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FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF ETORICOXIB

Authors:
  • Channabasweshwar Pharmacy College

Abstract and Figures

Fast dissolving tablet format is designed to allow administration of an oral solid dose form in the absence of water or fluid intake. Such tablets readily dissolve or disintegrate in the saliva. Currently it is approved in more than 60 countries worldwide. Etoricoxib is a COX-2 selective inhibitor. Current therapeutic indications of Etoricoxib are rheumatoid arthritis, psoriatic arthritis, osteo arthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout. Like any other COX-2 selective inhibitor, so those to treat the above diseases and to get quick action oral fast disintegrating tablets were prepared. The aim of this research is the development of fast dissolving tablet of Etoricoxib, to overcome solubility problem of Etoricoxib. Dissolution of Etoricoxib enhanced by solid dispersion technique in which Etoricoxib-carrier β-cyclodextrin solid dispersion were prepared by solvent evaporation technique, in three molar rations (1:1, 1:2 and 1:3).In formulation Croscarmellose sodium and Crospovidone used to maintain rapid disintegration. Preparation of tablet by direct compression and evaluation were done. In vitro and In vivo taste evaluation was done. Compatibility between drug and excipient examine by FTIR study.
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FORMULATION AND EVALUATION OF FAST DISSOLVING
TABLETS OF ETORICOXIB
Sachin Gholve1*, Ganesh Todkar1 , Omprakash Bhusnure1 , Atish Jadhav1 , Ravi
Rajurkar2 and Sanjay Thonte1
*1Channabasweshwar Pharmacy College (Degree), Kava Road, Basweshwar Chowk,
Latur, Maharashtra, India-413512
2Channabasweshwar Pharmacy Polytechnic Kava Road, Basweshwar Chowk,
Latur, Maharashtra, India-413512
ABSTRACT
Fast dissolving tablet format is designed to allow administration of an
oral solid dose form in the absence of water or fluid intake. Such
tablets readily dissolve or disintegrate in the saliva. Currently it is
approved in more than 60 countries worldwide. Etoricoxib is a COX-2
selective inhibitor. Current therapeutic indications of Etoricoxib are
rheumatoid arthritis, psoriatic arthritis, osteo arthritis, ankylosing
spondylitis, chronic low back pain, acute pain and gout. Like any other
COX-2 selective inhibitor, so those to treat the above diseases and to
get quick action oral fast disintegrating tablets were prepared. The aim
of this research is the development of fast dissolving tablet of
Etoricoxib, to overcome solubility problem of Etoricoxib. Dissolution
of Etoricoxib enhanced by solid dispersion technique in which
Etoricoxib-carrier β-cyclodextrin solid dispersion were prepared by solvent evaporation
technique, in three molar rations (1:1, 1:2 and 1:3).In formulation Croscarmellose sodium and
Crospovidone used to maintain rapid disintegration. Preparation of tablet by direct
compression and evaluation were done. In vitro and In vivo taste evaluation was done.
Compatibility between drug and excipient examine by FTIR study.
KEYWORDS: Etoricoxib, Croscarmellose Sodium, Crospovidone, Microcrystalline
cellulose, Super disintegrants.
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 5.210
Volume 4, Issue 10, 1357-1376. Research Article ISSN 2278 4357
Article Received on
03 Aug 2015,
Revised on 29 Aug 2015,
Accepted on 19 Sep 2015
*Correspondence for
Author
Sachin Gholve
Channabasweshwar
Pharmacy College
(Degree), Kava Road,
Basweshwar Chowk,
Latur, Maharashtra, India-
413512.
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1. INTRODUCTION
Oral delivery is currently the gold standard in the pharmaceutical industry where it is
regarded as the safest, most convenient and most economical method of drug delivery having
the highest patient compliance.[1] Tablet is the most popular among all dosage forms
existingtoday because of its convenience of self-administration, compactness and easy
manufacturing; however in many cases immediate onset of action is required
thanconventional therapy.[2] Oral routes of drug administration have wide acceptance up to
50-60% of total dosage forms.[4] Also solid oral delivery systems do not require sterile
conditions and are therefore, less expensive to manufacture. Patient compliance, high-
precision dosing, and manufacturing efficiency make tablets the solid dosage form of
choice.[2] Fast dissolving drug delivery systems (FDDD‟S) are a new generation of
formulations whichcombine the advantages of both liquid and conventional tablet
formulations and at the same time, offer added advantages over both the traditional dosage
forms.[3]
Clinically, nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently
prescribed by physicians forinflammatory disorders. NSAIDs exert their effect through
inhibition of cyclooxygenase-II, the main form of isozyme associated with inflammation. But
the simultaneous inhibition of cyclooxygenase-I and the resulting gastric and renal
dysfunction limit their frequent uses. Etoricoxib is a cyclooxygenase-II (COX-II) selective
NSAID used in the treatment of rheumatoid arthritis, osteoarthritis, postoperative dental pain,
chronic low back pain, acute gout and primary dysmenorrhea. The COX-I to COX-II
selectivity ratio is higher than other COX-II inhibitors such as Rofecoxib, Valdecoxib and
Celecoxib. Etoricoxib is practically insoluble in water and peak blood level. The Center for
Drug Evaluation and Research (CDER), US FDA defined Oral Disintegrating Tablets (ODT)
as “A solid dosage form containing medicinal substances, which disintegrates rapidly, usually
within a matter of seconds, when placed upon the tongue.”[5]
The faster drug dissolve into solution, quicker the absorption and onset of clinical effect.
