ArticlePDF Available

Radiosterilization of Fluoroquinolones and Cephalosporins: Assessment of Radiation Damage on Antibiotics by Changes in Optical Property and Colorimetric Parameters

Authors:
  • LNJN NICFS Delhi Campus of National Forensic Science University

Abstract and Figures

A most common problem encountered in radiosterilization of solid drugs is discoloration or yellowing. By pharmacopoeia method, discoloration can be assessed by measuring absorbance of solutions of irradiated solid samples at 450 nm. We propose to evaluate discoloration of solid samples directly by recording their diffuse reflectance spectra. Further, the reflectance spectrum is used to compute various color parameters: CIE XYZ tristimulus value, CIE Lab, DeltaE*(ab) (color difference), yellowness index (YI), dominant wavelength, and excitation purity by CIE method. The investigation of difference reflectance spectra and color parameters revealed that for fluoroquinolones, e-beam was more damaging than gamma radiation, whereas for cephalosporins, trend was reversed. The quantum of discoloration with gamma radiation and e-beam is found to be nearly equal when assessed by pharmacopeia method, and it is therefore inadequate to assess small color differences. The color parameters DeltaE*(ab) and DeltaYI are found to be reliable indicators of discoloration. The tolerance limits proposed in terms of DeltaE*(ab) and DeltaYI are +/-2 and +/-10 U, respectively. The dominant wavelength for all compounds has shifted to higher values indicating change in hue but defining color tolerance limit with this parameter requires adjunct excitation purity value.
Content may be subject to copyright.
Research Article
Radiosterilization of Fluoroquinolones and Cephalosporins: Assessment
of Radiation Damage on Antibiotics by Changes in Optical Property
and Colorimetric Parameters
Babita Singh,
1,2,3
D. V. Parwate,
1
and S. K. Shukla
2
Received 28 June 2008; accepted 26 November 2008; published online 15 January 2009
Abstract. A most common problem encountered in radiosterilization of solid drugs is discoloration or
yellowing. By pharmacopoeia method, discoloration can be assessed by measuring absorbance of
solutions of irradiated solid samples at 450 nm. We propose to evaluate discoloration of solid samples
directly by recording their diffuse reflectance spectra. Further, the reflectance spectrum is used to
compute various color parameters: CIE XYZ tristimulus value, CIE Lab, $E*
ab (color difference),
yellowness index (YI), dominant wavelength, and excitation purity by CIE method. The
investigation of difference reflectance spectra and color parameters revealed that for
fluoroquinolones, e-beam was more damaging than gamma radiation, whereas for
cephalosporins, trend was reversed. The quantum of discoloration with gamma radiation
and e-beam is found to be nearly equal when assessed by pharmacopeia method, and it is
therefore inadequate to assess small color differences. The color parameters $E
ab and ΔYI
are found to be reliable indicators of discoloration. The tolerance limits proposed in terms of
$E
ab and ΔYI are ±2 and ±10 U, respectively. The dominant wavelength for all compounds
has shifted to higher values indicating change in hue but defining color tolerance limit with
this parameter requires adjunct excitation purity value.
KEY WORDS: cephalosporin; color difference; fluoroquinolone; radiosterilization; yellowness index.
INTRODUCTION
The sterilization of antibiotics is essential because any
bio-burden may decrease potency of drug and reduce its shelf
life. Most antibiotics are heat sensitive, and therefore,
according to European Agency for the Evaluation of Medicinal
Products (EMEA), decision tree can be sterilized by isother-
mal techniques, namely, radiation sterilization or membrane
filtration (1). In EMEA decision tree, sterilization with high-
energy ionizing radiation (gamma and e-beam) is preferred
over membrane filtration because the former is a terminal
sterilization technique, and unlike the latter, does not require
aseptic handling after sterilization. Besides this, products
shape and physical dimensions require less consideration due
to high penetration ability of ionizing radiation. On the other
hand, radiation induces free radical formation and causes
radiolysis of active ingredient that may result in formation of
toxic compounds in small amounts (2). Also, a most common
problem encountered and reported in case of radiation
sterilization is the yellowing or discoloration of the drug
preparation due to radiolytic products formed (37). The
yellowing sometimes may be perceptible, and it may pose
limitation due to aesthetic unacceptability. In literature, the
discoloration was reported to be assessed by measuring
absorbance of drug solution at 450 nm (3) or studying UV-
visible spectrum (46) or diffuse reflectance spectrum (7). In
British Pharmacopoeia, two methods are described for deter-
mination of color of drug sample (a) by visual comparison of
drug solution with color standards that are combinations of
FeCl
3
, CoCl
2
, and CuSO
4
(brownyellowred color spectrum)
or (b) by measuring absorbance of drug solution of known
concentration at 450 nm (8).
Our objective is to study the effect of high-energy
ionizing radiation (gamma and e-beam) on antibiotics by
investigating optical properties of solid antibiotics, evaluate
discoloration using device-independent color parameters, and
propose color tolerance limit for irradiated solid drugs based
on color parameters. The color analysis of solid drugs was
1530-9932/09/0100-0034/0 #2009 American Association of Pharmaceutical Scientists 34
AAPS PharmSciTech, Vol. 10, No. 1, March 2009 (#2009)
DOI: 10.1208/s12249-008-9177-y
1
Department of Chemistry, RTM Nagpur University, Nagpur Uni-
versity Campus, Amravati Road, Nagpur, India 440033.
2
Central Forensic Science Laboratory, Ramanthapur, Hyderabad,
India 500013.
3
To whom correspondence should be addressed. (e-mail: singh
bab2001@rediffmail.com)
ABBREVIATIONS: EMEA, European Agency for the Evaluation
of Medicinal Products; CIE, Commission Internationale de
lEclairage; CD, Cefdinir; CX, Cefixime; CU, Cefuroxime axetil; CP,
Cefpodoxime proxetil; NFX, Norfloxacin; GFX, Gatifloxacin; SPX,
Sparfloxacin; DIN, Official German Standard Color System.
done by standard procedures of Commission Internationale
de lEclairage(CIE). The colorimetry has been extensively
reported to be used for color analysis of pigments (9), image
processing (10), and polymers (11), but its utility for color
analysis of drugs has not been reported.
