| Author | Message | ||
     Erik Skibsted |
Hi NIR Fellows Our next NIR project is determination of water in whole tablets. If you know some good references on that I'll be happy, also if you have some good starting points with respect to sampling, etc. My initial plan is to go for a transmission measurement, with a 8 cm-1 resolution. We want to test whetever we can make a model that can be used for several different formulations/products - they only vary very little in composition i.e. API concentration (but they are low drug content hormon tablet products so it should be possible). Also the tablets have different types of colored coating so thats why I am not considering reflectance, I have also been told that there might be an issue with how the water is distributed and bound in the tablet matrix - comments are welcomed. Thanks for a good forum Erik Skibsted | ||
| Tony Davies (Td) |
Dear Erik, We had an argument about this topic at the recent IDRC so you have provided me with a chance to re-state/explain my case. First your questions: I do not have any good reference to recommend. Your intended approach is what I would do (first). The spectroscopy could be very interesting. I expect the water will all be strongly bound but it may be bound differently to different components of the matrix. My experience is that at low moisture levels the shape of the water absorption varies quite rapidly as the moisture level increases. The argument: Someone was calibrating water in a pharmaceutical product using the Karl Fischer (KF) method. My comment was that KF is not an absolute reference method. It has to be calibrated via water in methanol mixtures so why not use these solutions to make an NIR calibration for water in methanol and use that rather than KF for determining the water content of your calibration samples? This would eliminate the error in the KF determination. Best wishes Tony | ||
| David W. Hopkins (Dhopkins) |
Tony, Aha! I did not understand then what you were getting at. So, you would be eliminating the error of the KF and introducing the error of the NIR method. That means you need to know the errors of each method to know what procedure is best. Can anyone share the levels of moisture in the tablets, and the accuracy of the KF and NIR methods for water at these levels? I agree with Tony, go ahead and try it. I think that Jim Drennen has published on the determination of water in pharmaceutical mixtures and tablets. Best regards, Dave | ||
| Tony Davies (Td) |
Dave, My experience (going back 45 years!! When I used to make Karl Fischer reagent!!!) was that it was not an easy titration and probably not very precise. Of course nowdays people have automatic titrators and they might be quite good. I would still guess that KF would not be as good as the NIR. I would like to see a ban on KF it is not a nice mixture to be putting into the environment. Tony | ||
| Gabi Levin |
Just a quick comment - few years back when I did one of my early on the fluid bed real time NIR moisture measurement in diffuse reflectance through a window in a pharma company we decided to try to compare the LOD with the KF. The NIR spectra were collected every 15 secconds, (100 scans in 4 seconds) and samples were pulled and immediately split into sealed bags. One smaple was used to do the LOD and one sample for KF. The results clearly showed that the error in the KF was larger than that assoicated with LOD. In several cases the KF gave us a moisture value at time X+ 5 minutes higher than at time X, which is of course an error because drying continued through these 5 minutes. For tablets, with moisture in the low percentage, I would say that NIR based on multiple LOD (would recommend oven, with patience untill no loss is observe as compared to the fast IR heaters because in dense tablets the vapors need longer to "travel"to be removed). Assuming none of the ingredients evaporates or sublimes, LOD is a very good method. Thank, Gabi Levin Brimrose | ||
| Erik Skibsted |
Well I agree with you all. KF is certainly not a helpfull reference analysis. I have also used LOD in other cases (online NIR in fluid bed etc.). We are starting this week with a preliminary investigation with NIR of various tablets samples, measured both in reflectance and transmittance. My worries are the different water bands which I might experience i.e. tightly bound water in the core of the tablets vs. less tightly bound water in the surface of the tablets. I have done some studies of the 2 derivatives on the water band around 5200 cm-1, where you can discriminate between the different types of -OH bonding, so I guess I have to look into that again ;-) Erik |