Some drugs area absorbed from the mouth, pharynx and esophagus as the saliva passes down
into the stomach. Insuch cases, bioavailability of drug is significantly greater than those
observed from conventionaltablets dosage form. The advantage of mouth dissolving dosage
forms are increasingly beingrecognized in both, industry and academics.[7]
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2. MATERIALS AND METHODS
2.1 MATERIALS
Etoricoxib procured from Glenmark Generics Limited, Gujarat-
cyclodextrin,Croscarmellose sodium,Crospovidone, Avicel(102), Talc, Magnesium Stearate
are procured from Research-Lab Fine chem. Industry, Mumbai.
2.2 METHODS
A. Preparation of standard curve of Etoricoxib in 0.1N HCl (pH 1.2)
100 mg Etoricoxib was dissolved in 100ml of water. 10ml of the resulting solution was
further diluted up to 100ml with 0.1 N HCL to make a stock solution of concentration
100μg/ml. Further serial dilutions were carried out with 0.1 N HCL to get drug concentration
between 1 to 12μg/ml. The absorbances of the dilutions were measured against water as a
blank at 235nm using Shimadzu double beam UV visible spectrophotometer. The plot of
absorbance vs. concentration was plotted and was found to obey Beers Lambert‟s law in the
range of 0 to 100 μg/ml. Data in this range was subjected to linear regression analysis. The
plot for standard calibration curve of drug in 0.1N HCL.
B. Drug- carrier interaction study
Pure Drug, Pure β-cyclodextrin and mixture of Drug+ β-cyclodextrin were analyzed for
interaction by Fourier Transform Infrared Spectroscopy (FTIR) using KBr disk method.
C. Preparation of Solid Dispersion
Accurately weighed quantity of Drug and all the carriers in various proportion, 1:1, 1:2, 1:3,
(drug : carrier) were carefully transferred in glass flask and dissolve suitable solvents like
Methanol, then solvent was removed by evaporation at400 C under reduced pressure by using
vacuum evaporator after that the obtained massis scraped, crushed, pulverized and shifted
through mesh No. 100.
D. Solubility Study of EtoricoxibSolid dispersion
Solubility studies of Etoricoxib in carrier solutions were carried out atroom temperature.
Excess amount of Etoricoxib was added to 0.1N HCL containing variousseries of stoppered
conical flasks and shaken for 48 hr. on a rotary flask shaker. The suspensions were filtered
through whatman filter paper and assayed for Etoricoxib using UV spectrophotometer at 235
nm against blank prepared using sameconcentration of the various carriers in 0.1N HCL. .
The solubility of Etoricoxib invarious solvents is calculated.
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E. Dissolution Study
All the ratios of Drug β-Cyclodextrin solid dispersions prepared were characterized by
dissolution studies. In-vitro dissolution study of the solid dispersions prepared wasperformed
using USP (Type-II) apparatus at a speed of 50 rpm. Dissolution study wascarried out using
900 ml of 1% 0.1N HCL as dissolution medium maintained at temperature of 37°C ±5ºC. At
appropriate intervals, 5 ml of the solution was takenand dissolution medium was replaced by
5 ml of fresh dissolution fluid to maintain constant volume. The samples were then analyzed
at 235 nm by UV/visiblespectrophotometer using 0.1N HCL as blank. The mean of three
determinations wasused to calculate the drug release from each of the solid dispersion.
2.3 Precompression parameter study
1. Physical appearance
It includes the visual inspection of solid dispersion.
2. Angle of repose
Angle of repose is defined as the maximum angle possible between the surfaceof pile of
powder and horizontal plane. The angle of repose was determined by thefunnel method. The
accurately weighed powder was taken in a funnel. The height ofthe funnel was adjusted in
such a way that the tip of the funnel just touched the apexof the heap of the powder. The
powder was allowed to flow through the funnel freelyonto the surface. The diameter of the
powder cone was measured. The angle of reposewas calculated by substituting the values of
the base radius „R‟ and pile height „H‟ inthe following equation (Aulton, 2003).