This study was performed on solid drugs belonging to
cephalosporin and fluoroquinolone antibiotic classes. These
are widely prescribed broad-spectrum antibiotics. The com-
pounds selected from cephalosporin class are cefdinir (CD),
cefuroxime axetil (CU), cefpodoxime proxetil (CP), and
cefixime (CX); and from fluoroquinolone class are norfloxacin
(NFX), gatifloxacin (GFX), sparfloxacin (SPX).
MATERIALS AND METHODS
Samples
The working standards of NFX, GFX, SPX, and CD
were provided by Lupin Pharmaceuticals, India. CU, CP, and
CX were from Orchid Healthcare, India. The samples were
used as received from the manufacturer.
Materials
BaSO
4
and NaOH used were of AR grade (Merck,
India). All solutions were prepared in doubly distilled water.
Irradiation
For irradiation, the solid samples were packed (12mm
thickness) in polythene bags. The samples were irradiated to an
absorbed dose of 25 kGy: dose required to attain sterility
assurance level of 10
6
(7) and 100 kGy: four times higher dose is
applied to estimate increase in discoloration with dose. In order
to study the effect of dose rate, samples were irradiated with
gamma radiation and e-beam (electron beam) having dose rates
0.85 kGy/h and 5 kGy/min, respectively. The gamma irradiation
was performed using GC-900
60
Co source (Manufacturer:
BRIT, BARC, India) at room temperature (27°C). The e-
beam irradiation was performed on e-beam accelerator (ILU 6,
Russian make, 2 MeV, 20 kW) at room temperature (30°C). The
dose rate was calibrated with alanine dosimeter.
Transmittance Spectra of Solutions
The solutions of unirradiated and irradiated samples of
all compounds were prepared in 0.1 N NaOH, as they were
all readily soluble in alkaline medium. The transmittance
spectra of cephalosporins were recorded within 30 min
because the lactam ring undergoes hydrolysis under alkaline
medium. The solution of fluoroquinolones in 0.1 N NaOH
was found to be stable up to 1 h and, if kept in the dark, up to
2 h. The concentrations of sample solutions (unirradiated and
irradiated) were 5% for NFX, GFX; 2% for SPX and 1% for
CD, CU, CP, and CX. The visible spectra were recorded on
Cintra 20e (Manufacturer: GBC, Australia) spectrophotometer
using 0.1 N NaOH as reference.
Diffuse Reflectance Spectra of Solids
The reflectance spectra were recorded using integrating
sphere assembly (Sphere diameter: 63 mm; Port/sphere
area ratio: 8%; Sample incident angle: 8°) of Cintra 20e
(Manufacturer: GBC, Australia) spectrophotometer. BaSO
4
was used as diluent and reference. The sample to BaSO
4
ratio
was 1:1 for NFX, CD, and CX; 2:1 for GFX, CU, and CP; and
1:3 for SPX. Mixing was done for several minutes with agate
mortarpestle. The spectra were recorded in the wavelength
range 380780 nm (the visible region of electromagnetic
radiation) at data interval of 1 nm. For each sample, three
spectra were recorded, and averaged data points were
converted to spectrum and used for color analysis.
Color Analysis
The color of drug sample before and after irradiation can
be simply obtained by comparison of solution of sample with
color standards of FeCl
3
CoCl
2
CuSO
4
(8). But due to mind-
dependency of color, visual comparison is always subjected to
error. Besides this in the method, the sample has to be
solubilized. To determine color of solid drug samples, their
diffuse reflectance spectra were recorded because it can be
used as a mind-independent characteristic and is unique for
every object. But with diffuse reflectance spectrum, the
problem of metamerism (where physically distinct spectra
will be percepted as same color) cannot be solved. Therefore,
for correct evaluation of the color of an object, we require
a method to convert reflectance spectrum data to color
parameters which truly represents human eye capabilities.
As we know, that color emerges from interaction of three
components: light source, objects reflectance characteristic,
and human vision system (Fig. 1). Thus, CIE XYZ color
space (Fig. 2) is appropriate for this purpose because, in this
color space, CIE XYZ tristimulus values are calculated from
CIE standard observer function (2° observing field) con-
sidering illumination and reflectance spectrum of objects
surface. The standard illuminant source being used is D65,
which is based on actual spectral measurement of daylight
with correlated color temperature of 6,504 K and is most
commonly used illuminant source for color analysis. Under
daylight condition, the vision process is mainly dependent on
the fovea, a part of the retina occupying the area where the
visual angle of observation is equal to 2° in the center of field
of vision (12). Therefore, the hypothetical observer used is
2° CIE standard observer. The calculation for XYZ was
performed using the following equations (12):
X¼KX
780
380
1H1x1$1
Y¼KX
780
380
1H1y1$1
Z¼KX
780
380
1H1z1$1
35Radiosterilization of Fluoroquinolones and Cephalosporins
Where,
ρ
λ
Spectral reflectance of the object at λ
HIlluminant function (D65) at λ
x1;y1;z1Color-matching functions of standard observer at λ
ΔλSpectral resolution or data interval (1 nm)
The illuminant function and color-matching functions
values are available in CIE 1931 document in wavelength
range 380780 nm at data interval of 1 nm (12), and the
graphical representation of these functions are shown in
Fig. 1a and b, respectively)
The normalizing factor Kcan be assigned any arbitrary
value. In most cases, only relative values of 1H1$1 are provided
becauseonlyrelativevaluesofX,Y,andZare required. In such
cases, the factor Kis so chosen that Yhas value 100.
K¼100
P
780
380
H1y1$1
Thus, the tristimulus values X,Y, and Zcalculated above
are coordinates of a three-dimensional vector space and used
to mathematically describe a color with color stimulus Fgiven
below,
F¼X:XþY:YþZ:Z
A major disadvantage with CIE XYZ color system is that
it does not constitute a physiologically equivalent color space,
i.e., the same distance in different parts of the color space
does not agree with the perceived color difference. Therefore,
it cannot mimic the nonlinear response of human eye.
However, the XYZ tristimulus values obtained are used as
starting point for the calculation of other color parameters
that are closer to human response.
CIE Lab and $E
ab
As discussed earlier, the human response to a stimulus is
nonlinear in nature. Additionally, although the eye sensed
color on RGB basis, at higher level of image processing in the
brain, the human perception of chromaticity appeared to
follow a space in which the two axes were redness vs.
