FIP Guidelines for Dissolution Testing of Solid Oral Products.

Dissolution testing is an important physiochemical test for the development of solid oral dosage forms, tablets, and capsules. As a quality control test, the dissolution test is used for assessment of drug product quality and is specified for batch release and regulatory stability studies. In vitro dissolution test results can often be correlated with the biopharmaceutical behavior of a product.This article provides a summary of views from major global agencies (Europe, Japan, United States), pharmacopoeias, academia, and industry. Based on available guidance and literature, this article summarizes highlights for development and validation of a suitable dissolution method, setting appropriate specifications, in vitro-in vivo comparison, and how to obtain a biowaiver.

Biorelevant in vitro performance testing of orally administered dosage forms-workshop report.

Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic.

FIP position paper on qualification of paddle and basket dissolution apparatus.

The qualification process for ensuring that a paddle or basket apparatus is suitable for its intended use is a highly debated and controversial topic. Different instrument qualification and suitability methods have been proposed by the pharmacopeias and regulatory bodies. In an effort to internationally harmonize dissolution apparatus suitability requirements, the International Pharmaceutical Federation's (FIP) Dissolution/Drug Release Special Interest Group (SIG) reviewed current instrument suitability requirements listed in the US, European, and Japanese pharmacopeias and the International Conference on Harmonization (ICH) Topic Q4B on harmonization of pharmacopoeial methods, in its Annex 7, Dissolution Test General. In addition, the SIG reviewed the Food and Drug Administration (FDA) Draft Guidance for Industry, "The Use of Mechanical Calibration of Dissolution Apparatus 1 and 2-Current Good Manufacturing Practice (CGMP)" and the related ASTM Standard E2503-07. Based on this review and several in-depth discussions, the FIP Dissolution/Drug Release SIG recommends that the qualification of a dissolution test instrument should be performed following the calibration requirements as indicated in the FDA (draft) guidance. If additional system performance information is desired, a performance verification test using US Pharmacopeia Reference Standard tablet or an established in-house reference product can be conducted. Any strict requirement on the use of a specific performance verification test tablet is not recommended at this time.

Precision from drug stability studies. Investigation of reliable repeatability and intermediate precision of HPLC assay procedures.

A multi-company investigation is presented to obtain and compare precision results for LC assay procedures. Forty-four drug substances and drug products of various types subjected to 156 stability studies, with 2915 assay values in total, were included. This provides an excellent source of real long-term precision estimates, as the same analytical procedure was applied during the whole stability study, extending from 12 to 60 months. Intermediate precision was calculated either using the residual standard deviation of the regression line or applying an analysis of variances, depending on whether there was a significant degradation of the analyte or not. The results show impressively the large intervals where the individually calculated parameters scatter. Distribution ranges and averages for repeatability, intermediate precision, and the ratio between the two precision levels are mainly dependent on the type of drug product. Repeatabilities were found up to 0.8% for solutions, 1.6% for drug substances, 1.9% for tablets, 2.3% for creams, and 3.4% for a bath. For intermediate precision, which includes additional variability factors due to the reference standard, operator, equipment, reagents, etc., a similar dependency was obtained with a slightly changed order: up to 1.1% for drug substances, 2.2% for solutions, 2.3% for tablets, 3.1% for creams, and 3.2% for a bath. The ratio between the precision levels is up to 2.5 and similar for all investigated drug product types, apart from solutions with up to 5.3. These differences for the types of drug product may be explained by the influence of the sample and/or the sample preparation: the more complex, the higher the variability contribution. For the investigated examples, the impact of the analyte and of the concentration (dosage) seems to be of less importance. Therefore, a classification of drug product types for orientation on acceptable precision (ranges) for LC assay seems to be possible.