Development and Evaluation of Fast Dissolving Tablets of Flurbiprofen

ISSN No : 2321 8630, V 1, I 1, 2014
Journal Club for Pharmaceutical Sciences (JCPS)

Manuscript No: JCPS/RES/2014/15, Received on: 03/08/2014, Revised on: 08/08/2014, Accepted on: 13/08/2014
RESEARCH ARTICLE
Development and Evaluation of Fast Dissolving Tablets of Flurbiprofen
1
Patel NS1, Patel VM1, Patel KA1, Modasiya KM1

APMC College of pharmaceutical education and research, College campus, Motipura,
Himmatnagar-383001, Sabarkantha, Gujarat.
ABSTRACT
The aim of the investigation is to prepare the fast dissolving tablet of flurbiprofen. Flurbiprofen,
a widely prescribed anti inflammatory analgesic drug belongs to BCS class II and exhibit low
and variable oral bioavailability due to its poor solubility and dissolution rate. The objective of
the present study is to develop flurbiprofen fast dissolving tablet formulations by direct
compression method by forming its inclusion complex with -cyclodextrin. The 9 batches were
prepared by using super disintegrants. The tablet weight is 350mg.The clathrate is having 1:1
proportion. Inclusion complex of BCD with drug enhance its dissolution and also improve the
taste Different super disintegrating agent like cross carmellose sodium, kyron T-314 and SSG in
different proportion to enhance solubility of flurbiprofen. The method used was direct
compression and directly compressible vehicle used was avicel PH 102, Mannitol was used to
fill up the tablet volume and was also acts as sweetener. All the evaluations were performed to
check the efficacy and effectiveness of tablet like disintegration time, hardness, friability,
wetting time and in-vitro dissolution test. From all the evaluations data batch B6 which contain
kyron T-314 as super disintegrating agent with 15mg in each tablet was evaluated as optimized
formula for the preparation of fast dissolving tablet of flurbiprofen.
KEYWORDS
Flurbiprofen, Fast dissolving tablet, Inclusion complex, kyron T-314
INTRODUCTION1,2
because of ease of administration, accurate
Oral routes of drug administration have wide
dosage, self -medication, pain avoidance and
acceptance up to 50-60% of total dosage
most importantly the patient compliance.
forms. Solid dosage forms are popular
The most popular solid dosage forms are

being tablets and capsules; one important
*Address for Correspondence

Sanket N. Patel,
66/Matruchhaya society.,
Near Bhumipujafarm society, Mahavirnagar,
Himmatnagar-383001,
Dist: Sabarkantha, Gujarat, India
Email ID: sanketthepharmacist@gmail.com
All Rights Reserved by Journals Club & Co.
drawback of this dosage forms for some

patients, is the difficulty to swallow.
Drinking water plays an important role in
the swallowing of oral dosage forms. Often
76

times people experience inconvenience in
(croscarmellose), sodium starch glycolate
swallowing conventional dosage forms such
(primogel, explotab), Kyron etc, which
as tablet when water is not available, in the
provide
case of the motion sickness (kinetosis) and
tablet after putting on tongue, their by
sudden episodes of coughing during the
release the drug in saliva.
common
cold,
allergic
condition
instantaneous
disintegration
of
and
bronchitis.
The bioavailability of some drugs may be
increased due to absorption of drug in oral
For these reason, tablets that can rapidly
cavity and also due to pregastric absorption
dissolve or disintegrate in the oral cavity
of saliva containing dispersed drugs that
have attracted a great deal of attention. Fast
pass down into the stomach. Moreover, the
dissolving tablets are those when put on
amount of drug that is subjected to first pass
tongue disintegrate instantaneously releasing
metabolism is reduced as compared to
the drug which dissolve or disperses in the
standard tablet.
saliva. The faster the drug into solution,

