Although the importance of the consistent dissolution of solid dosage form medicines is recognized, when disintegration was first added to the USP in 1950, it was understood to be an incomplete test. In the late 1960s a joint panel was formed by USP and the National Formulary (NF) to evaluate mechanisms for ensuring drug effectiveness. Their recommendations set the stage for officially sanctioned dissolution testing for oral dosage forms and, in 1970, USP published an official dissolution test in 12 monographs. The USP test measured the time to attain a specified amount dissolved, whereas NF and FDA used the more workable test for the amount dissolved at a specified time. During the 1970s, scientists found great variation between dissolution results from one apparatus to another, leading USP and FDA to work on standardization of dissolution testing. In1975, USP began developing calibrators for dissolution testing, and the FDA developed detailed bioequivalence and bioavailability regulations that were finalized in February 1977, followed by its guidance: Guidelines for Dissolution Testing.
In 1999, the dissolution and disintegration tests were made a priority for harmonization by the International Conference on Harmonization (ICH).The harmonized USP General Chapters <701> Disintegration and <711> Dissolution became official in 2006. The next year, a new FDA Draft Guidance for Industry, The Use of Mechanical Calibration of Dissolution Apparatus 1 and 2 - Current Good Manufacturing Practice (cGMP), was published, which replaced the use of "calibration tablets" with "mechanical calibration" when calibrating apparatuses used to comply with GMP requirements for dissolution testing. FDA stated that in the Agency's view the use of USP calibration tablets could lead to variability in the dissolution measurement system. To date, FDA's final guidance recommends that an enhanced mechanical calibration procedure may be used as an alternative to the current Apparatus Suitability procedure for Dissolution Apparatus 1 and 2 described in USP General Chapter <711> Dissolution, for GMP (but not compendial compliance) purposes.
Published Oct 7, 2010
