The presence of a slight hydrodynamic effect from the resident probes is anticipated.  This area has been researched thoroughly.  It has been shown that when USP calibrator tablets are analyzed using a USP Apparatus II (paddle) system, there is a slight increase in the release rate of the tablets. This effect is NOT seen with the basket apparatus.

The reason for this increase in dissolution rate is due to the presence of “the cone” at the bottom of the vessel when the paddle is used.  This region is a hydrodynamic dead zone, where solid particulate tends to collect.

The cone is a hydrodynamic dead zone, where solid particulate tends to collect.

Whenever any other item (sample probe) is introduced into the vessel, the increased turbulence from the object will tend to disturb “the cone” at the bottom of the vessel.  As a result, the solid dosage form is stirred up more, and may release at a slightly faster rate.

In a recent publication calibrator tablets were used to measure the effect of in situ probes on a formulation.  In fact, calibrator tablets are a perfect “worst case study” since they are selected because of their sensitivity to slight disturbances in the setup of a dissolution apparatus.  We sought to run a highly controlled study, so every experiment consisted of three test vessels, which contained probes, and three control vessels did not.  Additionally, between experiments we interchanged control and test probes, to remove any possibility of a vessel specific bias.  The results that were obtained demonstrated that a 2-4% bias is present when the probes are left in the vessel during a dissolution study of an immediate-release (IR) formulation.  Having quantified this offset, we then sought ways to avoid this effect.

There are two ways to deal with this effect.  The first is to simply validate the presence (or lack) of the effect, and factor any slight offset into the specification of the method that is being developed.  This small reproducible offset is tolerable when compared to the many sources of random error that have been eliminated from the dissolution process by this technique.  We were able to pass the calibration specification with both USP calibrator tablets, with probes resident throughout the dissolution test.

The second method, which will actually eliminate this effect, is to remove or raise the probes from the vessel between sampling measurements.  This can be accomplished using an automated sampling manifold available from manufacturers of dissolution baths.  Leaving the very tip of the probe submerged in the vessel can eliminate the problem of air-bubble entrapment and probe drying.  The probe in this position does not affect the rate of dissolution, because it is high enough so that the turbulence that it generates does not disrupt the cone at the bottom of the vessel.

Leaving the very tip of the probe submerged in the vessel can eliminate the problem of air-bubble entrapment and probe drying.