International Journal of Applied Pharmaceutics

ISSN- 0975-7058 Vol 10, Issue 3, 2018

Reveiw Article
COMBINATION OF HPMC AND PEG 400 AS A TASTE MASKING AGENT OF FILM-COATED
TABLETS CONTAINING MOMORDICA CHARANTIA LINN. EXTRACT

RADITYA ISWANDANA, DESI ARYANI TRI LESTARI, SUTRIYO*

Laboratory of Pharmaceutics and Pharmaceutical Technology Development, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, Indonesia
Email: [email protected]
Received: 29 Nov 2017, Revised and Accepted: 10 Mar 2018
ABSTRACT
Objective: The objective of this study was to formulate and prepare film-coated tablets containing Momordica charantia Linn. to mask its bitter taste.
Methods: The core tablets of Momordica charantia Linn. were prepared by wet granulation method using sodium carboxymethyl cellulose (CMC-
Na) as a binder, and then coated with hydroxypropyl methyl cellulose (HPMC) 5%. Film coating formulation was made in 3 formulae using the
additional amount of polyethylene glycol (PEG) 400 as the plasticizer at 16%, 20%, and 24% concentration of HPMC weight. The obtained film-
coated tablet was evaluated including organoleptic, the percentage of weight increase, surface morphology, coating thickness, disintegration time,
and taste masking evaluation. Taste masking evaluation was performed on 30 respondents by giving the bitter taste level questionnaire of the three
formulae film-coated tablets, core, and extract powders.
Results: Film-coated tablets that coated by using 20% PEG 400 as plasticizer had 4.78% of weight increase. The surface morphology was smooth
and showed±34.67 µm of coating thickness. Furthermore, it also disintegrated within 5.34±1.1 min and successfully masked the bitter taste.
Conclusion: Combination of HPMC and PEG 400 20% as a plasticizer can give a good appearance and masked the bitter taste of Momordica charantia Linn.
Keywords: Momordica charantia Linn. Extract, Bitter taste masking, Film-coated tablet, HPMC, PEG 400
© 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/ijap.2018v10i3.24025

INTRODUCTION stomach from drugs that cause irritation, and provides a delayed
drug release from the tablet [13].
Studies on traditional medicinal plants (herbs) continue to this day as an
effort of promotion, palliation, prevention, and rehabilitation. Bitter The objectives of this research work were to develop a film-coated
melon (Momordica charantia Linn.) is one of the most studied plants tablet which can mask a bitter taste from the bitter melon and to
which has many therapeutic effects such as antidiabetic, antioxidants, evaluate the effect of hydroxypropyl methylcellulose (HPMC) and
antiviral, anticancer, immunomodulator, and anthelmintic effects [1-3]. polyethylene glycol (PEG) 400 on the fabrication of the film-coated
The bioactive composition that contained in the bitter melon extract tablet.
includes charantine, a sesquiterpene, linalool, catechin, palmitoic acid,
curcubitane, diosgenine, momordicine, momordenol, and momordicilin MATERIALS AND METHODS
[4-6]. Momordicine content in bitter melon causes the bitter taste which Materials
makes bitter melon less consumed by people [7].
Momordica charantia Linn. extracts (Deltomed Laboratories, Indonesia),
Oral administration of pharmaceuticals is one of the most popular aerosil (Nippon Aerosil, Japan), avicel PH 101 (Alcma, USA), sodium
methods of drug delivery [8]. Oral administration of bitter drugs with an carboxymethyl cellulose (CMC-Na) (Ashland, USA), explotab (Evonik
acceptable degree of palatability is a key issue for health care providers, Industries, Germany), glycerin (Sinarmas Oleochemical, Indonesia),
especially for pediatric patients. Taste masking in the present day hydroxypropyl methyl cellulose (DOW Chemical Pacific, Singapore),
pharmaceutical industry has become a potential tool to improve patient magnesium stearate (FACI Asia Pte. Ltd., Singapore), polyethylene glycol
compliance and commercial success of the product [9]. 400 (Duchefa Biochemical, The Netherlands), sunset yellow (Sensient,
For the reasons above, a dosage form to mask the bitter taste of Indonesia), aquadest (Brataco, Indonesia).
bitter melon extract was developed, i.e., film-coated tablets. The Preparation of bitter melon extract core tablet
bioactive compounds in bitter melon are thermodynamically stable
and stay stable in the presence of water. Based on these properties, Core tablets were made by using wet granulation method. Bitter
wet granulation method can be used to produce core tablets [10]. melon powder extract, Avicel PH 101, and explotab were mixed until
Wet granulation method can improve the flow properties and homogeneous and CMC-Na solution was added to create a wet
compatibility of powder extract, thus easier in compressing process granular mass. Wet granular mass was sieved with mesh 16 and
[11]. The film-coated tablet is a tablet that coated with thin layer dried in the oven at 60 °C. Dry granules obtained were sieved with
polymer that is soluble or insoluble in water [12]. The purpose of mesh 18. Then, aerosil and Mg stearate were added. The flow rate,
the coating was to improve its physical appearance, mask an the angle of repose, and compressibility index of the mass were
unpleasant taste, odor and color, provide chemical and physical evaluated. After that, tablet mass was compressed into biconcave
protection for unstable drugs in an acidic environment, protects the tablets using a tablet press (Erweka, Germany).

