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Pasupulati et al Asian Journal of Pharmaceutical Research and Development. 2019; 7(5): 19-25
ISSN: 2320-4850 [19] CODEN (USA): AJPRHS
Available online on 15.10.2019 at http://ajprd.com
Asian Journal of Pharmaceutical Research and Development
Open Access to Pharmaceutical and Medical Research
© 2013-19, publisher and licensee AJPRD, This is an Open Access article which permits unrestricted non-
commercial use, provided the original work is properly cited
Open Access Research Article
Formulation, Characterization and In-vitro Evaluation of Cetrizine
HCL Oral Disintegrating Tablets
Harshita P*1, Phalguna Y1, Sandhya R2
1Bharat Institute of Technology, Mangalpally(V), Ibrahimpatnam(M), Ranga Ready, Hyderabad, Telangana, India
2Bharat school of Pharmacy, Mangalpally(V), Ibrahimpatnam(M), Ranga Ready, Hyderabad, Telangana, India
A B S T R A C T
The main objective of this work is to formulate and evaluate Cetirizine HCl MFDT’s using different concentrations of
superdisintegrants like croscarmellose sodium (CCS), sodium starch glycolate (SSG) and their combinations in different ratios.
The in vitro disintegration time of Cetrizine Hcl prepared by direct compression method by super disintegrates were found to be in
the range of 18 to 11sec fulfilling the official requirements. The bulk density and tapped bulk density for the entire formulation
blend varied from 0.508 gm/cc to 0.5438 gm/cc and 0.5941 to 0.6408 respectively. The friability was found in all designed
formulations in the range 0.42 to 0.74% to be well within the approved range (<1%). The weight variation was found in all
designed formulation in the range 97 to 102 mg. The wetting time were found to be in the range of 11 to 18sec. Water absorption
ratio for all the formulations found in the range 11 to 16%.combination of sodium starch glycolate and cross carmellose sodium
(6% of 25%-ssg&75%ccs)) promotes dissolution rate of drug release when compared to formulation of SSG & CCS alone. It may be
due to capillary and wicking mechanism of SSG & CCS.
Keywords: Super disintegrates, Cetrizine hydrochloride, Sodium starch Glycolate, Crosscarmellose.
A R T I C L E I N F O: Received 15 June 2019; Review Completed 14 August 2019; Accepted 06 Sept. 2019; Available online 15 Oct. 2019
Cite this article as:
Pasupulati H, Phalguna Y, Rudra S,Formulation, Characterization and In-vitro Evaluation of Cetrizine HCL Oral Disintegrating
Tablets, Asian Journal of Pharmaceutical Research and Development. 2019; 7(5):19-25,
DOI: http://dx.doi.org/10.22270/ajprd.v7i5.563
*Address for Correspondence:
Haritha Pasupulati, Bharat Institute of Technology, Mangalpally(V), Ibrahimpatnam(M), Ranga Ready,
Hyderabad, Telangana, India
INTRODUCTION
rug delivery systems (DDS) are a key device for
growing markets/signs, broadening item life cycles
and producing openings. DDS has made a significant
contribution to global pharmaceutical sales through market
segmentation, and are moving rapidly1. Orally disintegrating
tablets (ODT) are oral strong dose frames that break down in
the oral depression in simple swallow buildup. Orally
disintegrating tablets are also known as “Mouth dissolving
tablets”, “Orodispersible tablets”, “Melt- in-mouth Fast
dissolving drug delivery, Rapimelts tablets, Porous tablets,
Quick dissolving tablets” 2 etc. Recently ODT terminology
has been approved by United States Pharmacopoeia, British
Pharmacopoeia, and Centre for Drug Evaluation and
Research (CDER). US FDA characterized ODT tablets as "A
strong measurements structure containing restorative
substances which crumbles quickly as a rule inside merely
seconds, when set upon the tongue”. European
pharmacopoeia also adopted the term Orally disintegrating
tablet as a tablet that is to be placed in the mouth where it
disperses, rapidly before swallowing despite various
terminologies used. Recently, ODT have started gaining
popularity and acceptance as new drug delivery systems,
because they are easy to administer and lead to better patient
compliance especially in elderly and children. So as to enable
quick dissolving tablets to break down in the mouth, they are
made of either extremely permeable or delicate formed
networks or compacted into tablets with low pressure power,
which makes the tablets friable and additionally fragile,
which are hard to deal with, regularly requiring specific strip
off rankle bundling 3-6.