Tan θ= H / R ---------Equation I
Where, H = Pile height and R = Radius of Pile
Therefore; = tan 1 H / R
Table No. 2: Relationship between angle of repose (θ) and flow ability
Angle of repose (θ)
Flowability
< 20 Excellent
Excellent
20-30
Good
30-34
Acceptable
> 40
Very poor
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3. Bulk density
The sample equivalent to 25g was accurately weighed and filled in a 100 mlgraduated
cylinder and the powder was leveled and the unsettled volume, VOwasnoted. The bulk density
was calculated by the formula (Lachman et al, 1991)
Bulk density (ρo) = M/Vo--------Equation II
Where,
M = mass of powder taken, Vo = Apparent unstirred volume
4. Tapped density
The tapped density was determined by mechanically tapping the measuringcylinder and the
volume was noted (Lachman et al, 1991)
Tapped density (ρt) = M / Vt--------Equation III
Where,
ρt = tapped density, M = weight of granules, Vt = tapped volume of granules in cm3
5. Compressibility index
The bulk volume and tapped volume was measured and compressibility indexwas calculated
using the formula (Aulton, 2003).
Compressibility index =100 (Vo-Vf)/Vo--------Equation IV
Where,Vo = Bulk volume, Vf = Tapped volume
Table No.3: Relationship between % compressibility and flowability
6. Hausner’s ratio
Tapped volume and bulk volume were measured and the hausner‟s ratio was calculated using
the formula
Flowability
Excellent
Good
Fairly
Poor
Very pure
Extremely
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Hausner’s ratio = Vo/Vf--------Equation V
Where,
Vo = Bulk volume, Vf = Tapped volume
2.3.1 Preparation of fast dissolving tablets by direct compression technique:
Method: Fast dissolving tablets of Etoricoxib were prepared by direct compression method
according to the formula
Table No. 4: Formulations from F1 to F8
All the ingredients were passed through 60 # sieve separately, Magnesiumstearate & Talc
through 40 #. Then the ingredients were weighed and mixed in geometrical order and tablets
were compressed with 8 mm sizes flat round punch to get tablet using Rimek Compression
Machine.
2.4Post compression parameter study
1. Thickness
The thickness of the tablets was determined using a Vernier caliper. Five tablets from each
type of formulation were used and average values were calculated. It is expressed in mm.
(Lachman et al, 1991)
2. Hardness
The resistance of tablets to shipping, breakage, under conditions of storage, transportation
and handling before usage depends on its hardness. For each formulation, the hardness of 6
tablets was determined using the Monsanto hardness tester. The tablet was held along its
oblong axis in between the two jaws of the tester. At this point, reading should be zero
kg/cm2. Then constant force was applied by rotating the knob until the tablet fractured. The
value at this point was noted (Lachman et al, 1991).
Ingredients
Quantity in mg
SD1:1
SD1:3
F1
F2
F3
F4
F5
F6
F7
F8
Etoricoxib(equivalent to 30 mg)
60
60
60
60
120
120
120
120
Croscarmellose sodium
5.5
5.5
10.5
10.5
5.5
5.5
10.5
10.5
Crospovidone
4
8
4
8
4
8
4
8
Microcrystalline cellulose
123.5
119.5
118.5
114.5
63.5
59.5
58.5
54.5
Mg. Stearate
2
2
2
2
2
2
2
2
Talc
5
5
5
5
5
5
5
5
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3. Friability
Friability is the measure of tablet strength. Roche Friabilator was used for testing the
friability using the following procedure. This test subjects a number of tablets to the
combined effect of shock abrasion by utilizing a plastic chamber which revolves at a speed of
25 rpm, dropping the tablets to a distance of 6 inches in each revolution. A sample
ofpreweighed 6 tablets was placed in Roche Friabilator which was then operated for 100
revolutions i.e. 4 minutes. The tablets were then dusted and reweighed. A loss of less than 1
% in weight in generally considered acceptable.Percent friability (% F) was calculated as
follows (Lachman et al, 1991).
Initial weight - Final weight
% F = ------------------------------------------ × 100 -------------Equation VI
Initial weight
4. Weight variation test
To find out weight variation, 20 tablets of each type of formulation wereweighed individually
using an electronic balance, average weight was calculated andindividual tablet weight was
then compared with average value to find the deviation in weigh. (Indian pharmacopoeia,
1996).
Table No.5: Specifications for tablets as per Pharmacopoeia of India
Sr.No.
Average Weight of Tablet
% Deviation
1
80 mg or less
10
2
More than 80 mg but less that 250 mg
7.5
3
250 or more
5
5. Uniformity of drug content
Five tablets of each type of formulation were weighed and crushed in mortar and powder
equivalent to 50 mg of Etoricoxib was weighed and dissolved in 100 ml of 0.1N HCl (pH
1.2). This was the stock solution from which 0.2 ml sample was withdrawn and diluted to 10
ml with 0.1N HCl. The absorbance was measured at wavelength 235 nm using double beam
UV-Visible spectrophotometer. Content uniformity was calculated using formula.
