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Réponse :

Q représente la quantité cible de substance active qui se dissout dans un intervalle de temps spécifié, exprimée en pourcentage de la teneur indiquée sur l’étiquette. Il convient de considérer la « valeur Q » comme une « valeur de référence » à laquelle sont comparés les résultats de la dissolution. Cette comparaison s’applique aux formes à libération conventionnelle et à l’étape tampon de l’essai de dissolution des formes gastrorésistantes.

Pour plus d’informations sur l’essai de dissolution, voir le chapitre général 5.17.1. Recommandations relatives à l’essai de dissolution

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%

...

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 1^st specification point represents an upper limit and is set after 1 h or 2 h in acidic medium, and the 2^nd 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.