Along with the rapid market growth of ODT products, the
technologies, too, have advanced considerably over the
years. The most up to date age of ODTs can deliver
D
Pasupulati et al Asian Journal of Pharmaceutical Research and Development. 2019; 7(5): 19-25
ISSN: 2320-4850 [20] CODEN (USA): AJPRHS
progressively strong, adaptable tablets that defeat a portion
of the constraints of prior ODTs. Companies such as Eurand
can produce pleasant tasting tablets, overcoming the common
problem of poor drug taste compromising the benefits of an
ODT. In addition, some companies is developing controlled
release ODTs, significantly broadening the applications of
this dosage form. A key reason that companies choose an
ODT over other delivery technologies is that it is a relatively
easy and often less risky delivery option to develop. Since the
route of administration remains the same, ODTs that are
formulated as bioequivalent line extensions or generic
versions of an existing oral dosage form have minimal
clinical requirements to gain approval7.
MATERIALS AND METHODS
Materials
Cetrizine hydrochloride was gift sample from Aurobindo
Pharma., Hyderabad,India. Sodium starch glycolate,
Croscarmellous sodium were purchased from Nihal traders
Hyderabad, India. Magnesium stearate, Colloidal silicon di-
oxide, Lactose monohydrate were purchased from Span
Pharma Private Limited Hyderabad, India. All other reagents
used were of analytical grade.
Methods
Mouth fast dissolving tablets (MFDT’s) were set up by direct
pressure strategy as indicated by recipe given in Table 1. All
the ingredients were passed through mesh # 30 except
magnesium stearate8. Magnesium stearate was passed
through mesh # 40. Drug, and superdisintegrant were mixed
by taking small portion of each in ascending order and
blended to get a uniform mixture in a mortar. The other
ingredients were weighed and mixed in geometrical order
and tablets were compressed using 7mm round flat punches
on a Cadmach single punch machine.
Manufacturing steps for direct compression method
Direct compression involves comparatively few steps:
Milling of drug and excipients.
Mixing of drug and excipients.
Tablet compression.
.All the materials i.e., drug, Lactose monohydrate, colloidal
silicon dioxide, superdisintegrating agents were sifted
through mesh no.40 and were collected in mortar and mixed
well to get a uniform mixture9. Magnesium stearate was
sifted through mesh no.60 sieve, collected into the mortar
containing other ingredients and mixed (added lastly as it is
hydrophobic may affect dissolution and disintegration profile
due to more time of mixing). The lubricated directly
compressible blend was compressed by using direct
compression machine to get hardness above 2.5 kg/ cm2. The
tablets were sublimed at 40-50 0C in a vacuum stove for 24
hours to brilliant subliming agent. End purpose of procedure
is shown by complete expulsion of subliming specialist by
sublimation10-12.
Table 1: Formula of Cetrizine hcl ODTs prepared by direct compression
Ingredients
(mg)
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
F13
F14
F15
Cetrizine
hydrochloride
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
Lactose
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
Disintegrant
2%
SSG
4%
SSG
6%
SSG
2%
CCS
4%
CCS
6%
CCS
2%
SSG
+
CCS
4%
SSG
+
CCS
6%
SSG
+
CCS
2%
SSG
+
CCS
4%
SSG
+
CCS
6%
SSG
+
CCS
2%
SSG
+
CCS
4%
SSG
+
CCS
6%
SSG
+
CCS
Colloidal
silicondioxide
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
Magnesium
stearate
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
.052
CHARACTERIZATION OF TABLETS:
Pre-compression Parameters13-15
Angle of Repose(θ):
A funnel was filled to the brim, allowing the test sample to
flow smoothly under gravity through the orifice. The
measurement of the stack region was taken from the cone
created on the chart sheet, thus assessing the flow ability of
the granules. The pile's height was also measured.