Fig. 1. The color triangle: interaction of illuminant source (a), objects reflectance characteristic (b), and human
vision system (c); aRelative energy distribution of D65 illuminant; bCIE color matching function for 2° observer
36 Singh, Parwate and Shukla
greenness and yellowness vs. blueness. By taking all the
above-mentioned points into consideration, a new color space
called CIE Lab (color space CIE 1976, DIN 6174) was
devised. The CIE Lab color space is very close to human
response and device independent (the device dependent
spaces are RGB and CMYK used in monitors and printers,
respectively). The traditional designation of space is
L*a*b*, where the asterisks remind us of the nonlinear
nature of three variables. The calculation of CIE Lab from
CIE XYZ tristimulus is done as shown below (13)
L¼116 Y16; a¼500 XY
ðÞ;b
¼200 YZ
ðÞ
Assuming, U2X;Y;Zfg
U*¼ffiffiffiffiffiffi
U
Un
3
rfor U=Un>0:008856
7:787 U
Un
þ0:138 for U=Un0:008856
8
>
>
<
>
>
:
The subscript nrefers to the tristimulus values of the
perfect diffuser for the given illuminant and standard
observer. The exponent 1/3 in equation for tristimulus values
greater than 0.008856 provides the nonlinearity mentioned
earlier. For values less than 0.008856, linearity piece is kept so
as to avoid difficulty during conversion of Lab to XYZ
Also, L* designates lightness which is equivalent to
luminance like aspect of reflective color. The chrominance is
described by two variables a* and b* representing red vs.
green and yellow vs. blue axes, respectively. The spatial
representation of CIE Lab color space is shown in Fig. 3.
From CIE Lab values of unirradiated and irradiated
samples color difference ($E
ab ) was calculated using follow-
ing equation (13)
$E
ab L
1L
2

þa
1a
2

þb
1b
2

1=2
The subscripts 1 and 2 refer to the irradiated and
unirradiated samples, respectively.
The $E
ab value is useful for quantitation of color
difference and for defining color tolerance limit.
Dominant Wavelength and Excitation Purity
The dominant wavelength of a color correlates in an
approximate way with what would be called as the hue of the
color as observed under everyday conditions. It can also be
defined as the wavelength of the spectrum band, which, when
mixed with some specified achromatic stimulus, matches the
given color. The derivation of dominant wavelength form the
chromaticity coordinate is carried out by drawing a straight
line through the point representing the achromatic color D65
and the point Srepresenting the color to be evaluated, and
this line is produced in the direction D65 to S to intersect the
spectrum locus. The wavelength of the intersection is the
required dominant wavelength (λ
d
) of the given color as
depicted in Fig. 4.
The excitation purity of any color possessing a dominant
wavelength is an exactly defined ratio of distances in the
chromaticity diagram indicating how far the given color is
displaced from the achromatic color toward the spectrum
color (Fig. 4). Excitation purity is the degree of saturation
relative to the most concentrated form.
Fig. 2. The CIE XYZ color space chromaticity diagram. The outer
curved boundary from 380 to 780 nm through 520 nm is the spectral
locus of monochromatic colors. The straight line from 380 to 780 nm is
apurple line. The chromaticity point of illuminant is D65
Fig. 3. The cubical CIE Lab color space
37Radiosterilization of Fluoroquinolones and Cephalosporins
The excitation purity calculated from trichromatic values
is defined by
pe¼yyw
ybyw
¼xxw
xbxw
Yellowness Index (ASTM Method E313)
The yellowness index shows a degree where the hue
leaves white or achromatic color toward yellow. If it takes a
negative value, it moves in the blue direction. The yellowness
index for 2° observer and D65 illuminant is calculated by
following equation
YI ¼100 1:2985X1:1335ZðÞ
=Y½
The change of yellowness index is expressed by the
difference in yellowness indices of two samples.
$YI ¼YIiYIu
Where, subscripts iand udenotes irradiated and
unirradiated, respectively.
Fig. 5. Difference reflectance spectra of unirradiated and irradiated solid cephalosporins
Fig. 4. Derivation of dominant wavelength and excitation purity from
CIE chromaticity diagram
38 Singh, Parwate and Shukla
RGB Color Gamut and Color Palette
A large percentage of the visible spectrum can be
represented by mixing three basic components of colored
light in various proportions. These components are known as
the primary colors: red, green, and blue. The primary color
space is used in monitor display and the fill color options of
most of the softwares.
For 2
O
observer and D65 illuminant, the XYZ to RGB
conversion is performed as follows
X0¼X=100
Y0¼Y=100
Z0¼Z=100
R0¼X03:2406 þY01:5372ðÞþZ00:4986ðÞ
G0¼X00:9689ðÞþY01:8758 þZ00:0415
B0¼X00:0557 þY00:2040ðÞþZ01:0570
U02R0;G0;B0
fg
if U0>0:0031308ðÞ;U0¼1:055 U0^1=2:4ðÞ

0:055
else U0¼12:92 U0
U¼U0255
The RGB values were calculated from XYZ tristimulus
values to display the color palette on screen for audience. The
color given in the palette may differ from the original color of
the compound, as RGB color space is not equivalent to
human perception. But, for the sake of simplifying discussion
for readers depicting color by RGB, color palette is also
sufficient
Fig. 6. Difference reflectance spectra of unirradiated and irradiated solid fluoroquinolones
Fig. 7. Absorbance of solution of e-beam irradiated solid drug
samples at 450 nm. The plot shows absorbance as a function of dose
39Radiosterilization of Fluoroquinolones and Cephalosporins
RESULTS
The difference reflectance spectrum was obtained by
subtracting spectrum of unirradiated sample from spectrum of
irradiated sample. The difference reflectance spectra of
fluoroquinolones and cephalosporins are shown in Figs. 6
and 5, respectively. In the difference reflectance spectra of
irradiated drug samples, absorbance bands had emerged in
the visible region and the intensity of the absorption peak
increased with increase in dose from 25 to 100 kGy for both
gamma and e-beam irradiation. The fluoroquinolones showed
slight increase in absorbance in visible region at 25 kGy dose,
and at 100 kGy, the absorbance increase became significant.
It can be seen in Fig. 6that, for fluoroquinolones, e-beam was
more damaging than gamma radiation. Among cephalosporins,
CD has slight increase in absorbance, whereas CX, CP, and CU
had significant increase in absorbance even at 25 kGy dose
which further increased at 100 kGy dose. In the case of
cephalosporins, gamma radiation was found to be more
damaging than e-beam. Thus, from the difference reflectance
spectrum distinction can be made between gamma and e-beam-
irradiated samples.
