WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Lakshmi et al. World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 6.647

Volume 6, Issue 12, 1167-1175 Research Article ISSN 2278 – 4357

FORMULATION AND EVALUATION OF DOMPERIDONE CANDY

LOZENGES

B. Moulika Lakshmi*, Brahma K., G. Swathi, S. Sravani, P. Indira Rao and

Dr. P. Shailaja

A.U. College of Pharmaceutical Sciences, Department of Pharmaceutical Technology,

Andhra University, Visakhapatnam, Andhra Pradesh, India.

Article Received on
ABSTRACT
12 October 2017, In spite of several dosage forms available in the market for effective
Revised on 01 Nov. 2017,
Accepted on 22 Nov. 2017 action, the lozenges finds a special importance as they are the best
DOI: 10.20959/wjpps201712-10601 dosage forms for formulating large dose medicaments. The anatomy of
mouth and cheek favours easy and effective systemic absorption of
drug and also better patient compliance especially for paediatrics and
*Corresponding Author
B. Moulika Lakshmi geriatrics due to their palatable taste imparted by the excipients.
A.U. College of Domperidone is a selective serotonin receptor (5-HT3) antagonist and
Pharmaceutical Sciences, its lozenges are mainly used for the treatment of chemotherapy induced
Department of
nausea and vomiting. In the present study lozenges dosage form is
Pharmaceutical Technology,
chosen due to their benefits of good patient compliance due to its taste,
Andhra University,
Visakhapatnam, Andhra increased bioavailability, reduced gastric irritation, reduced first pass
Pradesh, India. metabolism and increased onset of action when compared to its tablet
dosage form which is in practice conventionally. The preparation
process involves mixing of Domperidone with all excipients, used in the formulation in
different ratios by using heat congealing technique in which sucrose and dextrose heated
separately up to 600c fusioned together and reheated upto 1600c after which polymer HPMC
K 100M, HPMC E5 and all other excipients are added and moulded. The lozenges were
subjected to evaluation viz., weight variation test, hardness, friability, drug content and in
vitro release studies.

KEYWORDS: Domperidone, Heat congealing, lozenges, Chemotherapy induced nausea and

vomiting.

www.wjpps.com Vol 6, Issue 12, 2017. 1167

Lakshmi et al. World Journal of Pharmacy and Pharmaceutical Sciences

INTRODUCTION
Lozenges are the flavoured medicated dosage forms intended to be administered and held in
the mouth or pharynx containing one or more medicaments usually in the sweetened base.
Lozenges are used for patients who cannot swallow solid oral dosage forms as well as for
medications designed to be released slowly to yield a constant level of drug in the oral cavity.

Lozenges are one of the very popular and better innovative dosage form and oral
confectionary products. It is a potentially useful for means of administration of drugs either
locally or systematically through the oral cavity. The reasons for this preference because of
the easy to administered for the geriatric and paediatric patient and wide spread acceptance
by patients. The development of new drug delivery systems for existing drug with an
improved efficacy, avoid first pass hepatic metabolism, no need of water intake and increase
bioavailability together with reduced dosing frequency.

It acts by two mechanisms. Firstly, it acts on dopamine receptors in the chemoreceptor trigger
zone (CTZ) in the area postrema. Second, it acts on D2-receptors at the gastro-oesophageal
and gastroduodenal junctions and thereby counteracts the gastric ‘dopamine brake’ associated
with nausea from any cause. Domperidone may also inhibit cholinesterase activity. All these
inhibits the activation of vomiting center which triggers emesis. At present Domperidone
drug is been formulated in market as oral tablet but its bioavailability is 13-17%. Further later
to increase its bioavailability it is formulated as intra muscular injection (bioavailability is
90%). To give domperidone as IM injection requires skilled person and also assisted with
patient compliance. To overcome, this problem I want to formulate as lozenge to improve
patient compliances and can be self-administered.

www.wjpps.com Vol 6, Issue 12, 2017. 1168

Lakshmi et al. World Journal of Pharmacy and Pharmaceutical Sciences

MATERIALS AND METHODS

Domperidone, HPMC K100 M, HPMC E5, Sucrose, Dextrose, Amaranth, Citric acid,
Menthol.

Method
Heating and congealing technique.