Tan θ =h/r
Where θ is the angle of repose
Bulk Density:
There was a determination of both loose bulk density (LBD)
and tapped bulk density (TBD). An appropriate quantity of
powder from each formulation was brought into a 10 ml
measuring cylinder, earlier slightly shaken to break
agglomerates formed. After the initial volume was observed,
the cylinder was allowed to fall from a height of 2.5 cm at
intervals of 2 seconds under its own weight onto a hard
surface.LBD and TBD were calculated using following
formula.
LBD= weight of the powder/ volume of the packing
TBD= weight of the powder/tapped volume of the packing
Pasupulati et al Asian Journal of Pharmaceutical Research and Development. 2019; 7(5): 19-25
ISSN: 2320-4850 [21] CODEN (USA): AJPRHS
Carr’s compressibility Index
Compressibility index of the powder was determined by
Carr’s compressibility index.
Carr’s index (%) = [(TBD-LBD) X 100] / TBD
Post-compression Parameters16-18:
Uniformity of weight:
The experiment was performed by the Indian pharmacopoeia.
Twenty tablets were weighed separately from each
formulation and the tablet weight average was calculated.
The percentage weight variation compared to the mean tablet
weight was calculated separately
Hardness:
The fracture strength, which is defined as the force required
to break a tablet by radial compression, was measured with a
tablet hardness tester (Monsanto hardness tester) (n=3).
Friability:
A tablet's pharmacopoeial friability test threshold is not more
than 1 percent using Tablet friability device, performed for 4
minutes at 25 rpm (100 rotations). This test again does not
apply to lyophilized and flash dose tablets, but is always
suggested for tablets prepared using direct compression and
moulding methods to guarantee sufficient mechanical
strength.
Percentage friability = 100(initial weight-final weight)/initial
weight (Or) % Friability = (Loss in weight / Initial weight) ×
100
Wetting time:
In a tiny Petri dish containing 6 ml of phosphate buffer pH
6.8, a piece of tissue paper folded twice was put. A tablet
was placed on the paper and measured the time required for
full wetting (n=3).).
Water absorption ratio:
The water absorption ratios of the tablet were carried out in
petri dishes with pH 6.8 phosphate buffer.Peroidically,the
tablets were withdrawn from the petri dishes and weighed on
electronic balance after removal of surface water by light
blotting with a lab tissue for change of their weight till a
constant weight is attained.
In vitro dispersion time19:
In vitro dispersion time was measured by using 10ml of
phosphate buffer pH 6.8 in 25 ml beaker at 37± 0.5 ˚C
temperature. Time required for dispersion of the tablets was
noted. In each formulation three tablets were tested (n=3).
In vitro dissolution study20:
ODTs have been assessed for conduct of dissolution.
Dissolution testing was performed using USP device 2, type
of paddle. Dissolution was performed at 50 rpm rotational
speed using 900 ml of phosphate buffer pH 6.8 as the
dissolution medium maintained at 37 ± 0.5 ° C. Samples
were removed at a predetermined interval of time, diluted
appropriately and analyzed for cumulative drug at 231 nm.
RESULTS & DISCUSSION:
Results of pre-compression parameters for Cetrizine
hydrochloride tablet
Angle of repose (θ):
The data obtained from the repose angle for all formulations
were found to be within the range of 24.19 ° and 28.56 °
which shows excellent flow properties. All formulations with
a rest angle of 30 ° indicate a decent flow property of the
granules.
Bulk density:
Bulk density (BD) was done for the mix and tapped density
(TD). The loose bulk density and tapped bulk density ranged
from 0.508 gm / cc to 0.5438 gm / cc and 0.5941 to 0.6408
respectively for the complete formulation mix.
