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Chris Hollick
Posted on Friday, May 13, 2005 - 4:32 am:   

My work involves developing quantitative NIR calibrations for the assay of actives in pharmaceutical products, mainly solid dose forms. These are used instead of the primary method for product / intermediate release. HPLC is generally used as the registered reference method and we look to replace this as a method of product release with NIR.

The question I have been asked is:

"What about degradation products. If this is on the release specification, can NIR detect the degs?"

My general feeling and experience tells me, no, it can't. These are usually at too low a level to detect and quantify. I am just wondering if I'm wrong. Has anybody had any experience or success with detecting degredation products by NIR to the point that regulatory organisations would accept your work?

Or has anybody found a way of working around this? Maybe just registering an HPLC method for the degs and the NIR method as an alternative for the main assay? Has this been done by anybody?

Also, has anybody had any experience or success with making an NIR calibration for tablet dissolution? I have not yet tried this but it is certainlty something I'm going to have a look at.

Thanks

Chris
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J.J. Moes
Posted on Friday, May 13, 2005 - 5:57 am:   

Chris,

Maybe these articles will be helpful for your dissolution study:

Spectrophotometric prediction of the dissolution rate of carbamazepine tablets Zannikosm, P.; Li, W.; Drennen, J.; Lodder, R Pharm. Res.; 1991 Vol. 8, p974-978, 5p

Prediction of Drug Dissolution from Tablets Using FNear‐Infrared Diffuse Reflectance Spectroscopy as a Nondestructive Method M. Donoso and Evone S. Ghaly Pharmaceutical Development and Technology; Volume 9, Number 3 / 2004; 247 - 263


Dissolution testing by nir spectroscopy: A comparison between diffuse reflectance and transmittance measurements Russell F, Ulmschneider M, Leuenberger H EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 23: S50-S51 Suppl. 1, OCT 2004

Non-destructive Dissolution Testing Correlation Kuny T., Schatz C., Ulmschneider M., Marrer S., Leuenberger H. Dissolution technologies 10 (1), 2003, 22-28


kind regards,

Johannes Moes
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Gabi Levin
Posted on Friday, May 13, 2005 - 8:28 am:   

I think that what Chris is talking about is not the dissolution determination by NIR but the concern general to the industry that you have an active, pack it in a tablet, and declare that it is good for X years. Some compounds tend to "spontaneously" break down into two or more molecules reffered to as "degradation products".

These are of prime concern as they could be toxic, carcinogenic and what not.

The concern is usually investigated during the trials preceding FDA approval of a new drug. Much less concern exists for drugs already approved and established in the market.

Assuming I am reading you correctly, then I think that you are right Chris about the lower applicability of NIR to the degradation products.

However, the applicability will be influenced by the following:

1. The concentration of the active in the product. Tablets or capsules with active above 30 to 40% could produce (which is very bad news anyway) high enough levels of degradation products to be detected by NIR.
2. It depends on the goal - if the goal is to detect such problem, then you may collect spectra from tablets on day 1, and continue at certain intervals and if there is non existent change over time in active content and spectra, you can deduce, but may still need to run few HPLC's that there was no degradation. If you see spectral changes, and content is down, then you can almost absolutely be sure there was degradation.

In general, NIR will not be a sharp enough tool to confirm that there is no degradation, but can be to confirm that there is degradation, but then, it is a little late any way.

I hope this is of any help.


Gabi Levin
Brimrose Corp.
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Chris Hollick
Posted on Monday, May 16, 2005 - 4:36 am:   

Johannes, Gabi

Thanks for that. Actually you're both correct, I should maybe have put this as 2 posts.

The first and main issue I have is about the degradation of drug substances/products, which your input is very useful Gabi. Thanks for that. I also want to know if anybody has used NIR for such low level quantitative work. Or how others have got around the issue of degs with the drug licensing authorities. If at all.

The second is about creating an NIR model applicable for tablet dissolution. For which I currently have a bit of knowledge, but not much. Just enough to annoy me, and I want to find out more. This is currently secondary on my list of things to do. But these texts look like what I'm after Johannes so thank-you for those.

Thank-you both for your help.

Chris

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