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Research article Rapports De Pharmacie Vol.

3 (2), 2017, 384-394


ISSN: 2455-0507
DEVELOPMENT AND CHARACTERIZATION OF QUERCETIN NANOGELS BY USING
SIMPLEX-LATTICE MIXTURE DESIGN
Shirley Wong Jing Wen, 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
Quercetin is a flavonoid with antioxidant/anti-inflammatory properties, quercetin nanogels are
developed as one of the most promising carriers for topical drug delivery. In this study, quercetin
loaded poloxamer based nanogels were utilized as a potential drug carrier for topical delivery.
Fourteen runs of nanogels were composed of water, oleic acid and poloxamer 407. A simplex-lattice
mixture design was used to optimize the process parameters including water phase (A), oil phase (B)
and surfactant: Co-surfactant ratio (C). Seven dependent variables globule size, pH, refractive index,
viscosity, gel strength, spreadability and bioadhesive force was measured as responses. The particle
size of nanogels was found to be 223.6-247.7nm. Gel strength was found to be in the range of 40.31-
299.52 seconds, and viscosity of formulations found to be in the range of 3939-25500 cps.
Keywords: Quercetin Nanogels, HPLC, Poloxamer 407, Simplex-lattice mixture design
INTRODUCTION
Quercetin (3,30,40,5,7-pentahydroxyflavone) is exposure. Anticancer activity of quercetin is not
a flavonoid present in a large number of edible preferable clinically due to low absorption when
vegetables and fruits [1,2]. This molecule has administered orally. To achieve targeted
many health-promoting effects, including therapeutic level of quercetin in systemic
improvement of cardiovascular health, reducing circulation, high dose is required which is
risk for cancer, and coping with inflammatory practically not beneficial [6]. So that we
disorders, mainly related to its strong prepared topical preparation of drug to avoid
antioxidant action, by which it upregulates the first pass metabolism and thereby improving the
endogenous free radical defenses [3,4]. permeation rate of formulation. Various
However, quercetin is extremely lipophilic in nanotechnological approaches have been used to
nature, so there is need to enhance the solubility enhance its solubility, dissolution rate, and
of Quercetin [5]. The main purpose of this hence, bioavailability, including solid
present work was to expand the application of dispersions, nanosuspensions, microemulsions,
mixed solvency technique to influence the solid lipid nanoparticles and prodrugs [7–11].
solubility of quercetin. In this present Therefore, a critical need exists to develop
investigation, we have objective that design and alternative formulative strategies to overcome
develop new suitable formulation with the shortcomings of quercetin nanogels and
increasing solubility and bioavailability. enhance its penetrability.
Quercetin containing topical preparation has MATERIALS AND METHODS
ability to inhabit oxidative stress and Materials:
inflammation which is induced due to UVB Quercetin and poloxamer 407 were obtained
Address for correspondence: from Sigma-Aldrich. Oleic acid and tween 80
Shirley Wong Jing Wen, was procured from R&M marketing, Essex, UK
Research student, and the other chemicals were used in the
AIMST University, experiment are analytical grade.
Bedong- Semeling, Kedah, Methods:
Malaysia 08100 Formulation of quercetin nanogels:

