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Life Science Archives (LSA)

ISSN: 2454-1354
Volume 1; Issue - 1; Year 2015; Page: 35 - 40

Research Article
MOUTH DISINTEGRATING STRIP: A NOVEL APPROACH FOR THE DELIVERY
OF TASTE MASKED CYPROHEPTADINE HYDROCHLORIDE
Minal Bonde1*, Nidhi Sapkal2, Vijay Mathur3 and Anwar Daud3
1

NIMS University, Jaipur, India.

Gurunanak College of Pharmacy, Nari, Nagpur, India.
3
Zim Laboratories Ltd., Nagpur, India.

Abstract
Difficulty in swallowing tablets or capsules has been identified as one of the contributing factor to
non-compliance of geriatric patients. Although orally disintegrating tablet was designed for fast
disintegration in mouth, the fear of taking solid tablets and the risk of choking for certain patient populations
still exist. The objective of this study was to develop and characterize taste masked mouth disintegrating
strips. Effects of polacrilin potassium, hydroxypropyl methylcellulose and propylene glycol were studied on
organoleptic properties, thickness, tensile strength, folding endurance, percentage elongation, drug content,
in vitro disintegration and dissolution. Also the optimum formulation was studied for surface morphology
and accelerated stability as per ICH guidelines. Mouth disintegrating strip was prepared using the solvent
casting method. Formulation containing drug to taste masking agent in 1: 1 ratio showed very good taste and
no bitterness. Increased concentration of hydroxypropylmethyl cellulose formed mouth disintegrating strip
with greater tensile strength, folding endurance and percentage elongation. Formulation F3C containing 20
mg of hydroxypropylmethyl cellulose per strip was better than other formulations. Almost 90% of the drug
was released within two minutes and the strips were stable for 3 months. Thus mouth disintegrating strip
containing taste masked of Cyproheptadine HCl was successfully developed and characterized.
Article History

Received : 06.02.2015
Revised : 19.02.2015
Accepted : 27.02.2015

Keywords: Polacrilin potassium, Organoleptic

evaluation, Accelerated stability and Surface

morphology

1. Introduction

Dissolvable mouth disintegrating strips

(MDS) are a proven technological development
for the systemic delivery of active pharmaceutical
ingredients. Pharmaceutical companies and
consumers, particularly pediatric and geriatric
patient populations, have adopted MDS as a
practical alternative to traditional medicines, such
as liquids, tablets and capsules because of the
unique advantages of MDS like better patient

* Corresponding author: Minal Bonde

Tel.: 0091-7118-271370,0091-7118-271990

E-mail: minalbonde@zimlab.in

compliance, lesser excipient load, and faster onset

of action (Dixit et al., 2009; Shukla et al., 2009).
Some patients have difficulty in
swallowing solid dosage forms. They are
unwilling to take these dosage forms due to a fear
of choking and difficulty in swallowing. In order
to assist these patients, several mouth dissolving
drug delivery systems has been developed as these

Minal Bonde /Life Science Archives (LSA), Volume 1, Issue 1, Page 35 to 40, 2015

dissolves rapidly in the saliva without the need of

water, releasing the drug which is absorbed from
the oral cavity, hence minimizing the onset of
action. Thus bioavailability of these formulations
significantly greater than those from conventional
tablet dosage form (Ciper et al., 2006).
Cyproheptadine (4-(5Hdibenzo [a,d] cyclohepten
-5-ylidene) ethylpiperidine), potentantihistaminic,
antimuscarine and antiserotonic drug andshows
sedative with calcium-channel blocking activity.
Cyproheptadine HCl well absorbed after oral
administration with maximum peak plasma
concentrations of about 30.0 g/L.
Hydroxypropylmethyl cellulose (HPMC) is
typically used as film formers. Polacrilin
potassium was used as taste masking agent. The
main objective of this study was to develop and
characterize taste masked MDS, which was
prepared using different concentrations of taste
masked resin and polymer. Effects of polacrilin
potassium, hydroxypropyl methylcellulose and
propylene glycol were studied on organoleptic
properties, thickness (Rowe et al., 1980), tensile
strength (TS) (Shinde et al., 2008), folding
endurance (FE), percentage elongation (PE), drug
content (Anand et al., 2007), in vitro
disintegration test (DT) and dissolution (Kunte et
al., 2010) of MDS formed were studied.
2. Methodology
2.1. Materials
Cyproheptadine HCl was procured as a gift
sample from Shilpa chemicals, India. Polacrilin
potassium was received as a gift from Coral
pharma, Ahmadabad, India. HPMC, polysorbate
80, sucralose were procured as gift sample from
Unijules, Nagpur, India. Mentha oil and spearmint
oil were obtained from Firminch, Mumbai, India.
All other chemicals and reagents were of
analytical grades. Distilled water was used
throughout the study.

