Kemper MS, Magnuson EJ, Lowry SR, McCarthy WJ, Aksornkoae N, Watts DC, Johnson JR and Shukla AJ Use of FT-NIR Transmission Spectroscopy for the Quantitative Analysis of an Active Ingredient in a Translucent Pharmaceutical Topical Gel Formulation AAPS PharmSci 2001;
3
(3)
article 23
(https://www.pharmsci.org/scientificjournals/pharmsci/journal/01_23.html).
Figures and Tables
Table 1.
Composition of Carbopol Gel Formulations
|
Drug (Ketoprofen)
|
Triethanolamine
|
Carbopol 980
|
Water
|
Propylene Glycol
| |
% (wt/wt)
|
Grams
|
% (wt/wt)
|
Grams
|
% (wt/wt)
|
Grams
|
% (wt/wt)
|
Grams
|
% (wt/wt)
|
Grams
| |
0
|
0
|
8
|
2
|
1
|
0.25
|
45.5
|
11.375
|
45.5
|
11.375
| |
1
|
0.25
|
8
|
2
|
1
|
0.25
|
45.0
|
11.250
|
45.0
|
11.250
| |
2
|
0.50
|
8
|
2
|
1
|
0.25
|
44.5
|
11.125
|
44.5
|
11.125
| |
4
|
1.00
|
8
|
2
|
1
|
0.25
|
43.5
|
10.875
|
43.5
|
10.875
| |
6
|
1.50
|
8
|
2
|
1
|
0.25
|
42.5
|
10.625
|
42.5
|
10.625
| |
8
|
2.00
|
8
|
2
|
1
|
0.25
|
41.5
|
10.375
|
41.5
|
10.375
|
Figure 1.Structures of compounds in gel formulations.
Figure 2.Structure of Carbopol in the presence of triethanolamine.
Figure 3.Transmission experiment on the Antaris Fourier transform near-infrared instrument.
Table 2.
Data Collection Parameters Used
|
Mode of Measurement
|
Transmittance
| |
Spectral Range
|
4000 cm-1 to 10 000 cm-1
| |
Resolution
|
4 cm-1
| |
Coaveraged Scans
|
64
| |
Data Collection Time
|
47 seconds
| |
Apodization
|
Norton-Beer medium
| |
Detector
|
InGaAs*
|
* Denotes Indium Gallium Arsenide detector
Figure 4.Unprocessed Fourier transform near-infrared spectrum for ketoprofen raw material.
Figure 5.Full-range second derivative Fourier transform near-infrared calibration spectra.
Table 3.
Results of Various Calibration Models for Topical Gel Formulations
|
Type of Calibration
|
Type of Derivative
|
Derivative Segment
|
MSC
|
Details
|
Correlation Coefficient (R Value)
|
RMSEC (%)
| |
SMLR
|
Norris
|
25
|
No
|
8792 cm-1
|
0.9996
|
0.0775
| |
SMLR
|
Norris
|
15
|
No
|
8798 cm-1
|
0.9996
|
0.0836
| |
SMLR
|
Norris
|
5
|
No
|
8805 cm-1
|
0.9975
|
0.200
| |
SMLR
|
S-G*
|
25
|
No
|
8776 cm-1
|
0.9998
|
0.0616
| |
SMLR
|
S-G*
|
15
|
No
|
8780 cm-1
|
0.9987
|
0.141
| |
SMLR
|
S-G*
|
7
|
No
|
8830 cm-1
|
0.9844
|
0.495
| |
SMLR
|
S-G*
|
25
|
Yes
|
8776 cm-1
|
0.9995
|
0.0851
| |
SMLR
|
Norris
|
25
|
Yes
|
8776 cm-1
|
0.9994
|
0.0955
| |
PLS
|
None
|
None
|
Yes
|
3 factors; 7500-9500 cm-1
|
0.9929
|
0.335
| |
PLS
|
S-G*
|
25
|
No
|
2 factors; 7500-9500 cm-1
|
0.9994
|
0.0948
| |
PLS
|
Norris
|
25
|
No
|
2 factors; 7500-9500 cm-1
|
0.9995
|
0.0906
|
*S-G indicates Savitzky-Golay second derivative using a third-order polynomial.
MSC = multiplicative scatter correction; RMSEC = root mean squared error of calibration; SMLR = stepwise multiple linear regression; PLS = partial least squares.
Figure 6.Expanded overlay for the averaged second derivative spectra of the area used for calibration. R indicates correlation coefficient; RMSEC, root mean squared error of calibration; RESECV, root mean squared error of cross validation; SMLR, stepwise multiple linear regression.
Figure 7.Calibration curve for ketoprofen content of gels.
Table 4.
Predicted Ketoprofen Composition of Carbopol Gel Formulations
|
Actual Ketoprofen Content (%)
|
Predicted Ketoprofen Content (%)
|
Difference Between Actual and Predicted Ketoprofen Content (%)
| |
1.00
|
1.00
|
0
| |
4.00
|
4.02
|
0.50
| |
6.00
|
5.98
|
-0.33
|
| 