Carr’s compressibility index:
The findings for the entire formulation mix of Carr's
consolidation index or compressibility index (percent) ranged
from 14.30 percent to 17.53 percent showed outstanding
compressibility index values of up to 15 percent, resulting in
good to outstanding flow properties. As shown in the job of
prior studies. Tabulate all the outcomes in Table 2.
Table 2: Results of pre-compression parameters for Cetrizine hydrochloride tablet
Formulation code
Bulk density g/cc
Tapped density (g/cc)
Angle of repose
Carr’s index(%)
F1
0.543±0.01
0.63±0.03
25.28±0.02
14.30±0.05
F2
0.52±0.02
0.62±0.05
27.20±0.04
17.19±0.01
F3
0.59±0.04
0.60±0.01
25.14±0.08
15.75±0.02
F4
0.50±0.01
0.59±0.06
24.19±0.02
15.00±0.06
F5
0.54±0.05
0.64±0.02
26.41±0.01
15.04±0.03
F6
0.53±0.03
0.62±0.01
28.56±0.07
16.29±0.02
F7
0.51±0.04
0.62±0.03
25.71±0.04
17.53±0.04
F8
0.53±0.08
0.64±0.02
26.38±0.09
16.63±0.08
F9
0.50±0.05
0.59±0.06
26.01±0.02
14.35±0.04
F10
0.53±0.06
0.58±0.04
27.01±0.06
14.34±0.02
F11
0.50±0.03
0.56±0.05
26.98±0.04
15.98±0.01
F12
0.54±0.01
0.54±0.08
26.87±0.07
14.34±0.03
F13
0.54±0.05
0.52±0.04
27.82±0.01
16.87±0.06
F14
0.57±0.02
0.58±0.02
27.97±0.03
15.87±0.02
F15
0.57±0.01
0.58±0.01
26.87±0.05
15.87±0.04
Pasupulati et al Asian Journal of Pharmaceutical Research and Development. 2019; 7(5): 19-25
ISSN: 2320-4850 [22] CODEN (USA): AJPRHS
Results of post-compression parameters for Cetrizine
hydrochloride tablet
Hardness:
All tablets were preserved in hardness from 2.00 kg / cm to
4.00 kg / cm. Tabulate the mean outcomes of the hardness
test in Table 3.
Friability test:
Friability was discovered to be well within the authorized
range (< 1%) in all constructed formulations in the range
0.42 to 0.74%. The findings of the friability research were
summarized in Table 3.
Weight variation test:
The weight variation was discovered in the range of 97 to
102 mg in all constructed formulations. Tabulate the mean
weight variation test outcomes in table 3.All tablets passed
weight variation test as the average weight variation was
within 7.5 percent i.e. the pharmacopie limits.
In-vitro disintegration time:
The time taken to undergo standardized disintegration is
evaluated in vitro. Rapid disintegration was noted in all
formulations within several minutes. Cetrizine Hcl's in vitro
disintegration moment, prepared by super disintegrate using
a direct compression technique, was discovered to be
between 18 and 11 seconds in line with official requirements.
Based on the in vitro disintegration time, formulation F12and
F15 were found to be promising and showed a disintegration
time of 18 and 11 sec respectively.
Disintegrating study showed that the disintegrating times of
the tablets decreased with combination of both sodium starch
glycolate and cross carmellose with different concentrations.
It also showed least disintegration time in comparison with
the all other formulation because of their lowest hardness and
the porous structure is responsible for faster water uptake,
hence it facilitates swelling action in bringing about fast
disintegration.
Wetting time:
Wetting time closely related to the inner structure of the
tablet. The results of wetting time are shown in table. The
wetting time were found to be in the range of 11 to 18sec.
Water absorption ratio: Water absorption ratio for all the
formulations found in the range 11 to 16%. The results of
water absorption ratio for tablets were shown in Table 3.