36

To prepared and evaluate the MDSs

Solvent casting machine (Optimag, Germany),
Digital micrometer (Mitutoyo, Japan), Shimadzu
UV spectrophotometer (Shimadzu, Mumbai),
scanning electron microscope (Phenome world,
Netherland),
tensile
strength
instrument
(Saurashtra, Mumbai.) were used.
2.2. Preparation of the taste masked MDS of
Cyproheptadine HCl
Taste masked MDS of Cyproheptadine
HCl was prepared using solvent casting method. It
involves preparation of two solutions: a) Base
strip solution and b) Drug solution
a) Base strip solution
Required quantity of HPMC 15 cps was
dispersed in measured quantity of hot water and
allowed it to dissolve followed by addition of
remaining amount of cold water. To this propylene
glycol was added with stirring.
b) Drug solution
It involves the addition of other the
ingredients expect those were added in the base
strip. Initially the drug is wetted with small
quantity of hot water to get semisolid consistency.
To this, different ratio of polacrilin potassium was
added (Table - 1) and stirred for 30 minutes. To
this solution, polysorbate 80, sucralose, citric acid
monohydrate and mentha oil was added with
continue stirring. To the drug solution, base strip
solution was added slowly with stirring. The
prepared solution was kept aside to remove air
bubbles. The dispersion was then casted on
solvent casting machine by adjusting the thickness
of formulations to get desired dose per strip of
specified area. Process parameters of the machine
were selected (temperature 120 oC and machine
speed 0.1 m/min) on the basis of preliminary
experiments. The casted strip were then removed
and cut into desired size.

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Minal Bonde /Life Science Archives (LSA), Volume 1, Issue 1, Page 35 to 40, 2015

37

Table - 1: Composition for selection of taste masked ratio

Ingredients

F1

F2
F3
All quantities are given in mg/strip
1
1

F4

Cyproheptadine HCl

Polacrilin potassium

0.5

1.5

HPMC 15 cps

30

30

30

30

Propylene glycol

4.5

4.5

4.5

4.5

Polysorabate 80

1.25

1.25

1.25

1.25

Sucralose

1.47

1.47

1.47

1.47

Mentha oil

0.73

0.73

0.73

0.73

Citric acid monohydrate

0.1

0.1

0.1

0.1

Water

QS

QS

QS

QS

3. Results
3.1. Organoleptic study
All the subjects were completely informed
concerning the pertinent details and the purpose of
the study. A written consent form was supplied,
understood and signed by each subject prior to
dispensing the test materials. Each strip from
different formulations was randomly administered
to 6 healthy human volunteers and results are
tabulated in Table - 2.
The selected ratio of Cyproheptadine and
polacrilin potassium were incorporated in different
formulations of varying concentrations of HPMC
(Table - 3) using the previous procedure to cast
the strip.

Formulation F3A and F3B failed in the

proper formation of strip or their removal from
polyester belt. Formulations F3C, F3D and F3E
showed good strip formation and surface removal
and thus were evaluated for organoleptic studies
and results are tabulated in Table - 4.
Formulation F3C, F3D and F3D were further evaluated
for thickness, folding endurance, tensile strength,

percentage elongation, in vitro disintegration test

and dissolution. Formulation F1 and F3C was
studied for surface morphology.

