Preparation and Evaluation of Fast Dissolving Tablets of Celecoxib

Journal of Current Pharmaceutical Research 04 (2010) 4-11
JCPR 2010, 04: 4-11
© 2010 Medipoeia
Received: 11-12-2010
Revised: 15-12-2010
Accepted: 22-12-2010
Preparation and Evaluation of Fast Dissolving
Tablets of Celecoxib
Vijay Tiwari*, Dhana jay kinikar, Krishna Pillai, and P.D.Gokulan
Vijay Tiwari, Dhana jay kinikar,
Krishna Pillai, and P.D.Gokulan
Department of Medicinal Chemistry,
Shri Ramnath singh Institute Of
Pharmaceutical science & technology 1 ,
ABSTRACT
Objective: The purpose of this research was to study fast dissolving tablets of Celecoxib using
solid dispersion of Celecoxib and sorbitol by holt melt extrusion process, and superdisintegrants
(sodium starch glycolate), binder (polyvinylpyrrolidone), sweetner (saccharine sodium), flavour
(menthol).
Material and methods: Six different formulation of solid dispersion is prepared and the batch
having the best drug release profile is used for the preparation of nine batches of fast dissolving
tablets by direct compression method. The tablet is characterized by hardness, wetting time,
weight variation, in-vitro drug dissolution, and in-vivo taste evaluation.
Results: All batches of solid dispersion and fast dissolving tablets are satisfactory in terms of
dissolution profile. The hardness, wetting time, drug content analysis and taste evaluation of
tablets are also shows the satisfactory result. The batch of solid dispersion containing maximum
concentration of sorbitol polymer is showing best drug release. In fast dissolving tablets the
batch containing maximum concentration of superdisintegrant is showing the best drug release.
Conclusion: The FDT6 batch of fast dissolving tablets is shows the 99.74 % cumulative drug
release in 30 min. The FDT6 is best in all nine formulations of fast dissolving tablets of
Celecoxib. So the bioavailability of Celecoxib is increased by fast dissolving dosage form.
Keywords: Celecoxib, Solid dispersion, Fast dissolving tablet, sorbitol
1. INTRODUCTION
Correspondence:
Vijay Tiwari
Department of Medicinal Chemistry,
Sri Ram Nath Singh Institute Of
Pharmaceutical science & technology,
Sitholi,Gwalior India.
email: gokulakila@yahoo.co.in
Fast dissolving tablets are best alternate to deliver the drug having bitter taste and poor
oral bioavailability. Celecoxib (CXB) is a non-steroidal antiinflamatory drug (NSAIDS), acting by
inhibition of prostaglandins, by inhibiting the activity of the enzyme cyclooxygenase-2 (COX-2).
It is selective and non-competitive for COX 2 inhibitor. Celecoxib is preferred over conventional
NSAIDs, as the latter may lead to serious gastrointestinal complications such as ulcer, severe
bleeding and perforation, resulting in hospitalization, and even death. It is mainly used for the
osteoarthritis, rheumatoid arthritis, and dysmenorrhea. The drug is available in tablet form, and is
yet not official in any Pharmacopoeia. Celecoxib is practically insoluble in water resulting in
absorption problem. It is well absorbed in the gastrointestinal tract. When taken with a high fat
meal, peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption
(AUC) of 10% to 20%(http://www.drugbank.ca/drugs/DB00482). The rate and extent of
dissolution of the drug from any solid dosage form, determines the rate and extent of absorption of
the drug. In the case of poorly water- soluble drugs, dissolution is the rate-limiting step in the
process of drug absorption. Potential bioavailability problems are prevalent with extremely
hydrophobic drugs (aqueous solubility less than 3.3 mg/ml at 37°)
(http://www.rxlist.com/celebrex-drug.htm), due to erratic or incomplete absorption from GIT. The
solid dispersion approach has been widely and successfully applied to improve the dissolution,
solubility, and consequently the bioavailability of poorly water-soluble drugs. A number of drugs
have been shown to improve their dissolution character, when converted to solid dispersions.

Journal of Current Pharmaceutical Research 04 (2010) 4-11
To date, some reports on the formulation of these systems
have appeared. Because of its poor aqueous solubility, Celecoxib
may pose dissolution related absorption problem. Hence, an
attempt was made to improve the dissolution of CXB by preparing
its solid dispersion and finally into fast dissolving tablets using
sodium starch glycolate as superdisintgrants.
2. MATERIALS AND METHODS
Material
Celecoxib drug was procured from Exim Pharma
international, Mumbai. The sorbitol is used for the preparation of
solid dispersion. Sodium starch glycolat was provided by Vjalak
Pharma LTD., Hyderabad. Magnessium sterate and Saccharin
sodium was procured from Central Drug House, New Delhi,
Sorbitol, PVP and Quinine sulphate was purchased from R.K.
