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Research J. Pharm. and Tech.

14(5): May 2021

ISSN 0974-3618 (Print) www.rjptonline.org


0974-360X (Online)

RESEARCH ARTICLE

Formulation and Evaluation of Medicated Chewing gum consisting of


Dextromethorphan and Guaifenesin for the treatment of cough
Muthukumar. S*, Nijanthan. S, Vinesha. R, Sundarajan. R, Sridevi. M, Salabha. A
Department of Pharmaceutics, KMCH College of Pharmacy, Coimbatore.
*Corresponding Author E-mail: pharmmuthu@gmail.com

ABSTRACT:
Common cold is the most frequently recurring disease in the world and is a leading cause of doctor visits and
missed days from school and work. Cold reliever medicated chewing gum (MCG) will be a definitive patient
acceptable solution for this condition. Dextromethorphan hydrobromide and guaifenesin will be easily released
from chewing gum into the salivary fluid within few minutes of chewing and can be easily permeated from oral
mucosa by the pressure created by the chewing action and absorbed to a larger extent into the systemic
circulation. Therefore, ultimately patients will get quick relief from symptoms of common cold with greater
compliance compared to other conventional dosage forms. This study mainly focuses on taste masking of
dextromethorphan hydrobromide and guaifenesin with Kyron T-114, its formulation development in the MCG
form and its quality and performance evaluation with the study of potential factors affecting drug release by 3 2
full factorial experimental design. Formulation ingredients, such as elastomers, softeners, bulking agents, play an
important role in the feel of the final product and its consistency; while sweeteners and flavours play a very
essential character in its sensory properties. Inter individual variation in chewing frequency and chewing
intensity is the main factor which affects release of active ingredient from MCG; while salivary dilution and
involuntary swallowing are main reasons for variability in the absorption site, i.e., either from buccal mucosa or
from gastrointestinal tract.

KEYWORDS: Medicated chewing gum, taste masking, quality performance, full factorial experimental
design, Dissolution.

INTRODUCTION: Medicated chewing gum are appropriate for the


Medicated chewing gums (MCG) are solid, single dose treatment of diseases of the oral cavity and the throat
preparations that contain one or additional active because they can be retained within the mouth for an
ingredients that are released by chewing1. This drug extended period of time3. Most of the drug released from
delivery system provides extra patient benefits and the gum through mastication is rapidly absorbed via the
compliance, giving many advantages over tablets or buccal cavity due to its large vascularization; therefore, a
liquid formulations therein, the therapeutic system is not faster absorption results in a shorter duration of action.
to be swallowed and this will increase patient Alternatively, drug released from medicated chewing
compliance, particularly for geriatrics and pediatrics gum which is not absorbed through the oral cavity
with swallowing disorders; moreover, the product can be membranes will be swallowed and reach the stomach in
taken anyplace and at any time because it does not a very fine dispersed form, thus being easily available
require liquids to assist swallowing2. for gastro-intestinal absorption with a consequent fast
onset of action. Drugs absorbed via the buccal cavity
have direct access to the systemic circulation which
bypasses the intestinal and hepatic first-pass metabolism,
thus potentially increasing their extent of absorption.
Received on 08.01.2020 Modified on 26.03.2020 Therefore, it might be possible to administer a reduced
Accepted on 25.06.2020 © RJPT All right reserved dose in chewing gum in contrast to other oral drug
Research J. Pharm. and Tech. 2021; 14(5):2445-2451. delivery systems4.
DOI: 10.52711/0974-360X.2021.00430