% Purity = 10 C (Au / As) -------Equation VII
Where, C - Concentration,
Au and As - Absorbance‟s obtained from unknown preparation and standard Preparation.
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6. Wetting time
The method was applied to measure tablet wetting time. A piece of tissue paper folded twice
was placed in a small Petri dish (i.d. = 6.5 cm) containing 10 ml of water, a tablet was placed
on the paper, and the time for complete wetting was measured. Three trials for each batch
were performed and standard deviation was also determined.
7. In vitro disintegration time
The process of breakdown of a tablet into smaller particles is called as disintegration. The in-
vitro disintegration time of a tablet was determined using disintegration test apparatus as per
I.P. specifications. I.P. Specifications: Place one tablet in each of the 6 tubes of the basket.
Add a disc to each tube and run the apparatus using distilled water maintained at 37° ± 2°C as
the immersion liquid. The assembly should be raised and lowered between 30 cycles per
minute in the 0.1 N HCL maintained at 37° ± 2°C. The time in seconds taken for complete
disintegrationof the tablet with no palpable mass remaining in the apparatus was measured
and recorded.
2.5 In vitro drug release studies details
Apparatus used : USP XXIII dissolution test apparatus
Dissolution medium : 0.1 N HCL
Dissolution medium volume : 900 ml
Temperature : 37 ± 0.5°C
Speed of basket paddle : 50 rpm
Sampling intervals : 5 min
Sample withdraw : 10 ml
Absorbance measured : 235 nm
2.5.1 In vitro drug release kinetics
To analyze the mechanism of the drug release rate kinetics of the dosage form, the
Obtained were graphed as:
1. Cumulative percentage drug released Vs. Time (Zero order plots)
2. Cumulative percentage drug released Vs Square root of time (Higuchi plots)
3. Log cumulative percentage drug remaining Vs Time (First order plots)
4. Log percentage drug released Vs Log time (Peppas plots)
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1. Zero order release rate kinetics
To study the zero order release kinetics the release rate data are fitted to the following
equation
F= kt
Where F is the fraction of drug release, K is the release rate constant, t is the release time
When the data is plotted as cumulative percent drug release Vs time, if the plot is linear then
the data obeys zero order release kinetics with a slope equal to K. This model represents an
ideal release in order to achieve prolonged pharmacological action. This is applicable to
dosage forms like transdermal systems, coated forms, osmotic systems, as well as Matrix
tablets containing low soluble drugs.
2. First order rate kinetics
The equation for first order treatment is represented as
Log c = Logco- kt/2.303
Where, c is amount of drug remaining unreleased at time t,
Cois initial amount of drug in solution,
K is first order rate constant.
The model is applicable to hydrolysis kinetics and to study the release profiles of
pharmaceutical dosage forms such as those containing water soluble drugs in porous
matrices.
3. Higuchi release model
To study the Higuchi release kinetics, the release rate data were fitted to the following
equation:
F= K. t ½
Where F is the amount of drug release , K is the release rate constant, t is the release time
When the data is plotted as cumulative drug released Vs square root of time, Yields a straight
line, indicating that that the drug was released by diffusion mechanism. The slope is equal to
K This model is applicable to system with drug dispersed in uniform swellable polymer
matrix as in case of matrix tablets with water soluble drug.
4. Korsmeyer and Peppas release model
The release rate data were fitted to the following equation
Mt / M∞ = Ktn
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Where, Mt / M∞ is the fractional release of drug, „t‟ denotes the release time, „K‟ represents
a constant incorporating structural and geometrical characteristics of the device, „n‟ is the
diffusion exponent and characterize the type of release mechanism during the release process.
This model is used to analyze the release from polymeric dosage forms, when the release
mechanism is not well known or when there is a possibility of more than one type of release
phenomenon being involved.
Table No.6 Diffusional exponent standard values for Korsmeyer Peppas
Release Exponent ‘n’
Drug Transport Mechanism
0.5
Fickian diffusion
0.5<n<1.0
Anomalous transport
1.0
Case-II
>1.0
Super case-II transport
3. RESULTS
3.1 UV-Visible spectrophotometric study
λ max determination
Fig. 1: UV Spectra of Etoricoxib
a) Preparation of standard calibration curve of Etoricoxib
Table No.7: Standard calibration curve of Etoricoxib in 0.1N HCL
Sr. No.
Concentration ( μg/ml)
Absorbance at 235 nm
1
0
0
2
2
0.242
3
4
0.382
4
6
0.559
5
8
0.709
6
10
0.884
7
12
1.057
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Fig.2: Standard curve of Etoricoxib in 0.1 N HCL (Ph 1.2)
3.2 Infrared Spectroscopy
Fig.3: FT-IR Spectrum of Etoricoxib
Fig.4: FT-IR Spectrum of Etoricoxib: β-cyclodextrin
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Fig. 5: FT-IR Spectrum of Mixture
3.2.1 Infrared Spectroscopy Result
FTIR studies were conducted and the spectrum was recorded in the range of 4000-400 cm-1.