In the transmittance spectra of the solution of irradiated
solid drug samples, the absorbance band appeared in the
visible region, and the absorbance increased with increase in
dose form 25 to 100 kGy. The plot of absorbance at 450 nm
against the dose is shown for e-beam and gamma-irradiated
samples in Figs. 7and 8, respectively. It was found that the
quantum of discoloration, as assessed by increase in absor-
bance at 450 nm, by electron beam and gamma radiation, was
nearly equal at a particular dose. This did not agree with
reflectance results and the visual observation. Thus, this
method, although can be used to distinguish an unirradiated
sample from an irradiated one, cannot differentiate between
gamma and e-beam-irradiated samples.
The complete set of color parameters determined
(spectral 1.7 software) are shown in Table Ifor cefixime.
For the sake of brevity, XYZ tristimulus, CIE Lab, and RGB
values are not given for other compounds, since they are only
useful for calculation of other color parameters and do not
have any relevance in further discussion. The color parame-
ters for remaining cephalosporins and fluoroquinolones are
given in Tables II and III, respectively. The color parameters
were determined to quantitate color difference and to define
color tolerance limit.
The calculated color difference ($E
ab) between CIE Lab
values of irradiated and unirradiated samples was found to be
very sensitive parameter, with which assessment of small
difference in color that was not even visually perceptible can
be done. The investigation of color difference values indicated
that for fluoroquinolones, e-beam was more damaging than
gamma radiation, whereas for cephalosporins, gamma radiation
was found to be more damaging than e-beam. These results are
in conformation with the results obtained by studying diffuse
reflectance spectra. In case of ΔYI, which is difference of
yellowness indices of irradiated and unirradiated samples,
Fig. 8. Absorbance of solution of gamma irradiated solid drug
samples at 450 nm. The plot shows absorbance as a function of dose
Table I. Color Parameters for Unirradiated and Irradiated Solid Cefixime (CX) Computed Using 2° Observer and D65 Illuminant
Color parameter Notation Unirradiated 25kGy e-beam 100kGy e-beam 25kGy gamma 100kGy gamma
Tristimulus values
X 75.66 (0.84) 66.38 (0.42) 66.21 (0.27) 66.10 (0.39) 64.85 (0.18)
Y 80.21 (0.67) 69.83 (0.50) 69.57 (0.31) 69.48 (0.44) 67.91 (0.13)
Z 78.51 (0.16) 61.04 (0.06) 59.82 (0.09) 60.80 (0.23) 56.91 (0.32)
CIE Lab values
L* 91.78 (0.18) 86.91 (0.22) 86.78 (0.14) 86.74 (0.20) 85.96 (0.06)
a* -1.18 (0.01) 0.99 (0.09) 0.19 (0.03) 0.14 (0.02) 0.68 (0.01)
b* 6.49 (0.24) 12.53 (0.33) 13.42 (0.16) 12.45 (0.14) 14.70 (0.18)
Color difference
*
ab
E
1.18 (0.03) 1.65 (0.02) 1.12 (0.02) 2.13 (0.02)
Dominant wavelength (nm) 573.37 (0.03) 576.20 (0.05) 576.42 (0.01) 576.38 (0.03) 576.94 (0.05)
Excitation purity pe 0.065 (0.001) 0.137 (0.004) 0.147 (0.001) 0.136 (0.001) 0.163 (0.002)
Yellowness index YI 11.54 (0.11) 24.33 (0.23) 26.12 (0.18) 24.35 (0.16) 29.00 (0.19)
YI YIi - YIu12.79 (0.26) 14.58 (0.21) 12.81 (0.19) 17.46 (0.23)
RGB values
R 234.6 (3.4) 227.7 (1.7) 228.3 (1.2) 227.4 (1.5) 227.7 (0.7)
G 231.6 (1.4) 216.8 (1.6) 216.2 (1.1) 216.2 (1.4) 213.5 (0.3)
B 219.0 (0.3) 194.0 (0.5) 192.0 (0.2) 193.7 (0.6) 187.4 (1.1)
Color palette (RGB)
Means and (SDs) for three replicates are given
40 Singh, Parwate and Shukla
Table II. Color Parameters for Solid Cephalosporins for Determination of Color Tolerance Limit
Color parameter Notation Unirradiated 25kGy e-beam 100kGy e-beam 25kGy gamma 100kGy gamma
Cefdinir (CD)
Color difference
*
ab
E
- 0.22 (0.05) 0.68 (0.04) 0.43 (0.04) 1.19 (0.04)
Dominant wavelength (nm) 578.11 (0.04) 578.17 (0.03) 578.09 (0.01) 578.22 (0.02) 577.95 (0.07)
Excitation purity pe 0.148 (0.006) 0.155 (0.005) 0.164 (0.001) 0.163 (0.002) 0.182 (0.001)
Yellowness index YI 27.01 (0.44) 28.30 (0.35) 29.66 (0.13) 29.60 (0.29) 32.55 (0.37)
YI YIi - YIu1.29 (0.56) 2.65 (0.46) 2.59 (0.53) 5.54 (0.58)
Color palette (RGB)
Cefpodoxime (CP)
Color difference
*
ab
E
- 2.03 (0.03) 3.35 (0.02) 2.01 (0.03) 3.91 (0.03)
Dominant wavelength (nm) 572.36 (0.02) 574.46 (0.01) 575.76 (0.01) 574.37 (0.02) 575.66 (0.02)
Excitation purity pe 0.051 (0.006) 0.125 (0.004) 0.179 (0.004) 0.129 (0.005) 0.214 (0.005)
Yellowness index YI 8.96 (0.65) 21.71 (0.38) 30.90 (0.44) 22.37 (0.49) 36.29 (0.49)
YI YIi - YIu- 12.75 (0.76) 21.94 (0.79) 13.41 (0.82) 27.33 (0.82)
Color palette (RGB)
Cefuroxime (CU)
Color difference
*
ab
E
- 3.89 (0.05) 5.91 (0.06) 5.23 (0.04) 8.66 (0.05)
Dominant wavelength (nm) 570.52 (0.01) 577.81 (0.08) 578.84 (0.06) 577.86 (0.06) 579.37 (0.06)
Excitation purity pe 0.026 (0.006) 0.157 (0.008) 0.242 (0.008) 0.212 (0.006) 0.349 (0.006)
Yellowness index YI 4.43 (0.71) 28.48 (0.86) 42.80 (0.88) 37.41 (0.69) 59.64 (0.65)
YI YIi - YIu- 24.05 (1.11) 38.37 (1.13) 32.98 (0.99) 55.21 (0.96)
Color palette (RGB)
Means and (SDs) for three replicates are given
Table III. Color Parameters for Solid Fluoroquinolones for Determination of Color Tolerance Limit
Color parameter Notation Unirradiated 25kGy e-beam 100kGy e-beam 25kGy gamma 100kGy gamma
Gatifloxacin (GFX)
Color difference
*
ab
E
- 0.93 (0.03) 1.83 (0.03) 1.29 (0.05) 2.15 (0.05)