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Why use chewing gum as a drug delivery system?5: neutralization, fresh breath, disinfection, anti-caries,
Chewing gum provides new competitive advantages over antiplaque, antifungal, antibacterial are available9.
conventional drug delivery system. They have fast onset
of action and high bioavailability, with pleasant taste. MATERIALS AND METHODS:
They exhibit higher compliance (easy and discreet MATERIALS USED:
administration without water) and ready for use. They Dextromethorphan, Aspartame, Titanium Dioxide
have high acceptance by children. (Caplin Point), Guaiphenesin (Sterile Gene), Kyron T-
114 (Corell Pharma), Health in gum (Cafosa Gum),
Absorption of drug across the oral mucosa6: Peppermint oil, Menthol, Talc, PEG, Magnesium
The oral cavity is point of entry for oral drug stearate (KMCH college of Pharmacy).
formulations but their contact with the oral mucosa is
brief. So, in to order to take advantages of these METHODOLOGY:
properties or to treat the mucosa locally, this delivery Analytical method for dextromethorphan
system have been designed to prolong residence in this hydrobromide and guaiphenesin:
area. The total surface area available for drug absorption Preparation of standard stock solution:
is quite limited being only approximately 100cm2. The A standard stock solution containing 1mg/ml is prepared
oral cavity is rich in blood vessels and lymphatic, so by dissolving 100mg of DXM in 100ml of water. A
rapid onset of action and high blood levels obtained standard stock solution containing 1mg/ml is prepared
quickly. In order to absorb orally, the drug must be by dissolving 100mg of GUA in 100ml of water.
dissolved in saliva. Extremely hydrophobic materials
will not dissolve well and are likely to be swallowed Preparation of working standard solution:
intact unless a specialized delivery system is used to From stock solution 10ml is further dilute to 100ml with
prevent them to mucosa. distilled water to get the solution having concentration
100μg/ml. From the above stock solution 10ml is further
Procedure for preparing chewing gum7: dilute to 100ml with distilled water to get the solution
Three types of manufacturing processes are available for having concentration 10μg/ml.
the production of chewing gum.
1. Melting method or conventional production process Determination of absorption maximum:
2. Cooling, grinding and tableting method Dextromethorphan hydrobromide:
3. Direct compression process From the above working standard solution, Transfer 5ml
into a 10ml volumetric flask and make up the volume to
Therapeutic uses of medicated chewing gum: the mark with distilled water to prepare a concentration
The use of sugar free gum to counteract dental caries by of 5μg/ml. Then scan the sample in UV-VIS
stimulation of saliva secretion has led to a more Spectrophotometer in the range 200-400nm using
widespread use and acceptance of gums. It has been reagent blank and find the wavelength corresponding to
proved that chewing non-MCG increases plaque pH, maximum absorbance (λ max)10.
stimulates saliva flow and decrease decay8. MCG
containing Chlorhexidine for treatment of gingivitis and Guaiphenesin:
plaque has been available. The use of Medicated From the above working standard solution, Transfer 5ml
Chewing Gum in the treatment of oral infections has also into a 10ml volumetric flask and make up the volume to
been reported [18]. The active ingredient is released from the mark with distilled water to prepare a concentration
the Medicated Chewing Gum and sufficient of 5μg/ml. Then scan the sample in UV-VIS
concentration is achieved in the oral cavity to prevent or Spectrophotometer in the range 200-400nm using
treat local conditions of oral cavity. Chewing Gum is reagent blank and find the wavelength corresponding to
also useful delivery system for agents intended for maximum absorbance (λ max)11.
systemic delivery. Drug that is released from gum within
oral cavity can be absorbed via buccal mucosa. The Preparation of calibration curve:
MCG can also be used as an alternative tool to buccal
and sublingual tablets which are intended to act From the above working standard stock solution transfer
systemically because active ingredient is released more 2ml, 4ml, 6ml, 8ml, 10ml into series of 10ml volumetric
uniformly and cover greater area of absorption in oral flask and the volume is made up to the mark with
cavity. Oral diseases are prevented or cured with distilled water to prepare a concentration of 2µg/ml,
Medicated Chewing Gum. MCG for systemic effect in 4µg/ml, 6µg/ml, 8µg/ml, 10µg/ml.
conditions like vitamin C deficiency, pain and fever, • Measure the absorbance of DXM hydrobromide at
alertness, motion sickness, smoking cessation, as well as maximum absorbance (λ max) against reagent blank
for local effect in the conditions like plaque acid and a calibration curve is constructed. Measure the