Preparation of Candy Lozenges: Required quantity of sugar syrup was prepared mixing
sugar and water. Dextrose was dissolved in small quantity of water and heated it to 110 oC till
dextrose dissolves completely forming as clear viscous syrup. Then the dextrose solution was
poured into the sugar syrup and heated to 160oC till the colour changes to golden yellow. The
temperature was brought down to 90oC and drug, polymer and other ingredients were added.
The solution was poured into the mould. The prepared tablets were wrapped in aluminium
foil and stored in desiccators to prevent moisture uptake.

Formulae for heat congealing technique

Ingredients F1 F2 F3 F4 F5 F6
Drug 10 10 10 10 10 10
HPMCk100M 16 32 48 - - -
HPMC E5 - - - 16 32 48
Sucrose 1966 1950 1934 1966 1950 1934
Dextrose 974 974 974 974 974 974
Citric acid 32 32 32 32 32 32
Menthol 1 1 1 1 1 1
Amaranth 1 1 1 1 1 1
Total 3000 3000 3000 3000 3000 3000

FT-IR results
FT IR spectra of pure drug sample, mixture of different formulation of lozenges can be seen
in the below figures. These peaks were not affected and there is no interaction between drug
and excipients. The FT-IR studies were performed and the corresponding graphs were
represented from Figure 1 to Figure 3.

www.wjpps.com Vol 6, Issue 12, 2017. 1169

 Transmittance [%]
Transmittance [%]

Fig
2:
100
20 40 60 80
0 100
20 40 60 80
Lakshmi et al.

4000
3922.80

www.wjpps.com
4000
3888.75 3923.67

FT-IR
3870.55 3891.87
3857.83 3873.11
3839.37 3859.02
3825.07 3842.63
3768.17 3826.94
3737.26 3771.36

OF
3695.65 3740.97
3665.18

3500
3711.77
3645.32 3699.19

3500

D:\FTIR DATA\2017 OCT\MOULIKA.4

3604.69 3648.67

D:\FTIR DATA\2017 OCT\MOULIKA.3

3551.58 3499.27

acid+Menthol+Amaranth).
acid+Menthol+Amaranth).
3500.57 3469.68
3473.40 3360.12
3300.60 3241.30
3271.88
3243.52 3108.07
3212.72 3052.55

Mixture

3000

MIXTURE 2
3117.39

3000

MIXTURE 1
3054.47 2944.36
3012.76
2939.46
2887.42
2817.40
2674.91

SOLID
2687.61

SOLID
2532.48 2538.01

2500
2500
2377.70 2375.19
2347.04 2349.32
2310.05 2311.06

Page 1/1

Page 1/1
2165.85

Wavenumber cm-1

1(Drug+HPMC

Wavenumber cm-1
1962.23

2000

Vol 6, Issue 12, 2017.

1914.14

2000
1866.39
1837.03 1821.75
1794.45 1791.53
1757.49 1706.30
1690.03 1688.23
Fig 1: FT-IR of Domperidone.

1622.57
1544.51 1563.46
1516.82 1516.62
1484.92

1500
1482.98
1417.13

1500
1458.29
1425.33 1387.85
1368.68 1314.80
1271.05 1288.94
1236.45 1204.75
1144.01 1104.05
1104.32 1050.35
1039.77 1017.68
988.15

1000
943.74
909.19 891.59

1000
857.33 830.75
836.45
774.63
755.22 723.18
728.54 679.63
688.44 630.56

10/7/2017
629.96 583.49
597.70

10/7/2017
576.76

Fig 3: FT-IR Studies of mixture 2 (Drug+HPMC E5+ Sucrose+Dextrose+Citric

K100M+Sucrose+Dextrose+Citric

1170
World Journal of Pharmacy and Pharmaceutical Sciences
Lakshmi et al. World Journal of Pharmacy and Pharmaceutical Sciences

Evaluation tests
Average weight and Weight variation test: 20 lozenges were selected and weighed
collectively and individually on an electronic balance. From the collective weight, average
weight was calculated. Each lozenge weight was then compared with average weight to
assure whether it was within permissible limits or not. Not more than two of the individual
weights deviated from the average weight by more than 7.5% for 300 mg tablets and none by
more than double that percentage.
Average weight = weight of 20 lozenges
20
%weight variation= average weight - weight of each tablet
Average weight ×100

Friability test: The friability of the 20 tablets from each batch was tested by a fribilator. At a
speed of 25 rpm for 4 min. The lozenges were then dedusted, reweighed and percentage
weight loss was calculated by the equation,
% Friability = (initial Wt.- Wt. after friability) × 100 / initial Wt.