quicker the absorption and onset of clinical
effect. Some drugs are absorbed from the
Poorly water-soluble drugs are associated
mouth, pharynx and esophagus as the saliva
with
passes down into the stomach. In such cases,
eventually
bioavailability of drug
bioavailability. Flurbiprofen is a poorly
greater
than
those
is significantly
observed
from
slow
drug
to
absorption
inadequate
and
leading
variable
water soluble drug with a well known chiral
conventional tablets dosage form. According
non-steroidal
to European pharmacopoeia, the FDT should
possessing analgesic and antipyretic activity.
disperse/disintegrate in less than three

minutes.
anti
inflammatory
agent
It is one of the most potent inhibitors of

platelet aggregation, and it is used to treat
gout, osteoarthritis, rheumatoid arthritis and
The basic approach in development of FDT

is the use of super disintegrants like cross
linked
carboxymethyl
cellulose
sunburn. However, it has poor water

bioavailability due to
its poor
water
solubility (10.45 3.2g/ml). Several
77

attempts have reported for enhancing the
character. This cavity enables cyclodextrins
solubility and bioavailability of flurbiprofen.
to complex the guest drug molecules and
In the present study an attempt has been

made
to
increase
flurbiprofen
using
the
and
solubility
of
complexation
in so doing alters the physicochemical

properties of the drug.
MATERIALS & METHODS
techniques. Complexation of drugs with
Flurbiprofen was purchased from Yarrow
cyclodextrin has been used to enhance
chem. Products, Mumbai, Cross carmeloose
aqueous solubility and drug stability.
sodium was obtained from, SSG was

obtained from, Kyron T-314 was purchased
Cyclodextrins are useful excipients, having

the ability to interact with poorly watersoluble drugs and drug candidates, resulting
in an increase in their apparent water
solubility.
These
oligosaccharides
are
derived
cyclic
from
from Corel pharma chem. All other reagents

and solvents were of analytical grade and
double distilled water was used throughout
the study.
and
starch
Preparation of Inclusion Complex of
containing six ( CD), seven (-CD), Eight
Flurbiprofen
( -CD), nine ( -CD) or more (-1,4)-linked
clatherate(1:1)5
-D-glucopyranose units, the cyclodextrin

take the shape of a truncated cone or torus,
rather than a perfect cylinder.
with
-cyclodextrin
BCD (4.56 g, 3.42 mmoles) was dissolved in

water (75 ml) at 100C. Flurbiprofen (0.84
g, 3.42 mmoles) was added and the resulting
The primary hydroxyl group is oriented to
solution was cooled to 1C to give a white
the narrow edge of the cone at the exterior
precipitate which was isolated by filtration
and the secondary group to the wider edge.
and dried at 50C in a convection oven. The
The central cavity of the cyclodextrins
product, a white powder, was sieved through
molecule is linked with skeletal carbons and
a 100 m screen to yield 4.24 g of
ethereal oxygens of the glucose residue,
BCD/flurbiprofen clathrate.
which gives it
a relatively lipophilic
General Procedure for Preparation of
Fast
dissolving
tablets
containing
Formulation of Fast Dissolving Tablet of
Flurbiprofen prepared by direct compression
Flurbiprofen
78

Table 1: Formulation of Different Batches of Fast Dissolving Flurbiprofen Tablet
Ingredients
(mg)
Drug + cyclodextrin
Cross
carmellose
sodium
Kayron
SSG
Mannitol
Avicel pH 102
Talc
Magnesium
stearate
Total weight
in (mg)
F1
F2
F3
F4
F5
F6
F7
F8
F9
284
284
284
284
284
284
284
284
284
10
15
10
15
30.5
20
7
25.5
20
7
20.5
20
7
30.5
20
7
25.5
20
7
20.5
20
7
5
30.5
20
7
10
25.5
20
7
15
20.5
20
7
3.5
3.5
3.5
3.5
3.5
3.5
3.5
3.5
3.5
350
350
350
350
350
350
350
350
350
method accurately weighed -cyclodextrin
TDT-06T (Electrolab, Mumbai, India) using
and
water as test fluid.
flurbiprofen
clatherate
and
other
polymers are passed through sieve no.100

and mix together and ready for compression
Evaluation
parameters
of
FDT
RESULT AND DISCUSSION