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Research J. Pharm. and Tech. 14(5): May 2021

absorbance of the sample solution, and determine the FORMULATION OF DRUG – RESIN COMPLEX:
amount of the drug by referring to the calibration Accurately weighed 31.5 gm of resin was dispersed in a
curve or computed from the regression equation. beaker containing 300 ml of distilled water and allowed
• Measure the absorbance of GUA is measured at to swell for 25-30 minutes. The pH of resin solution was
maximum absorbance (λ max) against reagent blank adjusted to 6.0-6.5 by using 1 M KOH. Accurately
and a calibration curve is constructed. Measure the weighed 10.5gm of dextromethorphan and guaiphenesin
absorbance of the sample solution, and determine the was added slowly and stirred for 3-4 hr. During stirring,
amount of the drug by referring to the calibration pH of solution was measured frequently and adjusted to
curve or computed from the regression equation. 6.0-6.5 by using 1 M KOH. After 3-4 hr, the drug resin
complex (DRC) was separated from dispersion by
DRUG EXCIPIENT COMPATIBILITY STUDIES: filtration and washed with three portions of 75 ml of
FT-IR Spectroscopy: distilled water [17]. Complex was dried and then
IR spectra was compared and checked for any shifting in evaluated for taste and drug-loading efficiency [18].
functional peaks and non-involvement of functional
group. The samples were studied using FTIR JASCO Effect of drug-resin ratio:
4100 in the wavenumber range from 500 to 4,000 cm−1 Ratio of drug to resin can greatly impact on complex
12 formation and ultimately affects taste masking ability. It
.
was necessary to find out the optimum drug to resin
PREFORMULATION EVALUATION: ratio. To optimize the ratio, different proportion of drug
Evaluate the Pre-compression parameters such as Bulk to resin was taken as mentioned in Table 4. As per
Density, tapped density, Carr’s Index and Hausner’s different proportion, drug-resin complex was formed as
ratio which are indicative parameters for flow and shown in procedure which was mentioned earlier19.
compressibility with formulated chewing gum13.
Table 1: Composition of drug/ resin formulation: Drug:Resin (1:3)
- (110:330) [ DRUG-Dextromethorphan(10mg),
POST FORMULATION EVALUATION: DRUG/RESIN QUANTITY FOR EACH TABLET
Texture analysis, Uniformity of mass (weight variation (mg)
test), Uniformity of content, Friability test, In-vitro drug Ratio 1:1 1:2 1:3 1:4
release study [14-16]. Dextromethorphan 10 10 10 10
Guaiphenesin 100 100 100 100
Kyron T -114 110 220 330 440

Table 2: Selection and optimization of excipient in dextromethorphan and guaiphenesin MCG formulation Guaiphenesin(100mg) :
RESIN-Kyron T-114(330mg)]
S. No INGREDENTS F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12
1 DRUG: RESIN 440 440 440 440 440 440 440 440 440 440 440 440
2 HEALTH IN GUM 649 638 627 616 605 594 615 614 612 611 610 610
3 MENTHOL 11 11 11 11 11 11 11 11 11 11 11 11
4 PEPPERMINT OIL 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4
5 ASPARTAME 11 22 33 44 55 33 33 33 33 33 33
6 AEROSIL 1.1 2.2 3.3 4.4 5.5 4.4
7 TALC 11
8 Mg- STEARATE
9 PEG
10 Tio2
TOTAL 1100 1100 1100 1100 1100 1100 1100 1100 1100 1100 1100 1100
S. No INGREDENTS F13 F14 F15 F16 F17 F18 F19 F20 F21 F22 F23
1 DRUG: RESIN 440 440 440 440 440 440 440 440 440 440 440
2 HEALTH IN GUM 598 587 567 556 593 588 582 577 571 566 555
3 MENTHOL 11 11 11 11 11 11 11 11 11 11 11
4 PEPPERMINT OIL 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4
5 ASPARTAME 33 33 33 33 33 33 33 33 33 33 33
6 AEROSIL 4.4 4.4 4.4 4.4 4.4 4.4 4.4 4.4 4.4 4.4 4.4
7 TALC 22 33 44 55 22 22 22 22 22 22 22
8 Mg- STEARATE 5.5 11 16.5 11 11 11 11
9 PEG 5.5 11 16.5 11
10 Tio2 11
TOTAL 1100 1100 1100 1100 1100 1100 1100 1100 1100 1100 1100

