The Effect of Sampling Cannula on In Vitro Dissolution Testing with USP Paddle Method

Abstract

In vitro dissolution tests are widely used as quality control tools for drug products in development and manufacturing. Dissolution acceptance criteria are one of the important factors assessed during the regulatory review process. Understanding potential sources of variability is critical and a key to assuring reliable results are obtained when using a standardized system for in vitro dissolution testing. Sampling cannulas are commonly used to withdraw sample aliquots from dissolution medium and are potentially one of the testing factors that can contribute to variabilities in dissolution testing. However, there are still no clear requirements on the size or setting (intermittent or stationary) of sampling cannulas for dissolution testing. Thus, the objective of this study is to evaluate whether various sizes and sampling cannula settings yield different dissolution results using the USP 2 apparatus. Sampling cannulas with outer diameter (OD) ranging from 1.6 mm to 9.0 mm were used in dissolution testing with either intermittent or stationary setting to collect sample aliquots at multiple time points. The dissolution results at each time point were statistically analyzed for effects of both OD and setting of sampling cannula on drug release from 10 mg prednisone disintegrating tablets. Dissolution results indicated both size and setting of the sampling cannula may cause significant systematic errors, even though the dissolution apparatus has been calibrated. The degree of interference in dissolution results was directly related to the OD of the sampling cannula. Size of sampling cannula and setting of sampling procedure should be documented in standard operating procedures (SOP) for dissolution testing during method development.

Keywords: USP apparatus; dissolution testing; medium hydrodynamics; sample cannula; sampling process; variability.