Dominant wavelength (nm) 572.86 (0.01) 573.12 (0.06) 573.09 (0.04) 573.30 (0.12) 574.54 (0.15)
Excitation purity pe 0.038 (0.004) 0.060 (0.004) 0.095 (0.004) 0.075 (0.002) 0.096 (0.007)
Yellowness index YI 6.78 (0.09) 10.61 (0.19) 16.49 (0.14) 13.14 (0.10) 16.92 (0.13)
YI YIi - YIu- 3.83 (0.22) 9.71 (0.17) 6.36 (0.13) 10.14 (0.16)
Color palette (RGB)
Norfloxacin (NFX)
Color difference
*
ab
E
- 1.64 (0.02) 3.88 (0.03) 1.04 (0.03) 3.51 (0.03)
Dominant wavelength (nm) 570.84 (0.03) 572.29 (0.05) 574.19 (0.08) 573.05 (0.04) 573.58 (0.10)
Excitation purity pe 0.049 (0.001) 0.110 (0.002) 0.155 (0.001) 0.084 (0.003) 0.151 (0.002)
Yellowness index YI 8.43 (0.16) 18.38 (0.19) 26.45 (0.16) 14.57 (0.38) 25.47 (0.34)
YI YIi - YIu- 9.95 (0.25) 18.02 (0.22) 6.14 (0.41) 17.04 (0.37)
Color palette (RGB)
Sparfloxacin (SPX)
Color difference
*
ab
E
- -0.69 (0.02) -0.64 (0.03) -0.73 (0.02) -0.82 (0.03)
Dominant wavelength (nm) 568.71 (0.04) 569.04 (0.04) 569.95 (0.06) 568.96 (0.04) 569.71 (0.01)
Excitation purity pe 0.247 (0.002) 0.246 (0.003) 0.249 (0.006) 0.239 (0.004) 0.237 (0.005)
Yellowness index YI 35.88 (0.23) 36.00 (0.36) 37.06 (0.72) 35.05 (0.47) 35.37 (0.56)
YI YIi - YIu- 0.12 (0.43) 1.18 (0.75) -0.83 (0.52) -0.51 (0.61)
Color palette (RGB)
Means and (SDs) for three replicates are given
41Radiosterilization of Fluoroquinolones and Cephalosporins
similar trends were observed. The basis for selection of ΔYI for
assessment of discoloration was that the observed color change
for most of the studied fluoroquinolones and cephalosporins
was from white to off-white to sand to brownish. The tolerance
limits proposed for $E
ab and ΔYI are ±2 and ±10 U,
respectively, because, within these limits, the change in color is
not conspicuous as can be seen in the color palette (Tables I,II
and III). NFX, GFX, SPX, and CD at 25 kGy dose fall within
this limit, whereas CU, CP, and CX were outliers.
The dominant wavelength for all compounds had shifted
to higher values indicating change in hue. The shift of 1 nm
did not result in much discoloration, as can be seen in the case
of NFX 25 kGy e-beam and NFX 25 kGy gamma-irradiated
samples (Table III). Sometimes, 2-nm shift was also found to
be acceptable, but in such cases, the increase in excitation
purity should be moderate. For example, (a) the dominant
wavelength increase between NFX 25 kGy e-beam, and NFX
100 kGy e-beam samples was 1.90 nm, and the corresponding
excitation purity difference was 0.045, as a result, there was
no striking perceptible difference between them; (b) the
dominant wavelength increase between CU 25 kGy gamma
and CU 100 kGy gamma-irradiated samples was 1.49 nm, and
excitation purity difference was 0.137 here ,although the
dominant wavelength increase was less but due to large
difference in excitation purity, the perceptible color difference
was found to be significant.
DISCUSSION
The discoloration of solids on irradiation can be attributed
to free radical species trapped in solid matrix and/or molecular
radiolytic species (3). The study of difference reflectance
spectra revealed that the fluoroquinolones were more suscep-
tible to damage by e-beam, whereas for cephalosporins,
gamma ray was more damaging. The plausible explanation
for this behavior can be that the radiation chemical yield of
two color-rendering species, i.e., free radical species and
molecular radiolytic product is dependent on the nature of
the compound and dose-rate of ionizing radiation (e-beam has
higher dose rate than gamma radiation).
In case of CX, CP, and CU significant absorbance
increase was obtained even at 25 kGy dose. The reason for
such a significant increase of absorption in visible region can
only be due to unsaturated chromophore systems in the
radiolytic products of these compounds.
The increase in absorbance at 450 nm obtained in
solution of irradiated samples may be attributed to molecular
radiolytic products formed during irradiation of solids and
from radical reactions (inter-radical, radical-oxygen, and
radical-solvent) occurring upon dissolution (7). The absor-
bance at 450 nm of e-beam and gamma-irradiated samples
was nearly same. Therefore, distinction between e-beam and
gamma irradiated was not observable in solutions of irradi-
ated samples. Thus, reflectance measurement has clear
advantage over transmittance measurement of solution in
assessing discoloration of irradiated drugs.
Among color parameters, $E
ab and ΔYI were found to
be suitable for defining color difference. The proposed color
tolerance limits for ΔE
*ab
and ΔYI are ±2 and ±10 U,
respectively, because, in this range, the perceptible color
difference between irradiated and unirradiated sample was
not significant. All fluoroquinolones at 25 kGy dose were
within this range. The radio-resistance of fluoroquinolones
can be attributed to the aromatic character of quinolone
moiety (14). In case of cephalosporins, CU, CP, and CX were
outliers and, hence, radiosensitive, whereas CD was found to
be radio-resistant. From the structure of cephalosporins, it
seems that the lactam ring might be responsible for their
radio-sensitivity. The radio-resistance of CD, however, could
not be explained.
As dominant wavelength values should always be
accompanied with excitation purity, therefore, defining color
tolerance limit with this parameter would be cumbersome.