Table 3: Results of post compression parameters for Cetrizine hydrochloride tablet
Formulation
code
Hardness
Friability
Thickness
Weight variation
In-vitro dispersion
time(sec)
Wetting
time(sec)
Water absorption (%)
F1
3.5±0.4
0.69
3.21
100±1.5
32± 2
27±3
13±2
F2
3.5±0.2
0.46
3.30
99±2.0
28±6
25±4
17±4
F3
3.9±0.1
0.72
3.12
101±0.8
26 ±8
18±5
18±3
F4
3.8±0.2
0.72
3.29
102±0.5
50±4
33±2
13±1
F5
3.6±0.3
0.68
3.34
99±1.2
40± 3
25±1
16±6
F6
3..5±0.4
0.43
3.36
98±1.8
30±2
21±6
15±4
F7
4.0±0.0
0.42
3.29
99±1.0
30±8
29±4
14±3
F8
3.8±0.1
0.45
3.36
97±1.8
26±7
26±3
14±1
F9
3.7±0.2
0.54
3.30
100±0.5
20±5
20±5
13±5
F10
3.9±0.1
0.57
3.21
98±1.2
26±6
26±4
14±4
F11
3.8±0.2
0.53
3.33
100±0.2
24±1
24±2
13±2
F12
3.7±0.3
0.41
3.12
101±0.5
18±2
23±1
12±3
F13
3.5±0.4
0.52
3.42
99±1.2
23±5
20±3
13±1
F14
3.3±0.6
0.40
3.32
100±0.2
19±4
15±6
12±2
F1
3.5±0.4
0.69
3.21
100±1.5
32± 2
27±3
13±2
DISSOLUTION STUDY
In vitro dissolution studies:
Dissolution rate was studied by using USP type-2 apparatus
using 900ml of phosphate buffer pH (6.8) as dissolution
medium. Temperature of the dissolution medium was
maintained at 37±0.5ºc, aliquot of dissolution medium
withdrawn at every 15 sec interval and filtered. The
absorbance of the filtered solution was measured by UV
spectrophotometric method at 231nm and concentration of
the drug was determined from the standard calibration
curve.The dissolution profile of Cetrizine hydrochloride from
the tablets is shown in the Table no: 4 and comparative
release profiles were shown in the Figures 1-3.
Table 4: Cumulative Percentage Drug Release Profiles
Time
(Sec)
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
F13
F14
F15
15
32.7
40.7
41.7
34.3
35.5
36.3
29.5
31.4
36
29
33.7
30
33.4
36.6
47.6
30
36.8
43.3
43.7
38.8
39.7
43
34.7
38.7
40.8
34
38.5
38.7
36.6
44.3
56.4
45
43.1
47.8
48.1
4.19
44.4
49.7
36
42.3
44.7
38.8
40.4
44.4
41.8
51.4
64.8
60
56.6
57.4
58.4
44
50.1
59.4
40.4
48.2
58.8
42
45
60.6
42.5
54.7
70.6
75
61
65.8
68.8
50
57
67.6
44.7
55.7
62.8
46.4
53.5
66.3
48.3
53.9
75.7
90
65.9
66.4
69.3
60.7
62.5
70.9
49
65.5
67.7
51.5
67
70.2
51.9
66.5
81
Pasupulati et al Asian Journal of Pharmaceutical Research and Development. 2019; 7(5): 19-25
ISSN: 2320-4850 [23] CODEN (USA): AJPRHS
Figure 1: Release profile of formulations F1, F4, F7, F10, F13
Figure 2: Release profile of formulations F2, F5, F8, F11, F14
Figure 3: Release profile of formulations F3, F6, F9, F12, F15
CONCLUSION
Dissolution rate of tablets with CCS and SSG improves when
concentration increased from 2% to 4% and 4% to 6%.
Dissolution rate of tablets with SSG was significantly less
when compared to the tablets with CCS at initial time points.
