Research article Rapports De Pharmacie Vol.

3 (2), 2017, 371-383

ISSN: 2455-0507
OPTIMIZATION AND IN-VITRO CHARACTERIZATION OF ERYTHROMYCIN
NANOGELS BY USING SIMPLEX-LATTICE MIXTURE DESIGN
Lim Kuan Ting, Jaya Raja Kumar
1Research student, Asian Institute of Medicine, Science and Technology (AIMST)
University, Bedong 08100, Kedah, Malaysia
2Unit of Pharmaceutical Technology, Faculty of Pharmacy, Asian Institute of Medicine,
Science and Technology (AIMST) University, Bedong 08100, Kedah, Malaysia
ABSTRACT
Erythromycin nanogels (EM-NGs) are established as one of the most promising carriers for topical delivery
system. Therefore, the aim of the present study was to develop a poloxamer based nanogels of erythromycin
with a view to improve its high capacity to hold water, without dissolving into the aqueous medium. Nanogels
of erythromycin were developed by probe sonicator and evaluated in vitro for, Fourier transforms infra-red
(FTIR) spectroscopy, with good particle size, refractive index, gel strength, spreadability, mucoadhesive force
and viscosity. In vitro characterizations of the erythromycin nanogels revealed that the mean globule sizes of
the nanogels ranged from 192 nm to 247 nm, the refractive index ranged from 1.371 to 1.395, the gel strength
values were in the range of 9 to 120 seconds, the spreadability were between 3.61 and 64.64 gm.cm/sec, the
viscosity ranged from 15.3 to 809 cps and the mucoadhesive force was in the range of 15890.9 to 30193.9
dynes/cm.
Keywords: Erythromycin, Nanogels, Probe Sonicator, Simplex-Lattice Mixture Design
INTRODUCTION
Polymeric nano systems which include micelles, foreign molecules and their special physical
liposomes, nanoparticles, and nanogels have been properties provide them a lot of biomedical
the most investigated drug delivery systems. Due to applications. They actively participate in the
their prolonged circulation time, significant delivering process due to their characteristic
improved accumulation in the targeted site via the properties like stimuli-responsive behavior, softness
enhanced permeability and retention (EPR) effect, and swelling to help achieve a controlled, triggered
decreased adverse effects, and improved, drug response at the target site [16-22]. Erythromycin is
tolerance [1–7]. Compared to other nanosystems, in a class of medications called macrolide
nanogels with internally cross-linked 3D structures antibiotics. It works by stopping the growth of
are highly interesting for controlling drug delivery at bacteria. The main advantage of erythromycin is to
the target site in fast response to external stimuli as treat or prevent various types of infections caused by
well as for improving drug bioavailability [8–13]. bacteria. For instance infections of the respiratory
Nanogels are 3D network hydrogel materials in the tract, including bronchitis, pneumonia, pertussis,
nanoscale size range formed by crosslinked pertussis (whooping cough; a serious infection that
swellable polymer networks with a high capacity to can cause severe coughing); diphtheria (a serious
hold water, without dissolving into the aqueous infection in the throat); sexually transmitted diseases
medium. Their characteristics such as size, charge, (STD), including syphilis; and ear, intestine,
porosity, amphiphilicity, softness, and degradability gynecological, urinary tract, and skin infections. It is
can be fine-tuned by varying the chemical also used to prevent recurrent rheumatic fever.
composition of the nanogels. They are mostly However, antibiotics such as erythromycin will not
spherical particles and allow fabrication of the work for colds, flu, or other viral infections.
nanogels of different shapes [14, 15]. Nanogels are Poloxamers are nonionic polyoxyethylene-
mostly hydrophilic in nature and highly polyoxypropylene copolymers used primarily in
biocompatible with a high loading capacity for pharmaceutical formulations as emulsifying or
solubilizing agents. The polyoxyethylene part is
Address for correspondence: belong to hydrophilic while the polyoxypropylene
Lim Kuan Ting, part is hydrophobic. Poloxamers are white, waxy,
Research student, free-flowing prilled granules, or as cast solids. They
AIMST University,Bedong- Semeling, Kedah, are odorless and tasteless. They are colorless liquid
Malaysia 08100 at room temperature. The pH of poloxamers is 5.0-