CONCLUSIONS
The color parameters $E
ab and ΔYI obtained from
color analysis of diffuse reflectance spectrum can be reliably
used for assessing discoloration of solid fluoroquinolones and
cephalosporins. The distinction between gamma and e-beam-
irradiated samples can be done by color parameters derived
from reflectance spectrum, which was not possible by measuring
absorbance of solution at 450 nm. All fluoroquinolones were
found to be radio-resistant, whereas in case of cephalosporins,
only CD was radio-resistant.
The proposed tolerance limits are not restricted for these
antibiotics only, but its use can be extended to study the effect
of ionizing radiations on other drugs also.
ACKNOWLEDGEMENTS
The authors thank (a) the Head, Department of Chemistry,
Rashtrasant Tukadoji Maharaj Nagpur University for providing
laboratory and gamma irradiation facilities, (b) the Board of
Radiation and Isotope Research, Bhabha Atomic Research
Centre, Vashi, Mumbai for providing e-beam-irradiation facility.
One of the authors Ms. Babita Singh would like to thank Central
Forensic Science Laboratory, Directorate of Forensic Science,
Ministry of Home Affairs, Hyderabad for providing her
fellowship.
REFERENCES
1. The European agency for the Evaluation of Medicinal Products.
Decision tree for the selection of sterilization methods (CPMP/
QWP/ 054/ 98 corr). EMEA committee for proprietary medicinal
products, London, 5 April 2000.
2. G. O. Mercanoğlu, A. Y. Özer, S. Colak, M. Korkmaz, M. Özalp,
M. Ekizoğlu, N. Barbarin, and B. Tilquin. Radiosterilization of
sulfonamides I: determination of the effects of gamma irradiation
on solid sulfonamides. Rad. Phy. Chem. 69:511520 (2004).
3. A. S. Crucq, C. Slegers, V. Deridder, and B. Tilquin. Radio-
sensitivity study of cefazolin sodium. Talanta.52:873877 (2000).
4. M. Gibella, and B. Tilquin. Detection of the radiolysis of solid
ampicillin by UV spectroscopy. Analusis.27:657662 (1999).
5. B. Marciniec, Z. Plotkowiak, L. Wachowski, M. Kozak, and M.
Popielarz-Brzeziñska. Analytical study of beta irradiated anti-
biotics in the solid state. J. Therm. Anal. Calorim. 68:423436
(2002).
6. A. S. Crucq, V. Deridder, and B. Tilquin. Radiostability of
pharmaceuticals under different irradiation conditions. Rad. Phy.
Chem. 72:355361 (2005).
7. L. Varshney, and P.B. Dodke. Radiation effect studies on
anticancer drugs, cyclophosphamide and doxorubicin for radia-
tion sterilization. Rad. Phy. Chem. 71:11031111 (2004).
42 Singh, Parwate and Shukla
8. British pharmacopoeia, Appendix IIB and Appendix XVIII,
2004.
9. A. Tücks, and H. P. Beck. The photochromic effect of bismuth
vanadate pigments. Part I: Synthesis, characterization and
lightfastness of pigment coatings. J. Solid State Chem. 178:1145
1156 (2005).
10. G. Paschos. Fast color texture recognition using chromaticity
moments. Pattern Recogn. Lett. 21:837841 (2000).
11. S. A. Nouh, N. Ibrahim El-Tayeb, A. F. Said, M. M. Radwan, and
S. A. El-Fiki. Structural and optical studies of electron beam-
irradiated Makrofol nuclear track detector. Radiat. Meas. 42:813
(2007).
12. G. Wyszecki, and W. S. Stiles. Color Science, Concepts and
Methods: Quantitative Data and Formulas, Wiley, New York,
1967.
13. K. Nassau. Color for Science, Art and Technology, Elsevier, New
York, 1998.
14. J. E. Williard. Radiation chemistry of organic solids. In I.
Farhataziz, and Michael A. J. Rodgers (eds.), Radiation Chemistry:
Principles and Applications, VCH, New York, 1987, pp. 410.
43Radiosterilization of Fluoroquinolones and Cephalosporins
... In other interpretations, DW represents the principal wavelength of the colour, i.e. DW correlates with the colour's hue [40]. In general, the larvae processing resulted in fluctuations in DW around the steady-state value of 577 nm (Table 3), pointing to the presence of yellow pigments. ...
... Therefore, it can be concluded that these parameters are not suitable for mealworms differentiation. The excitation purity of any colour possessing a DW is an exactly defined ratio of distances in the chromaticity diagram indicating how far the given colour is displayed from the achromatic colour toward the spectrum colour [40]. Values of excitation purity differed significantly from each other (p < 0.05). ...
Article
Full-text available
The colour of processed mealworms is an important attribute that affects their utilization in food industry. Totally 15 colour and related spectral variables of powders prepared from differently processed (oven drying, freeze-drying, microwave drying, blanching, and their combinations) mealworms larvae (Tenebrio molitor) were evaluated by UV/Vis spectroscopy and multivariate analysis. The results obtained confirmed deterioration of mealworms colour after processing. In general, processing led to a decrease of lightness (L*), hue angle (h°), whiteness-blue-reflectance, whiteness index (WI) and tinting index coinciding with an increase in the yellowness index (YI), redness (a*), browning index (BI) and total colour difference (ΔE) compared to untreated larvae. Oven drying at higher temperature caused the pronounced darkening described by the highest BI and ΔE values (ΔE = 28.54 ± 0.37, BI = 53.78 ± 0.31). On the other hand, freeze-drying was the most suitable colour protection method. Based on lower BI and ΔE values, the combination of 3 min blanching with microwave and oven drying can be recommended as a proper alternative to freeze-drying. Most of the colour descriptors of processed larvae differed significantly from each other (p < 0.05). Absolute discrimination of processed mealworms larvae was achieved through principal component analysis and discriminant analysis. Values of L*, yellowness (b*), chroma, BI, ΔE and whiteness-blue-reflectance were identified as the most discriminating. Moreover, mutual correlations of monitored parameters, e.g. tinting and WI; a*, b* and C* values; or L* and ΔE were revealed by principal component factoring.
... The coordinate L* stands for lightness, the a* value indicates the red-green component of color, and the yellow and blue components are represented by the b* value. The color change is evaluated using the total color difference ∆ ab * , which considers both the lightness difference and the difference in the chromatic plane (Singh et al. 2009). ...