Determination of Maximum Wavelength3
of
100 mg of Flurbiprofen was weighed
flurbiprofen10,16
accurately, dissolved in 20 ml of methanol

All the tablets prepared were evaluated for
content of active ingredients, hardness,
friability,
and
disintegration
time
and
dissolution rate as per official (IP) methods.

Hardness of tablets was tested using
Monsanto Hardness tester. Friability of the
tablets
was
friabilator.
determined
Disintegration
in
a
time
Roche
and finally the volume was made up to 100

ml by methanol to produce a stock solution
having a concentration of 1mg/ml. The
absorbance of the resulting solution was
measured
using
UV-Visible
spectrophotometer in the wavelength range

of 200-400 nm.
was
determined in a Dissolution test apparatus-
Preparation of Standard Solution
79

An aliquot of 10 ml of the stock solution
by appropriately diluting the standard
was diluted to 100 ml to prepare standard
solution with phosphate buffer saline pH
solution having a concentration of100
6.4. The absorbance of each working
mcg/ml by using phosphate buffer saline pH
standard solution was measured at 246.6 nm
6.4.
using a Shimadzu UV spectrophotometer
Preparation of Working Standard Solution
using phosphate buffer saline pH 6.4 as a

blank. Data for each and every experiment
Working standard solution in concentration
was obtained in triplicates and statistically
ranging from 2 to 16 mcg/ml were prepared
analyzed.
Fig. 1a: Flurbiprofen Standard Curve
Compatibility
Study
of
Drug
and
excipients are shown in figure 1 a and figure
Excipients3
1b respectively.
FTIR technique has been used to here study
From the figure, it was observed that there
the
were no change in this mail peak in IR
physical
and
chemical
interaction
between drug and excipients used.
spectra of formulation, which shows there

were no physical interactions because of
some bond formation between the drug and
Infrared
spectra
of
Flurbiprofen
and
polymer.
formulation containing drug and all other
80

Fig. 1b : FTIR of Flurbiprofen
70
%T
60
50
40
30
4
5
7
.1
4
7
0
7
.9
0
8
40
.9
9
8
1
5
.9
2
7
6
7
.6
9
87
9
.57
9
2
5
.8
6
1
2
6
5
.3
5
13
6
1
.7
9
69
8
.25
4
1
8.5
7
1
4
1
1
.9
4
1
4
19
.66
15
0
6
.4
6
1
4
73
.6
6
15
3
3
.4
6
3
3
1
9
.6
0
3
35
4
.32
10
3
3
3
8
.8
9
20
-10
4000
A
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400
1/cm
Fig. 1c : FTIR of Drug and -cyclodextrin

60
%T
52.5
45
37.5
30
22.5
4
0
1
.2
1
7
2
9
.1
2
6
9
4
.4
0
7
6
5
.7
7
1
0
0
4
.9
5
1
0
2
6
.1
6
1
1
5
7
.3
3
1
0
8
0
.1
7
1
4
1
9
.6
6
3
1
7
3
.0
1
3
1
8
2
.6
5
3
2
0
0
.0
1
3
2
4
0
.5
2
3
2
7
7
.1
7
3
2
8
4
.8
8
3
3
3
3
.1
0
3
4
8
9
.3
4
3
3
4
6
.6
1
15
7.5
-7.5
-15
4000
B
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400
1/cm
Fig. 1d : FTIR of Drug and Polymers