Table - 2: Results of organoleptic studies for taste masked complex

FC

Organoleptic evaluation*
Taste

Bitterness

F1

Not good

Highly bitter

F2

Good

Slightly bitter

F3

Very good

No bitterness

F4

Very good

No bitterness

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Minal Bonde /Life Science Archives (LSA), Volume 1, Issue 1, Page 35 to 40, 2015

38

Table - 3: Composition of taste masked MDSs of Cyproheptadine HCl

F3A

Ingredients
Cyproheptadine HCl
Polacrilin potassium
HPMC 15 cps
Propylene glycol
Polysorabate 80
Sucralose
Mentha oil
Citric acid monohydrate
Water

4
4
5
0.75
1.25
1.47
0.73
0.1
QS

F3B
F3C
F3D
All quantities are given in mg/strip
4
4
4
4
4
4
10
20
30
1.5
3.0
4.5
1.25
1.25
1.25
1.47
1.47
1.47
0.73
0.73
0.73
0.1
0.1
0.1
QS
QS
QS

F3E
4
4
40
6.0
1.25
1.47
0.73
0.1
QS

*n=6
Table - 4: Results of organoleptic studies for taste masked MDSs of Cyproheptadine HCl
FC

Organoleptic evaluation
Taste

Bitterness

F3C

Very good

No bitterness

F3D

Very good

No bitterness

F3E

Very good

Slightly bitter

3.2. Drug content

Individual strip was weighted and
transferred to 50 ml volumetric flask, 30 ml
methanol was added in it and sonicates the
volumetric flask for 30 min. The solution were
filtered and diluted to 50 ml by methanol. The
formulation was analyzed at 287 nm in ultraviolet
spectrophotometer. Cyproheptadine HCl content
was calculated using a standard calibration curve
(Table - 5).
3.3. In vitro dissolution studies
Dissolution studies were carried out using
USP dissolution apparatus II. The USP dissolution
apparatus was thermo stated at the temperature
of 372 0C and 500 ml stimulate d salivary fluid

(pH 6.8) as dissolution medium at 50 rotations per

minute. Ten ml aliquots were withdrawn at the
consecutive interval of 1 minute and were
replaced by same amount of fresh dissolution
medium. Samples were filtered through whatman
filter paper and analyzed spectrophotometrically at
287 nm and the content was calculated.
3.4. Accelerated Stability studies
Stability studies of optimized MDS were
conducted as per ICH guidelines at 40C
2C/75% 5% RH, Table - 6. The strips were
checked for FE, TS, PE, drug content and in vitro
disintegration after 1, 2 and 3 months.

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Minal Bonde /Life Science Archives (LSA), Volume 1, Issue 1, Page 35 to 40, 2015

39

Table - 5: Evaluation of taste masked MDSs of Cyproheptadine HCl

FC

Thickness
(mm)

FE

TS

PE (%)

Drug content

DT

(%)

(sec)

(kg/cm2)
F3

0.060.01

80.120.95

15.910.43

1030.47

100.230.21

200.31

F4

0.0650.01

85.470.78

18.00.86

1090.85

100.890.1

250.4

F5

0.070.01

96.50.71

21.980.51

1130.24

101.010.78

380.3

Table - 6: Stability studies of optimized taste masked MDSs of Cyproheptadine HCl

FC

FE

TS

PE (%)

(kg/cm2)

Drug content

DT

(%)

(sec)

F3

81.230.21

14.210.12

102.670.19

100.190.2

200.31

F4

80.470.12

14.00.24

102.180.28

99.900.19

250.4

F5

80.160.27

14.01010

101.890.24

99.670.27

380.3

4. Discussion
No bitterness and very good taste was
reported in the formulation F3 and F4. As
formulation F3 contains lower ratio of taste
masked resin compared to formulation F4, thus
considered as optimum and hence was further
used for proposed studies. Formulation F3A and
F3B failed to form the proper film and its removal
from surface may be due to lower concentration of
HPMC as a film former. Whereas formulations
F3C, F3D and F3E showed good film formation
and surface removal and were further studies for
various parameters.
Formulation F3C, F3D and F3E showed
very good taste but F3E showed slight bitterness
as aftertaste. This may be because of the
formulation F3E is exposed to the salivary fluid
for longer duration due to higher concentration of
HPMC which lead to dissociation of taste masked
complex and leaves the bitter drug in mouth.

