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

© All Rights Reserved by “Journals Club & Co.” 76

Development and Evaluation of Fast Dissolving Tablets of Flurbiprofen

Patel NS1, Patel VM1, Patel KA1, Modasiya KM1

1APMC 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 β-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

Oral routes of drug administration have wide

acceptance up to 50-60% of total dosage

forms. Solid dosage forms are popular

because of ease of administration, accurate

dosage, self -medication, pain avoidance and

most importantly the patient compliance.

The most popular solid dosage forms are

being tablets and capsules; one important

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

*Address for Correspondence Sanket N. Patel, 66/Matruchhaya society., Near Bhumipujafarm society, Mahavirnagar, Himmatnagar-383001, Dist: Sabarkantha, Gujarat, India Email ID: [email protected]

mailto:[email protected]



times people experience inconvenience in

swallowing conventional dosage forms such

as tablet when water is not available, in the

case of the motion sickness (kinetosis) and

sudden episodes of coughing during the

common cold, allergic condition and

bronchitis.

For these reason, 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 clinical

effect. Some drugs are absorbed from the

mouth, pharynx and esophagus as the saliva

passes down into the stomach. In such cases,

bioavailability of drug is significantly

greater than those observed from

conventional tablets dosage form. According

to European pharmacopoeia, the FDT should

disperse/disintegrate in less than three

minutes.

The basic approach in development of FDT

is the use of super disintegrants like cross

linked carboxymethyl cellulose

(croscarmellose), sodium starch glycolate

(primogel, explotab), Kyron etc, which

provide instantaneous disintegration of

tablet after putting on tongue, their by

release the drug in saliva.

The bioavailability of some drugs may be

increased due to absorption of drug in oral

cavity and also due to pregastric absorption

of saliva containing dispersed drugs that

pass down into the stomach. Moreover, the

amount of drug that is subjected to first pass

metabolism is reduced as compared to

standard tablet.

Poorly water-soluble drugs are associated

with slow drug absorption leading

eventually to inadequate and variable

bioavailability. Flurbiprofen is a poorly

water soluble drug with a well known chiral

non-steroidal anti inflammatory agent

possessing analgesic and antipyretic activity.

It is one of the most potent inhibitors of

platelet aggregation, and it is used to treat

gout, osteoarthritis, rheumatoid arthritis and

sunburn. However, it has poor water

bioavailability due to its poor water

solubility (10.45 ± 3.2μg/ml). Several



attempts have reported for enhancing the

solubility and bioavailability of flurbiprofen.

In the present study an attempt has been

made to increase the solubility of

flurbiprofen using and complexation

techniques. Complexation of drugs with

cyclodextrin has been used to enhance

aqueous solubility and drug stability.

Cyclodextrins are useful excipients, having

the ability to interact with poorly water-

soluble drugs and drug candidates, resulting

in an increase in their apparent water

solubility. These are cyclic and

oligosaccharides derived from starch

containing six (α CD), seven (β-CD), Eight

or more (α-1,4)-linked (CD-ߜ) nine ,(CD-ߛ)

α-D-glucopyranose units, the cyclodextrin

take the shape of a truncated cone or torus,

rather than a perfect cylinder.

The primary hydroxyl group is oriented to

the narrow edge of the cone at the exterior

and the secondary group to the wider edge.

The central cavity of the cyclodextrins

molecule is linked with skeletal carbons and

ethereal oxygens of the glucose residue,

which gives it a relatively lipophilic

character. This cavity enables cyclodextrins

to complex the ‘guest’ drug molecules and

in so doing alters the physicochemical

properties of the drug.

MATERIALS & METHODS Flurbiprofen was purchased from Yarrow

chem. Products, Mumbai, Cross carmeloose

sodium was obtained from, SSG was

obtained from, Kyron T-314 was purchased

from Corel pharma chem. All other reagents

and solvents were of analytical grade and

double distilled water was used throughout

the study.

Preparation of Inclusion Complex of

Flurbiprofen with β-cyclodextrin

clatherate(1:1)5

BCD (4.56 g, 3.42 mmoles) was dissolved in

water (75 ml) at 100°C. Flurbiprofen (0.84

g, 3.42 mmoles) was added and the resulting

solution was cooled to 1°C to give a white

precipitate which was isolated by filtration

and dried at 50°C in a convection oven. The

product, a white powder, was sieved through

a 100 μm screen to yield 4.24 g of

BCD/flurbiprofen clathrate.

