Reliability and Reproducibility of Vertical Diffusion Cells for Determining Release Rates from Semisolid Dosage Forms

Abstract

USP has formed Advisory Panels to ensure the integrity of laboratory procedures for non-oral routes of administration and expects that the panels will recommend performance tests (performance qualification, PQ) for these dosage forms as well as performance verification tests (PVT) for those PQ tests. An integral part of PQ is PVT, in which a standard formulation is first tested in a metrologically sound collaborative study to set acceptance criteria. Individual laboratories can then test the performance of their product by comparing their results to those obtained from the USP collaborative study. These studies are guided by metrological principles, e.g., those of the International Organization for Standardization (ISO) 43-1, which succinctly states that "one of the main uses of proficiency testing schemes is to assess laboratories' ability to perform tests competently." Four laboratories conducted two collaborative studies to determine the reliability and reproducibility--understood in metrological terms--of release rates from semisolid dosage forms using the vertical diffusion cell (VDC). The experiments reported here from the second study found that the major contributor to variability is the interlaboratory component that may include intermediate precision considerations other than analyst. Because all laboratories used the same model equipment, one might expect that the observed reproducibility CV was lower than if the laboratories used different models or equipment made by different manufacturers. Also, more variability was observed with the creams than the other dosage forms. The results from the preliminary collaborative study found inconsistency among the laboratories. After operator training, the results from the second study were more consistent, suggesting the initial results were associated with variations among the laboratories in performing the methods and procedures and conducting the protocols. Those results emphasize that although the in vitro release procedure is simple and reproducible, training is needed. The data presented suggest that testing of in vitro release by VDCs should be considered as a PVT for topical semisolid dosage forms. Thus, a standard semisolid product is needed, along with a means for setting acceptance criteria. The SUPAC-SS Guidance may be helpful in the latter regard.