Table 1: Composition of bitter melon core or uncoated tablet formulations prepared by wet granulation method
Components F1 (mg) F2 (mg) F3 (mg) F4 (mg)
Bitter melon powder extract 200 200 200 200
CMC-Na 6 9 12 15
Explotab 12 12 12 12
Aerosil 1.5 1.5 1.5 1.5
Mg stearate 1.5 1.5 1.5 1.5
Avicel PH 101 79 76 73 70
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Flow properties of granule horizontally in the machine, and the start button was pressed to
commence the test.
Flow rate and angle of repose
Friability
The measurement was done using a flow meter (Erweka GDT,
Germany), ±25 g of the sample was placed in flow meter funnel and The analysis was done using friability tester (Erweka TAR,
the surface was evenly levelled without any pressure. The flow Germany). Twenty tablets were cleaned from dust, weighed, placed
meter was run and the time for all sample to flow through the funnel in the machine which was run at 25 rpm for 4 min. The tablets were
was recorded. The flow rate was expressed in g/sec. The angle of taken out, dusted and weighed. The loss due to abrasion is a
repose (α) was obtained by measuring the height (h) and radius (r) measure of tablet friability.
of the pile of the sample that flowed through the funnel [13].
Disintegration time
Compressibility index
The disintegration test was carried out using the disintegration
Compressibility index and Hausner ratio are a measure of the tendency tester (Electrolab ED-2-SAPO, India). Each of the tablets was placed
of the powder to be compressed. The tablet mass was added to a in each basket. Water with a temperature of 37±2 °C was used as a
measuring glass (50.0 ml) and evaluated using the standard procedure medium. At the time limit, the basket was taken out, and the tablet
by measuring the original volume (V0) and final tapped volume (Vf) [14]. was observed [14].

Evaluation of the core tablet Preparation of film coated tablet

Weight uniformity All components were weighed according to the formulations. HPMC
was added to a beaker glass, and aquadest was added gradually
Twenty tablets were weighed individually, and the average weight while being stirred until homogeneous. PEG 400, glycerin and sunset
was calculated. The individual tablet weight was then compared to yellow were added, the volume was adjusted using aquadest to 100
the average weight [14]. ml. Tablet coating was done by spraying the coating solution
Hardness gradually and evenly on the tablet surfaces using a rotating coating
pan. Tablets were then left rotated in the pan until it reached the
The analysis was done using hardness tester (Erweka TBH 28, room temperature. Film-coated tablets were weighed and stored in
Germany). In this study, six tablets were used. Tablet was placed a clean and dry container.

Table 2: Formulations of coating solution

Components FA (%) FB (%) FC (%)
HPMC 5 5 5
PEG 400 0.8 1 1.2
Glycerin 1.5 1.5 1.5
Sunset yellow 0.05 0.05 0.05
Aquadest ad. 100 100 100

Bitter taste evaluation The core tablet physical appearance test was done by observing
the shape and color of the tablet [17]. Physical appearance is the
Bitter taste evaluation was performed on 30 respondents by giving first thing that affects patient acceptance of a pharmaceutical
the bitter taste level questionnaire of the three formulae of film- dosage form. All tablet formulations had the same physical
coated tablets, core, and extract powders. The questionnaire results appearance with a smooth surface due to magnesium stearate
were analyzed using statistical package for the social sciences (SPSS) that acts as a glidant.
program with Kruskal Wallis method. The bitterness level is from 1
(not bitter) until 5 (very bitter) [15, 16]. Core tablets F1-F4 qualify the weight variation requirements within
a range of 85.0-115.0% from what was written on the label with
RESULTS AND DISCUSSION
relative standard deviation ≤6. This has proven that powder mass of
The core tablet mass evaluation was done to measure the flow rate, the bitter melon core tablet had a good flowability and could produce
angle of repose and the ability of the mass to be compressed into a tablet. tablets with a good weight and content uniformity [18].

