Dissolution tests are routinely carried out in the pharmaceutical industry to determine the dissolution rate of solid dosage forms. Dissolution testing serves as a surrogate for drug bioavailability through in vitro–in vivo correlation (IVIVR), and it additionally helps in guiding the development of new formulations and in assessing lot-to-lot consistency, thus ensuring product quality. The United States Pharmacopoeia (USP) Dissolution Testing Apparatus 2 is the device most commonly used for this purpose. Despite its widespread use, dissolution testing using this apparatus remains susceptible to significant error and test failures. There is documented evidence that this apparatus is sensitive to several geometric variables that can affect the release profile of oral dosage forms, including tablet location during the dissolution process.
In this work, the dissolution profiles of disintegrating calibrator tablets containing Prednisone were experimentally determined using two systems, i.e., a Standard USP Dissolution Testing Apparatus 2 (Standard System) and a Modified Standard USP Dissolution Testing Apparatus 2 (Modified System) in which the impeller was located 8 mm off the vessel centerline. The dissolving tablets were located at different off-center positions on the vessel bottom to test the effect of tablet location in these two systems.
Tablet dissolution in the Standard System was found to be strongly dependent on tablet location, as previously reported by this and other research groups. This apparatus appears to generate variable results that may not be associated with the tablets undergoing testing but with the hydrodynamic characteristics of the apparatus itself and the location of the tablet on the vessel bottom. However, when the same experiments were conducted in the Modified System, the dissolution profiles for the same tablets were found to be nearly completely insensitive to tablet location.
The dissolution process in the Modified System was faster than that in the Standard System because of the improved mixing performance of the Modified System resulting from the non-symmetrical placement of the impeller. However, when the Modified System was operated at 35 rpm, the dissolution profiles for centrally located tablets were found to be very similar to those for the Standard System operating at 50 rpm. Unlike the Standard System however, the dissolution profiles obtained at 35 rpm in the Modified System were found to be insensitive to tablet location.
It can be concluded that the newly proposed Modified System for dissolution testing is a simple and yet robust and valid alternative to the current dissolution testing practice using the Standard USP Dissolution Testing Apparatus.
See more of this Group/Topical: Topical I: Comprehensive Quality by Design in Pharmaceutical Development and Manufacture