No significant interaction between the drug and excipients was observed. All the spectrum
i.e. drug and excipients were concordant with that of the standard IR spectra of pure drug
Etoricoxib.
3.3 Evaluation of Solid Dispersion
3.3.1 Solubility study of Etoricoxib solid dispersion
Table No. 8: Solubility study of solid dispersion
Sr. No.
Drug : carrier ratio
Solubility µg/ml
1
Pure drug
2.05
2
Etoricoxib+β-cyclodextrin (1:1)
19.22
3
Etoricoxib+β-cyclodextrin (1:2)
11.81
4
Etoricoxib+β-cyclodextrin (1:3)
23.09
Solubility of all solid dispersion can be increased as compared to pure drug by solid
dispersion. Solubility of at 1:1, 1: 2, 1:3 ratios gives respectively. Increasing the
concentration of polymer was 1:1 & 1:3 for SD1and SD2 respectively more soluble than pure
drug.
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Fig. 6: Solubility study of solid dispersion
% Drug release from solid dispersion
Table No. 9: % Drug release from solid dispersion
Sr. No.
Time(min)
Solid Dispersion
(1:1)
Solid Dispersion
(1:2)
Solid Dispersion
(1:3)
1
5
22.45
18.79
26.11
2
10
47.57
41.34
53.14
3
15
65.68
54.25
69.11
4
20
74.09
64.47
81.96
5
25
86.25
72.03
90.91
6
30
94.14
79.77
97.02
The drug release profile for all formulations shown in table. The drug release of β-
cyclodextrin at 1:1, 1:2, and 1:3 ratios gives 94.14, 79.77and 97.02% respectively. The
optimized batch sd1which contain β-cyclodextrin and Etoricoxib at 1:1 ratios which give
94.14 % drug release in 30 min and SD3 which contain β-cyclodextrin and Etoricoxib at 1:3
ratios which give 97.02% drug release in 30 min respectively.
Fig. 7: % Drug release from solid dispersion
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3.3.2 Precompression parameter study
Table No. 10: Precompression parameter study
Formulation
Code
Angle of
repose
Bulk
Density (wt/ml)
Taped
Density (wt/ml)
Hausner’s
ratio (%)
Compressibility
Index(%)
F1
26.10±0.56
0.41±0.02
0.49±0.04
1.17±0.01
13.47±0.23
F2
27.92±0.70
0.42±0.03
0.48±0.02
1.12±0.02
15.00±0.46
F3
25.74±0.45
0.42±0.03
0.49±0.04
1.14±0.02
12.82±0.45
F4
28.36±0.63
0.41±0.02
0.48±0.02
1.18±0.04
14.91±0.36
F5
27.40±0.69
0.42±0.03
0.48±0.02
1.13±0.03
11.86±0.17
F6
28.23±0.14
0.43±0.02
0.51±0.01
1.16±0.05
14.03±0.21
F7
26.56±0.60
0.42±0.03
0.49±0.04
1.15±0.06
13.67±0.11
F8
28.17±0.85
0.42±0.03
0.48±0.02
1.16±0.07
13.44±0.17
The values represents Mean±SD, n = 3
3.3.3 Post compression parameter study
Table No. 11: A-Post compression parameter study
Formulation
Code
Hardness
(kg/cm2)
Friability
(%)
Weight
variation (mg)
Thickness
(mm)
F1
4.5±0.12
0.34±0.08
202.1±0.05
3.20±0.02
F2
4.0±0.13
0.37±0.04
200.1±0.06
3.28±0.02
F3
4.3±0.11
0.33±0.03
202.0±0.03
3.35±0.02
F4
3.7±0.09
0.38±0.08
201.3±0.08
3.25±0.05
F5
3.5±0.10
0.39±0.03
200.0±0.03
3.30±0.02
F6
3.4±0.15
0.36±0.05
200.3±0.02
3.20±0.03
F7
3.5±0.10
0.35±0.06
200.0±0.03
3.30±0.02
F8
3.2±0.11
0.39±0.06
201.1±0.05
3.25±0.01
The values represents Mean±SD, n = 3
Table No.12: B Post compression parameter study
Formulation
Code
Drug content (%)
Wetting time (sec)
Disintegration
time (sec)
F1
95.23±1.26
38±1.25
67±1.35
F2
93.12±1.19
36±2.03
52±1.34
F3
94.01±1.46
38±1.56
59±1.56
F4
99.32±1.18
37±1.30
45±1.78
F5
98.10±1.95
24±1.86
47±1.86
F6
97.61±1.23
25±1.49
32±1.56
F7
97.21±1.43
24±1.15
44±1.56
F8
99.81±1.84
21±1.19
29±1.67
The values represents Mean±SD, n = 3
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3.4In-vitro dissolution study of F1 to F8 Formulation batches
Table No.13: In-vitro dissolution study of F1 to F8 batches.