384
Shirley Wong Jing Wen,: Quercetin nanogels by using simplex-lattice mixture design
The preparation of nanogels as shown in (figure and was compressed to uniform thickness by
1) placing 1000g weight for 5 min. weight (50 g)
Determination of pH: was added to the pan. The time in which the
The pH of the nanogels was determined by upper glass slide moves over to the lower plate
using a calibrated PH meter (HANNA INS was taken as measure of spreadability [16].
PH211). Measurements were considered after S= ML/T
reaching equilibrium. The reading of all runs Where, M = weight tide to upper slide (g)
was noted. L = length moved on the glass slide (cm)
Viscosity studies: T = time taken (sec)
The viscosities of the various formulations were In-vitro drug release:
determined by using Brookfield programmable Quercetin loaded nanogels (0.05 g) were
DVII +Model pro II type (USA). The viscosity dispersed in flasks containing 100 mL
was noted in Centipoise [12]. phosphate buffer solution (PBS) (pH 7.4). The
Determination of mucoadhesive force: dissolution medium was kept under stirring at
The mucoadhesive force has been derived from 100 rpm min−1and at 37◦C. At predetermined
a previously published method [13,14]. A time intervals, 2 mL release medium was taken
section of sheep nasal mucosa was cut from the out from flask and replaced with 2 mL fresh
slaughter house and instantly fixed with PBS to keep the volume constant [17]. The
mucosal side out onto each glass vial using concentration of drug in the medium was deter-
rubber band. The vial with nasal mucosa was mined by using HPLC method.
connected to the balance in inverted position The solution was determined by RP HPLC
while first vial was placed on a height adjustable method. RP HPLC chromatographic separation
pan. The formulations were added onto the was performed on a Shimadzu liquid
mucosa of first vial. Then the height of second chromatographic system equipped with a LC-
vial was so adjusted that the mucosal surfaces of 20AD solvent delivery system (pump), SPD-
both vials come in intimate contact. Two 20A photo diode array detector, and SIL-
minutes time of contact was given to the vials. 20ACHT injector with 50μL loop volume. The
Then, the switch of the infusion apparatus was LC solution version 1.25 was used for data
opened to make the water drop into the glass collecting and processing (Shimadzu, Japan).
vial with a constant flow rate of 5 mL/min. The The HPLC was carried out at a flow rate of 1.0
weight of the water in the glass vial kept ml/min using a mobile that is phase constituted
increasing until the gel and the mucosal tissue of acetonitrile, 20mm AA: 20mm ACN (pH 5.5)
were detached. Mucoadhesive force, the (20:80, v/v), and detection was made at 354nm.
detachment stress (dyne/cm2), was determined The mobile phase was prepared daily, filtered
from the minimal weights that detached the gel. through a 0.45μm membrane filter (Millipore)
The sheep nasal mucosa pieces were changed and sonicated before use. A Thermo C18
for each measurement. column (25cm × 4.6mm i.d., 5μ) was used for
Determination of gel strength: the separation.
Gel strength was measured by placing 50 g of Optimization data analysis and validation of
formulation in a 100 ml graduated cylinder and optimization model
gelled at 37°C using thermostat. A piston of For the studied design, the simplex lattice
weight 27 g was placed onto the gelled solution design type was applied to fit full mixture
and allowed to penetrate 5 cm in the gel. Time component in terms of L_Pseudo equation with
taken by weight to sink 5 cm was measured added interaction terms to correlate the studied
[15]. responses with the examined variables using
Spreadability: Design Expert software version 10 (Stat-Ease,
For the determination of spreadability, excess of Minneapolis, MN). A simplex-lattice mixture
sample was applied in between two glass slides design of degree m consists of m+1 points of

385
Shirley Wong Jing Wen,: Quercetin nanogels by using simplex-lattice mixture design
equally spaced values between 0 and 1 for each data to the quadratic model. Both the
component. If m = 2 then possible fractions are polynomial equations were found to be
0, 1/2, 1. For m = 3 the possible values are 0, statistically significant (P<0.01), as determined
1/3, 2/3, 1. The points include the pure using ANOVA, as per the provision of Design
components and enough points between them to Expert software (DX10).
estimate an equation of degree m. This design During the quecertin nanogels development, a
differs from a simplex-centroid design by three-level 14 full factorial experimental design
having enough points to estimate a full cubic was used to identify and estimate the main and
model. interaction effects of three different formulation
These equations represent the quantitative effect factors water phase (A), oil phase (B), and
of water phase (A), oil phase (B) and surfactant: surfactant: Co-surfactant ratio (1:3) (C) on
Co-surfactant ratio (C) and their interaction on critical quality attributes of the developed
globule size (R1), pH (R2), Refractive Index nanogels. Based on the experimental design, the
(R3), Viscosity (R4), Gel Strength (R5), factor combinations yielded different responses
Spreadability (R6) and Bioadhesive Force (R7). as presented in Table 1. These results clearly
The values of the coefficient A, B and C are indicate that all the dependent variables are
related to the effect of these variables on the strongly dependent on the selected independent
responses R1, R2, R3, R4, R5, R6 and R7. variables as they show a wide variation among
Coefficients with more than one factor term and the 14 batches. Mathematical relationship
those with higher order terms represent generated in terms of L. pseudo components
interaction terms and quadratic relationship analysis for the studied variables are expressed.
respectively. A positive sign represents a Mathematical relationship generated using
synergistic effect, while a negative sign multiple linear regression analysis for the
indicates an antagonistic effect. A backward studied variables are expressed as shown in
elimination procedure was adopted to fit the Table 3.