Hardness test: To evaluate the diametrical crushing strength, 3 tablets from each formulation
were tested using a MAC hardness tester. The mean±SD values were calculated.

In vitro mouth Dissolving Time

Mouth Dissolving Time was determined by each batch formulation using USP disintegration
apparatus, where lozenges were placed in each tube of the apparatus and time taken for the
lozenges to dissolve completely was noted by using 100ml phosphate buffer of pH 6.8 at
370c. This test was done in triplicate. The average dissolving time for lozenges was calculated
and presented with standard deviation.

Drug Content
Lozenges were powdered and dissolved in 5mL of methanol in 50 ml volumetric flask and
volume made up to 50 ml with pH 6.8 Phosphate buffer. From this solution 1 ml taken and
diluted with pH 6.8 Phosphate buffer in 50 ml volumetric flask then sonicated for 30 min
then filtered using filter paper. The absorbance of this solution was measured at 280 nm using

www.wjpps.com Vol 6, Issue 12, 2017. 1171

 Lakshmi et al. World Journal of Pharmacy and Pharmaceutical Sciences

appropriate blank. The drug content of domperidone lozenges was calculated using
calibration curve.

Moisture content analysis

The sample was weighed and crushed in a mortar. From this, one gram of the sample was
weighed and placed in a desiccator for 24 hours. After 24 hours the sample is weighed. The
moisture content is determined by the abstracting the final weight from initial weight of
lozenges.

In vitro buoyancy studies

The rate of the drug absorption was determined by the rate of drug dissolution from the
lozenges. Thus, the rate of dissolution and bioavailability may be directly related to the
efficacy of the lozenge. The magnetic stirrers were used and the dissolution medium pH 6.8
phosphate buffer, 100mL was placed in the beaker containing the lozenges and stirred at
100rpm. 5mL aliquot samples were withdrawn at 5 min. interval and replaced immediately
with an equal volume of fresh fluid i.e.., simulated salivary fluid. Each aliquot was diluted
and they were analysed at 280 nm, by UV Visible spectrophotometer.

Stability studies
All the prepared formulations were subjected to stability studies at temperature i.e.., 400c
/75% RH for a period of 1 month. After 1 month drug content, weight variation, colour,
hardness and moisture content were determined.

RESULTS
Organoleptic examination of prepared candy lozenges
Parameters Result
Shape Spherical
Colour Red
Texture Smooth
Taste Sweet

Results of candy lozenges

Hardness Weight In vitro mouth Drug Moisture content
Formulation 2 Friability
Kg/cm variation dissolving time (min) content analysis
F1 10.16±0.002 2.91±0.002 2.90±0.008 21±0.003 98.5±0.005 0.6±0.100
F2 11.16±0.005 2.90±0.005 2.87±0.005 22±0.005 98.8±0.006 0.7±0.002
F3 11.83±0.008 2.98±0.009 2.85±0.006 24±0.004 97.9±0.004 0.6±0.003
F4 10.14±0.006 2.87±0.005 2.87±0.004 21±0.008 98.9±0.005 0.6±0.005
F5 11.16±0.003 2.67±0.003 2.66±0.12 21±0.005 99.5±0.009 0.8±0.005
F6 11.16±0.005 2.99±0.004 2.92±0.153 24±0.002 99.3±0.004 0.6±0.006

www.wjpps.com Vol 6, Issue 12, 2017. 1172

Lakshmi et al. World Journal of Pharmacy and Pharmaceutical Sciences

Stability test for candy lozenges

Evaluation parameters 0 day After stability study of 1 month
Organoleptic examination No change No change
Hardness 10.14±0.115Kg/cm2 10.12±0.115kg/cm2
Weight variation 2.87±0.002% 2.85±0.005%
% friability 2.87±0.055% 2.82±0.106%
In vitro mouth dissolving time 21±0.005min 20±0.004min
Drug content 98.9±0.007% 97.2±0.009%
Moisture content 0.6±0.138% 0.5±0.213%

In vitro Dissolution profile of Candy lozenges

Time % Drug released
(mins) F1 F2 F3 F4 F5 F6
0 0 0 0 0 0 0
5 34.71 28.79 26.21 41.57 39.94 36.82
10 51.53 39.43 35.66 58.15 51.18 49.46
15 65.38 49.71 46.03 75.09 69.98 63.72
20 79.62 60.09 55.97 86.91 80.19 72.03
25 88.59 71.84 68.18 95.42 87.76 78.83
30 95.11 85.05 79.35 92.06 93.24 87.29
35 93.39 96.49 88.42 90.41 95.41
40 91.6 98.76 91.76
45 94.21

Fig4: Dissolution profile of candy lozenges. Fig5: Zero order kinetics of candy lozenges.