Time
(min)
% Drug release
F1
F2
F3
F4
F5
F6
F7
F8
0
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
5
20.98
20.25
18.42
17.69
19.52
27.58
18.79
22.45
10
34.04
34.40
33.28
31.80
34.39
38.87
35.48
33.69
15
66.28
67.74
67.34
64.39
64.80
62.38
60.42
67.03
20
76.54
79.11
76.51
72.42
77.24
78.45
70.98
72.16
25
81.03
83.64
80.64
82.11
82.11
87.36
84.57
86.13
30
93.10
94.43
92.50
95.35
93.99
96.00
94.27
98.79
3.4.1 Percentage (%) Drug release
The In-vitro drug release from fast dissolving tablets prepared by direct compression method
were found to be in the range of 92.50 to 98.79
3.5 Release kinetics of Etoricoxib Tablets
3.5.1 Zero order release kinetic data
Fig.8: Zero order release kinetic of F1-F4
Fig.9: Zero order release kineticof F5-F8
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3.5.2 First order release kinetic data
Table No.14:First order release kinetic data
Sr.No.
Time
(min)
Log% cumulative drug remain to be released
F1
F2
F3
F4
F5
F6
F7
F8
1
0
2
2
2
2
2
2
2
2
2
5
1.897
1.901
1.911
1.915
1.905
1.859
1.909
1.889
3
10
1.819
1.816
1.824
1.833
1.816
1.786
1.809
1.821
4
15
1.527
1.508
1.514
1.551
1.546
1.575
1.551
1.518
5
20
1.370
1.319
1.370
1.440
1.357
1.333
1.462
1.444
6
25
1.275
1.213
1.286
1.252
1.252
1.101
1.188
1.142
7
30
0.838
0.745
0.875
0.667
0.778
0.602
0.758
0.082
Fig.10: First order release kinetic of F1-F4
Fig.11: First order release kinetic of F5-F8
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3.5.3 Higuchi matrix release kinetic data
Table No. 15:Higuchi matrix release kinetic data
Sr. No
√T
% Cumulative drug release
F1
F2
F3
F4
F5
F6
F7
F8
1
0
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
2
2.236
20.98
20.25
18.42
17.69
19.52
27.58
18.79
22.45
3
3.162
34.04
34.40
33.28
31.80
34.39
38.87
35.48
33.69
4
3.872
66.28
67.74
67.34
64.39
64.80
62.38
60.42
67.03
5
4.472
76.54
79.11
76.51
72.42
77.24
78.45
70.98
72.16
6
5
81.03
83.64
80.64
82.11
82.11
87.36
84.57
86.13
7
5.477
93.10
94.43
92.50
95.35
93.99
96.00
94.27
98.79
Fig.12 : Higuchi matrix release kinetic of F1-F4
Fig.13: Higuchi matrix release kinetic of F5-F8
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3.5.4Peppas release kinetic data
Table No.16: Peppas release kinetic data
Sr. No.
LogT(min)
Log % drug release
F1
F2
F3
F4
F5
F6
F7
F8
1
0
0
0
0
0
0
0
0
0
2
0.6989
1.321
1.306
1.265
1.247
1.290
1.440
1.273
1.351
3
1
1.531
1.536
1.522
1.502
1.536
1.589
1.549
1.527
4
1.176
1.821
1.830
1.828
1.808
1.811
1.765
1.781
1.826
5
1.301
1.883
1.898
1.883
1.859
1.887
1.894
1.851
1.858
6
1.397
1.908
1.922
1.906
1.914
1.914
1.941
1.927
1.935
7
1.477
1.968
1.975
1.966
1.979
1.973
1.982
1.974
1.994
Fig.14: Peppas release kinetic of F1-F4
Fig.15: Peppas release kinetic of F5-F8
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Table No.17: Release kinetic of formulation F1-F8
Formulation
Zero order
(R2)
First order
(R2)
Higuchi’s
(R2)
Peppas
R2
N
F1
0.953
0.9498
0.9388
0.9614
0.8971
F2
0.9505
0.9493
0.9343
0.9611
0.9248
F3
0.9468
0.9535
0.9284
0.9574
0.9549
F4
0.9692
0.9044
0.9268
0.9705
0.9896
F5
0.9604
0.9441
0.9375
0.9701
0.9301
F6
0.9695
0.9347
0.9644
0.9814
0.7581
F7
0.9823
0.9362
0.9435
0.9877
0.9395
F8
0.9705
0.8003
0.9369
0.9648
0.8813
4. CONCLUSION
In present work, a fast disintegrating Etoricoxib tablets were developed by direct
compression method using synthetic Superdisintegrants. In the preliminary part, FT-IR study
was carried out which suggested that there was no significant drug interaction between
Etoricoxib with β -cyclodextrin, Superdisintegrants and other excipients. UV scan of had
shown Etoricoxibabsorption at wavelength 235 nm in 0.1N HCL Physical parameters like
hardness, weight variation, thickness and friability were within pharmacopoeial limit.