Figure 1: Preparation of quercetin nanogels

386
Shirley Wong Jing Wen,: Quercetin nanogels by using simplex-lattice mixture design

Table-1: Factorial design of quercetin nanogels


C:P 188
Refract Gel Bioadhesive
A:Water B:OA :Tween Size Viscosity Spreadability
Run pH ive Strength Force
w/w w/w 80 nm cps gm.cm/sec.
Index seconds Dynes/cm2
(1:3)
1 6 1 2 240.1 3.56 1.378 18755 200.11 10.32 20989.3
2 4.6 1.6 2.6 225.4 3.9 1.394 6800 60.21 3.73 21324.3
3 5.3 1.3 2.3 229.3 3.95 1.386 4500 51.44 126.37 30250.3
4 5 2 2 231.6 3.58 1.401 17216 135.27 173.87 23904.5
5 5 1 3 229.6 4.18 1.395 10900 80.46 9.73 21894.9
6 4 1 4 224.8 4.07 1.414 25500 299.52 148.81 22626.8
7 4 3 2 247.7 3.89 1.419 3939 40.31 58.84 17019.7
8 4 3 2 246.7 3.87 1.419 3945 42.22 56.72 17009.1
9 5 2 2 232.4 3.59 1.401 17220 136.56 170.22 23900.3
10 6 1 2 242.3 3.59 1.378 18740 199.12 10.36 20985.1
11 4 2 3 227.4 3.56 1.408 23000 253.28 5.56 15890.1
12 4.3 2.3 2.3 223.6 3.46 1.402 7659 65.33 59.85 18359.4
13 4 1 4 224.2 4.06 1.414 25510 298.31 142.33 22620.3
14 4.3 1.3 3.3 226.5 4.13 1.407 3239 39.15 50.41 18359.4

Table 2: Multiple linear regression analysis


Size = +241.09A +247.09B +224.39C -49.23AB -14.29AC-35.09BC +9.61A2BC +9.61A2BC -742.79AB2C +481.75
ABC2
pH = +3.57 A +3.88 B +4.06 C -0.57 AB +1.44 AC -1.65 BC +16.89 A2BC-24.69 AB2C+19.60 ABC2
Refractive Index = +1.38A +1.42 B +1.41C +0.010 AB -3.850 AC -0.034 BC -0.34 A2BC -0.56 AB2C +0.38 ABC2
Viscosity = +18450.14 A +3644.64 B +25207.64 C +22303.55 AB -48473.35 AC +29537.65 BC-3.542 A2BC
+84369.73 AB2C -9.204 ABC2
Gel Strength = +196.91 A +38.56 B +296.21 C +51.07 AB -707.70 AC +300.28 BC -754.85 A2BC +224.35 AB2C
Spreadability = +12.33 A +59.77 B +147.56 C +559.90 AB -249.02 AC -360.58 BC +4561.09 A2BC -4180.79 AB2C -
2660.66 ABC2
Bioadhesive = +21051.78 A +17078.98 B +22688.13 C +19864.71AB +1133.04 AC -14940.56 BC +7.031A2BC -2.220
AB2C

Experimental design results revealed that the an F-value this large could occur due to noise.
mean glouble size of quecertin nanogels was Values of “Prob > F" less than 0.0500 indicate
significantly affected by water phase (A), oil model terms are significant. In this case A, B, C,
phase (B) and surfactant: Co-surfactant ratio AB, BC, AB2C, ABC2 are significant model
(1:3) (C). Globule size analysis of quecertin terms. The "Lack of Fit F-value" of 10.84
nanogels was found to be in the range of 223.6 – implies the lack of fit is significant. There is
247.7 nm as shown in Table 1 and Figure 3a. only a 3.02% chance that a "Lack of Fit F-
The Model F-value of 44.95 implies the model value" this large could occur due to noise. All
is significant. There is only a 0.03% chance that the three variables having the positive effect on

387
Shirley Wong Jing Wen,: Quercetin nanogels by using simplex-lattice mixture design
the globule size, which means these factors, are Figure-4: Response 2D contour plot
directly proportional to the response. The presenting the interaction between the water
influence of the main and interactive effects of phase, oil phase and surfactant: Co-
independent variables on the globule size was surfactant ratio affecting the globule size
further elucidated using the trace graph (piepel),
2D contour, 2D real contour and 3D response
surface plots are shown in Figure 3, 4, 5 and 6.

