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Calibrating Your Dissolution Tester
There have been a number of changes relating to equipment qualification over the past few years. Today there is basically a choice between running the USP qualification which involves both physical testing and running a calibrator tablet, or calibrating to physical parameters only, the ASTM Physical testing parameters.
In response to the ASTM proposals, the USP published a 'USP Dissolution Toolkit' which suggests tighter physical parameters in addition to the calibrator tablets, Prednisone.
One argument put forward is that if a dissolution tester is mechanically perfect, then there is no need to run calibrator tablets, technically that might be correct, except there are a number of external parameters that can have an effect on the dissolution test which fall outside simple physical testing. One of these is the operator, and a reasonable argument can be made that operators should be able to run the calibrator tablets as part of their training to ensure that they are competent to perform everyday tests on other pharmaceutical products.
An excellent article by Gregory Martin and Vivian Gray, published in Dissolution Technologies Journal discusses Dissolution Instrument Qualification and Common Pitfalls and is well worth reading.
In terms of the mechanical calibration requirements, both the ASTM guidelines and the USP Toolkit require reasonably tight specifications. This is required to maintain a good correlation between each testing position.
| Calibration Paramete | ASTM Mechanical Calibration Specifications | USP Toolkit Specifications |
| Shaft Wobble | ≤1.0 mm runout, 2 cm above the paddle or basket | ≤1.0 mm runout, 1 cm above the paddle or basket |
| Shaft Verticality | <0.5° from vertical at 2 points 90° apart | <0.5° from vertical at 2 points 90° apart |
| Basket Wobble | ≤1.0 mm runout at bottom of basket | ≤1.0 mm runout at bottom of basket |
| Centering | ≤1.0 mm, at 2 mm and 60 mm above basket or at 2 mm and 80 mm above paddle | ≤2.0 mm, not more than 2 cm below the flange of the vessel |
| Vessel Verticality | <1.0° from vertical at 2 points 90° apart | <0.5° from vertical at 2 points 90° apart |
| Height of basket or paddle, above bottom of vessel | 25 ± 2 mm | 25 ± 2 mm |
| Rotational Speed (50 rpm) | ±2 rpm | ±1 rpm |
| Temperature | 37 + 0.5 °C | 37 ± 0.5 °C, range not more than 0.4 °C |
The Prednisone Calibrator tablets are available from the country USP representative. The Pass/Fail criteria are lot dependent and published with the tablets as are the CV% allowed between vessels.
Prednisone is very sensitive and can fail for a number of reasons. If a failure occurs then there may be implications for any tests performed since the last calibration and so it is important to keep everything about the tester in top condition and constantly checked.
Failures due to poor degassing, vibration, vessels, physical tester parameters and poor storage are not uncommon.
It is highly advisable to maintain a logbook for each dissolution tester, to include all serial numbers, locations and all procedures on the equipment. It helps you should things go wrong and enables traceability at all times.
In general, equipment calibration is repeated every six months.
If the tester is moved for any reason it will need to be re-calibrated
If only paddles or only baskets are used, then it is not necessary to calibrate for both methods
As mentioned at the top of this page, variables can be physical or operator related. The table below is not exhaustive but provides some insight into some of these parameters.
As you can see there are a lot of parameters to consider. In the following pages we will aim to examine some of these.