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Etoricoxib tablets employing cyclodextrin-poloxamer 407 - pvpk30 inclusion complexes,
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... This results in relaxation of arteriole smooth muscle leading to a decrease in total peripheral resistance, reducing blood pressure. Ramipril undergoes first-pass metabolism and has an oral bioavailability of about 28-30% [7]. Presently, Ramipril is marketed in the form of oral disintegrating tablets (ALTACE The drug is directly absorbed into the systemic circulation which by-passes the first pass metabolism, improving the bioavailability of the drug [5]. ...
... ® ) and immediate release tablets (CARDACE ® Few reports were published on formulation and evaluation of ramipril oral disintegrating, immediate release tablets, buccal patches and films. In most of the works reported so far, MDFs were prepared in petri plates, moulds etc. and the films were dried at 40-45 °C overnight and this procedure may not result in uniformity of thickness and drug content and thereby, vary the drug release rates [7][8][9][10][11][12]. Moreover, no works on the influence of formulation variables like film thickness, polymer viscosities, surfactants and saliva stimulating agents were reported. ...
Article
Full-text available
Objective: The present investigation was aimed at preparation and evaluation of mouth dissolving films (MDFs) of Ramipril to enhance patient convenience, compliance and to improve bioavailability. Methods: MDFs with 0.5% w/w Ramipril were prepared by a solvent casting method using a wet film applicator. The effects of film formers, wetting/solubilizing, saliva stimulating agents and film modifiers on the physicomechanical and in vitro Ramipril release from MDFs were evaluated. Results: The MDFs prepared were transparent, smooth and showed no re-crystallization upon storage. MDFs casted with hydroxypropyl methylcellulose (HPMC) E3 as film former and polyethylene glycol (PEG-400) as plasticizer showed superior Ramipril release rates and good physicomechanical properties when compared to MDFs with E5 and E15 as film formers. HPMC E3 MDFs with polyvinyl pyrrolidone K30 (PVP K30) and sodium lauryl sulphate (SLS) gave superior drug release properties than MDFs without PVP K30 and SLS. The HPMC E3 MDFs with citric acid (CA) as saliva stimulating and xylitol as soothing agent gave significantly superior in vitro drug release than the MDFs without CA and xylitol. Release kinetics data reveals diffusion as a drug release mechanism. Conclusion: From the obtained results, it can be concluded that the administration of Ramipril as MDF may provide a quick onset of action with enhanced oral bioavailability and therapeutic efficacy.
... Some tablets are designed to dissolve in saliva remarkably fast, within a few seconds, and are true fast-dissolving tablets. FDDTs, as a novel dosage form, have several characteristics to distinguish them from the more traditional dosage forms [11,12]. Taste-masking is of critical importance in the formulation of an acceptable FDDT. ...
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Oral administration is the most popular route for systemic effects due to its ease of ingestion, pain, avoidance, versatility and most importantly, patient compliance. The development of enhanced oral protein delivery technology by mouth dissolving Tablets which may release these drugs in the mouth are very promising for the delivery of high molecular weight protein and peptide. Good mouth feel property of MDDS helps to change the basic view of medication as "bitter pill", particularly for pediatric patients. To prepare mouth dissolving tablet using SSG & CCM by using Antihypertensive as model drug. Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme and it is a key component of the renin-angiotensin-aldosterone system. The ƛmax of Captopril was determined by scanning the 10µg / ml solution of drug using UV-Spectrophotometer and was found to be 271nm. The linear correlation was found to be 0.9995.The Fast dissolving tablets of captopril were prepared by direct compression method. Captopril can be successfully formulated as mouth dissolving tablets using various super disintegrate in different concentrations by direct compression method. The formulation containing 10% of crospovidone as super disintegrated was found to be outstanding than other formulations in terms of disintegration time and rate of dissolution.