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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels
7.4 while the melting point is 52-57degree celcius.
Poloxamers are used as emulsifying agents in
intravenous fat emulsions, and as solubilizing and
stabilizing agents to maintain the clarity of elixirs
and syrups. Furthermore, it may also be used as
wetting agents; in ointments, suppository bases, and
gels; and as tablet binders and coatings. Poloxamer
188 has been used as an emulsifying agent for
fluorocarbons and also used as artificial blood
substitutes and in the preparation of solid-dispersion
systems. Poloxamer 188 is incompatible with
phenols and parabens depends on the relative
concentration [23]. In this paper, Erythromycin
nanogels with desired globule size, high gel strength
METHOD OF PREPARATION: (Figure 1)
and mucoadhesive force were obtained by using
simplex-lattice mixture design (Stat-Ease Design-
Expert software-DX9). The nanogel networks offer
several advantages including prolonged drug release,
excellent mucoadhesive properties, and
spreadability.
MATERIALS
Erythromycin was gift sample from SM
Pharmaceuticals Sdn Bhd, Malaysia .Tween 20 was
purchased from R&M Chemical. Poloxamer 188
was purchased from Merck KGaA (Darmstadt,
Germany). All water used in the formulation was of
Milli-pore grade.

Figure 1: Preparation of erythromycin nanogels

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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels
IN-VITRO EVALUATION
Determination of pH:
The pH of the nanogels was determined by using a
calibrated PH meter (HANNA INS PH211).
Measurements were considered after reaching
equilibrium. The reading of all runs was noted.
Viscosity studies:
The viscosities of the various formulations were
determined by using Brookfield programmable DVII
+Model pro II type (USA). The viscosity was noted
in Centipoise [24].
Measurement of Spreadability: A small portion of
the nanogels was applied on a glass slide and was
compressed to uniform thickness by placing 50 g for
5 minutes [25]. The time in which the upper glass
slide move over the lower slide was taken as
measurement of spreadablility (S)
S= ML/T where,
M= weight tide to upper slide (g)
L= length moved on the glass tide (cm)
T= time taken (sec)
Measurement of gel strength:
A sample of 50gm of nanogels was placed in a 100
ml graduated. The apparatus for measuring gel
strength (weighing 27 gm) was allowed to penetrate
in gel. The gel strength, which means the viscosity
of the nanogels was determined by the time
(seconds), the apparatus took to sink 5cm down
through the prepared gel [26].
Determination of mucoadhesive force:
The mucoadhesive force of nanogels was determined
as follows, a section of the chicken skin fixed with
mucosal side out onto each glass vial using rubber
band. The vial with chicken skin was connected to
the balance in inverted position while first vial was
placed on a height adjustable pan. Nanogels were
added onto the skin of first vial. Then the height of
second vial was so adjusted that the mucosal
surfaces of both vials come in intimate contact. Two
minutes time of contact was given. Then weight was
kept rising in the pan until vials get detached.
Mucoadhesive force was the minimum weight
required to detach two vials. The chicken skin was
changed for each measurement [25].
Particle size analysis of nanogels:
Particle size of nanoparticles was determined using
malvern particle size analyzer (Zetasizer 4000S,
Japan).
Determination of refractive index:
The refractive index of nanogels was determined by
using Lan Optics. A small portion of samples were
placed on the glass slide of the equipment. The
refractive index will be shown by the equipment.
Measurement was considered after reaching
equilibrium.
In-vitro permeation studies of nanogel formulations:
In-vitro studies of the gel were carried out across the
egg membrane extracted by using the concentrated
hydrochloric acid. The receptor compartments were
filled with phosphate buffered saline (PBS) pH 6.8,
Study was carried out using excised egg membrane.
The entire setup was placed on a thermostatic
magnetic stirrer and the temperature was maintained
at 37◦C throughout the study.
Permeability studies were carried out over a period
of 8 hrs at regular intervals. Samples were
withdrawn and analyzed spectrophotometrically at
264 nm.
RESULT AND DISCUSSION
Optimization of process variables for the
erythromycin nanogels:
The effects of the three factors (Water, Oleic Acid
and Tween 20: Poloxamer 188) on the refractive
index, globule size, gel strength, spreadability,
mucoadhesive force and viscosity were tested.
Through preliminary screening the water, oleic acid
and surfactant/Co-surfactant ratio were identified as
the most significant variables within the range of 5-
7g, 1-3g and 1-3g, respectively. On the basis of the
preliminary trials a simplex-lattice mixture design
was employed to study the effect of each
independent variable on dependent variables
(refractive index, globule size, gel strength,
spreadability, mucoadhesive force and viscosity). A
simplex-lattice mixture design of degree m consists
of m+1 points of equally spaced values between 0
and 1 for each component. If m = 2 then possible
fractions are 0, 1/2, 1. For m = 3 the possible values
are 0, 1/3, 2/3, 1. The points include the pure
components and enough points between them to
estimate an equation of degree m. This design differs
from a simplex-centroid design by having enough
points to estimate a full cubic model. The
independent factors and the dependent variables
used in the design are listed in Table 1. The
experiments were conducted as for the design of
experiments and the responses for the dependent
variables were entered in Table 2. The response
surfaces of the variables inside the experimental
domain were analyzed using Stat-Ease Design-
Expert software (DX9). Subsequently, three
additional confirmation experiments were conducted
to verify the validity of the statistical experimental
strategies.
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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels

Table-1: List of Independent variable and Dependent variables in simplex-lattice mixture design
Independent variable Levels
Variable Name Units Low Middle High
A Surfactant % 5 7
B Speed rpm 5000 6500 8000
C Time time 60 120 180
Dependent variable Goal
Y1 Refractive index
Y2 Globule size
Y3 Gel strength
Y4 Spreadability Optimized value
Y5 Mucoadhesive force
Y6 Viscosity

Table 2: Factorial design of erythromycin nanogels

Tween Muco-
Refrac Gel Spread-
A:water B:oil 20:P188 Size adhesive Viscosity
Run -tive strength ability
w/w w/w (1:3) nm force cps
index sec g.cm/sec
w/w dynes/cm
1 5 2 2 1.387 192 90 3.61 30193.9 449.9
2 6.3 1.3 1.3 1.371 195 9 10.21 15890.9 15.3
3 5.6 1.6 1.6 1.377 198 12 16.67 15940.5 18.1
4 5 3 1 1.394 214 22 18.39 15880.5 60.4
5 6 1 2 1.38 229 18 64.64 15891.1 55.3
6 5 1 3 1.393 190 90 13.62 28691.9 403.1
7 5.3 1.3 2.3 1.384 195 120 12.13 28469.6 809.3
8 5.3 2.3 1.3 1.383 193 21 31.31 15890.3 60.2
9 6 2 1 1.373 232 19 60.82 15885.7 55.4
10 5 1 3 1.393 189 90 13.55 28692.5 402.8
11 7 1 1 1.364 246 31 11.86 20679.2 100.2
12 5 3 1 1.395 213 23 18.21 15879.5 77.1
13 7 1 1 1.363 247 32 11.63 20678.2 105.6
14 6 2 1 1.374 231 18 59.15 15895.1 58.6

