New EMA Guideline for Products with modified Active Substance Release

In September 2012 the EMA released a draft of the "Guideline on Quality of Oral Modified Release Products". The commenting period lasts until 15 March 2013.

There are a lot of pharmaceutical dosage forms in which the release of the active substance changes in comparison with the conventional release - for instance to extend the therapeutic effectiveness or to reduce toxic effects.

The guideline basically differentiates between oral dosage forms with prolonged release of the active substance and delayed release of the active substance.

One of the areas this guideline mainly focuses on is the development of dissolution methods. Here the active substance release rate is supposed to be verified by in vitro release procedures. In this in vitro dissolution test it is important that it is able to

  • discriminate between the batches with regard to critical variables in manufacturing that possibly have an impact on the desired bio-availability, 
  • verify the consistence of the batches (clinical testing, bio-availability, production batches), 
  • determine the stability of the relevant release characteristics across the entire shelf-life.

For that reason the formulation with the extended API release has to be verified in vitro - with different conditions regarding medium, pH-value, apparatus, stirring speed etc. The test conditions with the best discrimination results are the conditions that are supposed to be selected. 

Further detailed recommendations for the testing of the API release can be found in the EMA draft guideline.

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