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EXPRESSION OF DISSOLUTION SPECIFICATIONS FOR ORAL DOSAGE FORMS

The dissolution specification is expressed in terms of the quantity (Q) of active substance dissolved in a specified time, expressed as a percentage of the content stated on the product label.

Conventional-release dosage forms

In most cases, when tested under reasonable and justified test conditions, the acceptance criterion at level S1 is 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, since, as indicated in Table 2.9.3.-1, 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.

- An example for a conventional release tablet with a labelled content 100 mg of active substance:

  • Acceptance criterion at level S1: at least 80% (80 mg) of active substance is released within the specified testing time
  • The Q value then corresponds to 75%

Prolonged-release dosage forms

The dissolution test acceptance criterion for prolonged-release dosage forms is normally expected to consist of 3 or more points. The 1st specification point is intended to prevent unintended rapid release of the active substance (‘dose dumping’). It is therefore set after a testing period corresponding to a dissolved amount typically of 20 per cent to 30 per cent. The 2nd specification point defines the dissolution pattern and so is set at around 50 per cent release. The final specification point is intended to ensure almost complete release, which is generally understood as more than 80 per cent release.

Delayed-release dosage forms

A delayed-release dosage form may release the active substance(s) fractionally or totally according to the formulation design when tested in different dissolution media, e.g. in increasing pH conditions. Dissolution specifications therefore have to be decided on a case-by-case basis.

Gastro-resistant dosage forms require at least 2 specification points in a sequential test and 2 different specification points in a parallel test. In a sequential test, the 1st specification point represents an upper limit and is set after 1 h or 2 h in acidic medium, and the 2nd after a pre-set time period of testing in an adequate buffer solution (preferably pH 6.8).

In most cases the acceptance criterion at level B1 is that at least 80 per cent of the active substance is released. This corresponds to a Q value of 75 per cent, since, as indicated in Table 2.9.3.-4, for level B1 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.

Explanations are also given in general chapter 5.17.1 Recommendations on dissolution testing.

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