Drug dissolution testing: Limitations of current practices and requirements

To avoid potential frustrations and unnecessary workloads, when conducting dissolution tests one should be watchful of the following limitations of the currently suggested practices and requirements (please follow the links provided within brackets for further details on the topic).

  • Mechanical qualification and performance verification testing of apparatuses (paddle/basket) are made up compliance requirements which do not establish that the apparatuses are dissolution testers or capable of providing dissolution characteristics of products (Links: 1, 2, 3).
  • Conducting a dissolution test as a QC test, or for checking lot-to-lot consistency of products, is also a made-up requirement or practice and of limited value. Such tests, as conducted presently, are not linked to any of the product quality characteristics (Links: 1, 2, 3).
  • Currently used dissolution testers, in particular the paddle and basket, are not qualified and/or validated for dissolution testing purposes (Links: 1, 2).
  • Drugs and products specific tests, as currently described in literature, are scientifically invalid (Links: 1, 2).
  • Similarly, developing a drug and/or product specific dissolution test is scientifically invalid practice and should be avoided. The practices of developing product specific dissolution methods, and/or using such developed methods, are pretty much waste of time and resources.  Following such practices scientists/analysts will never know the dissolution characteristics of a product but determine experimental conditions to achieve desired dissolution results (Links: 1, 2).
  • Developing discriminatory tests for detecting formulation and/or manufacturing differences has no meaning or practical use, as products having such differences (e.g. generics) can be bioequivalent and of perfectly acceptable qualities (Links: 1, 2, 3, 4).
  • Experimental conditions such as de-aeration, vibration-free environment, use of sinkers etc. can make a dissolution test potentially invalid as these test conditions are not physiologically relevant (Links: 1, 2).
  • Developing an in vitro-in vivo correlation (IVIVC) is a futile exercise because dissolution tests are conducted based on the principle that IVIVC always exists (Links: 1, 2, 3).
  • Plasma drug levels from dissolution results can only be predicted/estimated using the convolution-based technique. The IVIVC and/or de-convolution techniques cannot be applied/used for such purposes (Links: 1, 2).
  • For predicting/estimating plasma drug levels from dissolution results it must be ascertained that results are bio-relevant and obtained using physiologically relevant experimental conditions (Link: 1).
  • Biopharmaceutic Classification System (BCS) is based on drug characteristics and not that of the products. Therefore, its use for products evaluation/development may be of limited relevance or use (Link: 1).
  • Bio-waivers require that dissolution results must be obtained using bio- or physiologically relevant dissolution tests. As currently described methods are generally not bio- or physiologically relevant, therefore, bio-waivers using such methods should be considered a scientifically weak case (Link: 1).

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