Instrumental Color Measurement: A Method for Judging the Appearance of Tablets

MICHAEL WIRTH Received September 27, 1989, from the Department of Analytical Chemistry, AB Hassle, S-431 83 Mdlndal, Sweden. publication December 11, 1990.

Accepted for

Abstract 0 An instrumental method for the quantification of the color and the discoloration of tablets is presented. The results are not influenced by external factors and are more rapidly accessible compared with visual determination. Two of the measured parameters, lightness (AL') and yellowishness (Ab') were found to reflect the changes in coloration observed in stability tests on white metoprolol tablets. Corre- lation studies between visual judgments and instrumental measurements are presented. The instrumental performance was carefully examined, and the results indicate that the employed instrument gives color parameters in the same range for tablet samples irrespective of whether the examined tablet surface has an engraving on it or not.

The appearance of tablets is one of the characteristics investigated during the stability studies carried out on phar- maceutical formulations.' Deviation from this property is one of the first things that a patient notices. Therefore, it is important that this parameter is correctly quantified during the stability study. The judgment of appearance is often made by visual inspection of the tablets. We have found that such a subjective judgment does not always yield unbiased infor- mation. It tends to be influenced to a great extent by external factors,' such as the type of illumination, the location, time of day, etc.

Tristimulus colorimeters have been used by others in order to measure surface color of tablet^,^ tablet colorants: and color stability of tablet^,^ and to predict color stability of tablets using accelerated test condition^.^ We have replaced the visual judgment of color difference with a photometric measurement using a commercial instrument. The visual inspection of appearance has to account for factors such as the surface structure, cracks in the tablet surface, and swelling due to water uptake. The instrument can be used to yield some quantitative measure of the color change on the surface of tablets due to aging at different storage conditions (type of package, humidity, and temperature), which may be related to possible degradation of the active component. Degradation products can be followed employing chromatographic meth- ods, while the color is investigated by the photometric mea- surement and quantified in terms of three parameters.

Experimental Section Instrument-The measurements were carried out using a com-

mercial instrument from Dr. Lange GmbH (XENO COLOR LS 100). A schematic picture of the instrument is presented in Figure 1. The xenon flashlamp is situated inside a collecting sphere, with holes cut out. One is acting as sample holder, one is holding the end of 16 lightguides for the reference signal, and the last one is holding the end of 16 lightguides for the sample signal. The samples are illuminated with a short flash from the xenon flashlamp, and the reflected light is collected in 16 channels each equipped with an interference filter. The light from the illumination source is collected into 16 reference channels, and the sample signal is divided with the reference signal, thus yielding a reflectance spectrum where noise and intensity fluctuations from the xenon lamp are divided out. This

Tablet Sample

ight

Collecting Sphere

Computer 1 I I

I I Sample

1 I I P I - .

I 16 Fiber Optic Light Guides , - , I , Monochromators t I L J

Reference

Figure 1-Schematic view of the instrument showing the main units and the measuring geometry employed.

instrument measures reflected light with a diffuse reflectance geom- etry, and the spectra can be collected using either a 2" or a 10" spacial angle. Throughout the measurements presented here, the lo" angle was used together with the D65 illumination standard.' The 16 values constructing the reflectance spectrum are then transferred to a microcomputer and transformed to yield values of lightness (L*), reddishness (a*), and yellowishness (b*) in the CIE-LAB colorsys- tem.2.g The color shades corresponding to L*, a*, and b* are presented in Table I.

Samples and Measurements-The examined samples were meto- prolol tablets of different strengths (both Seloken and Seloken ZOC tablets were used). The Seloken tablets are circular and have an engraving and a score on one side, while the other side is smooth. The Seloken ZOC tablets are also circular, but have the engraving and the score on opposite sides. Both tablet types are coated in order to render a white appearance.

Long-time storage during accelerated conditions in hot and humid environments changes the color of the tablets. Reference samples, stored at 13 "C, do not show any sign of discoloration.

Table I-Extreme Values of the Parameters Deflned accordlng to the CIE-LAB Standard and the Correspondlng Colorshades

Corresponding Colorshade Lower Limit Upper Limit Color

Par a m e t e r

L'

a'

b'

0 - Black - 100 White

- 50 - Green - + 50 Red

- 50 - Blue - + 50 Yellow

Journal of Pharmaceutical Sciences I 11 77 Vol. 80, No. 12, December 1991

0022-3549/91/1200- 1 177$02.50/0 0 1991, American Pharmaceutical Association

The color of samples stored in different environments was deter- mined vieually by several persons using samples of the same pro- duction batch stored at 13 “C as a reference. These subjective values are reported using an arbitrary scale of six different orders from “no visible change” (“1”) through “minute visible change” C Y ) , “small visible change” ( “ 3 9 “moderate visible change” (“4‘7, “off-white” (“5”) to “change in color” (“6“).

The same tableta were measured using the instrument. Usually, five tablets from the same batch and storage environment were measured and the average values of the color parameters were reported. In order to control the instrument performance, the m e sample was measured repeatedly. The tablets were removed between each repeated measurement. In order to control the batch homoge- neity several samples from the m e batch were measured, each tablet five times.

Results and Discussion A comparison between the two measured parameters AL*

and Ab* and the visual subjective judgment is shown in Figure 2. As can be seen, samples with AL* values < - 1.0 and Ab* values > 3.0 are usually judged to be colored by the visual judgment. During storage in different environments, no eignificant change in the a* parameter was noticed for white tablets. Therefore, only L* and b* were used as significant parameters. The definition of the color parameters can be found in the In Table I, the limiting values and corresponding colors are presented for the color parameters.