Article
Full-text available
This study focuses on the effectiveness of a new substance in stabilizing paper information carriers - hydrotalcite applied to the paper in a partially polar environment. The effect of modification on the stabilization of paper during accelerated aging was investigated by measuring chemical (surface pH, rate of glycosidic bond cleavage), mechanical (coefficient of the relative increase of the lifetime for folding endurance), optical (colorimetry - CIE L*a*b*), and spectral (FTIR) properties. Three types of hydrotalcites differing in composition, particle size, and preparation conditions, were tested and compared. After the modification, all the properties of acidic test papers improved. The most promising type of hydrotalcite was prepared under the nucleation action of citric acid. The atomic ratio of Mg2+ to Al3+ of this hydrotalcite was equal to 5. Modification by this hydrotalcite led to an increase in surface pH by 1.3 to 2.7 units.
... The coordinate L* stands for brightness, the a* value indicates the red-green component of color, and the yellow and blue components are represented by the b* value. The color change is evaluated using the total color difference ∆ ab * , which takes into account both the lightness difference and the difference in the chromatic plane (Singh et al. 2009). As a result of aging, the L* coordinate decreases, at the same time the a* and b* coordinates also change. ...
Preprint
Full-text available
Stabilization and deacidification of paper information carriers is still a highly discussed topic. It is very important to continue in searching for new, more effective, and affordable methods of paper stabilization because none of the currently known processes is ideal. This study focuses on the effectiveness of a new substance in stabilizing paper information carriers - hydrotalcite, applied to the paper in a partially polar environment. The effect of modification on the stabilization of paper during accelerated aging was investigated by measuring chemical (surface pH, rate of glycosidic bond cleavage), mechanical (coefficient of the relative increase of the lifetime for folding endurance), optical (colorimetry - CIE L*a*b*), and spectral (FTIR) properties. Three types of hydrotalcites differing in composition, particle size, and preparation conditions, were tested and compared. After the modification, all the properties of acidic test papers improved. The most promising type of hydrotalcite was prepared under nucleation action of citric acid. The atomic ratio of Mg2+ to Al3+ of this hydrotalcite was equal to 5. Modification by this hydrotalcite led to an increase in surface pH by 1.3 to 2.7 units.
... Para evaluar el color, se obtiene el Delta-E con la calculadora Cie94. Para comprender los ejes en las tres dimensiones del color con las coordenadas X, Y, Z, es necesario indicar lo mencionado por Singh et al. (2009) ...
Article
Full-text available
La búsqueda de alternativas más sostenibles y menos contaminantes para la industria textil ha llevado a explorar el uso de pigmentos naturales y orgánicos para el teñido de tejidos. El objetivo de esta investigación es analizar la formación de nanopigmentos con extracto de achiote para su uso en el teñido de algodón 100%. El método científico utilizado es el experimental y la observación, además se utiliza varias técnicas cualitativas y para la extracción pasa por la maceración dinámica, rotavapor, separación con hidróxidos y de los extractos se toma una muestra al azar y por conveniencia se realiza la mezcla homogénea con la nanoarcilla donde se obtuvieron los nanopigmentos mediante un proceso de síntesis en el cual se utilizó arcilla hidratada de Trimethyl Estearil Ammonium como soporte, y se insertaron moléculas orgánicas de achiote. Luego se procede a Tinturar varias muestras de algodón mediante receta prevista, para posterior realizar el lavado. Los nanopigmentos obtenidos se caracterizaron mediante diversas técnicas, como microscopía electrónica de barrido SEM y con el espectrofotómetro se evalúa la solidez del color al lavado y mediante la calculadora Cie94 se obtiene el Delta-E. Entre los hallazgos SEM la muestra Co_9 Trimethyl + P tiene una valoración (2)= presencia de NP, con un color anaranjado rojizo ladrillo con (∆E = 58.61) lo contrario sucede con la muestra Co_5 Trimethyl + R, se valora como (1) = reducida presencia NC, tiene un color: Amarillento pálido muy débil (∆E = 3.46) y se evaluó la solidez del colorante y también se valora el frote en seco y húmedo con la escala de grises. Asimismo, se obtiene el rendimiento promedio de 9.09%, obteniéndose resultados en términos de solidez 1 y cambio de color 5 en los tejidos teñidos con pigmento solido contrario a la baja solidez en los tejidos con colorante líquido. Por ello se concluye que los nanopigmentos de achiote obtenidos son una alternativa viable y sostenible para el teñido de textiles y su aplicación en la industria textil.
... Reproduced with permission. [160] Copyright 2009, Springer Nature. ...
Article
Full-text available
The use of smartphone‐based analysis systems has been increasing over the past few decades. Among the important reasons for its popularity are its ubiquity, increasing computing power, relatively low cost, and capability to acquire and process data simultaneously in a point‐of‐need fashion. Furthermore, smartphones are equipped with various sensors, especially a complementary metal–oxide–semiconductor (CMOS) sensor. The high sensitivity of the CMOS sensor allows smartphones to be used as a colorimeter, fluorimeter, and spectrometer, constituting the essential part of point‐of‐care testing contributing to E‐health and beyond. However, despite its myriads of merits, smartphone‐based diagnostic devices still face many challenges, including high susceptibility to illumination conditions, difficulty in adapter uniformization, low interphone repeatability, and et al. These problems may hinder smartphone‐enabled diagnosis from passing the FDA regulations of medical devices. This review discusses the design and application of current smartphone‐based diagnostic devices and highlights challenges associated with existent methods and perspectives on how to deal with those challenges from engineering aspects on constant color signal acquisition, including smartphone adapter design, color space transformation, machine learning classification, and color correction. This review discusses the design and application of current smartphone‐based diagnostic devices and highlights challenges associated with existent methods and perspectives on how to deal with those challenges from engineering aspects on the constant color signal acquisition, including smartphone adapter design, color space transformation, machine learning classification, and color correction.