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Etoricoxib is a novel, selective second generation cyclo-oxygenase-2 inhibitor administered orally as an analgesic and anti-inflammatory drug that is used for the treatment of osteoarthritis, rheumatoid arthritis and gouty arthritis. The poor aqueous solubility of the drug leads to variable dissolution rates. In the present investigation an attempt has been made to prepare oro-dispersible tablets of etoricoxib with enhanced dissolution rate. The another purpose of the present investigation was to evaluate effect of superdisintegrants like Crospovidone (Polyplasdone XL), Croscarmellose Sodium (Ac-Di-Sol) and Sodium starch glycolate (Primojel) on dissolution of poorly soluble, selective COX-2 inhibitor in oro-dispersible tablets. In the study, the effect of superdisintegrants specifically at 2 and 4 % level in oro-dispersible tablet formulation on the in vitro dissolution was evaluated. These levels included optimum concentrations of selected superdisintegrants. It was concluded that oro-dispersible tablets of etoricoxib with enhanced dissolution rate can be made using selected superdisintegrants. Keywords: Etoricoxib, Oro-dispersible tablet, Crospovidone (Polyplasdone XL), Croscarmellose Sodium (Ac-Di-Sol) and Sodium starch glycolate (Primojel).
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Celecoxib spherical agglomerates were prepared with polyvinylpyrrolidone (PVP) using acetone, water and chloroform as solvent, non-solvent and bridging liquid, respectively.The agglomerates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), IR spectroscopic studies and scanning electron microscopy (SEM). The IR spectroscopy and DSC results indicated the absence of any interactions between drug and additives. XRD studies showed a decrease in crystallinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The loading efficiency (% or mg drug per 100 mg crystals) was in the range of 93.9 ± 2.3 and 97.3 ± 1.3% (n = 3) with all formulations. The aqueous solubility and dissolution rate of the drug from crystals was significantly (p < 0.05) increased (nearly two times). The solubility and in vitro drug release rates increased with an increase in PVP concentration (from 2.5 to 10%). The SEM studies showed that the crystal posseses a good spherical shape with smooth and regular surface. Based on these results, formulation prepared using 10% w/v PVP K 30 selected as optimized formulation. In vivo studies carried out on human volunteers with optimized formulation and the pharmacokinetic parameters were compared with marketed formulation. The celecoxib spherical crystals have shown enhanced therapeutic activity than the marketed formulation.
Article
The main aim of the present study is to improve the solubility of highly water insoluble drug Etoricoxib by using solid dispersion technology. Etoricoxib, the drug being studied is a Non steroidal anti-inflammatory drug belonging to "Specific COX-2 inhibitors" classification. It is a drug which is highly insoluble in water, hence dissolution is rate limiting. Therefore the aim is to increase its solubility by using polymers such as PEG4000, PEG6000 & Urea. This Solid dispersion technology can be used to improve the dissolution properties of poorly soluble drugs. Etoricoxib is one of the drugs which are practically insoluble in water. Solid dispersions of Etoricoxib in various carriers (PEG 4000, PEG 6000 & Urea) were prepared to enhance its dissolution rate of the drug.
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The basic objective of this study was to prepare oral fast dissolving tablet to achieve better patient compliance. Often times people experience inconvenience in swallowing conventional dosage forms such as tablet when water is not available, in such cases tablets that can rapidly dissolve or disintegrate in the oral cavity have attracted a great deal of attention. Fast dissolving tablets are those when put on tongue disintegrate instantaneously releasing the drug which dissolve or disperses in the saliva. The faster the drug into solution, quicker the absorption and onset of action. Absorption of the drug is increased and first pass metabolism is reduced. The lowest disintegration time and high drug release was shown by KM3 formulation and selected as optimized formulation. From present study it can be concluded that bitter taste of Etoricoxib can be successfully masked with aspartame and solubility of Etoricoxib is increased using urea as hydrophilic carrier by kneading method. Well palatable and patient compliant Fast Dissolving Tablet can successfully prepared using Kneading method. The prepared optimized tablet showed quick disintegration as well as rapid dissolution as compared to marketed tablet. Thus, the Rapid Disintegrating Tablet of bitter drug having bitter taste and pleasant mouth feel can be successfully formulated.
VenkataramuduThanda, FastDissolving Tablets: A Novel Approach to Drug Delivery – A Review
  • Rajesh Roshanrai
  • Pavithra Chirra
Rajesh RoshanRai, Pavithra Chirra, VenkataramuduThanda, FastDissolving Tablets: A Novel Approach to Drug Delivery – A Review, International Journal of Preclinical and Pharmaceutical Research., 2012; 3(1): 23-32.
SnehalHase, PriyaPande, Immediate Drug Release Dosage Form: A Review
  • Kishorsalunkhe Kiranwale
  • Mahesh Ishwargundecha
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An Overview on Fast Dissolving Drug Delivery System
  • Chandra Bankim
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Bankim Chandra Nandy, BhaskarMazumder, KadambariPathak, NidhiSaxena, Swati Jain, Stuti Sharma, RughaniAmishaben, ArtiShrivastava, An Overview on Fast Dissolving Drug Delivery System, Asian Journal of Pharmaceutical Sciences and Research, 2011; 1(2).
Formulation and in-vitro evaluation of Etoricoxib Oral Fast Disintegrating Tablets
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