The dissolution specification is expressed in terms of the quantity (Q) of active substance dissolved in a specified time. Using a percent value as a standard allows for easier standardization across all of the monographs and also helps to more easily apply limits based on statistics.
As per USP,
Q is the amount of dissolved active pharmaceutical ingredient (API).
As per EP,
Q represents the targeted amount of active substance, which should be dissolved within a certain time and expressed as a percentage of the label claim.
How to Calculate Q Value?
Let see, USP dissolution acceptance criteria for immediate release dosage form (below figure) -
Let's assume that Q = 85% dissolved. Using this, then our acceptance criteria for this table would be:
- S1 - 6 units tested. Each unit is not less than 90% (Q+5%)
- S2 - 6 additional units tested. Average of 12 units (Stage 1 plus Stage 2) is equal or greater than 85% (Q), and no unit is less than 70% (Q-15%).
- S3 - 12 additional units tested. Average of 24 units (Stages 1 + 2 + 3) is equal to or greater than 85% (Q), not more than 2 units are less than 70% (Q-15%), and no unit is less than 60% (Q-25%).
Why we need to add 5% or 10% to Q value?
We do this because the specifications are all based on n=12. When you start with a smaller sample set with n=6, you need to have tighter criteria since you don’t have as much statistical confidence.
As you increase the sample set of data, you get closer to being able to use Q since you gain more confidence in your data being an accurate representation of the full lot.
As per EP,
For most cases in conventional-release dosage forms, when tested under reasonable and justified test conditions, the acceptance criteria at level S1 are that at least 80 per cent of the active substance is released within a specified time, typically 45 min or less.
This corresponds to a Q value of 75 per cent, for level S1 the individual value of each of the 6 units tested is not less than Q + 5 per cent, i.e. not less than 80 per cent.
Typically, a single-point acceptance criterion is sufficient to demonstrate that the majority of the active substance has been released, although in certain circumstances it may be necessary to test at additional time point(s), in order to demonstrate adequate dissolution.
Read also:
