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International Journal of Universal Pharmacy and Bio Sciences 3(6): November-December 2014
INTERNATIONAL JOURNAL OF UNIVERSAL
PHARMACY AND BIO SCIENCES IMPACT FACTOR 2.093***
ICV 5.13*** Pharmaceutical Sciences RESEARCH ARTICLE……!!!
“DEVELOPMENT AND OPTIMIZATION OF MEDICATED CHEWING
GUM CONTAINING DIMENHYDRINATE” Abhijit V. Jadhav *, Shrinivas K. Mohite
Department of Pharmaceutics, Rajarambapu College of Pharmacy, Kasegaon-415 404, Sangli,
Maharashtra, India.
KEYWORDS:
Dimenhydrinate,
Medicated Chewing
Gum, Nausea, Patient
compliance.
For Correspondence:
Abhijit V. Jadhav*
Address: Department of
Pharmaceutics,
Rajarambapu College of
Pharmacy, Kasegaon-415
404, Sangli, Maharashtra,
India.
E-mail:
abhijit_jadhav26@rediff
mail.com
ABSTRACT
Oral route is most convenient for the patient therefore it is very popular
in the society. Chewing gum delivery system is convenient, easy to
administer anywhere, anytime and is pleasantly tasting, making it patient
acceptable. It is a novel drug delivery system containing masticatory gum
base with pharmacologically active ingredient and intended to use for
local treatment of mouth diseases or systemic absorption through oral
mucosa. Chewing gum is the convenient and effective means of rapidly
administering Dimenhydrinate, as it is readily soluble, permeable and
used to relieve symptoms of nausea, motion sickness and vomating. In
present study medicated chewing gum of Dimenhydrinate has been
formulated using gum base, sorbitol, mannitol, magnesium stearate, agar,
menthol. This medicated chewing gum was prepared by direct
compression method and formulated by using various compositions of
gum base and agar like 30-35-40 % and 10-15-20 % accordingly. In the
formulation Agar was used as an emulsifying agent and it was found that
it acted on the drug release to some extent. When concentration of Agar
was increased, drug release was also found to be increased.
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INTRODUCTION :
Medicated chewing gum is solid, single-dose preparations that have to be chewed & not swallowed;
chewing gums contain one or more active ingredient that is released by chewing. A medicated
chewing gum is intended to be chewed for a certain period of time, required to deliver the dose,
after which the remaining mass is discarded. During the chewing process the drug contained in the
gum product is released from the mass into saliva & could be absorbed through the oral mucosa or
swallowed reaching stomach for gastro-intestinal absorption. Medicated chewing gum is a novel
drug delivery system containing masticatory gum base with pharmacologically active ingredient
and intended to use for local treatment of mouth diseases or systemic absorption through oral
mucosa. Chewable tablets and chewing gum have been very well received by the parents for use in
children with full dentition. Children in particular may consider chewing gum as a more preferred
method of drug administration compared with oral liquids and tablets; hence attempt is made to
prepare medicated chewing gum to increase compliance. The use of medicated chewing gum is
feasible in local treatment of diseases of oral cavity as well as treatment of systemic conditions.
Chewing gum has been used for centuries to clean the mouth and freshen the breath. The first patent
for the production of chewing gum was filed in 1869 and was issued to WF Semple in Ohio under
US patent no. 98,304. A medicated chewing gum containing acetyl salicylic acid was commercially
introduced in 1928. In 1991, chewing gum was approved as a term for pharmaceutical dosage form
by the Commission of European Council.
Dimenhydrinate is a histamine H1 antagonist used in nausea, vomiting, dizziness, and vertigo. It
has also been used in veterinary applications. It generally causes less drowsiness and sedation than
Diphenhydramine. The mechanism of action of Dimenhydrinate is related to it’s central
anticholinergic actions. It diminish vestibular stimulation and depress labyrinthine function. An
action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect.
Dimenhydrinate's anti-emetic effect is probably due to H1 antagonism in the vestibular system in
the brain. The half-life of Dimenhydrinate is 1-4 hr., the protein binding of drug is 99%.
MATERIALS AND METHODS
Materials: The dimenhydrinate was obtained as a gift sample from S. S. Pharmachem Tarapur,
Thane. Agar was obtained as a gift sample from SD Fine lab Chemicals, Mumbai. Gum base was
obtained as a gift sample from Cafosa SPA, Spain. All other chemicals and solvents used were of
analytical grade.
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Table 1: Ingredients of medicated chewing gum tablets.
Contents
(mg)
Formulation Batches
F1 F2 F3 F4 F5 F6 F7 F8 F9
Drug 25 25 25 25 25 25 25 25 25
Gum Base 300 300 300 350 350 350 400 400 400
Agar 100 150 200 100 150 200 100 150 200
Sorbitol 100 100 100 100 100 100 100 100 100
Menthol 10 10 10 10 10 10 10 10 10
Mannitol 225 175 125 175 125 75 125 75 25
Mg. Stearate* 10 10 10 10 10 10 10 10 10
Aerosil 10 10 10 10 10 10 10 10 10
Xylitol 20 20 20 20 20 20 20 20 20
Total 800 800 800 800 800 800 800 800 800
*All quantities were taken in mg, *Mg= Magnesium.
Preparation of the chewing gum tablet
Direct compression method was used to prepare the chewing gum tablet. Weighed quantity of gum
base powder and active ingredient were mixed well in morter. To it, accurately weighed agar,
sorbitol and menthol were added. The xylitol was added as sweetening agent. After thorough
mixing, the lubricant and glidant were also mixed. The powder was compressed into tablets using
flat faced punches of 13 mm diameter by keeping hardness between 1-2 kg/cm2
using KBr press,
Technosearch.
Characterization of Dimenhydrinate
Melting Point of Drug
Melting point of Dimenhydrinate was determined by open capillary method using Thiel’s tube. The
temperature at which the drug started melting was noted. Average of three results was noted as the
melting point of drug.
λmax Determination
UV-spectrum of pure Dimenhydrinate was taken in artificial saliva pH 7.4. Drug (10 mg) was
dissolved in 100 ml Artificial Saliva pH 7.4 to obtain the stock solution of concentration 100 µg/ml.
From this stock solution, 1 ml was withdrawn and diluted to 10 ml. Absorbance was checked using
UV-spectrophotometer. It should give 1 peak corresponding to its λmax at 277 nm.
Calibration curve of Dimenhydrinate in artificial saliva pH 7.4
Calibration curve of Dimenhydrinate has been carried out in artificial saliva pH 7.4. 10 mg of drug
was dissolved in 100 ml of dissolution medium to obtain stock solution of concentration 100 μg/ml.
From this 0.2 ml, 0.4 ml, 0.6 ml, 0.8 ml, 1.0 ml, 1.2 ml and 1.4 ml aliquots were withdrawn and
diluted to 10 ml to give the solutions of concentration 2-14 μg/ml. Absorbances were recorded at
277 nm using UV-Spectrophotometer (Jasco V630, Japan) and standard curve was plotted and
values of slope, intercept and coefficient of correlation were calculated.
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Preparation of calibration curve of Dimenhydrinate by HPLC:
The solutions of concentration 10, 20, 30, 40, 50, 60 μg/mL were prepared from Dimenhydrinate
stock solution in solvent mixture [Methanol: Acetonitrile] (85:15) and the same solvent mixture
was used as a mobile phase for performing HPLC analysis using C18 column.
Powder X - Ray diffraction (PXRD):
PXRD was performed busing a D/Max X-ray fluorescence spectrophotometer with a CuKa line as
the source of radiation. Standard runs were carried out using a voltage of 56 kV, a current of 182
mA and a scanning rate of 2⁰ min-1 over a 2-theta range of 5-50⁰C.
Infrared (IR) Spectroscopy:
IR study was carried out to check purity of drug. It was determined by Fourier Transform Infrared
spectrophotometer (FTIR Jasco 4100, Japan). The baseline correction was done by blank
background measurement. The scanning range was 400-4000 cm-1
.
Differential Scanning Calorimetry (DSC):
Thermograms of pure drug, physical mixture and optimized formulation were recorded using
Mettler-Toledo DSC 821e instrument equipped with an intracooler. Samples were sealed in
aluminum pans and heated at the rate of 10oC/min from 30
oC-300
oC under nitrogen atmosphere of
flow rate 10 ml/min.
RESULTS AND DISCUSSION
Melting Point
Temperature was noted at which solid drug changes into liquid. It was found to be 1040C. (std. -
102-1070C)
max Determination
The standard solution of Dimenhydrinate of concentration 10 g/ml showed maximum absorbance
of 0.2743 at 277 nm wavelength in artificial Saliva pH 7.4.
