Pharmaceutical Technology Europe - May 2010 - (Page 4)

Innovations in dissolution testing It is widely acknowledged that the rate at which a tablet or capsule dissolves (the dissolution rate) is critical to its therapeutic effectiveness. Unfortunately, as with any in vitro test, the accuracy of the results is only as good as the instrument used to conduct it — the more variables in the apparatus, the more variables in the results. Recent studies conducted by the FDA and US Pharmacopeia (USP) have tried to identify different sources of mechanical variation within the USP Dissolution Apparatus that lead to variability in results. This has resulted in calls from both regulators and industry alike for a tightening of the original mechanical specifications relating to Dissolution Testers laid down in the USP. of a dissolution tester and therefore the most likely to affect the accuracy of results were the ones making up the actual test station — namely the dissolution vessel itself, the dissolution vessel lid and the stirring element appertaining to it. The dissolution community has long recognised that one of the major problems with respect to results variability relates to vessel dimensions and irregularities. In our product development, we managed to resolve the problems arising from the vessel by vacuum-forming the vessel as opposed to extruding it. Having resolved the problems relating to the dissolution vessel, it was then a relatively simple matter to design a dissolution vessel lid and stirring element to match it. and still the accepted practice with the industry, has been to calibrate dissolution testers on a 6-monthly basis, using a combination of mechanical checks and performance verification reference tablets. Performance verification testing (PVT) is time-consuming, and concerns have been raised in some quarters about the wide acceptance ranges and variability of the results generated by the reference tablets used. Current FDA and International Pharmaceutical Federation thinking would suggest the use of enhanced mechanical calibration as an alternative to PVT. Other sources, including USP themselves, argue that there is still a place for PVT testing on the grounds that it is not possible to pick up every variable through mechanical means alone. I have no doubt that this debate will rumble on for some time to come. Either way, enhanced mechanical calibration, either standalone or as a precursor to PVT, can only be beneficial in reducing instrument induced variability and thereby improving the accuracy of results. PTE Based on a contribution by Tony Copley, Managing Director of Copley Scientific. To read the full version of this article, go to www.pharmtech. com/tonycopley www.copleyscientific.co.uk Limiting variability Based on our own research, we recognised that the critical elements Where do we go from here? Currently, the method of calibration adopted by USP in Chapter 711, 1 CONTENTS 5 NIR CHEMICAL IMAGING 2 BIOANALYSIS 6 PARTICLE SIZE ANALYSIS 3 POWDER BEHAVIOUR 10 SAMPLE PREPARATION 4 DISSOLUTION TESTING 12 TOP TECHNOLOGIES http://www.pharmtech.com/tonycopley http://www.pharmtech.com/tonycopley http://www.copleyscientific.co.uk

Table of Contents for the Digital Edition of Pharmaceutical Technology Europe - May 2010

Table of Contents

Pharmaceutical Technology Europe - May 2010

Bioanalysis: Hurdles and Hopes
Understanding Power Behaviour
Innovations in Dissolution Testing
When Should the Pharmaceutical Industry Use NIR Chemical Imaging?
Predicting New Promise in Particle Size Analysis
LC-MS Today and Tomorrow
New Possibilities for X-Ray Analysis
Industry Must Improve Sample Preparation Techniques
Sample Analysis: Automation is Crucial
Thirteen Latest Technologies Showcased

Pharmaceutical Technology Europe - May 2010