Mathematical relationship generated using multiple linear regression analysis for the studied variables are
expressed as shown in Table 3.
Table 3: Multiple linear regression analysis
Y1 +1.36 A+1.39 B+1.39 C-0.022 AB+7.085 AC-0.027 BC-0.050 ABC
Y2 +245.91A+212.91 B+188.91 C+3.62AB+36.86 AC-45.14 BC-2698.81 A2BC
-394.81AB2C+818.01 ABC2
Y3 +30.06 A+19.78 B+98.65 C-61.42 AB-165.91 AC+132.38 BC
Y4 +11.43 A+17.98 B+13.27 C+178.57 AB+204.06 AC-53.17 BC-3222.27A2BC+1017.63 AB2C-
1028.63 ABC2
Y5 +20750.64 A+15951.93 B+28764.12 C-9268.19 AB-34314.40 AC+32494.26 BC-1.598 A2BC-
5.020 AB2C+3.90ABC2
Y6 +111.50 A+77.35 B+411.55 C-80.92 AB-687.35 AC+959.35 BC-18663.79 A2BC -26790.79
AB2C+41523.11 ABC2

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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels
The quartic mixture model represent the
quantitative effect of Water (A), Oil (B) and ratio
of surfactant: Co-surfactant (C) and their
interaction on Refractive index (Y1), Globule size
(Y2), Gel strength (Y3), Spreadability (Y4),
Mucoadhesive force (Y5) and Viscosity (Y6). The
values of the coefficient A, B and C are related to
the effect of these variables on the responses Y1 to
Y6. Coefficients with more than one factor term
and those with higher order terms represent
interaction terms and quadratic relationship
respectively. A positive sign represents a
synergistic effect, while a negative sign indicates an
antagonistic effect. A backward elimination
procedure was adopted to fit the data to the
quadratic mixture model. Both the polynomial
equations were found to be statistically significant
(P <0.01), as determined using ANOVA, as per the
provision of Design Expert software (DX9). Figure 2: Trace graph (piepel) shows the main
Refractive index of erythromycin nanogels was effect of water (A), oil (B) and surfactant: Co-
found to be in the range of 1.371– 1.395 as shown surfactant ratio (C) on refractive index.
in Table 2. The factorial equation for refractive
index exhibited a good correlation coefficient
(1.000) and the Model F-value of 771.58 implies
the model is significant. There is only a 0.01%
chance that an F-value this large could occur due to
noise. Values of "Prob > F" less than 0.0500
indicate model terms are significant. In this case A,
B, C, AB, AC, BC, ABC are significant model
terms. All the three variables having the positive
effect on the refractive index, which means these
factors, are directly proportional to the response.
The influence of the main and interactive effects of
independent variables on the refractive index was
further elucidated using the perturbation and 3D
response surface plots. The individual main effects
of A, B and C on particle size are as shown in
Figure 2. It is found that all the variables are having
interactive effects for the response Y1. The trace
graph (piepel), 2D contour, 2D real contour and 3D
response surface plots of the response Y1 are Figure 3: Response 2D contour plot represents
shown in Figure 2, 3, 4 and 5 to depict the the interaction between the water, oil and
interactive effects of independent variables on surfactant: Co-surfactant ratio affecting the
response Y1. refractive index.

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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels
this case A, B, C, A2BC are significant model
terms. It was found that all the variables are having
interactive effects for the response Y2. The trace
graph (piepel), 2D contour, 2D real contour and 3D
response surface of the response Y2 were shown in
figure 6, 7, 8 and 9 to depict the interactive effects
of independent variables on globule size. During
erythromycin nanogels preparation, we sonicated
the emulsion for 5 min using a probe sonicator set
at 50 Amplitude power. As a result, we achieved a
size under 250 nm globule sizes shown in figure 10.

Figure 4: Real contour graph represents the

interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the
refractive index.

Figure 6: Trace graph (piepel) shows the main

effect of water (A), oil (B) and surfactant: Co-
surfactant ratio (C) on refractive index.