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EVALUATION OF FACTORS AFFECTING DRUG the validity of the model generated. Subsequently, the
RELEASE FROM MCG: resultant actual experimental data of the response
Selection and optimization of factors affecting % drug properties were quantitatively compared with those of
release from MCG by 32 Full Factorial Experimental the predicted values by regression as well as x2 values.
Design Independent significant factors [chewing time Then linear regression plot between observed and
(A) and amount of gum base (B)] affecting the predicted values of the response properties was drawn
dependent factor (% CTZ release from MCG) were first using MS-Excel.
extracted out by means of ANOVA and then extracted
Table 4: Experimental testing runs along with their variable
factors were optimized by 32 Full factorial experimental factors
design. Here full factorial 32 designs were used for the Experimental test run Chewing time Chewing gum
optimization procedure, because it is suitable for 1 10 70
investigating the quadratic response surfaces and for 2 10 80
3 15 75
constructing a second order polynomial model, thus
4 10 75
enabling optimization of the chewing time and the 5 15 80
amount of gum base to achieve sufficient drug release 6 5 75
from MCG20. Mathematical modeling, evaluation of the 7 5 80
ability to fit to the model, and response surface 8 15 70
methodology(RSM) were performed by employing 9 5 70
Design-Expert® software(Version 7.1.2, Stat-Ease Inc., RESULTS and DISCUSSION:
Minneapolis, MN). RSM is a collection of mathematical Estimation of absorption maximum (λmax):
and statistical techniques useful for the modeling and The λmax of DXM and GUA was estimated by scanning
analysis of problems in which a response of interest is the 10µg/ml concentration of the drug solution in buffer
influenced by several variables and the objective is to solution of phosphate pH 6.8. It showed the λmax for
optimize this response21. The most extensive dextromethorphan at 273nm and guaiphenesin at 278nm.
applications of RSM are in the industrial world,
particularly in situations where several input variables Preparation of standard curves:
potentially influence some performance measure or The standard curves of DXM and GUA prepared
quality characteristic of the product or the process. This separately by using phosphate buffer pH (6.8). The linear
performance measure or quality characteristic is called correlation coefficient was found to be 0.994 for
the response. DXMand 0.999 for GUA obeys the Beer’s law within
the concentration range of 2 to 10µg/ml.
Table 3: Independent and dependent variables along with their
levels
Factors Levels used Response
(Independent variable) (dependent variable)
-1 0 +1 Drug release Drug
A Chewing time 5 10 15 (DXM) release
B Chewing gum 70 75 80 (GUA)

Statistical analysis of the data and validation of the


model:
Various RSM computations for the current optimization
study were performed employing Design Expert
software (Version8.0.0.2, Stat-Ease Inc, Minneapolis,
MN). Polynomial models including interaction (A*B)
and quadratic terms (A2 or B2) were generated for the Figure 1: Calibration curve of DXM in phosphate buffer in pH 6.8
response variable using the Multiple Linear Regression
Analysis (MLRA) approach. Statistical validity of the
polynomials (A and B) was established on the basis of
ANOVA provision in the Design Expert software. A
model is considered significant if the P-value
(significance probability value) < 0.05. 2D contour plots
and 3D response surface graphs were constructed using
the same software. One final formulation corresponding
to the predicted amount of gum base was chewed
according to the predicted chewing time and three
additional random check points covering the entire range
of experimental domain were carried out to determine Figure 2: Calibration curve of GUA in phosphate buffer in pH 6.8
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Drug excipient compatibility studies:


From FT-IR analysis, it was found that there is no
prominent shift in function group peaks. Therefore ther
is no incmpatibility between the drug and the excipient.
Effect of drug – resin complex formation:
DXM and GUA was a bitter drug so, Kyron T-114, an
ion weak cations exchange resin was selected for the
taste masking of combination of both DXM and GUA.
The effect of drug – resin ratio was studied. Drug and
resin were used in different proportion like 1:1, 1:2 and
1:3 respectively. The Drug-kyron T-114 in ratio 1:3 was
showing drug loading of DXM and GUA were 83% and
89%. Thus 1:3 ratio was selected for formulation Figure 3: Texture analysis graph for MCG
development.
Evaluation of medicated chewing gum:
Table 5: Effect of Drug- Resin ratio on % of drug loading In-vitro dissolution study:
Sl. Drug: Resin % Drug Loading % Drug From the results mentioned in Table 19, it was seen that
No Ratio of DXM Loading of GUA
1 1:1 65 58
F23 showed drug release of 95.94% for DXM and
2 1:2 79 73 96.06% for GUA at the end of 25 minutes.

3 1:3 86 89 Table 9: In-vitro Drug release for DXM-GUA medicated chewing


gum (F23) formulation
Table 6: Pre-Formulation studies TIME(MIN) % DRUG RELEASE % DRUG RELEASE
Batch Bulk Tapped Angle of Carr’s Hausner’s FOR DXM FOR GUA
code density density repose (ɵ) index ratio 0 0 0
(g/ml) (g/ml) (%) 5 54.38±4.42 46.16±1.27
F23 0.68±0.014 0.85±0.021 29º41’±1.2 20 1.25 10 77.5±1.77 74.34±2.97
15 88.75±1.77 92.22±1.37
Formulation development: 20 93.13±0.88 94.65±0.33
Post formulation evaluation: 25 95.94±0.44 96.06±0.40
Texture analysis:
As the texture analyzer probe compressed DXM-GUA- Evaluation of factors affecting drug release from mcg
MCG, a small constant force was needed to reach the optimization of drug release from MCG by 32 FFED:
breaking point imitated the initial biting resistance or To develop an MCG drug delivery system, the amount of
gum firmness, i.e. a bearing load of 4903.583 g/cm as gum base (%) and chewing time (min) are the most
presented important factors affecting the drug release profile,
regardless of the core composition. A multivariate
Table 7: Texture analysis report for MCG optimization strategy was carried out with the aim of
Test ID Batch Hard- Sticki- finding the optimum amount of gum base and chewing
ness ness time to achieve a sufficient amount of drug release
G G
Force 1 Force 2 within few minutes of chewing. DXM-GUA release
Start Batch Unknown profiles of the nine experimental runs performed in 3 2
Unknown Full Factorial Experimental Design (FFED) in
Tablet Unknown 4903.583 4903.583 accordance with Table10.
smoothness1
End Batch Unknown
Table 10: Experimental 32 = 9 test experimental run with
Unknown
corresponding response
Average: Unknown(F) AVERAGE 4903.583 4903.583
Factor 1 Factor 2 Response 1 Response 2
("BATCH")
Run A:Chewing B:Gum Drug release Drug release
S.D. Unknown(F) STDEVP 0.000 0.000
time base (DXR) (GUA)
("BATCH")
min % % %
C.V. Unknown (F) STDEVP 0.000 0.000
1 10 70 83.8 82.6
("BATCH")/
AVERAGE 2 10 80 88.4 86
("BATCH")*1 3 15 75 92.3 93.1
00 4 10 75 85.2 85.6
5 15 80 93.8 94.2
Table 8: Post-Formulation studies 6 5 75 74.7 75.3
Batch Hardness Friability Weight variation 7 5 80 78.7 72.5
code (kg/cm2) (%) (mg) 8 15 70 91.6 89.8
F23 3.78±0.019 0.27±0.007 1095.33±2.081 9 5 70 72.8 71.6