Chemical distributors, Meerut. Menthol was procured from Bhagat
Aromatics Limited, India.
3. EXPERIMENTAL
3. 1 Preparation of solid dispersion
Solid dispersion of Celecoxib was prepared with sorbitol
polymer with various drug-polymer ratios (1:1, 1:2, 1:4, 1:6, 1:8,
1:10). Hot melt extrusion method was used to prepare the solid
dispersion. Hot melt extrusion approach represent the
advantageous mean of preparation of solid dispersion by using the
twin screw hot melt extruder where only thermostable components
are relevant. The extruder consists of a hopper, barrel, a die, a
kneading screw and heaters. The physical mixture is introduced
into the hopper that is forwarded by feed screw and finally is
extruded from the die. Melt extrusion is essentially the same as the
fusion method except that intense mixing of the components is
induced by the extruder. When compared to melting in a vessel, the
product stability and dissolution are similar, but melt extrusion
offers the potential to shape the heated drug-matrix mixture into
implants, ophthalmic inserts, or oral dosage forms (Patidar K et al.,
2010).
Table 1 Various formulations of solid dispersion with varying
drug-polymer ratio
Formulations
Drug : Polymer
SD 1 1 : 1
SD 2 1 : 2
SD 3 1 : 4
SD 4 1 :6
SD 5 1 : 8
SD 6 1 : 10
3.2 Evaluation and selection of solid dispersion
All six batches of solid dispersion were evaluated for their
drug content uniformity and dissolution profile to select the
optimized batch. Batch SD6 showed best dissolution profile and
was selected for the preparation of fast dissolving tablets.
3.3 Drug content analysis
Drug content was determined by dissolving the 100 mg of
solid dispersion into 100 ml buffer having pH 1.2. Allow to stand
the samples for one night. Then filter the solution and measure the
absorbance on UV-spectrophotometer at suitable wavelength (252
nm). The experiment was conducted in triplicate. Dilution was
performed if required necessary.
3.4 In-vitro dissolution study and selection of best blend to
prepare FDT
In-vitro dissolution study for all six batches of solid
dispersion was performed in USP Dissolution Apparatus II paddle
type and batch having best drug release profile is selected for the
preparation of fast dissolution tablets.
3.5 Formulation of tablets of celecoxib-sorbitol solid dispersion
(Batch SD6 Formula)
The fast dissolving tablets are prepared by direct
compression method. It is the easiest way to manufacture tablets.
Conventional equipment, commonly available excipients and a
limited number of processing steps are involved in direct
compression. Also high doses can be accommodated and final
weight of tablet can easily exceed that of other production methods
(Bhowmik D et al., 2009).
3.6 Evaluation of powdered blend
Powdered blends were evaluated for following bulk
properties.
Bulk characterization
3.6.1 Bulk density
Density is defined as weight per unit volume. Bulk
density is defined as the mass of the powder divided by the bulk
volume.
Apparent bulk density was determined by pouring pre- sieved drug
excipient blend into a graduated cylinder and measuring the
volume and weight “as it is”. It is expressed in g/cm 3 and is given
by
D b = M / V 0
Where, M is the mass of powder and V 0 is the Bulk volume of the
powder.
3.6.2 Bulkiness
Specific bulk volume or reciprocal of bulk density is
called bulkiness or bulk. Bulkiness increases with a decrease in

Journal of Current Pharmaceutical Research 04 (2010) 4-11
Table 2 Various formulations with varying concentration of excipient (superdisintegrants and binder)
S.No. FDT 1 FDT 2 FDT 3 FDT 4 FDT 5 FDT 6 FDT 7 FDT 8 FDT 9
Ratio of A vs B 1:1 1:2 1:3 1:4 1:5 5:1 4:1 3:1 2:1
Solid dispersion (mg) 550 550 550 550 550 550 550 550 550
Sodium starch glycolate (Superdisintegrant) (A) 10 6.66 5 4 3.33 16.6 16 15 13.3
Poly vinyl pyrolidone (Binder) (B) 10 13.3 15 16 16.6 3.33 4 5 6.66
Saccharin sodium (Sweetener) 2 2 2 2 2 2 2 2 2
Magnesium sterate (Glidant) 1 1 1 1 1 1 1 1 1
Flavour 1 1 1 1 1 1 1 1 1
particle size. In mixture of material of different sizes, however the
smaller particle shifts between the larger particles and tends to
reduce the bulkiness. The bulkiness can be calculated by the
following formula
Bulkiness= I/ D b
where, D b = Bulk Density.