60
%T
52.5
45
37.5
30
22.5
4
0
1
.2
1
4
8
9
.9
4
4
2
0
.5
0
6
1
3
.3
8
6
8
6
.6
8
6
9
4
.4
0
1
0
0
3
.0
2
1
0
2
8
.0
9
1
1
3
0
.3
2
1
0
7
4
.3
9
1
1
5
3
.4
7
1
3
3
8
.6
4
1
3
6
1
.7
9
1
4
0
8
.0
8
3
1
6
5
.2
9
3
2
1
1
.5
9
3
2
2
8
.9
5
3
2
5
4
.0
2
3
3
9
6
.7
6
7.5
3
2
7
9
.1
0
15
0
-7.5
4000
C
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400
1/cm
81

Table 2 : Preformulation Data of Prepared Granules
Tapped
Compressibilit
Density
y Index (I)*
(gm/ml)*
29.48 0.410
0.590 0.025
0.685 0.020
18.58 0.51
27.56 0.390
0.611 0.015
0.714 0.028
16.79 0.46
28.24 0.350
0.592 0.020
0.686 0.015
15.92 0.67
26.65 0.215
0.642 0.030
0.756 0.025
17.61 0.36
26.84 0.190
0.561 0.025
0.653 0.015
16.28 0.38
22.47 0.160
0.579 0.001
0.667 0.002
15.19 0.21
28.32 0.360
0.600 0.015
0.695 0.020
15.83 0.75
27.91 0.310
0.604 0.025
0.715 0.030
18.46 0.59
26.49 0.250
0.618 0.15
0.724 0.020
17.10 0.44
Table 2a : Post Compression Data of Prepared Granules
Angle of
Repose ()*
Formulations
F1
F2
F3
F4
F5
F6
F7
F8
F9
Formula
F1
F2
F3
F4
F5
F6
F7
F8
F9
Hausners
Ratio*
1.1600.010
1.1610.015
1.1580.020
1.1770.020
1.1630.015
1.1510.005
1.158 0.025
1.1830.015
1.1710.010
Thickness
Hardness
Weight
Friability %***
(mm)***
(Kg/cm2)**
variation(mg)***
5.1 0.1
4.7 0.25
0.94 0.08
351 3.6
5.03 0.05
4.3 0.26
0.95 0.05
349 3.0
5.13 0.05
4.8 0.49
0.95 0.03
346 4.0
5.13 0.1
4.5 0.25
0.98 0.08
346.66 4.72
5.16 0.5
4.2 0.5
0.94 0.02
353.33 2.08
5.03 0.5
4.5 0.25
0.86 0.1
351 1.0
5.2 0.1
5.1 0.1
0.95 0.6
353.7 3.78
5.06 0.5
5.2 0.2
0.98 0.05
352 3.46
5.2 0.5
5.03 0.15
0.97 0.02
348.7 3.51
Table 2b: Evaluation Parameters FDT of flurbiprofen
Formulation
F1
F2
F3
F4
F5
F6
F7
F8
F9
Bulk Density
(gm/ml)*
Diameter(mm)
(n=3)
10.4 0.06
10.5 0.05
10.5 1.00
10.4 1.00
10.4 0.05
10.3 0.02
10.5 1.00
10.4 1.10
10.4 1.254
In vitro Disintegration
time (seconds)(n=3)
143 4.58
135 4.08
129 3.49
120 3.21
112 4.85
88 3.56
136 4.04
138 4.69
131 5.73
Wetting time
(seconds)(n=3)
62 4.46
58 5.67
55 4.48
52 6.64
49 5.23
42 3.15
67 5.69
64 6.82
60 6.71
82

Table 2c : % Cumulative Release of FDTof Flurbiprofen Batches F1-F6
Time
% Cumulative Drug Release of batches F1-F6

