Journal of Drug Delivery Science and Technology 37 (2017) 141e146

Contents lists available at ScienceDirect

Journal of Drug Delivery Science and Technology

journal homepage: www.elsevier.com/locate/jddst

Can the surface color of pharmaceutical tablets be used as a unique

product identifier?
Turki Al Hagbani a, Michael A. Veronin c, Mohammad T. Nutan d, Sami Nazzal a, b, *
a
College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA
b
College of Pharmacy, Taipei Medical University, Taipei, Taiwan
c
Department of Pharmaceutical Sciences, College of Pharmacy, University of Texas at Tyler, Tyler, TX, USA
d
Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University Health Science Center, Kingsville, TX, USA

a r t i c l e i n f o a b s t r a c t

Article history: There is an ongoing need for new or alternate approaches to distinguish between innovative pharma-
Received 2 November 2016 ceutical products from counterfeit or visually similar medicines. In this study we hypothesized that the
Received in revised form quantitative measurement of the color on the surface of tablets, using the CIE L*a*b* color space, might be
14 December 2016
used to accomplish this objective. Several proof-of-concept studies were carried out in which ColorQuest
Accepted 25 December 2016
Available online 27 December 2016
XE colorimeter was used to measure the tristimulus L*, a*, and b* color values from the surface of white
and colored pharmaceutical tablets. Tristimulus values represent the red to green scale (a*); the blue to
yellow scale (b*); and the lightness extreme (L*). In a preliminary experiment, we demonstrated that
Keywords:
Counterfeit
each tablet from 54 products have a unique L*a*b* parameter within the 3D tristimulus color space. The
Tristimulus colorimeter utility of colorimetry in identifying imitator products was then demonstrated by comparing the color
Colorimetry signatures of the innovator Viagra® tablets with imitator sildenafil tablets, which were procured from
Quality control nine different online suppliers. While not an infallible technique, data in this study demonstrated that
Identifier colorimetry might be used as a simple technique to identify innovative products and potentially alleviate
Tablet the pandemic of counterfeit medicines, especially in areas around the world where counterfeiting is
Surface color prevalent while sophisticated tools for their detection are not readily available.
© 2016 Elsevier B.V. All rights reserved.

1. Introduction
The distribution of counterfeit medicines and drug products is a
major health concern, especially in developing countries with poor
regulatory oversight [1]. Drug products that are identified as
counterfeit are those that are ineffective, substandard, or illegal
reproductions of innovator products. Counterfeiting therefore can
apply to both branded and generic products and may include
products with the correct ingredients, without active ingredients,
with insufficient active ingredients, or with fake packaging and
inadequate dosages [2].
To deter counterfeiting, drug products, and particularly tablets,
have been manufactured with unique and identifiable codes and
shapes. Serialization approach, for example, will be a requirement
* Corresponding author. Department of Basic Pharmaceutical Sciences, School of
Pharmacy, College of Health and Pharmaceutical Sciences, University of Louisiana at
Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
E-mail address: nazzal@ulm.edu (S. Nazzal).
for all licensed product sold in the US from November 2017, and at
the beginning of 2019 serialization will be a legal requirement in
Europe for licensed drug products. In addition to deterring coun-
terfeiting, this approach was devised to prevent reimbursement
fraud and theft throughout the supply chain. The serialization
approach however has created a real challenge for the pharma-
ceutical industry due to the complexity of performing serialization
in multiple production lines in multiple locations [3]. Unfortu-
nately, hallmarks or features are relatively easy to mimic. As a
result, many of the pharmaceutical tablets cannot be readily
distinguished from a genuine product by a casual observer or naked
eye. Therefore, there is an ongoing effort to use alternative identi-
fication hallmarks that are difficult to emulate and/or to develop
rapid and inexpensive techniques that can be operated by a layman
person to identify products, and, if possible, to distinguish genuine
products from counterfeit medicines.
In this study we present data that support the idea that
quantitative measurement of the color on the surface of tablets
with a colorimeter could be used as a unique product identifier.
Colorimetry is simply “the measurement of color” by a