General Procedure for Preparation of

Formulation of Fast Dissolving Tablet of

Flurbiprofen

Fast dissolving tablets containing

Flurbiprofen prepared by direct compression



Table 1: Formulation of Different Batches of Fast Dissolving Flurbiprofen Tablet

method accurately weighed β-cyclodextrin

and flurbiprofen clatherate and other

polymers are passed through sieve no.100

and mix together and ready for compression

Evaluation parameters of FDT of

flurbiprofen10,16

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 determined in a Roche

friabilator. Disintegration time was

determined in a Dissolution test apparatus-

TDT-06T (Electrolab, Mumbai, India) using

water as test fluid.

RESULT AND DISCUSSION Determination of Maximum Wavelength3

100 mg of Flurbiprofen was weighed

accurately, dissolved in 20 ml of methanol

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.

Preparation of Standard Solution

Ingredients (mg)

F1 F2 F3 F4 F5 F6 F7 F8 F9

Drug + β-cyclodextrin 284 284 284 284 284 284 284 284 284

Cross carmellose sodium

5 10 15 - - - - - -

Kayron - - - 5 10 15 - - - SSG - - - - - - 5 10 15 Mannitol 30.5 25.5 20.5 30.5 25.5 20.5 30.5 25.5 20.5 Avicel pH 102 20 20 20 20 20 20 20 20 20 Talc 7 7 7 7 7 7 7 7 7 Magnesium stearate 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.5

Total weight in (mg) 350 350 350 350 350 350 350 350 350



An aliquot of 10 ml of the stock solution

was diluted to 100 ml to prepare standard

solution having a concentration of100

mcg/ml by using phosphate buffer saline pH

6.4.

Preparation of Working Standard Solution

Working standard solution in concentration

ranging from 2 to 16 mcg/ml were prepared

by appropriately diluting the standard

solution with phosphate buffer saline pH

6.4. The absorbance of each working

standard solution was measured at 246.6 nm

using a Shimadzu UV spectrophotometer

using phosphate buffer saline pH 6.4 as a

blank. Data for each and every experiment

was obtained in triplicates and statistically

analyzed.

Fig. 1a: Flurbiprofen Standard Curve

Compatibility Study of Drug and

Excipients3

FTIR technique has been used to here study

the physical and chemical interaction

between drug and excipients used.

Infrared spectra of Flurbiprofen and

formulation containing drug and all other

excipients are shown in figure 1 a and figure

1b respectively.

From the figure, it was observed that there

were no change in this mail peak in IR

spectra of formulation, which shows there

were no physical interactions because of

some bond formation between the drug and

polymer.