3.6.3 Drug content uniformity
Drug content was determined by dissolving the 100 mg of
bulk powder into 100 ml distilled water. Allow to stand the
samples for one night. Then filter the solution and measure the
absorbance on UV-spectrophotometer at suitable wavelength (252
nm). The experiment was conducted in triplicate. Dilution was
performed if required necessary.
3.6.4 Tapped density
It was determined by placing a graduated cylinder,
containing a known mass of drug excipient blend, on mechanical
tapping apparatus. The tapped volume was measured by tapping
the powder to constant volume. It is expressed in g/ml and is given
by
Dt = M / Vt Where, M is the mass of powder and Vt is the tapped
volume of the powder.
3.6.5 Void volume
The volume of the spaces is known as the void volume “v” and is
given by the Formula:
V=V b -V p
Where, Vb = Bulk volume (volume before tapping)
V = True volume (volume after tapping)
3.6.6 Angle of repose
Angle of repose is used for the measurement of frictional
force in a loose powder. Angle of repose was determined by using
funnel method suggested by Newman. Powder was poured from a
funnel that can be raised vertically until a maximum cone height, h,
was obtained. Diameter of heap, D, was measured. The angle of
repose, Ө, was calculated by formula tan Ө = h / r, Ө = tan-1 (h / r)
Where, Ө is the angle of repose, h is the height in cm and r is the
radius.
Angle of repose less than 30 0 shows the free flowing of the
material.
3.6.7 Carr’s index
It is expressed in percentage and is expressed by
I = D t – D b / D t
Where, D t is the tapped density of the powder
Db is the bulk density of the powder.
3.6.8 Hausner ratio
It is expressed in percentage and is expressed by
H= D t / D b
Where, D t is the tapped density of the powder
D b is the bulk density of the powder.
3.6.9 Percent porosity
The porosity € of powder is defined as the ratio of void
volume to the bulk volume of the packaging. The porosity of the
powder is given by €= V b – V p / V p =1- V p /V b
Porosity is frequently expressed in percentage and is given as %€ =
(1 – V p / V b ) X 100

Journal of Current Pharmaceutical Research 04 (2010) 4-11
3.6.10 Percent Compressibility
It is an important measure obtained from bulk density and
is defined as,
C=D b -D u /D b x100
Where, D b is bulk density of the powder and D u is loose bulk
density.
If the bed of particles is more compressible the blend will be less
flowable and flowing materials.
3.7 Compression of various powdered blends
The various powder blends were compressed with a
rotatory tablet press machine (Cad Mack). Every formulation
tablets 574 mg in weight were prepared by using 12 mm round, flat
faced punches. For the preparation of tablets, the fill volume of the
die was adjusted to corresponding 574 mg weight. Then the tablets
were compressed one by one, with compression force of 24 kg.
3.8 Evaluation of tablets of celeecoxib-sorbitol dispersion SD6:
3.8.1 Appearance, size, shape, thickness and diameter of tablet
The size and shape of the tablet can be dimensionally
described, monitored and controlled. Thickness of tablets is an
important characteristic for appearance and also in counting by
using filling equipment. Some filling equipment utilizes the
uniform thickness of the tablets as a counting mechanism. Ten
tablets were taken and their thickness and diameter were measured
by electronic screw gage.
3.8.2 Weight variation
Indian Pharmacopoeia procedure for uniformity of weight
was followed, twenty tablets were taken and their weight was
determined individually and collectively on a digital weighing
balance. The average weight of one tablet was determined from the
collective weight. The weight variation test would be a satisfactory
method to determining the drug content uniformity.
3.8.3 Friability
Friabillator consist of a plastic-chamber that revolves at
25 rpm, dropping those tablets at a distance of 6 inches with each
revolution. The tablets were rotated in the friabillator for at least 4
minutes. At the end of test tablets were dusied and reweighed, the
loss in the weight of tablet is the measure of friability and is
expressed in percentage as (Jain CP et al., 2009):
%Friability = initial weight- final weight/initial weight x 100
3.8.4 Hardness
Hardness of tablet is defined as the force applied across
the diameter of the tablet in the order to break the tablet. The
resistance of the tablet to abrasion or breakage under condition of
storage transformation and handling before usage depends on its
hardness. Hardness of the tablet of each formulation was
determined using Pfizer Hardness tester (Jain CP et al., 2009).
3.8.5 Drug content uniformity
Six tablets were placed in 100 ml volumetric flask
individually. Volume was made up 100 ml by adding distilled
water. After one night filter the sample and measure the
absorbance on UV spectrophotometry at 252 nm. Dilute the
solution if necessary (Shinde AKJ et al., 2010).