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Multiple regression and mathematical model ANOVA for Quadratic model:


building: Response 2: Drug release (GUA)
The targeted response parameters were statistically Source Sum of df Mean F- p-
analyzed by applying one-way ANOVA (analysis of Squares Square value value
Model 585.52 5 117.10 169.83 0.0007 significant
variance), at the 5% significance level and the A-Chewing 554.88 1 554.88 804.72 <
significance of the model was estimated using the time 0.0001
statistical package Design-Expert®. The individual B-Gum 12.62 1 12.62 18.29 0.0235
parameters were evaluated using the F-test, and the base
mathematical relationship was generated between the AB 3.06 1 3.06 4.44 0.1257
A² 7.87 1 7.87 11.41 0.0432
factors (dependent variables) and response (independent B² 7.09 1 7.09 10.29 0.0491
variable) using multiple linear regression analysis, for Residual 2.07 3 0.6895
determining the levels of factors which yield optimum Cor Total 587.59 8
dissolution responses. A second-order polynomial
regression equation that fitted to the data is as follows: Factor coding is Coded.
Sum of squares is Type III - Partial
DR = C + b1A + b1B + b12AB + b11A2 + b22B2 The Model F-value of 169.83 implies the model is
Where c is the intercept representing the arithmetic significant. There is only a 0.07% chance that an F-value
averages of all the quantitative outcomes of nine runs; this large could occur due to noise.
b1, b2, b12, b11 and b22 are the coefficients computed
P-values less than 0.0500 indicate model terms are
from the observed experimental values of DR; and A and
significant. In this case A, B, AB, A², B² are significant
B stand for the main effects. The terms AB, A 2, and B2i model terms. Values greater than 0.1000 indicate the
= 1 and 2 represent the interaction and quadratic terms, model terms are not significant. If there are many
respectively, used to simulate the curvature of the
insignificant model terms (not counting those required to
designed sample space. Factor effects of the 32 FFED
support hierarchy), model reduction may improve your
model and associated P-values for the response (drug
model.
release) are represented in Table (drug release DXM)
and Table (Drug release GUA), a factor is considered to Here the P value (Drug release GUA) for the term AB
influence the response if the effects significantly differ (0.1257) was greater than 0.100. Therefore, a backward
from zero and the P-value is not more than 0.100. The elimination procedure was adopted to fit the data into
predicted equation of % drug release in terms of coded predictor equations. The final equation for the %
factors is mentioned below: predicted drug release (DR) is given below:
DR (DXM) = +85.28 + 8.58A +2.12B -0.9250AB – DR (GUA) = +85.99 + 9.62A +1.45B– 1.98A2-1.88B2
1.82A2+0.7833B2
DR (GUA) = +85.99 + 9.62A +1.45B +0.8750AB – Where A is the chewing time in minutes, B is the
1.98A2-1.88B2 Amount of gum base in %.
Where A is the chewing time in minutes and B is the The equations represent the quantitative effect of factors
amount of Gum base in %. ANOVA for Quadratic model (A and B) upon the response (Drug release DXM and
GUA). Coefficients with one factor represent the effect
Response 1: Drug release (DXR)
of that particular factor while the coefficients with more
Source Sum of df Mean F-value p-
Squares Square value than one factor and those with second order terms
Model 480.17 5 96.03 1128.59 < Significant represent the interaction between those factors and the
0.0001 quadratic nature of the phenomena, respectively. A
A-Chewing 442.04 1 442.04 5194.83 < positive sign in front of the terms indicates synergistic
time 0.0001
B-Gum 26.88 1 26.88 315.91 0.0004
effects while the negative sign indicates the antagonistic
base effect of the factors.
AB 3.42 1 3.42 40.22 0.0079
A² 6.60 1 6.60 77.57 0.0031 Response surface analysis:
B² 1.23 1 1.23 14.42 0.0321 The quadratic models generated by regression analysis
Residual 0.2553 3 0.0851 were used to construct the 2-dimensional contour plot
Cor Total 480.43 8 and 3-dimensional response surface plot in which
Factor coding is Coded. response parameter DR was represented by a curvature
Sum of squares is Type III - Partial surface as a function of A and B A numerical
The Model F-value of 1128.59 implies the model is optimization technique using the desirability approach
significant. There is only a 0.01% chance that an F-value was employed to develop a new formulation with the
this large could occur due to noise. desired responses.