Figure-5: Response 2D real contour plot


presenting the interaction between the water
Figure-3a: Size distribution of nanogel phase, oil phase and surfactant: Co-
surfactant ratio affecting the globule size

Figure-3: Trace graph (piepel) showing the


main effect of water phase (A), oil phase (B)
and surfactant: Co-surfactant ratio (C) on
globule size
Figure-6: 3D surface plot presenting the
interaction between the water phase, oil
phase and surfactant: Co-surfactant ratio
affecting the globule size
Rheological behavior of quecertin nanogels was
found to be in the range of 3239-25510 cps as
shown in Table 1.The factorial equation for
viscosity exhibited a good correlation
coefficient (1.000) and the Model F value of
7.44 which implies the model is significant.
Values of "Prob> F" less than 0.0500 indicate
model terms are significant. In this case A, C,
AC are significant model. All the three variables
having the positive effect on the viscosity,
388
Shirley Wong Jing Wen,: Quercetin nanogels by using simplex-lattice mixture design
which means these factors, are directly
proportional to the response. The influence of
the main and interactive effects of independent
variables on the viscosity was further elucidated
using the perturbation and 3D response surface
plots. It is found that all the variables are having
interactive effects for the response (viscosity).
The trace graph (piepel), 2D contour, 2D real
contour and 3D response surface of the response
(viscosity) are shown in figure 7, 8, 9 & 10 to
depict the interactive effects of independent Figure-9: Response 2D real contour plot
variables on viscosity. presenting the interaction between the water
phase, oil phase and surfactant: Co-
surfactant ratio affecting the viscosity

Figure-10: 3D surface plot presenting the


interaction between the water phase, oil
phase and surfactant: Co-surfactant ratio
Figure-7: Trace graph (piepel) showing the affecting the viscosity
main effect of water phase (A), oil phase (B) Gel strength of quecertin nanogels was found to
and surfactant: Co-surfactant ratio (C) on be in the range of 39.15- 299.52 seconds as
viscosity shown in Table 1. The factorial equation for gel
strength exhibited a good correlation coefficient
(1.000) and the Model F value of 12.47 which
implies the model is significant. Values of
"Prob> F" less than 0.0500 indicate model terms
are significant. In this case A, C, AC, ABC2 are
significant model. All the three variables having
the positive effect on the gel strength, which
means these factors, are 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
individual main effects of A, B and C on gel
strength are as shown in Figure 1. It is found
that all the variables are having interactive
Figure-8: Response 2D contour plot effects for the response (gel strength) The trace
presenting the interaction between the water graph (piepel), 2D contour, 2D real contour and
phase, oil phase and surfactant: Co- 3D response surface of the response (viscosity)
surfactant ratio affecting the viscosity are shown in figure 11, 12, 13 & 14 to depict the

389
Shirley Wong Jing Wen,: Quercetin nanogels by using simplex-lattice mixture design
interactive effects of independent variables on
gel strength.

Figure-11: Trace graph (piepel) showing the


main effect of water phase (A), oil phase (B)
and surfactant: Co-surfactant ratio (C) on gel Figure-14: 3D surface plot presenting the
strength interaction between the water phase, oil
phase and surfactant: Co-surfactant ratio
affecting the gel strength
The spreadability was found to be significant
with F-value of 10.17 implies the model is
significant. There is only a 1.03 % 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 B, C,
AB, BC are significant model terms. The
influence of the main and interactive effects of
independent variables on the spreadability was
further elucidated using the trace graph (piepel),
Figure-12: Response 2D contour plot 2D contour, 2D real contour and 3D response
presenting the interaction between the water surface of the response shown in figure 15, 16,
phase, oil phase and surfactant: Co- 17 and 18.
surfactant ratio affecting the gel strength

