20/21 September 2022
The dissolution test is a key test parameter for assessing the performance of solid and semi-solid dosage forms in both drug development and quality control.
In part 1 of this article, we gave you a summary of the test's purpose and the apparatuses according to the European Pharmacopoeia. However, there are also many requirements laid down in dissolution guidances and associated documents. In part 2, we would therefore like to provide you with an overview of these documents.
Already in August 1997, the U.S. Food and Drug Administration (FDA) has published a Guidance for Industry on "Dissolution Testing of Immediate Release Solid Oral Dosage Forms" which can be downloaded.
Another Guidance for Industry entitled "Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations" was published in September 1997. It is available as a PDF file.
A Guidance for Industry from August 2018 deals with "Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances". It is also available for download on the FDA's website.
In August 2021, the FDA announced the availability of a Draft Guidance for Industry entitled “Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA.” It provides recommendations to applicants planning to include bioequivalence (BE) information in abbreviated new drug applications (ANDAs) and ANDA supplements. The guidance document was published on the FDA's website, the news New FDA Draft Guidance for Industry on Bioequivalence Studies provided a summary.
Further documents and supporting information can be found using the FDA Guidance Document Search.
For a drug product that does not have a dissolution test method in the United States Pharmacopeia (USP), the FDA Dissolution Methods Database provides information on dissolution methods presently recommended by the Division of Bioequivalence, Office of Generic Drugs. The database is updated quarterly.
The "Dissolution Methods Database Search" is available following this link. The FDA has also published a section entitled "Dissolution Methods Database Frequently Asked Questions" which is published on the FDA's website.
In 2017, the European Medicines Agency (EMA) had published a reflection paper on the dissolution specification for generic solid oral immediate release products with systemic action. The document discusses the suitability of the dissolution method and the specifications for in vitro dissolution of orally administered generic drug products with immediate release characteristics. Further information and the possibility to download can be found on the EMA website.
The ICH Q4B Annex 7(R2) "Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Dissolution Test General Chapter" is the result of the Q4B process for Dissolution Test. The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 2.9.3. Dissolution Test for Solid Dosage Forms, JP 6.10 Dissolution Test, and USP <711> Dissolution can be used as interchangeable in the ICH regions subject to the conditions described in the document.