http://dx.doi.org/10.1016/j.jddst.2016.12.010
1773-2247/© 2016 Elsevier B.V. All rights reserved.
142 T. Al Hagbani et al. / Journal of Drug Delivery Science and Technology 37 (2017) 141e146
colorimeter to identify an unknown color in reference to known
colors [4]. Colorimeters measure the reflection or transmission
properties of a subject as a function of wavelength that occupy
the Z, X and Y planes in the CIE (international commission on
illumination) three-dimensional uniform color space (Fig. 1).
Three models, RGB (red, green, and black), CMYK (cyan, magneta,
yellow, and key), and Lab, are commonly used to express color
within the XYZ plane as a number. Lab color model is based on
the opponent color theory [5], which states that, during visual
perception, cone photoreceptors in the eye are linked together to
form there opposing color pairs blue/yellow, red/green, and
black/white [6]. When quantified by a colorimeter, these color
pairs are expressed as tristimulus L*, a*, and b* values, where a*
represents a value in the red to green scale, b* represents a value
in the blue to yellow scale, and L* that measures lightness ex-
tremes, which ranges from a maximum value of 100 representing
a perfect reflecting diffuser (white) and a minimum of zero
representing black, a perfect absorber or non-reflecting object.
The asterisks (*) in the Lab color space indicates that subsequent
transformations of color data into coordinates are based on the
mathematical models developed by CIE in 1976 as opposed to the
models developed by Hunter in 1948. The only difference be-
tween the two is that CIE coordinates are calculated based on a
cube root transformation of the color data, while the Hunter
coordinates are based on a square root transformation of the data
[6]. In the present study, Lab model was used to measure the
tristimulus L*, a*, and b* values. Using the Lab model is advan-
tageous because it is device independence and includes all
perceivable colors that approximate human vision. Therefore, its
gamut exceeds those of the RGB model that has been used in
several studies where color is constructed from the combination
of the red, green and blue colors using a video spectral
comparator (VSC) [7].
Historically, colorimetry has been used by the paint industry
and to monitor the quality and stability of food and pharmaceutical
products [8]. Colorimetry, for example, has been used to determine
lycopene content and to establish a correlation between color and
tomato quality and nutrition [9]. In more pertinent applications,
several studies have demonstrated the utility of colorimetry in the
pharmaceutical industry as a tool to monitor the quality of excipi-
ents and to measure the discoloration kinetics of tablets during
stability testing [7,10e13].
Data presented in the present study suggests that the surface
color of tablet as measured by a colorimeter may be used as
unique product identifiers. The tristimulus L*a*b* color parame-
ters of manufactured tablets measured prior to packaging could
Fig. 1. CIE L*a*b* color space (courtesy of BYK Gardner, Columbia, MD).
be recorded for each lot and used as a primary or supplementary
identification codes to distinguish the product from counterfeit
or generic tablet of visually similar shape and color. As high-
lighted in the subsequent sections, the authors recognize that
colorimetry is not a fool proof technique, especially when one
considers the effect of time, homogeneity and stability on color.
These factors are important but are beyond the scope of this
discussion. Furthermore, it should be recognized that colorimetry
is a quantitative measure of the reflected spectrum and is not
specific or selective for an analyte. Therefore, it should not sub-
stitute for chromatographic and spectroscopic techniques, such
as nuclear magnetic resonance (NMR), Fourier transform infrared
(FT-IR), near infrared (NIR), mass spectroscopy (MS), and Raman
spectroscopy that have been developed to aid regulatory agencies
in identifying authentic or counterfeit products chemically
[14e16].
2. Materials and methods
A HunterLab ColorQuest XE tristimulus colorimeter (Hunter As-
sociates Laboratory Inc., Reston, VA) was used to measure the
tristimulus L*, a*, and b* values from the surface of tablet samples.
Tablet samples were obtained from either commercial suppliers or
purchased from online retailers as previously reported [17]. Mea-
surement parameters were standardized to daylight illumination
and 10-degree standard observer (D65/10). Spring loaded sample
clamp was used to hold the specimen at the reflectance port with a
0.375-inch view area. A magnetic white ceramic disk on the face of
the clamp ensured a consistent white background during measure-
ments. One measurement from six tablets was performed to calcu-
late the average and standard deviation of the L*, a*, and b* values,
which were then used to calculate chroma, color intensity, whiteness
index, and total color difference based on the difference between the
standard (D65/10) and sample's L*, a*, and b* values [18].
Chroma (C*ab) measures the color degree of an area viewed to the
brightness of an object and can be mathematically estimated from
the following relationship:
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
 
C*ab ¼ a*2 þ b*2 (1)
Color intensity (CI*) measures the difference in location be-
tween a point and a central axis in the Lab color space [13]. CI* can
be calculated by:
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
CI* ¼
2
ð100  L* Þ þ a*2 þ b*2 (2)
Whiteness index (WI E313) measures the degree of departure of
the object from a perfect white [19] and can be calculated as
follows.
WI E313 ¼ Y þ 800ðxn  xÞ þ 1700ðyn  yÞ (3)
x and y are the chromaticity coordinates of the specimen where:
X Y
x¼ and y ¼
XþY þZ xþyþz
xn and yn are the chromaticity coordinates for the D65/10 standard,
where xn ¼ 0.3138 and yn ¼ 0.3310.
Total color difference (DE*or dE* ) between any two points in the
color space, is estimated by applying the following relationship:
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
DE* ¼ DL*2 þ Da*2 þ Db*2 (4)
 T. Al Hagbani et al. / Journal of Drug Delivery Science and Technology 37 (2017) 141e146 143

Fig. 2. The L*, a* and b* values of white tablets (A) and colored (nonwhite) tablets (B) within the Z, X and Y 3D CIE (international commission on illumination) color space.
144 T. Al Hagbani et al. / Journal of Drug Delivery Science and Technology 37 (2017) 141e146

Table 1
The surface color measurements from white, visually identical tablets (when excluding surface markings) of similar dimensions from four different products. Color was
measured from the flat non-marked surface of the tablets.