Figure-15: Trace graph (piepel) showing the


Figure-13: Response 2D real contour plot main effect of water phase (A), oil phase (B)
presenting the interaction between the water and surfactant: Co-surfactant ratio (C) on
phase, oil phase and surfactant: Co- spreadability
surfactant ratio affecting the gel strength
390
Shirley Wong Jing Wen,: Quercetin nanogels by using simplex-lattice mixture design
significant. There is only a 0.06% 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, BC, A2BC, AB2C, ABC2 are significant
model terms. The relationship between the
dependent and independent variables was
further elucidated using trace graph (piepel), 2D
contour, 2D real contour and 3D response
surface of the response shown in figure 19, 20,
21 and 22.
Figure-16: Response 2D contour plot
presenting the interaction between the water
phase, oil phase and surfactant: Co-
surfactant ratio affecting the spreadability

Figure-17: Response 2D real contour plot


presenting the interaction between the water
phase, oil phase and surfactant: Co-
surfactant ratio affecting the spreadability Figure-19: Trace graph (piepel) showing the
main effect of water phase (A), oil phase (B)
and surfactant: Co-surfactant ratio (C) on
biodhesive force

Figure-18: 3D surface plot presenting the


interaction between the water phase, oil
phase and surfactant: Co-surfactant ratio
affecting the spreadability Figure-20: Response 2D contour plot
The mathematical model generated for presenting the interaction between the water
biodhesive force was found to be significant phase, oil phase and surfactant: Co-
with F-value of 33.07 implies the model is surfactant ratio affecting the spreadability
391
Shirley Wong Jing Wen,: Quercetin nanogels by using simplex-lattice mixture design
144.2
140

130

120

110

100

90
5904.23

80
5761.21
5774.11 5330.19
5812.95 5310.99
6006.19 5536.18
5724.05
5694.10
5715.80
5749.10
5797.02
6257.435916.34 5398.25
5381.46
70 6630.38
6640.19 5806.33 5355.61
5885.39
5925.83
5939.78
6770.09 6040.92 5596.895236.40
5252.58
6166.34
6030.71 5277.58
5839.37 5413.01 5025.22
6459.50
6348.03 5284.82
6558.52 6105.21 5169.93
4855.89 4344.54
6081.06
%T 60 5853.34 4293.06
4255.88
4268.44
4752.94 4241.80
5044.94 4136.43
6094.22 4022.62
3987.18
4034.56
4553.01 4060.43
6071.03 5084.87 962.70
50 914.05 564.07
571.92
3677.04 904.23
3712.43 2279.14
2347.38
6944.09 3837.51 2122.79
2310.76
2150.20
2333.94
2173.99
2374.26
3737.21 1049.63
40 945.04
6704.58
1031.11
994.02
6853.08
1112.84
1103.71
30 7051.40
9104.17 1094.81 590.13
7308.68
865.81
1013.39
20 7801.24 7224.67
7836.33
7779.79 683.84
669.56
9837.30 3572.85
8344.31 1424.02
10
7960.51 7483.24 2717.72
2739.88
7976.31 2810.86 1171.93 734.05
615.83
721.76
7613.12 3379.03
3560.65 2763.67 1439.07
1387.69 836.93
3024.04 1412.17
9768.72
0 3391.00
3275.77
3319.12
1397.63 1200.15
9518.14 2951.89 1189.73
3348.71
3446.20
3328.83
3055.00 1258.45
9930.00
9659.00
9445.00
9259.50
9155.50
8950.00
8691.50
8422.00
8283.50
8210.50
8089.00
7921.50
7719.50
7418.00
7156.00 3540.00
3525.00
3514.00
3429.00
3362.02
3311.00
3295.00
3169.00 1660.00
1520.50 622.00
602.00
-10

-20.0
10000.0 9000 8000 7000 6000 5000 4000 3000 2000 1500 1000 370.0
cm-1

Figure-24: FTIR spectra of quercetin


429.0

400

Figure-21: Response 2D real contour plot 350

300

presenting the interaction between the water 250

200

phase, oil phase and surfactant: Co- 150


5407.06
5352.81
5305.55
5287.99
5285.69

surfactant ratio affecting the spreadability 100

50
5293.23 5270.31 5048.50
5395.93
0 5311.12
5095.26 5023.44 4944.88
%T 5089.42
5343.74 5315.88 4950.01
5416.99 5125.73
5297.02 5123.41 5105.57 5061.93 5027.86
-50 5239.21 5130.45 5068.79
5374.78 5181.94 5039.05
5361.72 5189.43 5102.19 5043.16 4984.95 4968.31
5250.94 5217.99 5197.97 5117.88 4996.42
5366.65 4980.90
5019.07
-100 5332.05 5144.95
5154.51 5001.76
5338.78 5213.98 5114.03
5348.54 5321.24 5260.67 5169.96 5149.89
5223.49 5172.95
5401.51
-150 5413.02 5083.80
5245.89
5387.99 5014.16
5009.99