From the above results of the study it can be concluded that
combination of sodium starch glycolate and crosscarmellose
sodium (6% of 25% SSG & 75% CCS) could be the
alternative approach to increase the dissolution of tablets
Pasupulati et al Asian Journal of Pharmaceutical Research and Development. 2019; 7(5): 19-25
ISSN: 2320-4850 [24] CODEN (USA): AJPRHS
when compared to the formula with sodium starch glycolate
and crosscarmellose alone as disintegrate. Hence the
combination of sodium starch glycolate and crosscarmellose
sodium (6% of 25% SSG &75% CCS) promotes dissolution
rate of drug release when compared to formulation of SSG &
CCS alone .It may be due to capillary and wicking
mechanism of SSG & CCS.
ACKNOWLEDGMENTS
The authors would like to thank the Management of Bharat
Institute of Technology, Mangalpally (V), Ibrahimpatnam
(M), R.R-Dist. for providing facilities to evaluate the
formulations.
REFERENCES
1. Sreenivas SA. Orodispersible tablets: New‐ fangled drug delivery
system‐ A Review. IndianJ.Pharm.Educ.Res 2005; 39(4):177‐81.
2. Chein YW. Oral Drug Delivery and Delivery systems, 2nd ed., New
York: Marcel Dekker, 1992.
3. Rakesh RK. Orally Disintegrating Tablets novel tablets novel
approach to drug delivery. Pharma Review 2004; 2(12):34‐ 36.
4. Kuchekar BS, Badhan AC, Mahajan HS. Mouth dissolving tablets: a
novel drug delivery system. Pharma Times 2003; 35:1‐8
5. Brown D. Orally disintegrating tablets-taste over speed. Drug
Delivery Technology 2003; 3(6):58-61.
6. Klauke J. Dissolution testing of orally disintegrating tablets.
Dissolution Technologies| 2003; (1):6-8.
7. Harmon TM. Beyond the First Generation of Orally Disintegrating
Tablets. Emerging Technology. Tablets and Capsules.2006; 9(3).
8. Jashanjit Singh,1 Anil K. Philip,1 and Kamla Pathak Optimization
Studies on Design and Evaluation of Orodispersible Pediatric
Formulation of Indomethacin AAPS Pharm Sci Tech.2008; 9(1).
9. Gohel M. Tablet Disintegrants. Pharmainfo. 2013.
10. R. F. Shangraw, Vol. 4, 2nd Ed., Marcel Dekker, Newyork USA, p.
85, 1988.
11. M. Jivraj, L. G. Martini and C. M. Thomson, PSTT.2008; 3-58.
12. Gohel MC, Jogani PD, A review of co-processed directly
compressible excipients. J Pharm Sci. 2005; 8(1):76-93.
13. Leon Lachman, Herbert Liberman, Joseph L. Kanig, in: Theory and
Practice of Industrial Pharmacy, 2nd Edn. Varghese Publication,
1985.
14. Herbert A. Lieberman, Leon lachman and Joseph B. Schwartz;
Pharmaceutical Dosage forms; Tablet, Vol. – I 2nd.
15. Raymond C Rowe, Paul J Sheskey and Marian E Quinn; Handbook
of Pharmaceutical excipients. 6 edition.
16. Battu SK, Repka MA, Majumdar S, Rao MY. Formulation and
evaluation of rapidly disintegrating tablet Fenoverine tablets: Effect
of superdisintegrants. Drug Dev Ind Pharm. 2007; 33:1225–32.
17. Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N.
Formulation design and optimization of mouth dissolve tablets of
nimesulide using vacuum drying technique. AAPS Pharm Sci Tech.
2004; 5:e36.
18. Bi Y, Sunada H, Yonezawa Y, Danjo K, Otsuka A, Iida K.
Preparation and evaluation of a compressed tablet rapidly
disintegrating in the oral cavity. Chem Pharmaceut Bull (Tokyo).
1996; 44:2121–7.
19. El-Arini SK, Clas SD. Evaluation of disintegration testing of
different fast dissolving tablets using texture analyzer. Pharm Dev
Technol, 2002; 7(3):361-371.
20. Klancke J. Dissolution testing of orally disintegrating tablets.
Dissolution Technol, 2003; 10(2):6-8.