Color parameter (average ± SD)

L* a* b* WI E313 dE* C*ab CI*

A 100.1 (0.2) 0.3 (0.06) 5.0 (0.2) 80.9 (1.3) 101.1 (0.2) 5.0 (0.2) 5.1 (0.2)

B 100.4 (0.3) 0.2 (0.23) 3.4 (0.1) 86.5 (0.8) 100.4 (0.3) 3.4 (0.1) 3.4 (0.2)

C 98.9 (0.3) 0.4 (0.07) 0.7 (0.1) 93.9 (0.8) 98.9 (0.3) 0.84 (0.1) 1.4 (0.2)

D 99.3 (0.1) 0.2 (0.02) 0.7 (0.1) 95.3 (0.3) 99.3 (0.1) 0.72 (0.1) 0.1 (0.07)

P-value <0.005 <0.005 <0.005 <0.005 <0.005 <0.005 <0.005

Product A: Verapamil Hydrochloride, 125 mg, Lot # 1K4721, Mylan Inc.

Product B: Quinidine Gluconate Extended Release, 324 mg, Lot # 56808, URL Pharma Inc.
Product C: Simvastatin, 40 mg, Lot # 1692934, Ranbaxy Laboratories Inc.
Product D: Tolbutamide, 500 mg, Lot # 1K0822, Mylan Inc.

Where were generated, one representing the color variations of 27 white

DL* ¼ L*Sample  L*Standard
Da* ¼ a*Sample  a*Standard
Db* ¼ b*Sample  b*Standard
3. Results and discussion
Several sets of studies were carried out to demonstrate the
utility of colorimetry in identifying tablets as discussed in the
introduction. Initially, the surface color of round tablets, both
coated and uncoated, from 54 different commercial products was
measured with the ColorQuest XE colorimeter. Tablets from these
products varied in their dimensions, active ingredient, color, and
manufacturer. The objectives of this preliminary study were
twofold; to illustrate that tablets differ in their color dimensions
and to establish the hypothesis that tablets from different products
could be distinguished by their surface color based on Lab color
model. To satisfy this hypothesis, the surface color of six fresh
tablets from the same batch of each of the 54 product was
measured and the average L*, a*, and b* values were plotted within
a 3D CIE color space (Fig. 2). After collecting the data, two plots
tablets (Fig. 2A) and the other representing the variations in the
surface color of 27 colored (nonwhite) tablets (Fig. 2B). The scat-
tering of the surface color measurements within the 3D color space
(Fig. 2) suggests that tablets from different products could poten-
tially be identified by their surface color. While visible differences
in surface color could be readily used to differentiate between
colored (nonwhite) tablets, Fig. 2A shows that by utilizing a color-
imeter it is also possible to identify the unique color signatures of
white tablets, which otherwise cannot be differentiated by the
naked eye.
To confirm the ability of the colorimetric method to differentiate
between visually similar tablets, the surface color of white, visually
identical, tablets of similar dimensions from four different com-
mercial products was measured (Table 1). The average L*, a*, b*, WI
E313, dE*, C*ab and CI* values from six independent readings from
each of the four products were recorded (Table 1) and the analysis
of variance (ANOVA) was applied to analyze the differences in the
mean between the four tablet groups. Significant differences (P-
value < 0.005) were found between the groups in their L*, a*, and b*
values as well as in the dE*, CI* and C*ab values (Table 1). Quantifiable
differences between the groups satisfied our hypothesis that color
parameters measured from the surface of tablets might be used to
distinguish between visually identical products. Colorimetry is not
a fool-proof technique. It has its drawbacks, such as its sensitivity to
surface contamination, homogeneity of the surface, handling, and
the possibility of color change with time [20]. Another drawback of
 T. Al Hagbani et al. / Journal of Drug Delivery Science and Technology 37 (2017) 141e146 145

Table 2
Characteristics of Sildenafil tablet samples and their colorimetric parameters (dE*, C*ab and CI*).

