How to Set In-Vitro Dissolution Test Apparatus?

Dissolution Specifications

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

Major Pharmacopoeias lists three levels of testing; compliance with level 2 is expected during routine manufacture.

Dissolution specifications should ensure that products meet clinical performance and that manufacturing processes are performing as expected to ensure batch-to-batch consistency.

The Discriminatory Power of the Dissolution Specifications

The discriminatory nature of the method should be shown for the time point that is specified in the finished product specification, as routine Quality Control (QC) testing will be based on a single time point, rather than on multiple-point dissolution profiles.

Before setting the Q value, the time range allowing discrimination should be considered from the dissolution profile of the bio-batch.

Dissolution Specifications are set based on which Data?

The dissolution profile of the bio-, pivotal, or clinical batches, using test conditions providing discriminatory power should be used to set a suitable specification for quality control and batch release.

Same Dissolution Specifications throughout the Product Lifecycle

To ensure continuous batch-to-batch equivalence of the product after scale-up and postapproval changes in the marketplace, dissolution profiles should remain comparable to those generated for the batches used to support bioequivalence or pivotal clinical trials.

Once a dissolution specification is set for the generic product based on the batch that showed acceptable performance in vivo (i.e., those batches used in the in-vivo bioequivalence studies), the generic product should comply with that specification throughout its shelf life.

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Decision tree for setting specifications based on the dissolution results of the bio-batch

Decision Tree Explained

The recommendations in the decision tree are meant as guidance for setting the specification:

• If dissolution of the bio-batch is larger than or equal to 95% in 15 minutes, the specification may be set to Q=85% after 15 minutes
• If dissolution of the bio-batch is less than 95% but larger than or equal to 85% in 15 minutes, the specification (Q) may be set to 75%, 80%, or 85% whichever is closer to Q=bio-batch result -10% at 15 minutes
• If dissolution of the bio-batch is larger than or equal to 85% only after 30 minutes, the specification (Q) may be set to 75%, 80% or 85% whichever is closer to Q=bio-batch result -10% at 30 minutes
• If the dissolution of the bio-batch is larger than or equal to 85% only after 45 minutes, the specification may be set to 75%, 80% or 85% after 45 minutes.

• In case the dissolution of the bio-batch is less than or equal to 85% after 45 minutes, a minimum of 75% at 45 minutes should be specified if possible.
• Otherwise, if the dissolution specification (Q) is less than 75% after 45 minutes, the dissolution specification should be based on more than a one-time point.

Note:

• Similar dissolution of two batches may be assumed in case of differences of less than 10% of the label claim in their mean results. Therefore, the Q value is recommended to be set based on the bio-batch dissolution result (mean value of 12 units) minus 10%.
• The discriminatory power is closely linked to the time point and Q value chosen. If time point values other than those proposed in the decision tree would lead to discriminatory power, this is also acceptable.

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