5276.41
-200 4955.78
5178.79
5265.60 5234.80
5427.01 5327.06 5226.73 5209.98
5204.01 5159.12
5165.24 5138.00 5078.14 5031.86 4989.16
5054.50 4961.21
-250 5422.50 5357.50 4975.50
5382.50

-300

-350

-400

-428.3
5432.1 5400 5300 5200 5100 5000 4937.9
cm-1

200.0
Figure-25: FTIR spectra of poloxamer 407
190

180

170

160

150

140

130

120

110

100

90

80

70
6282.57
60 6362.65
6768.51
6655.04
6862.86 6086.10
5663.55
6491.60 6053.56
%T 50 6432.46
6468.81 6110.28
6345.25
5435.94
5468.66
5458.06
5406.69
6943.75 6448.87 5523.91
5724.60 5306.36
5325.88
5540.16
5556.99
5875.37
40 5975.22
6186.78
5963.12
7003.63 6321.35
4546.01
4613.28
4492.26
4512.38
30 5110.74
5076.36
5134.81
5169.23
5156.38
4346.36
20 3751.01
8762.00 7900.00 7120.83 3984.66
3736.41
7875.53 7356.34
10 418.69
7713.87 2397.82

Figure-22: 3D surface plot presenting the


2043.24
2008.69
09936.08
9911.86
9959.59
9863.87
9883.86 1706.86
9662.17 3658.77 961.56
9800.07 8837.34 8236.99 3108.19 2602.46
2558.61 1162.271013.77
-10 8260.33 3491.33 3125.44
3224.982921.10 1344.64 1132.79 953.59
939.29
994.26
908.89
793.30
8887.74 3619.873309.593024.90
3089.53 2585.83 1509.22 1045.83
1178.981038.04
1021.09
1108.20
2977.04
3206.87 2772.59 1152.32
1075.82
3061.81
-20 9733.00
9551.50
9463.00
9320.50
9121.50 8678.00
8483.00
8314.00
8291.00
8119.50
8005.00 7566.00
7466.00 3568.00
3559.91
3465.50
3452.00
3432.85
3438.08
3424.50
3406.50
3400.50
3188.50
3174.50
3391.50 3002.50
2988.03
2900.50
2876.50 1648.00
1609.501440.00
1325.00
1311.00
1212.00
1189.00
1091.00
1065.50
1054.50
984.00
972.00
892.00
768.50
754.00
733.50
618.00
520.00

interaction between the water phase, oil -30

-40

-50

phase and surfactant: Co-surfactant ratio -60

-70

-80

affecting the spreadability -93.4


10000.0 9000 8000 7000 6000 5000
cm-1
4000 3000 2000 1500 1000 370.0

mAU
Figure-26: FTIR spectra of quercetin and
QUERCETIN/4.119

3000
poloxamer 407
2500
FT-IR analysis was performed to ensure that no
2000 chemical interaction between the drug and the
1500
polymer had occurred. FT-IR spectra of
quercetin, poloxamer 407, quercetin and
1000
poloxamer 407 are shown in Fig.24, 25 &26.
500 CONCLUSION:
0
In the future, topical drug delivery will be used
extensively to impart better patient compliance.
0.0 1.0 2.0 3.0 4.0 5.0 6.0 min Since nanogels is helpful in enhancing
Figure-23: Typical chromatogram of spreadability, adhesion and viscosity, this novel
quecertin drug delivery become popular. Moreover, they
392
Shirley Wong Jing Wen,: Quercetin nanogels by using simplex-lattice mixture design
will become a solution for loading hydrophobic The statistical analysis (analysis of variance,
drugs in water soluble gel bases for the long ANOVA) showed that generated models for
term stability. Similarly in the study, topical globule size, pH, refractive index, viscosity, gel
nanogels of quercetin were formulated and strength, spreadability and bioadhesive force
subjected to physicochemical studies i.e. were significant (p < 0.05), indicating that three
rheological studies, spreading coefficient listed responses are well described by the
studies, gel strength and bioadhesion strength. proposed models.

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