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Table 11: Composition of optimum and random checkpoint formulations, the predicted and experimental values of responses and
percentage prediction error
Formulation composition Observed value Predicted value Chicalvalue %Relative error
DXM GUA DXM GUA DXM GUA DXM GUA
15:80 93.8 94.2 94.019 94.064 0.0005 0.0002 -0.233 +0.145
12.265:79.248 90.3 89.8 90.800 90.147 0.0028 0.0013 -0.550 +0.169
10.594:78.262 88.1 86.4 87.915 87.316 0.0004 0.0096 +0.210 -1.049
8.116:74.384 80.1 81.2 81.493 81.916 0.024 0.0063 -1.70 -0.874
5:70 72.8 71.6 72.619 71.931 0.0006 0.0015 +0.249 -0.460

In this study optimization was performed with REFERENCES:


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14. Instrumental Texture Analysis Method adopted from official website of
compressible taste masked MCG of Dextromethorphan Brookfield: -www.brookfieldengineering.com/ products/texture-
hydrobromide-Guaiphenesin present a better alternative analysis/qts-25.asp.
15. S. J. Daharwal, Veena Devi Thakur, Bhanu Pratap Sahu. The preformulation
to any other dosage form because it will give quick study of Ambroxol HCl for formulation of medicated chewing gum. Asian J.
symptomatic relief from common cold due to direct Research Chem. 6(9): September 2013; Page 868-870.
intraoral absorption without producing sedation. 16. Azra Shaikh, Ankit Agrawal, Neetesh K Jain, Mahesh Kumar Gupta.
Formulation and Evaluation of Medicated Chewing Gum of Dolasetron as
Moreover, Dextromethorphan hydrobromide- an Antiemetic Agent. Journal of Drug Delivery and Therapeutics. 2017;
Guaiphenesin-MCG can be taken anywhere anytime 7(4):125-128.
17. Shiv Kumar Gupta, Babita Kumar, Pramod Kumar Sharma. Study on Taste
without preventing patient from living an active life Masking of Ranitidine HCl Using Ion Exchange Resin. Asian J. Pharm.
which promotes very high patient acceptance and higher Tech. 3(2): April-June. 2013; Page 60-62.
18. S.D. Ghanchi, S.C. Dhawale. Taste Masking Technologies of
patient compliance. Pharmaceuticals. Research J. Pharm. and Tech, 2011; 4(10); 1513-1518.
19. T.N. Patel, R.P. Patel, B.V. Patel, Taste masking of topiramate by newer
ACKNOWLEDGEMENT: range of ion exchange resin, International Journal of Pharmaceutical
Sciences and Nanotechnology, 2010; 3(3); 1105-1110.
The authors are grateful to the authorities of KMCH 20. Anderson MJ, Whitcomb PJ. DOE Simplified - Practical Tools for Effective
College of Pharmacy, Coimbatore for the facilities. Experimentation. 2nd ed. New York NY: Productivity Inc.; 2007.
21. Anderson, MJ, Whitcomb PJ. RSM Simplified – Optimizing Processes
Using Response Surface Methods for Design of Experiments. New York
CONFLICT OF INTEREST: NY: Productivity Inc; 2008.
The authors declare no conflict of interest.

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