No Product name (source) Manufacturer dE* C*ab CI* Image

1 Viagra Innovator Pfizer, USA 60.32 21.71 36.49

product-Pfizer purchased from Harrell's Pharmacy (Kingsville, TX) (0.18) (0.20) (0.26)

2 Sildigra purchased from Quality-Online-Generics DRJLPL, Nagpur, India 46.53 25.66 49.87
http://review-pharmacy.net/Quality-Online-Generics.com.htm. (0.63) (0.76) (0.28)

3 Viprogra-100 purchased from Official Canadian Pharmacy Vipro Life Science, Ahmedabad, India 47.82 37.26 57.29
http://www.ednf.org/index.php?option¼com_ (0.24) (1.72) (0.94)
content&task¼view&id¼1204&Itemid¼88888988

4 Aurogra® 100 purchased from PrescriptionRxPharma.com Aurochem Labs, Mumbai, India 49.77 23.20 45.54
http://www.prescriptionrxpharma.com (0.05) (0.56) (0.53)

5 Kamagra purchased from Generic4u Ajanta Pharma, Mumbai, India 46.58 38.58 60.21
http://www.generic4u.com (0.16) (1.24) (1.03)

6 Sildenafil Tablets 100 mg no specific brand purchased NA, Mumbai, India 47.45 23.21 47.58
from XL Pharmacy (0.35) (0.86) (1.03)
http://www.xlpharmacy.com

7 Mygra-100 purchased from My-xlpharmacy.com Jpee Drugs, Mumbai, India 54.14 25.90 43.77
http://www.my-xlpharmacy.com (0.26) (0.37) (0.59)

8 Intagra purchased from Mexican Online Pharmacy G.S. Pharmaceuticals, Pvt., Ltd, 41.52 23.28 53.17
http://www.mexicanonlinepharmacy.net. Ahmedabad, India (0.02) (0.36) (0.15)

9 Perfopil-100 purchased from ShopPillRx Aurochem Laboratories, Mumbai, 49.57 21.62 44.81
http://ww2.shoppillrx.com. India (0.09) (0.72) (0.63)

10 Malegra-100 purchased from Online Pharmacy VG Sunrise Remedies, Mumbai, India 48.26 14.01 41.94
http://onlinepharmacy.vg (0.25) (0.45) (0.40)

P-value <0.005 <0.005 <0.005

this technique is that it does not allow for direct measurement of
color through a blister pack or bottle, which makes it a semi-
destructive technique. The impact of these variables on color
measurements was not investigated and was beyond the scope of
this study. Colorimetry, however, represents a possible and viable
screening technique that could be readily used by a non-expert on
the field to examine products for possible counterfeiting.
To provide a practical example to the utility of colorimetry,
ColorQuest XE colorimeter was used to measure and distinguish
between the innovator sildenafil tablets (Viagra®, Pfizer) from
generic/imitator sildenafil tablets. Nine blister strips or pack of
imitator sildenafil tablets were obtained from internet pharmacies
and other sources on the web whereas the reference Viagra® was
obtained by prescription from Harrel's Kingsville Pharmacy as
previously reported [17]. Internet pharmacies are becoming a major
access point for illegitimate sale of prescription drugs and coun-
terfeit medicines internationally [21].
As in previous experiments, the colorimetric parameters of
the generic/imitator sildenafil tablets and the innovator product
(Viagra®) were measured and subjected to ANOVA test
(Table 2). Significant differences (P-value < 0.005) were found
between the different products in their L*, a*, and b* values as
well as in their WI E313, dE*, CI* and C*ab values. Only dE*,
CI*and C*ab data, however, were provided in Table 2. Since there
were significant differences in the surface color parameters
between the tablets, it could be concluded that surface color
measurements could have been readily used to distinguish
between the imitator and innovator sildenafil tablets without
the need for specialized analytical testing tools. It is worth
noting that the majority of the tablets that were tested in this
study had an equivalent amount of the active ingredient but
varied in their level of impurities [17].
146 T. Al Hagbani et al. / Journal of Drug Delivery Science and Technology 37 (2017) 141e146
4. Conclusion
Tablets from different products have unique color dimensions
within the CIE color space. Therefore, the surface color of tablets
might be used as a unique identifier to distinguish genuine prod-
ucts from generic or counterfeit medicines, especially those that
cannot be easily differentiated from the innovator product by the
naked eye. The authors of this article recommend measuring and
documenting the L*, a*, b* values for each batch of tablet products
by their respective manufacturer to provide a measurable qualifier
to be used, when needed, by a relevant agency to determine
whether a product is authentic or not. Efforts could also be made to
manufacture tablets with a unique color combination that is diffi-
cult to emulate. Nonetheless, and as stated above, colorimetry is not
a fool proof technique, yet it presents a simple inexpensive tech-
nique that might help alleviate the pandemic of counterfeit medi-
cines, especially in areas around the world where counterfeiting is
prevalent while sophisticated tools for their detection are not
readily available.
Conflict of interest
The authors declare no conflict of interest.
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