Figure 5: 3D surface plot represents the

interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the
refractive index.
The independent variables A, B, C and the
quadratic term of A, B and C have significant Figure 7: Response 2D contour plot represents
effects on the globule size, since the Model F-value the interaction between the water, oil and
of 12.46 implies the model is significant. There is surfactant: Co-surfactant ratio affecting the
only a 0.65% chance that an F-value this large refractive index.
could occur due to noise. Values of "Prob > F" less
than 0.0500 indicate model terms are significant. In
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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels
Figure 8: Real contour graph represents the
interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the
refractive index.
Figure 9: 3D surface plot represents the
interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the
refractive index.
Figure 10: Particle size analyzer
Gel strength of erythromycin nanogels was found to
be in the range of 9-120 seconds as shown in Table
2. The factorial equation for response Y3 exhibited
a correlation coefficient (1.000) and the Model F-
value of 5.47 implies the model is significant.
There is only a 1.76% chance that an F-
value .Values of "Prob > F" less than 0.0500
indicate model terms are significant. In this case C
is a significant model term. The two variables were
having the positive effect on the gel strength, which
means these factors, were directly proportional to
the response. The influence of the main and
interactive effects of independent variables on the
gel strength was further elucidated using the
perturbation and 3D response surface plots. The
trace graph (piepel), 2D contour, 2D real contour
and 3D response surface of the response Y3 were
shown in figure 11, 12, 13 and 14 to depict the
interactive effects of independent variables on
response Y3.
Figure 11: Trace graph (piepel) shows the main
effect of water (A), oil (B) and surfactant: Co-
surfactant ratio (C) on gel strength.
Figure 12: Response 2D contour plot represents
the interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the gel
strength.
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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels

Figure 15: Trace graph (piepel) shows the main

effect of water (A), oil (B) and surfactant: Co-
Figure 13: Real contour graph represents the surfactant ratio (C) on spreadability.
interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the gel
strength.

Figure 16: Response 2D contour plot represents

the interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the
Figure 14: 3D surface plot represents the spreadability.
interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the gel
strength.
The response of Y4 was found to be in the range of
3.61- 64.64 gm.cm/sec as shown in Table 2. Results
of the equation indicate that the effect of A, B and
C is more significant. The Model F-value of 41.86
implies the model is significant. Values of "Prob >
F" less than 0.0500 indicate model terms are
significant. In this case A, B, C, AB, AC, BC,
A2BC are significant model terms. The influence of
the main and interactive effects of independent
variables on the spreadability was further
elucidated using the perturbation and 3D response
surface plots. The trace graph (piepel), 2D contour, Figure 17: Real contour graph represents the
2D real contour and 3D response surface plot interaction between the water, oil and
showing the main effects of A, B and C on the surfactant: Co-surfactant ratio affecting the
response Y4 in figure 15, 16, 17 and 18. spreadability.

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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels

Figure 20: Response 2D contour plot represents

Figure 18: 3D surface plot represents the the interaction between the water, oil and
interaction between the water, oil and surfactant: Co-surfactant ratio affecting the
surfactant: Co-surfactant ratio affecting the mucoadhesive force.
spreadability.

The mathematical model generated for response Y5

was found to be significant with F-value of 68.84 (p
< 0.0001). In this case A, B, C, AB, BC, A2BC,
AB2C, ABC2 were significant model terms. The P
values less than 0.0500 represented the significant
model terms as shown in Table 2. It was found that
all the variables were having interactive effects for
the response Y5. The trace graph (piepel), 2D
contour, 2D real contour and 3D response surface
of the response (viscosity) were shown in figure 19,
20, 21 and 22 to depict the interactive effects of Figure 21: Real contour graph represents the
independent variables on mucoadhesive force. interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the
mucoadhesive force.