Table 3 Drug content of various blends of solid dispersion
3.8.6 Wetting time
Formulation
In this method tablet wetting time was measured. Simple
tissue paper (12 cm X 10.75 cm) folded twice was placed in a
small Petri dish (Internal Diameter = 6.5 cm) containing 6 ml of
Sorenson’s buffer pH 6.8. A tablet was put on the paper, and the
time for complete wetting was measured. Three trials for each
batch and the standard deviation were also determined (Shinde
AKJ et al., 2010).
3.8.7 In-vitro disintegration time
In vitro disintegration time was measured by dropping a
tablet in a beaker containing 50 ml of Sorenson’s buffer pH 6.8.
Three tablets from each formulation were randomly selected and in
vitro disintegration time was performed.
3.8.8 In-vivo disintegration time
Drug Content (mg)
SD 1 0.53 ± 0.2
SD 2 0.25 ± 0.1
SD 3 0.178 ± 0.3
SD 4 0.133 ±0.1
SD 5 0.106 ± 0.2
SD 6 0.09 ± 0.2
The test was carried out in 3 tablets observed individually
by placing in mouth and the time in second taken for complete

Journal of Current Pharmaceutical Research 04 (2010) 4-11
disintegration of the tablet.
3.8.9 Modified disintegration time
Bi et al. suggested the use of a modified dissolution
apparatus, instead of the disintegration apparatus. In this
experiment, 900 ml of water maintained at 37 °C as the
disintegration fluid and a paddle at 100 rpm as stirring element
were used. Disintegration time was noted when the tablet
disintegrated and passed completely through the screen of the
sinker (3–3.5) mm in height and 3.5–4 mm in width, immersed at a
depth of 8.5 cm from the top with the help of a hook). This method
was useful in providing discrimination among batches which was
not possible with the conventional disintegration apparatus (Indian
Pharmacopoeias 1996).
Table 4 Dissolution data of various solid dispersion of Celecoxib.
Time
(Min) SD 1 SD 2 SD 3 SD 4 SD 5 SD 6
1 2.2 3 5 5 7 8
5 8 9.9 11 11.8 12 14.1
10 13.2 15.8 17.3 18.2 19.5 20.8
15 16.89 20.8 23 25.2 28.4 32
30 23 31 37 42 49 54
45 49.79 47 52 57 64 66
60 89 92 95 97 96 99
RESULTS AND DISCUSSION
Figure 1 % cumulative drug release of pure drug and blends of
solid of solid dispersion
The six batches of solid dispersions (SD1, SD2, SD3,
SD4, SD5, SD6) of Celecoxib and sorbitol are prepared. The
cumulative percentage drug release of SD1, SD2, SD3, SD4 SD5,
SD6 batches in 60 min are 89, 92, 95, 97, 96, 99 respectively
enlisted in Table 4. The SD6 batch show the best drug release
profile (% cumulative drug release in 60min is 99%). So SD6 batch
is used for the preparation of fast dissolving tablets. Nine batches
of fast dissolving tablets (FDT1, FDT2, FDT3, FDT4, FDT5,
FDT6, FDT7, FDT8, and FDT9) were prepared and their formulas
are enlisted in Table 2. The cumulative percentage drug release in
30 min of FDT1, FDT2, FDT3, FDT4, FDT5, FDT6, FDT7, FDT8,
FDT9 batches is 98.74, 97.14, 97.59, 97.16, 96.34, 99.74, 97.84,
97.14, 97.14 respectively. The FDT6 batch shows the best drug
release profile.
CONCLUSION
Figure 2 In-vitro drug release of tablet formulations
3.8.10 In-vitro dissolution study of tablets
In-vitro drug release profile of the formulations of fast
dissolving tablets were determined by USP Dissolution Apparatus
II paddle type, using 1.2 pH simulated gastric fluid using 900 ml at
37 o C. The paddle was rotated at 50 rpm for 60 min (Patel MM et
al., 2006).
Fast dissolving tablets dosage form proves its significance
for enhancing the bioavailability of water insoluble drug by
increasing its dissolution and solubility. The inclusion of solid
dispersion process as a step of preparation of fast dissolving tablets
have a synergistic effect on the bioavailability of final dosage form
by its contribution in improvement in solubility profile.
The solid dispersion batch SD6 having drug polymer ratio 1:10
showed best % cumulative drug release 99% with in 60 min among
the six batches.