Fig. 1: UV spectrum of Dimenhydrinate
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Calibration curve of Dimenhydrinate
The data for the calibration curve of Dimenhydrinate in artificial Saliva pH 7.4 is shown in table
no.2 the calibration plot is as shown in the figure 2.The Beer’s Lambert’s law was found to be
obeyed over the range of 0-14 μg /ml.
Fig. 2: Calibration curve of Dimenhydrinate in artificial Saliva pH 7.4
Table 2: Data for standard Calibration curve
R2 0.9998
Slope 0.0325
Intercept 0.00136
Preparation of calibration curve of Dimenhydrinate by HPLC
Calibration curve of Dimenhydrinate by HPLC was determined, using C18 column equipped with
UV detector at 277 nm using Methanol: Acetonitrile (85:15) as mobile phase. Equation of this
calibration curve was utilized to determine the unknown plasma concentration of Dimenhydrinate.
Calibration curves and values of slope, intercept and R2 are shown in Fig.3 and table 3 respectively.
Fig. 3: HPLC overlain chromatogram of dimenhydrinate
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Table 3: Various constants for calibration curves
Parameter Value for calibration curve in
Methanol : acetonitrile (85:15)
Slope 110375
Intercept 1681.85.
‘r2’ 0.9996
Powder X - Ray diffraction (PXRD)
X-ray diffraction analysis was performed (Fig.4). Existence of high intensity peaks at diffraction
angles 2-theta of 17.5⁰, 19.4⁰, 21.0⁰, 25.4⁰, 27.3⁰ and 28.8⁰ suggesting that dimenhydrinate is
purely crystalline in nature.
Fig.4: XRD of dimenhydrinate
FTIR Spectroscopy
IR spectra of Dimenhydrinate shows characteristic peak of C-Cl stretching at 750.174 cm-1
, C=O
stretching 1688.37 cm-1
, N-H Bend 1645.95cm-1
, C-C Stretch 1453.5cm-1
and Ter. amine 671.106
cm-1
. The FTIR spectra of optimized formulation showed same peak as that of pure drug. From
FTIR spectra it was observed that there was no any incompatibility between drug and carrier.
Fig. 5: IR spectra of Dimenhydrinate
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Fig. 6: IR of optimized formulation (F6)
Differential Scanning Calorimetry (DSC) The DSC curves obtained for pure drug and optimized
formulation were shown in figures. DSC analysis of crystalline drug showed single sharp
endothermic peak at 104.7 0C correspondence to its melting point. It is revealed from DSC
thermogram of optimized formulation showed sharp endothermic peak at 105.440C correspondence
to melting point of pure drug. From both of the DSC thermogram, it was concluded that there was
no any interaction between drug entity and excipients.
Fig. 7: DSC thermogram of Dimenhydrinate
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Fig. 8: DSC thermogram of formulation F6.
Evaluation of Powder Blends
Bulk densities of powder blends were found between 0.5013-0.5541 g/cc. Tap densities of powder
blends were found between 0.5860- 0.6810 g/cc. The angle of repose values varied from 19.33 -
23.63. Carr’s Index values varied from 8.70 % to 18.35 %. From these values it was observed that
all these blends had good flow properties.
Table 4: Evaluation of powder blend (F1-F9)
Batch Bulk Density
(g/cc)
Tapped
Density (g/cc)
Carr’s Index
(%)
Hausner’s
Ratio
Angle of
Repose (ɵo)
F1 0.5230 ±0.004 0.6410 ± 0.026 18.35 ± 3.884 1.22 ± 0.06 20.20 ±0.56
F2 0.5540 ±0.0017 0.6403 ± 0.0011 13.36 ± 0.11 1.15 ±0.001 20.53 ±1.28
F3 0.5301 ±0.008 0.6810 ± 0.007 8.70 ± 1.778 1.09 ± 0.02 21.47 ± 0.07
F4 0.5330 ±0.011 0.5862 ± 0.007 9.09 ± 1.312 1.12 ± 0.05 20.10 ± 0.08
F5 0.5270 ±0.002 0.6230 ± 0.008 15.34 ± 0.754 1.18 ± 0.01 19.33 ± 0.12
F6 0.5013 ±0.0012 0.5901 ±0.0017 15.02 ± 0.05 1.17 ±0.0007 24.07 ±0.005
F7 0.5270 ±0.0017 0.5860 ±0.0034 10.06 ± 0.83 1.11 ±0.010 22.66 ±1.03
F8 0.5541 ±0.002 0.6590 ± 0.007 15.96 ± 0.955 1.19 ± 0.01 21.54 ± 0.05
F9 0.5496 ±0.0017 0.5866 ±0.0023 10.51 ± 0.05 1.11 ±0.0007 23.63 ±1.004
*All values are expressed as mean ± SD; n = 3
Evaluation of chewing gum tablet
All batches of prepared tablets were evaluated for the different parameters. Weight variation for
prepared tablets was found within specifications of Indian Pharmacopoeia. Average weight for
tablet was in the range of 800 –801 mg. Hardness values for tablets of all formulations were in the
range of 3.5-4.2 Kg/cm2. Thickness values for of all tablets were in the range of 3.8-4.3 mm.