Figure 22: 3D surface plot represents the

Figure 19: Trace graph (piepel) shows the main
effect of water (A), oil (B) and surfactant: Co-
surfactant ratio (C) on mucoadhesive force.
interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the
mucoadhesive force.
Viscosity of nanogels was found to be in the range
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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels
of 15.3-809cps as shown in Table 2.The factorial
equation for viscosity exhibited a good correlation
coefficient (1.000) and the Model F value of 6.92
which implied the model were significant. Values
of "Prob> F" less than 0.0500 indicate model terms
were significant. In this case C, ABC2 are
significant model terms. The trace graph (piepel),
2D contour, 2D real contour and 3D response
surface of the response (viscosity) were shown in
figure 19, 20, 21 and 22 to depict the interactive
effects of independent variables on mucoadhesive
force.

Figure 21: Real contour graph represents the

interaction between the water, oil and
surfactant: Co-surfactant ratio affecting the
viscosity.

Figure 19: Trace graph (piepel) shows the main

effect of water (A), oil (B) and surfactant: Co-
surfactant ratio (C) on viscosity.

Figure 22: 3D surface plot represents the

Figure 20: Response 2D contour plot represents interaction between the water, oil and
the interaction between the water, oil and surfactant: Co-surfactant ratio affecting the
surfactant: Co-surfactant ratio affecting the viscosity.
viscosity.

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Research article Rapports De Pharmacie Vol.3 (2), 2017, 371-383
ISSN: 2455-0507
100.0

95

90
3901.63
3838.35
3916.38
3776.76
85
3990.33
3978.82

80

75
1935.98
1998.25
70 2501.66
2552.95 556.49
2522.26
2341.86
65

60
1567.06 502.84

55 1776.19
3618.08 1507.79
3054.61

50 3593.81
807.65
760.76
786.25
832.53
751.39
719.55
45 774.80
647.90 426.75
%T
40
2791.10
2783.41
909.53
35 3016.03
893.55
2832.82
30

25
3361.85
3314.86
1318.00
20 3346.51
3513.01 1237.13
1474.05
1426.05
3493.82 1725.87
15 1460.58
1412.22 1266.22 946.99
3333.21
2992.13 1450.01
10 2950.89 1399.92
1339.10 984.31
3389.05 1351.75 1025.61
996.07
973.38
1201.08
5

0 2975.08
1174.46
1049.63
-5
3464.00
3428.50
3401.50 1374.50 1167.17
1132.00
1117.00
1088.50
1155.50
1148.50 1065.00
1071.39 961.50

-10.0
4000.0 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600 400.0
cm-1

Figure 23: Shows FTIR spectra of erythromycin

100.0

95

90

85

80
720.32

75 1783.18
3831.87
3873.06
3818.29
3799.31
70
2521.12 2314.36 746.22
2083.03
65 2335.38
758.38
2143.35
60
2243.05
2168.76
55 594.97
3100.08
781.89
3081.85
50

1626.25
45
%T
40 862.44
878.24 607.30
651.60
639.15
1967.95 988.18
35
3258.40
1406.34
30 1381.67
802.45 617.76

25 971.04
3323.51 1390.47
3310.58
3420.73
3297.35 2706.77
20 3278.60 1367.30 1171.56
3455.71 1459.67 1336.70 1123.44
3609.33 3359.26
1047.14 826.74
15 1155.14
1094.98
1029.83
1068.75
1258.87
10 3541.80
3588.31
3493.73
3476.70 2783.10
2799.10
1103.75
5 1061.71
838.07
927.08
0
1082.45 819.67
2950.03
2934.02 543.56
-5 2899.47 937.70 846.53
2966.00 953.00 515.50