Fig 6: First order kinetics of candy lozenges. Fig 7: Higuchi plot of candy lozenges.

www.wjpps.com Vol 6, Issue 12, 2017. 1173

Lakshmi et al. World Journal of Pharmacy and Pharmaceutical Sciences

Fig 8: Koresmyers Peppas plot of candy lozenges.

DISCUSSION
As bioavailability is a major factor responsible for the pharmacological activity of any drug,
the present work is focused on the formulation of the active pharmaceutical ingredient (APIs)
as lozenges due to their various advantages. Lozenges increase bioavailability by increasing
the solubility. Firstly FT-IR studies were performed and from the FT-IR spectra it was
evident that there were no interactions between the drug and the excipients being used. The
lozenges of domperidone were prepared by using different polymers of different
concentrations by heat congealing technique (F1-F6), among the six formulations F4 (HPMC
E5) showed the highest percentage of drug release, drug content, less in vitro mouth
dissloving time. Hence, it was considered as the optimized formulation among the six
formulations. The stability studies were performed there is no change in drug content, in vitro
mouth dissolving time. Friability, weight variation.

CONCLUSION
The present work is focused on development of candy lozenges which serves the purpose of
increasing the bioavailability. To check if there are any interactions between the drugs and
various components of formulation, FT-IR was performed. Confining the compatibility, the
studies were continued with those excipients. The lozenges of domperidone were prepared by
using different polymers of different ratios. F4 is considered as the optimized formulation
based on the evaluation tests. The drug release kinetics of optimized formulation F4 fitted
best to the first-order (r2= 0.9740) indicating the drug release is following first order kinetics.
In the view of above findings, effect of polymers like, HPMC E5 shows better result in heat
congealing technique. Enhancement of bioavailability aided by enhanced solubility is the

www.wjpps.com Vol 6, Issue 12, 2017. 1174

Lakshmi et al. World Journal of Pharmacy and Pharmaceutical Sciences

current area of research. Avoiding first pass metabolism also helps in bioavailability
enhancement. Thus by this work, we could conclude that candy lozenges can be used as
efficient means of formulation to enhance solubility and bioavailability of the drug as carried
through oral cavity.

ACKNOWLEDGEMENT: I would like to thank my university to carry out my work.

REFERENCES
1. Pattanayak D, Das S. Formulation development and optimization of medicated lozenges
for paediatric use. International Journal of Pharmaceutical Sciences and research. 2012
Jan 1; 3(1): 138.
2. Nagoba SN, Rao KP, Sameer S, Gujrathi DS, Nagoba BS. Studies on candy based
Ketoconazole Pe diatric Tablet Lozenges. Int J Res Ayurveda Pharm. 2011; 2(1): 239-43.
3. Pundir S, Varma AM. Formulation development and evaluation of antiemetic Lozenges
of Ondansetron hydrochloride. International Journal of Pharmaceutical Research and Bio-
Science. 2014; 365-72.
4. Hymowitz N, Eckholdt H. Effects of a 2.5-mg silver acetate lozenge on initial and long-
term smoking cessation. Preventive medicine. 1996 Sep 1; 25(5): 537-46.
5. Pothu R, Yamsani MR. LOZENGES FORMULATION AND EVALUATION: A
REVIEW.
6. Esimone CO, Okoye FB, Odimegwu DC, Nworu CS, Oleghe PO, Ejogha PW. In vitro
antimicrobial evaluation of lozenges containing extract of garlic and ginger. International
Journal of Health Research. 2010; 3(2): 105-10.
7. Edwards WP. SWEETS AND CANDIES| Sugar Confectionery. Encyclopedia of Food
Sciences and Nutrition. 2003; 5703-10.

www.wjpps.com Vol 6, Issue 12, 2017. 1175