Correlation between visual color judgment and instrumen- tally measured parametera is presented in Figure 3. Samples of different whiteness were measured as well as judged Subjectively by 11 different technicians. The technicians were

0

* cl a

0

n

I

ab * Flgun 2-Instrumentally measured values of AL’ and Ab’ plotted versus each other for 225 different samples (many points obscured by others). wares represent samples which were judged to be acceptable in the subjective color judgment, whereas circles represent samples which were judged to have an off-white color. The dotted box h a s equal limits in AL* and AW, as does the full scale in Figures 4 and 5.

‘“T

a 1

a

0- I

0 a i 0 a I b Instrumental Judgment (AE )

*

Flgure SCorrelation between human and instrumental judgment of color. The color of 22 samples was measured with the instrument, and 11 persons were asked to arrange the same samples in color order ranging from white to yellowish (AE* represents the geometrical average of A r , Aa*, and Ab*). The dotted lines represent the 95% confidence interval, calculated using both instrumental and visual data.

asked to arrange the 22 different samples according to increasing whiteness. Each subjective judgment yielded a color order for the 22 samples. The correct color order, as given by the instrumental measurement, was used to transform the subjective color order to some arbitrary unit which should correlate with the geometrical average of AL*, Aa*, and Ab* (AE*). The data (each point representing one sample judged subjectively by one person) were plotted versus each other and the confidence limit of 95% for the individual values was included.

The possible error introduced upon different positioning of the sample on the instrument can be seen in Figure 4. Here, the same sample was measured repeatedly. Between each measurement the sample (Seloken ZOC 95-mg tablet) was removed from the instrument. No special care was taken to put the tablet back exactly where it had been during the previous measurement. No significant difference in the color parameters L* and b* was detected even when the tablet was placed upside down. One side of the tablet is deeply scored in the middle, while the other has an engraving composed of three letters on it. This indicates that the present measuring geometry is advantageous and well suited for tablet samples. The standard deviation for the color parameters AL* (light- ness) and for Ab* (yellowishness) could be calculated (uAL. = 0.053; uAb. = 0.089).

In Figure 5, the color parameters AL* and Ab* for 28 tablets from the same batch are presented; each one was measured five times and the average values were reported. As the center point, the average value for L* and b* for all 140 measure-

1 178 I Journal of Phannsoeutlcal sciences Vol. 80, No. 12, December 1991

0 . 6 C

A i * A t4 a -0.60 -0.a6 A

0.ee

A& 0.26 0.60

* J M A

a -0.60 -0.a6

A

-0.26

-0.60

Ab * Figure +Instrumentally measured values of AL* and Ab* plotted versus each other for 42 samples. One tablet removed and put back onto the instrument between each measurement was used as the sample.

ments was used. Standard deviations corresponding to the above-mentioned measurements could also be calculated for the batch variations (uAL* = 0.112; uAb* = 0.082). The calculated standard deviations show that the possible errors due to inaccurate placing of the tablets on the instrument are smaller than are the corresponding batch variations.

In Table I1 general instrumental values representing the subjective judgments “5” and “6” are presented for Seloken tablets and Seloken ZOC tablets.

The advantages gained by using an instrument for the color measurement can be summarized as follows: the measure- ment becomes much more reliable and uninfluenced by external factors such as illumination; the measurement yields numbers as a result instead of subjective statements ~1”,ft2~’,“3”,“4”,“5”,tf6”); the sample throughput can be in- creased; and reference samples stored at 13 “C can be checked for color changes due to aging since the results from the zero analysis made immediately after the production can be quantified and stored.

Conclusions An instrumental method for the determination of tablet

color has several advantages compared with the subjective judgment. For examples, the determined parameters become unbiased, and are uninfluenced by external factors, and the sample throughput can be increased. However, the method of instrumental color measurement for tablet samples presented here can never totally replace the subjective measurement because cracks in the surface, swelling of the sample, and spots on the surface will not be detected by the instrument.

l A -0.26t

1 -0.60

ab * Figure 5-Instrumentally measured values of AL“ and Ab’ plotted versus each other for 28 different samples from the same batch. Each sample was measured five times and the average values of the color parameters were calculated.

Table Il-Comparison between Subjective Appearance Judgments and instrumental Values’

Subjective Instrumental Values Judgment A r Ab’

“1 “5” “6’

-0.1-+0.1 <-1.0 <-3.0

-0.1-+0.1 >+3.0 >+5.0

~ ~~~

‘Only the values “l”, “5”, and “6’ could be quantified in terms of instrumental values due to large individual variations in the subjective judgments “2’, “3”, and “4 ’ .

The measuring geometry of the chosen instrument is also advantageous compared with older types of instruments where the results were dependent on the placing of the tablet samples in the instrument. No significant difference in the color parameters was detected for different placings of the oval tablets.

References and Notes 1. U.S. Pharmacopeia, 21st rev.; US. Pharmacopeial Convention:

Rockville, MD, 1985, pp 1231-1232 and 2870. 2. Hunter, R. S. The Measurement ofAppeamnce; Hunter Associates

Laboratory: Fairfax, VA, 1972, 1973. 3. Bogdansky, F. M. J . Phurm. Sci. 1975,64(2), 323429. 4. Vemuri, S.; Taracatac, C.; Skluzacek, R. Drug Dev. Znd. Phurm.

1985,11(1), 207-222. 5. Nyquist, H.; Nicklasson, M. Acta Pharm. Suec. 1984,21,367372. 6. Briickner, F. Kontmlle 1984, Jan 84, 33-35.

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