Article
Aims The present study aimed to evaluate the antibacterial effectiveness of newly formulated root canal irrigants derived from natural sources. In particular, this study investigated how these irrigants’ antimicrobial properties were affected by gamma radiation activation. Materials and Methods Fifty-three single-rooted extracted human teeth with straight canals were selected, fully prepared, and sterilized. The roots were then infected with Escherichia coli, Enterococcus faecalis, and Candida albicans for 21 days at 37°C. Based on the irrigating solution utilized, the roots were divided into seven groups: Group I: chitosan irrigant, Group II: chitosan irrigant gamma irradiated, Group III: curcumin irrigant, Group IV: curcumin irrigant gamma irradiated, Group V: sodium hypochlorite (NaOCl) 5% irrigant, Group VI: positive control (infected roots without treatment), and Group VII: negative control (uncontaminated roots). After cleaning and shaping, microbiological sampling was performed. The samples were then transferred to sterile centrifuge tubes containing 1 mL of saline to determine the microbial growth. Colony-forming unit counts were employed for assessing the antimicrobial action. Statistical analysis was conducted to compare the percentage reduction in the microbial count from the initial count. Results Group V and Group IV showed significantly higher values in microbial reduction than Group III and Group I. In addition, the results showed that Group II and Group III have significantly higher values than Group I. Conclusion Natural irrigating solutions exposed to gamma radiation exhibited promising antimicrobial activity that is comparable to that of NaOCl and may be used as effective antimicrobial agents in endodontic treatment.
Article
Full-text available
The effect of electron beam irradiation on the structural and optical properties of Makrofol solid state nuclear track detector (SSNTD) was investigated. Samples from Makrofol detector were irradiated with electron beam with doses at levels between 10 and 400 kGy. Structural and optical property studies using X-ray diffraction, FTIR spectroscopy, color difference measurements and electron paramagnetic resonance were performed on non-irradiated and irradiated Makrofol samples. The transmission of these samples in the wavelength range 200–2500 nm, as well as any color changes, was studied. A characteristic absorption bands with different intensities was observed. Using the transmission data, both the tristimulus and the Commission Internationale de l’Eclairage (CIE) LAB coordinate values were calculated. In addition, the color differences between the non-irradiated sample and those irradiated with different doses were calculated. The results indicate that the Makrofol detector is a material that does not have a high resistance to degradation, and its tendency to crosslinking is much lower than that of several other SSNTDs.
Article
Full-text available
Three antibiotics sulfafurazole (SFZ), sulfamethoxazole (SMZ) and sulfacetamide sodium (SSA-Na) belonging to sulfonamides were irradiated and changes in physico-chemical properties, pH, melting points, UV, IR, NMR, TLC, GC-MS, ESR characteristics, antimicrobial activities of active components were studied at normal and accelerated stability test conditions. Two radiolytic intermediates for both SFZ and SMZ and four radiolytic intermediates for SSA-Na were found in the irradiated solid samples after the GC-MS analysis. The results obtained under normal and accelerated stability test conditions were observed to be consistent with the unirradiated values.
Article
This paper reports results of the study on the influence of β-irradiation on the physical and chemical properties of selected salts of β-lactam antibiotics in solid state (sodium salt: ampicillin, azlocillin, benzylpenicillin, carbenicillin and piperacillin; potassium salt of benzylpenicillin, ampicillin anhydricum, ampicillin trihydricum, amoxicillin trihydricum and bacampicillin hydrochloride). The source of irradiation was a linear accelerator of electrons, and the irradiation effects were checked on the basis of the following: determination of mass, melting point and water contrent, and spectrophotometric (UV, IR) chromatographic and thermal (DTG, DSC) studies.
Article
We report on investigations of the photochromic effect of BiVO4 pigments. Emphasis is placed on an approach widely used in industrial color testing. By means of colorimetry ΔEab*-values, which measure the perceived color difference, can be calculated from reflectance spectra of non-illuminated and illuminated pigment coatings. Pigments were prepared by either wet-chemical precipitation or solid-state reactions. Depending on the choice of starting compounds, lightfastness was found to vary significantly. Small amounts of impurity phases do not seem to affect photochromism. In contrast, impurities like Fe and Pb cause intense photochromism. The role of Fe is suggested by trace analyses, which (in case of pigments synthesized by precipitation reactions) reveal a correlation between concentration and ΔEab*. Indications are found that other effects like pigment–lacquer interactions might also be of importance. Difference reflectance spectra turn out to vary in shape depending on the type and concentration of impurities or dopants. For BiVO4 at least three different mechanisms of photochromism can be assumed.
Article
Two anticancer drugs, cyclophosphamide (CPH) and doxorubicin hydrochloride (DOXO), in powder form were exposed to a range of doses of 60Co gamma and electron beam radiation to study the effects of ionizing radiation. Pharmacopoeia tests, discolouration, degradation products, effect of irradiation temperature and dose rate were investigated. CPH undergoes less than 2% degradation at 30kGy. Chromatographic studies revealed formation of several trace level degradation products, discolouration and free radicals in the irradiated CPH. N,N-bis (2-chloroethyl) group in the molecule is particularly sensitive to radiation degradation. Irradiation to 5kGy at low temperature (77K) did not result in significant changes. DOXO was observed to be quite radiation resistant and did not undergo significant changes in its physico-chemical properties and degradation product profile. It can be radiation sterilized at normal sterilization dose of 25kGy.
Article
We propose to detect the use of γ-rays in order to radiosterilize ampicillin by UV absorption spectroscopy. The UV absorption results are verified by comparison with HPLC-diode array analysis. The sensitivity is excellent (10-6 M). The wavelengths in the range from 287 to 335 nm are characteristics of radiolysis related substances. It is possible to use this range of wavelengths to detect the radiolysis of ampicillin with an usual UV spectrophotometer.
Article
A number of different approaches have been presented recently addressing the issue of color texture analysis. Most of these methods are based on elaborate mathematical modeling, including auto/cross-correlation, random fields, and Gabor multi-channel filtering. Furthermore, the computational requirements of these approaches are usually high. A simple yet effective method for color texture classification is presented here. The method uses the CIE xy chromaticity diagram of an image and a corresponding set of two-dimensional and three-dimensional moments to characterize a given color texture. Chromaticity is, thus, described by its two-dimensional shape, i.e., the chromaticity diagram, along with the associated two-dimensional distribution of chromaticity values. Using only a small number of moments the method achieves hit rates of over 90%. The method has been applied to the recognition of granite and marble images.
Article
In this paper, the products studied are cefazolin, glucagon and dobutamine HCl. The radioresistance of pharmaceuticals may depend on the conditions of irradiation. The best is to irradiate the drugs in solid state and the chemical transformations can be reduced also by lowering the temperature of the liquid. In solid state, the dose rate has no influence on the decomposition for the selected molecules and it should be noted that drug excipients selected for bioavailability reasons are not always radioprotectors. These results are important from a technical point of view in pharmaceutical industry.
Article
Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and how science impacts upon all aspects of society and life.