F2
F3
F4
F5
0.0
0.0
0.0
0.0
63.630.420 61.510.314 65.760.369 66.980.413
71.230.314 70.050.367 74.280.278 77.92 0.225
76.870.360 78.590.410 80.520.247 82.69 0.376
81.620.287 86.220.329 83.230.249 86.64 0.187
86.450.197 91.190.294 86.260.348 90.01 0.146
91.380.245 92.240.189 91.140.127 92.50 0.357
93.850.384 95.510.334 94.540.196 95.00 0.327
95.110.215 96.410.276 96.150.324 97.83 0.278
F1
0.0
64.550.341
74.280.256
80.220.145
86.570.358
91.460.257
93.060.412
94.650.373
95.960.246
0
5
10
15
20
30
40
50
60
In Vitro Dissolution Study
F6
0.0
79.140.124
83.700.187
88.53 .210
92.850.319
94.460.147
96.690.264
98.330.371
99.360.259
whatman filter paper replaced with fresh
The dissolution study was carried out using
dissolution
USP-II paddle apparatus at 37C 0.5C
spectrophotometrically at 246.6nm in UV.
using 900 ml of simulated saliva (pH 6.4) as
The last F batch is a batch without forming
dissolution medium. The agitation rate of
inclusion complex show poor solubility
paddle was 50 rpm. Five ml samples were
without formation of inclusion complex.
medium
and
analyzed
withdrawn at 5,10,15,20,30,40,50 and 60

minute time and were filtered through
Table 2d :% Cumulative Release of FDT of Flurbiprofen Batches F7-F9 & F
Time
F7
0
5
10
15
20
30
40
50
60
% cumulative drug release of batch F7-F9 & F

F8
F9
57.25 0.218
62.11 0.369
67.62 0.258
78.090.149
82.58 0.347
89.25 0.420
90.20 0.396
91.77 0.278
58.43 0.394
69.11 0.342
74.06 0.267
81.28 0.263
86.72 0.319
90.39 0.289
93.18 0.356
94.47 0.239
64.85 0.297
70.66 0.346
79.21 0.326
83.71 0.379
88.36 0.297
91.47 0.283
95.45 0.372
96.72 0.277
17.14 0.176
19.58 0.249
21.83 0.153
24.21 0.168
25.93 0.148
28.09 0.129
30.23 0.167
32.69 0.134
83

Fig. 1e : %Cumulative Release of Fast Dissolving Tablets of Flurbiprofen Batches F1-F6
% cumulative drug release
% cumulative Drug release of batches F1- F6

120
100
80
60
40
20
0
0
20
40
60
Time (min.)
80
%
cumulative Drug
release F1
%
cumulative Drug
release F2
%
cumulative Drug
release F3
%
cumulative Drug
release F4
Fig. 1f : % Cumulative Release of Fast Dissolving Tablets of Flurbiprofen Batches F7F9&F
CONCLUSION
method using super disintegrants. All the
Fast dissolving tablets of flurbiprofen were
evaluation parameters shows that results
prepared by forming inclusion complex with
show that after forming inclusion complex
-cyclodextrin
the dissolution is further enhanced and super
by
direct
compression
84

disintegrants make them suitable for fast
dissolving.
(Eds.). Clarkes Analysis of Drugs and

Poison, p. 248.
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HOW TO CITE THIS ARTICLE
Patel, N, S., Patel, V, M., Patel, K, A., Modasiya, K, M. Development and Evaluation of Fast
Dissolving Tablets of Flurbiprofen. Journal Club for Pharmaceutical Sciences (JCPS), 1(I), 76-86.
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Development and Evaluation of Fast Dissolving Tablets of Flurbiprofen

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Format Tersedia

ISSN No : 2321 8630, V 1, I 1, 2014

Journal Club for Pharmaceutical Sciences (JCPS)

Patel NS1, Patel VM1, Patel KA1, Modasiya KM1

because of ease of administration, accurate

Oral routes of drug administration have wide

dosage, self -medication, pain avoidance and

acceptance up to 50-60% of total dosage

most importantly the patient compliance.

forms. Solid dosage forms are popular

The most popular solid dosage forms are

*Address for Correspondence

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drawback of this dosage forms for some