A COLLABORATIVE STUDY OF THE INVITRO DISSOLUTION OF PHENACETIN CRYSTALS COMPARING THE FLOW THROUGH METHOD WITH THE USP PADDLE METHOD

A collaborative in vitro dissolution study has been performed comparing the flow through cell apparatus with the USP Paddle method. The objective was to compare the two methods regarding their suitability for measuring the in vitro dissolution of a drug substance per se. Phenacetin, a sparingly soluble compound was used as the test material. The results indicate that the flow through cell method shows less variation both within and among the laboratories compared with the USP Paddle method. The flow through cell method was also found to generate faster in vitro dissolution rates for phenacetin than those found with the USP Paddle method, probably caused by steeper concentration gradients at the vicinity of the crystals as well as better ability to uniformly wet the phenacetin crystals. Also, the flow through cell method was found to be less dependent on the hydrodynamics and the amount of substance tested in each run, which generated a better overall reproducibility of the in vitro dissolution data. The USP Basket method was tested in one of the laboratories but it was found to give substantially slower dissolution rates than the other two methods showing a high variability between each vessel.