-10.0
4000.0 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600 400.0
cm-1

Figure 24: Shows FTIR spectra of poloxamer 188

100.0

95

90

85

80

75

70
3802.26
3852.94
3838.00
65
2437.46
2415.20

60
2356.13
55

50 2186.69
2165.93

45 2207.87
850.94
%T
40 1539.97

2649.33 1965.60
35
1523.10 891.18

30 829.96
879.89
1605.74
735.10
25 1049.35
3613.09
3173.10
1034.98
1061.54
20 3181.19
3597.40 3198.56
700.97
870.92
3405.15
15
3582.27
1725.28 650.46
3317.55 1415.89
10 3213.90 1738.82
1456.02 1334.65 1023.32 661.64
3282.64 1233.16
3265.29
3226.34
3293.37 2997.21 686.82
3522.763359.81
5 945.60
3306.85 1135.21
3247.24 2879.76
1281.56
1253.05 1163.91
0 1144.13
3446.77 2869.92 1661.89 1001.48
2962.82
2981.38 1347.19
-5 2910.65 861.15
3376.01
3558.00
3543.00
3536.50
3422.00
3416.00
3388.503237.50 2972.50
2895.00 1387.00
1375.00
1362.50 983.50
965.50 672.00 528.50

-11.8
4000.0 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600 400.0
cm-1

Figure 25: Shows FTIR spectra of erythromycin and poloxamer 188

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 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels
90
80
70
60
% CDR
50
40
30
20
10
0
1 2 3 4
Time in hours
Figure-26: Showing the percentage of drug release
As depicted in Figure 23, 24 and 25 the FT-IR
spectra of erythromycin revealed high intensity
broad bands at approximately 2975.08, 2341.86,
1998.25 and 1725.87 cm−1. These peaks have also
been observed in a physical mixture of drug and
poloxamer 188 peaks at 2972.02, 2356.13, 1965.60
and 1725.28 cm−1.
Run 6 and Run 7 were selected according to
spreadability values. The in vitro release profile of
nanogels in PBS (pH = 6.8) is shown in Fig. 26.
Drug release at the end of 8 hours (approximately
81.3 and 82.4 %)
CONCLUSION
Erythromycin nanogels were prepared by using
probe sonicator. The application of factorial design
gave a statistically systematic approach for the
formulation of nanogels with ideal particle size. Oil
phase, water phase and surfactant: Cosurfactant
ratios were found to influence the globule size,
refractive index, gel strength, spreadability,
mucoadhesive force and viscosity of erythromycin
loaded nanogels. In vitro drug release study of
selected factorial formulations (run 6 and run 7)
showed 81.3 % and 82.4% release respectively at
the end of 8 hours. The overall results suggest that
erythromycin loaded nanogels could be a potential
option for topical delivery.
REFERENCE
[1] ME Davis, Z Chen, DM Shin, Nanoparticle
therapeutics: an emerging treatment
modality for cancer. Nat. Rev. Drug Discov.
7:771–782 (2008).
Run 6
Run 7
5 6 7 8 9
[2] D Peer, JM Karp, S Hong, OC Farokhzad, R
Margalit, R Langer. Nanocarriers as an
emerging platform for cancer therapy. Nat.
Nanotechnol. 2:751–760 (2007).
[3] N Wiradharma, Y Zhang, S Venkataraman,
JL Hedrick, YY Yang, Self-assembled
polymer nanostructures for delivery of
anticancer therapeutics. Nano Today 4: 302–
317 (2009).
[4] L Brannon-Peppas, JO Blanchette,
Nanoparticle and targeted systems for
cancer therapy, Adv. Drug Deliv. Rev.
64:206–212 (2012).
[5] M Elsabahy, KLWooley, Design of
polymeric nanoparticles for biomedical
delivery Applications. Chem. Soc. Rev.
41:2545–2561(2012).
[6] R Haag, F Kratz. Polymer therapeutics:
concepts and applications. Angew. Chem.