Table 3: Core tablet mass evaluation results

Evaluations F1* F2* F3* F4*
Flow rate (g/sec) 5.26±0.09 5.13±0.14 5.04±0.14 4.73±0.17
Angle of repose ( °) 19.96±0.57 21.14±0.39 22.05±0.59 22.32±0.90
Compressibility index 17.31±0.29 18.26±1.52 19.21±1.96 21.43±0.33
Hausner ratio 1.21±0.01 1.22±0.02 1.24±0.03 1.27±0.01
*n=3; Data are expressed as mean+/-SD.

Table 4: Core tablet evaluation results

Parameters F1 F2 F3 F4
Physical appearance Round, biconvex, light brown Round, biconvex, light brown Round, biconvex, light brown Round, biconvex, light brown
Average weight (mg)* 311.12±1.43 312.66±2.26 312.14±2.44 308.74±3.40
Tablet diameter (mm)* 9.21±0.01 9.21±0.01 9.21±0.01 9.21±0.01
Tablet thickness* 5.29±0.02 5.31±0.02 5.30±0.02 5.31±0.02
Friability (%) 0.13 0.20 0.22 0.24
Hardness (kP)† 8.91±0.39 8.92±0.68 7.28±0.81 9.48±1.31
Disintegration time 2.64±0.96 3.30±0.58 3.53±0.26 3.94±0.33
(min)†
*n=20; Data are expressed as mean+/-SD., †n=6; Data are expressed as mean+/-SD.

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In this study, friability evaluation was crucial since the core tablet the optimum concentration of a polymer in the coating solution [13].
will be coated. Core tablets must have a low friability during the Each formula had different concentration of PEG 400 as a plasticizer.
spraying process. The result showed that all formulae did not meet Variation was needed to understand the elasticity, flexibility and any
the criteria. F1 had a low friability value at 0.13%. Theoretically, the defect in the coating layer that was formed.
use of a binder in higher concentration causes lower friability value,
but in this case, the increase of CMC-Na increased the friability [19, Morphological evaluation of film-coated tablet was done to observe
20]. This might be because CMC-Na will produce a frailer and harder the tablet surfaces condition microscopically using scanning
tablet. F1 with the lowest CMC-Na concentration was chosen since it electron microscopy (SEM). Films were expected to keep forming
had the lowest friability and enough hardness to be processed as during the spraying process until all coating solution was used.
film-coated tablets. Overall, the tablet was coated with the coating solution. Based on
SEM images with 3000x magnification, FA surface was not as smooth
HPMC was used to mask the bitter and unpleasant taste also the as expected due to the low concentration of PEG 400 and the
stability of the formulation. Five percent was chosen because it was excessive heating process, while FB and FC surfaces were smooth.

(a) (b)

(c) (d)

(e) (f)
Fig. 1: Scanning electron microscope result for film coated surface with 3000x magnification (left) and thickness of coating layer with
200x magnification (right): FA (a,d), FB (b,e), and FC (c,f)

The thickness of coating layer of a tablet is usually about 10-100 proportional to the increase of film-coated tablets weight. Coating
µm. CTFA (coated tablet formula A) had a thickness of 91.03 µm, layer thickness is also affected by the viscosity of coating solution,
CTFB (coated tablet formula B) was 34.67 µm, and CTFC (coated the increase in viscosity will increase the thickness of coating
tablet formula C) was 48.93 µm. The thickness of coating layer was layer.

Tabel 5: Disintegration time of the film-coated tablet

Formula Disintegration time (min)*
A 7.95±0.6
B 5.34±1.1
C 4.59±0.6
*n=6; Data are expressed as mean+/-SD.

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Disintegration time evaluation results of film-coated tablets are The bitter taste evaluation showed 43.33% respondents stated
shown in table 5. Based on the data, film-coated tablets had a that there was a slightly bitter taste in core tablet. Most of the
considerably fast disintegration time but still slower than core respondents (70%) stated that CTFA did not have any bitter
tablet. This was due to the pores of core tablet that was shielded and taste and almost all respondents (93.3%) stated CTFB did not
protected by film coatings, in consequence, it made the medium have any bitter taste. 73% of the respondents also stated that
difficult to penetrate the tablet. Also, more time was needed as the CTFC did not have any bitter taste while 63.3% stated that F1
coating layer must be disintegrated first. had a bitter taste.

Fig. 2: Bitter taste evaluation result. Not bitter (1), slightly bitter (2), sparingly bitter (3), bitter (4), very bitter (5)

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bromide in orodispersible tablets. Int J Pharm Pharm Sci
The authors have no conflict of interest to declare 2014;S1:315-9.
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