Thickness of selected formulations was

increased with increase in amount of HPMC. The
thickness of strips were in order of F3> F4> F5.
This indicates that among all the strips
studied formulation F3 showed lowest DT and
formulation F5 showed highest DT. The low
standard deviation values for the thickness of
these formulations confirm the efficiency of the
method that was employed for the maintenance of
films thickness.
Similarly with increase amount of HPMC
and PG corresponding increase in values of FE,
TS and PE was observed (Liew et al., 2014). The
percentage drug content in all formulations was
between 100.890.1% and 101.01 0.21%, thus
complies the limit (Kumar et al., 2010) and also
indicates that drug was uniformly dispersed.
In vitro disintegration time was increased
with increase amount of HPMC. Formulation F3C
showed least disintegration time 200.31 seconds
as compared to formulation F3D and F3E having
disintegration time as 250.4 seconds and 380.3
seconds respectively. Increased in amount of

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Minal Bonde /Life Science Archives (LSA), Volume 1, Issue 1, Page 35 to 40, 2015

HPMC in formulations is directly related to

increase disintegration time. This must be due to
increase in swelling index due to increase in
amount of HPMC. Also it was reported in prior
work that disintegration behavior varied
depending on film thickness.
Similarly cumulative percentage drug
release was lower with increase in amount of
HPMC in formulations. The formulation F3C
showed rapid drug release up to 90% in 2 minutes
whereas, formulations F3D and F3E showed 90%
drug release after 5 minutes. SEM images revealed
that the morphology of taste masked MDS were
different when compared with without taste
masked MDS. The uniform white spots on image
(b) indicate that taste masked complex was
uniformly distributed which pertaining to uniform
drug distribution, drug content per strip.
Accelerated stability studies were carried
out on the optimized formulation F3C as per ICH
guidelines. The formulation did not show
significant changes during 3 months stability
studies in FE, TS, PE, drug content and in vitro
disintegration time and thus found to be stable.
5. Conclusion
The study conclusively demonstrated
significant taste masking and rapid disintegration
of taste masked mouth disintegrating strips of
Cyproheptadine HCl. Among the prepared
formulations, formulation F3C showed minimum
disintegration time of 20 0.31 seconds and was
found to be most stable under accelerated stability
conditions. In vitro evaluation of the strips
confirmed their potential as an innovative dosage
form to improve delivery of Cyproheptadine HCl.
Taste masked fast dissolving oral strips of
Cyproheptadine HCl are more palatable form.
Thus, patient-friendly dosage form of bitter drugs
can be successfully formulated using this
technology and it can be specially useful for
geriatric, bedridden and noncooperative patients
due to its ease of administration.

40

taste assessment of pharmaceuticals, Drug

Discovery Today. 257265.
2) Ciper M, Bodmeier R. 2006. Modified
conventional hard gelatin capsules as fast
disintegrating dosage form in the oral cavity.
Eur. J. Pharm. Biopharm. 62: 178184.
3) Dixit RP, Puthli SP. 2009. Oral strip
technology: Overview and future potential
Journal of Controlled Release.139: 94107.
4) Felton L, O'Donnell P, McGinity J. 2008.
Mechanical properties of polymeric films
prepared from aqueous dispersions, in:
Aqueous
polymeric
coatings
for
pharmaceutical dosage forms, 3rd edition,
J. McGinity, L. Felton (Eds). Drugs and the
pharmaceutical sciences. 176: 108.
5) Kumar M, Garg G, Kumar P, Kulkarni GT,
Kumar A. 2010. Design and in vitro
evaluation of mucoadhesive buccal films
containing famotidine. Int J Pharmacy and
Pharm Sci. 2(3): 86-90.
6) Kunte S, Taandale P. 2010. Fast dissolving
strips: A novel approach for the delivery of
verapamil. Journal of pharmacy and Bioallied
science. 2(4).
7) Liew KB, Tan YT, Peh KK. 2014. Effect of
polymer, plasticizer and filler on orally
disintegrating
film.
Drug
Dev
Ind
Pharm. 40(1):110-9.
8) Rowe RC, Forse SF.1980. The effect of film
thickness on the incidence of the defect
bridging of intagliations on film coated tablets.
J. Pharm. Pharmacol. 32(9):647648.
9) Shinde AJ, Garala KC, More HN. 2008.
Development
and
characterization
of
transdermal therapeutics system of tramadol
hydrochloride. Asian J. Pharm 2 (4):N265
269.
10) Shukla D, Chakraborty S, Singh S, Mishra B.
2009. Mouth Dissolving Tablets I: An
Overview of Formulation Technology. Sci
Pharm.77:309326.

6. References
1) Anand V, Kataria, M, Kukkar V, Saharan V,
Choudhury PK. 2007. The latest trends in the
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