore, the 5-minute point is usually discarded. If you do not add a dissolution sinker, you should not add a dissolution sinker for your own products. The conditions are the same.
It seems that the self-made dissolution sinker or winding coil is not very recognized now. You can refer to the Pharmacopoeia 2015 or the guidelines. I remember it seems to be changed.
Answer 3: did you use filament winding to make the capsule sink below the liquid level without dissolution sinker?
My reference preparation is tablet, and self-developed is capsule. Capsule is floating on the liquid surface 20 minutes before using paddle method without dissolution sinker. If paddle method with dissolution sinker or without dissolution sinker has little effect on dissolution, can we consider not adding dissolution sinker?
However, according to pharmacopoeia 2015 and the guiding principle, the capsule is sunk to the liquid level by paddle method, adding dissolution sinker or winding with thin thread. Therefore, it is worried that the paddle method without dissolution sinker needs to find a way to make the capsule sink to the liquid level.
Answer 4: after a USP training, the US teacher clearly said that as long as the capsule floats on the liquid surface, the FDA requires that a dissolution sinker (device) be added.
Domestic side did not find the exact statement, so, for reference only.
Answer 5: whether to add dissolution sinker or not is a question of dissolution method selection. If it has little effect on dissolution, it is really unnecessary to add it. But if you are still floating on the liquid surface for 20 minutes, it must be added. The reference is tablet, and self-developed is capsule. I think the dissolution behavior of tablet and capsule is much worse.
Can you really match the curve? Even if you match the CDE, will you accept it? Of course, now it’s all be filed first. If be passes, it may be easy to say anything. You should be a consistency evaluation project. I’ve also received one before. The reference is sugar coated tablets and self-developed capsules. The difference between the two formulations is 18000 Li, because the products sell well. Finally, the enterprise re established the project.
- If the sample floats in the dissolution process, a dissolution sinker should be added.
- The landlord said that adding dissolution sinker or not would not affect the dissolution data, not to mention the dissolution changes caused by different dissolution sinkers.
- Finally, if the reference tablet is changed to capsule, the release mechanism will be changed, and the conventional dissolution curve may have little significance, which needs to be determined.
Answer 6: A project I’m doing now is also in this case. The reference is tablets, and the self-made is capsules. API has high solubility in acid and low solubility in water and ph6.8 medium.
API is easy to aggregate, and the dissolution rate is significantly lower after aggregation. If the dissolution sinker is added, ph1.2 medium has no effect, pH4.0 medium has a little effect, and the effect is not big.
In water and ph6.8 medium, it has a significant effect. With the addition of dissolution sinker, the contents are easy to accumulate at the bottom of the cup, and API aggregation leads to insoluble. Without the addition of dissolution sinker, the contents fall down in a dispersive process, and the dissolution is relatively fast.
Because the dissolution in acid is fast, Tmax is only 1 hour, so we only look at the dissolution in acid, not the dissolution of ph6.8 and water medium, and the addition of dissolution sinker has no effect on us. I hope Chinese style can be passed later!