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Friability of all the formulations was in the range of 0.68-0.98 %. Drug contents for all the
formulations were found in the range of 94.53-99.04 %.
Table 5: Evaluation of dimenhydrinate Chewing gum tablet
Batch
Code
Color Weight
uniformity*
(mg)
Thickness
*
(mm)
Stickiness Hardness
*
(Kg/cm2)
Friability
*
(%)
Uniformity
Content*
(%)
F1 O. W 801.6 ± 1.15 4.1 ± 0.1 NS 3.8 ± 0.05 0.91 ±0.02 94.53± 0.33
F2 O. W 802 ± 1 3.8 ± 0.1 NS 4 ± 0.05 0.98 ±0.01 94.82± 0.40
F3 O. W 800.1 ± 1.52 4.3 ± 0.1 NS 3.9 ± 0.1 0.89 ±0.02 95.20± 0.45
F4 O. W 798.3± 1 4.1 ± 0.15 NS 3.8 ± 0.2 0.86± 0.06 98.06± 0.32
F5 O. W 800.1 ± 2.08 4.3 ± 0.15 NS 3.7 ± 0.15 0.74± 0.03 98.00± 0.22
F6 O. W 800 ± 1 3.8 ± 0.1 NS 3.5 ± 0.20 0.80 ±0.01 99.04± 0.42
F7 O. W 801.3 ± 1.52 4.3 ± 0.1 NS 4.1 ± 0.15 0.85± 0.02 96.96± 0.54
F8 O. W 800 ± 0.57 4.1 ± 0.15 NS 4.2 ± 0.15 0.68± 0.07 97.25± 0.38
F9 O. W 801.6 ± 0.57 3.9 ± 0.11 NS 4 ± 0.1 0.71± 0.06 97.42± 0.33
Mean ± SD (n=3) O.W: Off White * (n=20) N.S: Non sticky
In-vitro Drug Release
The medicated chewing gum tablet mainly consisted of gum base, active ingredient, emulsifying
agent, plasticizer, sweetening agent and flavoring agent. In the present formulations, we have varied
the concentrations of the Gum base and Agar which act as a base and emulsifier respectively. All
formulations were non sticky in nature. But, the formulation F6 released the drug more than 90 %.
This was due to the softness of the formulation F6 developed during the in-vitro dissolution study.
Formulation F6 contained highest amount of agar and less amount of base. The drug release from
various formulations was found to be in the range of 61.89 % - 96.88 %. It was found to be least for
F1 having the least concentration of both the base and the emulsifier, whereas it was found to be
maximum in F6 in which the concentration of both base and the emulsifier was found to be
optimum. From the in-vitro drug release data, it was observed that an increase in the concentration
of softener may reduce the hardness of the chewing gum tablet also it was observed that the
increase in the concentration of emulsifier and decrease in the concentration of base may increases
drug release from formulation.