Int. Ed. 45:1198–1215 (2006).
[7] TM Allen, PR Cullis. Drug delivery
systems: entering the mainstream, Science
303: 1818–1822 (2004).
[8] RT Chacko, J Ventura, J Zhuang, S
Thayumanavan. Polymer nanogels: a
versatile nanoscopic drug delivery platform.
Adv. Drug Deliv. Rev. 64: 836–851 (2012).
[9] L Zha, B Banik, F Alexis. Stimulus
responsive nanogels for drug delivery. Soft
Matter7 5908–5916 (2011).
[10] AV Kabanov, SV Vinogradov. Nanogels as
pharmaceutical carriers: finite networks of
infinite capabilities. Angew. Chem. Int. Ed.
48: 5418–5429 (2009).
382
 Lim Kuan Ting et al,: Optimization and in-vitro characterization of erythromycin nanogels
[11] EA Murphy, BK Majeti, R Mukthavaram,
LM Acevedo, LA Barnes, DA Cheresh.
Targeted nanogels: a versatile platform for
drug delivery to tumors. Mol. Cancer
Ther. 10: 972–982 (2011).
[12] G Liu, Z An. Frontiers in the design and
synthesis of advanced nanogels for
Nanomedicine. Polym. Chem. 5:1559–1565
(2014).
[13] Y Jiang, J Chen, C Deng, EJ Suuronen, Z
Zhong. Click hydrogels, microgels and
nanogels: emerging platforms for drug
delivery and tissue engineering.
Biomaterials 35:4969–4985 (2014).
[14] FR Kersey, TJ Merkel, JL Perry, ME
Napier, JM DeSimone. Effect of aspect ratio
and deformability on nanoparticle
extravasation through nanopores. Langmuir.
28:8773-8781 (2012).
[15] AV Kabanov, SV Vinogradov. Nanogels as
pharmaceutical carriers: finite networks
of infinite capabilities. Angew Chem Int Ed.
48:5418-5429 (2009).
[16] VP Torchilin. Multifunctional, stimuli-
sensitive nanoparticulate systems for drug
Delivery. Nat Rev Drug Discov. 13:813-
827(2014).
[17] L Zha, B Banik, F Alexis. Stimulus
responsive nanogels for drug delivery. Soft
Matter. 7: 5908-5916 (2011).
[18] S Mura, J Nicolas, P Couvreur. Stimuli-
responsive nanocarriers for drug delivery.
Nat Mater. 12: 991-1003 (2013).
[19] M Motornov, Y Roiter, I Tokarev, S Minko.
Stimuli-responsive nanoparticles, nanogels
and capsules for integrated multifunctional
intelligent systems. Prog Polym Sci. 35:
174-211 (2010).
[20] MAC Stuart, WT Huck, J Genzer, M
Müller, C Ober, M Stamm, et al. Emerging
applications of stimuli-responsive polymer
materials. Nat Mater. 9:101-113 (2010).
[21] JK Oh, R Drumright, DJ Siegwart, K
Matyjaszewski. The development of
microgels/nanogels for drug delivery
applications. Prog Polym Sci. 33:448-
477(2008).
[22] C Solans, P Izquierdo, J Nolla, N. Azemar,
MJ Garcia-Celma, Nano-emulsions. Curr.
Opin. Colloid Interface Sci. 10:102–110
(2005).
[23] http://pharmaenfo.com/Excipients/excipient
Detail/Poloxamer
[24] Liow HinTeng, Jaya Raja Kumar,
LeenaiLeng, MVRA Maivizhi Selvi, R
Kanagambikai. Nanoparticle loaded
thermosensitive nasal in-situ gels for
delivery of loratadine: in- vitro & in-vivo
evaluation studies. Rapports De
Pharmacie.1:17-27(2015).
[25] MVRA MaivizhiSelvi, Jaya Raja Kumar, R
Kanagambikai, Lee Ali Leng, LiowHin
Teng. In-vitro and in-vivo evaluation of
nanoparticles loaded temperature induced
oral gel drug delivery system of acyclovir.
Rapports De Pharmacie.1 (2):81-89 (2015).
[26] Jaya raja Kumar, Selvadurai Muralidharan,
V Vijayan. Development and
pharmacological evaluations of econazole
nitrate microsperes enriched gel. Rapports
De Pharmacie. 1(1):32-38 (2015).
383