The FDT6 batch of fast dissolving tablets showed best %
cumulative drug release 99.74% with in 60 min among all nine
batches of fast dissolving tablets. FDT6 have the highest
proportion of superdisintegrant (sodium starch glycolate) in all the
formulation. It is observed that wetting time (10±2.65) and
disintegration time (USP method-24, modified method-49) of
FDT6 batch was minimum in comparison to other batches of fast
dissolving tablets. So it proves that the concentration of

Journal of Current Pharmaceutical Research 04 (2010) 4-11
Table 5 Micromeritic evaluation property of bulk powder blends
Micromeritic
Property
FDT
1:1
FDT
1:2
FDT
1:3
FDT
1:4
FDT
1:5
FDT
5:1
FDT
4:1
FDT
3:1
FDT
2:1
Angle of repose (θ) 27.45 27.21 26.23 25.67 24.42 30.57 30.01 28.97 28.34
Bulk Density (g/cm 3 ) 0.47 0.44 0.41 0.42 0.38 0.43 0.41 0.44 0.38
Bulkiness 2.27 2.32 2.51 2.50 2.56 2.21 2.24 2.51 2.52
Tapped density (g/cm 3 ) 0.632 0.29 0.617 0.71 0.611 0.72 0.69 0.68 0.623
Void volume (ml) 1.3 0.8 0.7 1.4 1.1 1.4 0.9 0.7 1.8
Carr’s index (%) 11 11 11 10 12 12 13 12 13
Hausner’s Ratio(%) 1.48 1.53 1.51 1.54 1.58 1.51 1.53 1.54 1.51
Porosity (%) 12.12 13.08 15.07 19.41 10.7 11.17 12.16 12.11 16.04
Compressibility (%) 16.44 14.11 12.16 11.22 12.19 16.12 10.24 13.24 14.52
Table 6 Drug content of various FDT formulations
S.No. Batch Average Concentration (mg)
1 F1 49.82±0.23
2 F2 49.78±0.34
3 F3 49.65±0.45
4 F4 50.07±0.15
5 F5 49.92±0.36
6 F6 49.98±0.47
7 F7 49.74±0.41
8 F8 49.89±0.32
9 F9 49.87±0.22
Table 7 Percentage cumulative drug released data of formulations (F1-F5)
S.No. Time (min.)
Cumulative percentage drug release (mean±sd) (n=3)
FDT1 FDT2 FDT3 FDT4 FDT5
1 1 15.98 14.43 14..95 15.43 15.23
2 5 28.95 26.96 27.42 28.97 29.37
3 10 45.69 44.69 43.01 45.34 46.33
4 15 73.57 74.41 74.69 73.46 72.37
5 20 85.95 88.95 85.43 85.82 85.23
6 30 98.74 97.14 97.59 97.16 96.34
Table 8 Percentage cumulative drug released data of formulations (F6-F9
S.No.
Time (min.)
Cumulative percentage drug release (mean±sd) (n=3)
FDT6 FDT7 FDT8 FDT9
1 1 20.23 18.55 17.43 17.65
2 5 38.95 35.96 33.45 31.96
3 10 59.69 54.27 52.69 51.69
4 15 76.57 75.41 73.41 74.41
5 20 99.95 87.95 89.95 88.95
6 30 99.74 97.64 97.14 97.14

Journal of Current Pharmaceutical Research 04 (2010) 4-11
superdisintegrants in release profile of fast dissolving tablets play a
major role.
ACKNOWLEDGEMENTS
Authors are wishing to acknowledge Exim-Pharm international,
Mumbai for providing celecoxib for this experimental work.
REFERENCE
Bhowmik D., Chiranjib B., Krashnakanth., pankaj., Chandira RM.
Fast Dissolving Tablet: An Overview. J Chem Pharm Res.
2009; 1(1): 163-177.
Indian Pharmacopoeias, Controller of Publication, Government of
India, New Delhi. 1996; 735-736.
Jain CP., Naruka PS. Formulation and Evaluation of Fast
Dissolving Tablets of Valsartan. Int J Pharmacy and Pharm
Sci. 2009; 1(1): 219-226.
Patidar K., Soni M., Sharma DK., Jain SK. Solid Dispersion:
Approches, Technology involved, Unmet need and
Challenges. Drug Invention Today. 2010; 2(7): 349-357.
Patel MM., Patel DM. Fast Dissolving Valdecoxib Tablets
Containing Solid Dispersion of Valdecoxib. Ind J Pharm
Sci. 2006; 68(2): 222-226.
Shinde AKJ., Waghule AN., Paithane A., More HN. Development
and Characterisation of oral Fast Dissolving Tablet of
Nifedipine using Camphor as a subliming material. Res J
Pharm Bio and Chem Sci. 2010; 1(1): 46-50.