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Table 6: Cumulative % drug release of formulations F1-F9
Sr. No. Time
[min]
% Cumulative drug release*
F1 F2 F3 F4 F5 F6 F7 F8 F9
1 0 0 ±0.00 0 ±0.00 0 ±0.00 0 ±0.00 0 ±0.00 0 ±0.00 0 ±0.00 0 ±0.00 0 ±0.00
2 5 12.74
±0.025
22.06
±0.55
29.46
±0.44
15.84
±0.45
26.82
±0.34
27.51
±0.58
13.88
±0.40
23.19
±0.45
31.89
±0.16
3 10 25.05
±0.59
43.75
±0.34
45.18
±0.62
27.67
±0.70
35.31
±0.74
38.55
±0.63
25.92
±0.72
47.34
±0.53
55.03
±0.65
4 15 37.54
±0.55
57.79
±0.64
58.96
±0.35
44.05
±0.47
54.59
±0.96
67.19
±0.61
39.66
±0.23
56.33
±0.34
59.94
±0.86
5 20 50.11
±0.015
63.83
±0.21
67.34
±0.29
55.02
±0.31
69.37
±0.26
80.35
±0.72
49.88
±0.64
66.07
±0.69
67.59
±0.75
6 25 57.48
±0.56
67.16
±0.68
71.54
±0.74
58.29
±0.54
79.47
±0.42
88.07
±0.83
56.26
±0.54
68.33
±0.74
77.45
±0.46
7 30 61.89
±0.35
70.45
±0.45
75.96
±0.37
67.20
±0.49
84.63
±0.33
96.88
±0.78
62.62
±0.66
72.66
±0.48
82.57
±0.34
Fig. 9: Comparative % cumulative drug release profile of formulations F1-F9
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Data Analysis of Formulations: Traditional designing of the pharmaceutical formulations are
based on time consuming approach of changing one variable at a time which does not take into
consideration the joint effect of independent variables. Thus, factorial design can serve as an
essential tool to understand the complexity of the pharmaceutical formulations. The results can be
expressed either as simple linear or second order polynomial equation to statistically evaluate the
responses obtained after experiments. A 32
full factorial design was selected and the 2 factors were
evaluated at 3 levels, (table). The amount of gumbase (X1) and agar (X2) were selected as
independent variables and the dependent variables were hardness and percent drug release at 30 min
(% DR). The data obtained was treated using Stat-Ease Design Expert 9.0.2.0 software and
analyzed statistically using analysis of variance (ANOVA).
Table 7: Design summary
Response Name Unit Observations Analysis Min. Max.
Y1 Hardness kg/cm2 9 Polynomial 3.5 4.2
Y2 %DR Percent (%) 9 Polynomial 61.89 96.88
Table 8: The responses of all formulations
Responses X1 X2 Hardness
(kg/cm2)
%DR
(%)
F1 -1 -1 3.8 61.89
F2 -1 0 4 70.45
F3 -1 +1 3.9 75.96
F4 0 -1 3.8 67.20
F5 0 0 3.7 86.63
F6 0 +1 3.5 96.88
F7 +1 -1 4.1 62.62
F8 +1 0 4.2 72.66
F9 +1 +1 4 82.57
The drug release for 9 batches (F1-F9) showed a wide variation in responses Y1 and Y2. The
hardness was found to be decreasing from 3.8 to 3.5 if the concentration of independent variables
i.e. agar was increased. But as the concentrations of these independent variables were increased,
eventually the drug release was found to be increased from 61.89 to 96.88. The data clearly
indicated that hardness and %DR were strongly dependant on the selected independent variables.
The equations related with responses of hardness and %DR to transformed factors is shown below.
Hardness (kg/cm2) = + 3.93 + 0.22X1 - 0.27X2 - 0.050X1X2 – 0.083X1
2 – 0.033 X2
2 –
0.050X1
2 X2 + 0.050 X1 X2
2 …..Equation 1
(R2= 0.87)
%Drug Release = + 84.51 + 2.60X1 + 14.84X2 + 1.47X1X2 - 11.39X12 - 2.40X2
2 -
6.33X12X2 – 0.77X1X2
2 …..Equation 2
(R2= 0.99)
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In equation no. 1, positive sign for gum base (X1) and negative sign of agar (X2) indicates that the
hardness was increased with an increase in the concentration of gum and was decreased with an
increases in the concentration of agar.
In equation no. 2, the positive sign for gum base (X1) and positive sign of agar (X2) indicates that
percent drug release after 30 minutes increases as amount of gumbase and agar increases. The
information, the equation conveyed was the basis to study the effects of variables. The regression
coefficient values are the estimates of the model fitting. The R2 was high indicating the adequate
fitting of the quadratic model.
