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Figure 8: Statistical process control chart of 0.1-mg chlorpheniramine maleate content uniformity. The X control chart plots the target label
claim with 15% control limits. UCL is the upper control limit, and LCL is the lower control limit.
Figure 9: Statistical process control chart of 0.5-mg chlorpheniramine maleate content uniformity. The X control chart plots the target label
claim with 15% control limits. UCL is upper control limit, and LCL is lower control limit.
0.575
0.500
0.425
X Control chart
LCL
UCL
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256361:3-column 6/15/07 2:50 PM Page 173
Table III: Content uniformity test results for ten 0.1-mg
chlorpheniramine maleate tablets.
Test level 1
Sample Target Test result*
Percentage of
target
Pass or fail
1 0.100 0.091 91.491 Pass
2 0.100 0.099 98.655 Pass
3 0.100 0.103 103.421 Pass
4 0.100 0.101 101.487 Pass
5 0.100 0.100 99.782 Pass
6 0.100 0.099 98.910 Pass
7 0.100 0.101 101.139 Pass
8 0.100 0.100 99.987 Pass
9 0.100 0.100 99.649 Pass
10 0.100 0.102 101.616 Pass
* Relative standard deviation is 3.2%.
Table IV: Content uniformity test results for ten 0.5-mg
chlorpheniramine maleate (CPM) tablets.
Test level 1
Sample Target Test result*
Percentage of
target
Pass or fail
1 0.500 0.523 104.642 Pass
2 0.500 0.520 104.094 Pass
3 0.500 0.530 106.097 Pass
4 0.500 0.525 104.947 Pass
5 0.500 0.529 105.804 Pass
6 0.500 0.526 105.106 Pass
7 0.500 0.525 104.950 Pass
8 0.500 0.529 105.877 Pass
9 0.500 0.524 104.717 Pass
10 0.500 0.531 106.248 Pass
* Relative standard deviation is 0.7%.
Conclusion
Near-infrared assay and content uniformity of tablets
provides a fast, accurate means of monitoring tablets for
production that is in step with the US Food and Drug
Administrations process analytical technology initiative.
The data show promising results that could relieve labora-
tory workload of high-performance liquid chromatography
analysis and bring analysis closer to real time for process
monitoring. Ten tablets can be analyzed in 5 min. The
software provided with the instrument is used for data
collection and developing prediction models. The software
also provides dedicated routine analysis methods for
content-uniformity analysis yielding results in percent label
claim and percent relative standard deviation as well as
passfail indication.
The average repeatability result for five different tablets
measured 10 times of nominal 0.1-mg chlorpheniramine
maleate was 0.0039 with a bias of 0.0018. The repeatability
result for 5 tablets of 0.5 mg chlorpheniramine maleate was
0.0055 with a bias of 0.0057. Better precision and accuracy
can be achieved with a training set designed with smaller
increments around the target label claim.
References
1. Handbook of Near-Infrared Analysis, D.A. Burns and E.W.
Ciuczak, Eds.(Marcel Dekker, Inc., New York, NY, 2001).
2. US Food and Drug Administration, Guidance for Industry: PAT
A Framework for Innovative Pharmaceutical Development,
Manufacturing, and Quality Assurance, (FDA,Rockville, MD, Sept.
2004).
3. P.J. Larkin, E. Fruhling, and C. Longfellow, Comparison of
Fourier Transform (FT) and Grating Based NIR Spectrometers
for Content Uniformity of Pharmaceutical Solid Dosage Forms,
Am. Pharm. Review. 9 (6), 102109 (2006).
4. Q. Ji et al., Rapid Content Uniformity Determination of Low-
Dose TCH 346 Tablets by NIR, Am. Pharm. Review 9 (5), 2026
(2006).
5. R. Kramer, Chemometric Techniques for Quantitative Analysis,
(Marcel Dekker, Inc., New York, NY, 1998).
6. K.R. Beebe, R.J. Pell, and M.B. Seasholtz, Chemometrics: A Prac-
tical Guide, (John Wiley & Sons, Hoboken, NJ, 1998). PT
3.0
2.6
2.2
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-0.2
-0.6
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-1.0 -0.6 -0.2 0.2 0.6 1.0 1.4 1.8 2.2 2.6 3.0
HPLC CPM mg
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Calibration Set: NIR Predicted vs Lab Data
Figure 10 (Left): Calibration set. Predicted
versus high-performance liquid
chromatography (HPLC). CPM is
chlorpheniramine maleate.
2.0
1.8
1.6
1.4
1.2
1.0
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-1.0 -0.7 -0.4 -0.1 0.2 0.5 0.8 1.1 1.4 1.7 2.0
HPLC CPM mg
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Validation Set: NIR Predicted vs Lab Data
Figure 11 (Right): Validation set. One tablet
was left out of the calibration set at each
level for production-model validation.
CPM is chlorpheniramine maleate.
Reprinted from PHARMACEUTICAL TECHNOLOGY, April 2007 Printed in U.S.A.
256361:3-column 6/15/07 2:51 PM Page 174
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