All the polynomial equations were found to be statistically significant (P˂0.05), as determined
using ANOVA, as per the provision of Design Expert software. The polynomial equation can be
used to draw conclusion after considering the magnitude of coefficient and the mathematical sign it
carries; i.e. positive or negative.
a. ANOVA Study:
Evaluation and interpretation of research findings are utmost important and P-value serves a
valuable purpose in these findings. ANOVA and Multiple regression analysis were done using Stat-
Ease Design Expert 9.0.2.0 software. Table 9 and 10 represents ANOVA for the dependent
variables hardness and %DR respectively. The coefficient of X1 and X2 were found to be significant
at P˂0.05 and thus confirmed significant effect of both the variables on the selected responses.
Increasing the amount of gum base resulted in the decrease in the hardness but drug release was
found to be increased and vice versa i.e. increasing the amount of agar resulted in the increase in the
drug release but hardness was found to be decreased.
Table 9: Analysis of variance for hardness (kg/cm2)
Source Sum of
Squares
Degree of
Freedom
Mean
Square
F Value P Value Model
Significant/Nonsignificant
Model 0.42 7 0.063 9.09 0.0251 Significant
X1 0.042 1 0.020 2.88 0.0339 Significant
X2 0.027 1 0.045 6.48 0.02383 Significant
X1X2 0.023 1 0.023 3.24 0.0322 Significant
(X1)2 0.029 1 0.29 42.32 0.0974 Significant
(X2)2 0.036 1 0.036 5.12 0.0264 Significant
X12X2 0.021 1 0.021 3.00 0.033 Significant
X1X2 2 0.083 1 0.083 0.12 0.7877 Significant
Residual 6.944 1 6.944 - - -
Core Total 0.45 8 - - - -
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Table 10: Analysis of variance for percent drug release at 30 min (%DR)
Source Sum of
Squares
Degree of
Freedom
Mean
Square
F Value P Value Model
Significant/Nonsignificant
Model 1036.23 7 148.03 3356.76 0.0133 Significant
X1 13.57 1 13.57 307.76 0.01362 Significant
X2 440.45 1 440.45 9987.56 0.0064 Significant
X1X2 8.64 1 8.64 196.00 0.0454 Significant
(X1)2 259.24 1 259.24 5878.38 0.0083 Significant
(X2)2 11.52 1 11.52 261.22 0.0393 Significant
X12X2 53.51 1 53.51 1213.37 0.0183 Significant
X1X2 2 0.79 1 0.79 17.93 0.1477 Significant
Residual 0.044 1 0.044 - - -
Core
Total
1036.28 8 - - - -
b. Response Surface Plot: The quadratic surface model obtained from the regresion analysis was
used to build up contour and 3-D graphs in which the responses were represented by curvature
surface as a function of independent variables. The releationship between the response and
independent variables can be directly visualized from the response surface plots. The response
surface plots were generated using Design Expert 9.0.2.0 software and are presented in figure.
These were used to observe the effects of independent variables on the studied responses such as
hardness and % DR respectively. Graphical presentation of the data helped to show the relationship
between the response and the independent variables. The information given by graph was similar to
that of mathematical equation obtained from statistical analyses.
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Fig. 10: Contour plot for hardness
Fig. 11: Response 3-D surface plot for hardness
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Fig. 12: Contour plot for percent drug release at 30 min
Fig. 13: Response 3-D surface plot for percent drug release at 30 min
CONCLUSION
In present work chewing gum formulations were prepared in the tablet form by using agar and gum
base. This property is essential for the chewing gum base because it eliminates the possibility of
dissolution of gum base in saliva. From the results obtained in this work, it can be concluded that
synthetic gum base can be used as an excellent agent for formulation of chewing gum. For chewing
gum formulations all studies like stickiness, weight variation, friability and in-vitro release test
were performed. All the formulations were found to be complied for weight variation and
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uniformity of active content tests. It was also found that the chewing gum tablets were not friable
which confirmed the integrity of the formulation. In-vitro release test was performed using
modified disintegration apparatus for tablet. From the in vitro drug release data it was concluded
that drug release from the chewing gum tablet was satisfactory. In the formulation agar was used as
a emulsifier and it was found that it acted on the drug release to some extent. When concentration of
agar was increased, drug release was also found to be increased.
ACKNOWLEDGEMENTS:
The authors are grateful to S. S. Pharmachem Tarapur, Thane and Cafosa, Spain for providing gift
sample of Dimenhydrinate and Gum base respectively. Authors are also thankful to Shivaji
University, Kolhapur and Rajarambapu College of Pharmacy, Kasegaon for providing facility for
DSC studies and all research work respectively.
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