Fig. 1b : FTIR of Flurbiprofen

400600800100012001400160018002000240028003200360040001/cm

-10

0

10

20

30

40

50

60

70%T

3354

.32

3338

.89

3319

.60

1533

.46

1506

.46

1473

.66

1419

.66

1411

.94

1361

.79

1265

.35

925.86

879.57

840.99

815.92

767.69

707.90

698.25

457.14

418.57

A

Fig. 1c : FTIR of Drug and β-cyclodextrin

400600800100012001400160018002000240028003200360040001/cm

-15

-7.5

0

7.5

15

22.5

30

37.5

45

52.5

60%T

3489.34

3346.61

3333.10

3284.88

3277.17

3240.52

3200.01

3182.65

3173.01

1419.66

1157.33

1080.17

1026.16

1004.95

765.77

729.12

694.40

401.21

B

Fig. 1d : FTIR of Drug and Polymers

400600800100012001400160018002000240028003200360040001/cm

-7.5

0

7.5

15

22.5

30

37.5

45

52.5

60%T

3396.76

3279

.10

3254.02

3228

.95

3211.59

3165.29

1408.08

1361

.79

1338

.64

1153.47

1130

.32

1074

.39

1028.09

1003.02

694.40

686.68

613.38

489.94

420.50

401.21

C



Table 2 : Preformulation Data of Prepared Granules

Formulations Angle of Repose (θ)*

Bulk Density (gm/ml)*

Tapped Density

(gm/ml)*

Compressibility Index (I)*

Hausner’s Ratio*

F1 29.48 ± 0.410 0.590 ± 0.025 0.685 ± 0.020 18.58 ± 0.51 1.160±0.010 F2 27.56 ± 0.390 0.611 ± 0.015 0.714 ± 0.028 16.79 ± 0.46 1.161±0.015 F3 28.24 ± 0.350 0.592 ± 0.020 0.686 ± 0.015 15.92 ± 0.67 1.158±0.020 F4 26.65 ± 0.215 0.642 ± 0.030 0.756 ± 0.025 17.61 ± 0.36 1.177±0.020 F5 26.84 ± 0.190 0.561 ± 0.025 0.653 ± 0.015 16.28 ± 0.38 1.163±0.015 F6 22.47 ± 0.160 0.579 ± 0.001 0.667 ± 0.002 15.19 ± 0.21 1.151±0.005 F7 28.32 ± 0.360 0.600 ± 0.015 0.695 ± 0.020 15.83 ± 0.75 1.158 ± 0.025 F8 27.91 ± 0.310 0.604 ± 0.025 0.715 ± 0.030 18.46 ± 0.59 1.183±0.015 F9 26.49 ± 0.250 0.618 ± 0.15 0.724 ± 0.020 17.10 ± 0.44 1.171±0.010

Table 2a : Post Compression Data of Prepared Granules

Formula Thickness (mm)***

Hardness (Kg/cm2)** Friability %*** Weight

variation(mg)*** F1 5.1 ± 0.1 4.7 ± 0.25 0.94 ± 0.08 351 ± 3.6 F2 5.03 ± 0.05 4.3 ± 0.26 0.95 ± 0.05 349 ± 3.0 F3 5.13 ± 0.05 4.8 ± 0.49 0.95 ± 0.03 346 ± 4.0 F4 5.13 ± 0.1 4.5 ± 0.25 0.98 ± 0.08 346.66 ± 4.72 F5 5.16 ± 0.5 4.2± 0.5 0.94 ±0.02 353.33 ± 2.08 F6 5.03 ± 0.5 4.5 ± 0.25 0.86 ± 0.1 351 ± 1.0 F7 5.2 ± 0.1 5.1 ± 0.1 0.95 ± 0.6 353.7 ± 3.78 F8 5.06 ± 0.5 5.2 ± 0.2 0.98 ±0.05 352 ± 3.46 F9 5.2 ± 0.5 5.03 ± 0.15 0.97 ±0.02 348.7 ± 3.51

Table 2b: Evaluation Parameters FDT of flurbiprofen

Formulation

Diameter(mm) (n=3)

In vitro Disintegration time (seconds)(n=3)

Wetting time (seconds)(n=3)

F1 10.4 ± 0.06 143 ± 4.58 62 ± 4.46 F2 10.5 ± 0.05 135 ± 4.08 58 ± 5.67 F3 10.5 ± 1.00 129 ± 3.49 55 ± 4.48 F4 10.4 ± 1.00 120 ± 3.21 52 ± 6.64 F5 10.4 ± 0.05 112 ± 4.85 49 ± 5.23 F6 10.3 ± 0.02 88 ± 3.56 42 ± 3.15 F7 10.5 ± 1.00 136 ± 4.04 67 ± 5.69 F8 10.4 ± 1.10 138 ± 4.69 64 ± 6.82 F9 10.4 ± 1.254 131 ± 5.73 60 ± 6.71



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

In Vitro Dissolution Study

The dissolution study was carried out using

USP-II paddle apparatus at 37˚C ± 0.5˚C

using 900 ml of simulated saliva (pH 6.4) as

dissolution medium. The agitation rate of

paddle was 50 rpm. Five ml samples were

withdrawn at 5,10,15,20,30,40,50 and 60

minute time and were filtered through

whatman filter paper replaced with fresh

dissolution medium and analyzed

spectrophotometrically at 246.6nm in UV.

The last F batch is a batch without forming

inclusion complex show poor solubility

without formation of inclusion complex.

Table 2d :% Cumulative Release of FDT of Flurbiprofen Batches F7-F9 & F

Time % cumulative drug release of batch F7-F9 & F F7 F8 F9 F 0 0 0 0 0 5 57.25± 0.218 58.43± 0.394 64.85 ± 0.297 17.14 ± 0.176 10 62.11± 0.369 69.11± 0.342 70.66 ± 0.346 19.58 ± 0.249 15 67.62± 0.258 74.06± 0.267 79.21 ± 0.326 21.83 ±0.153 20 78.09±0.149 81.28± 0.263 83.71 ± 0.379 24.21 ± 0.168 30 82.58± 0.347 86.72± 0.319 88.36 ± 0.297 25.93 ± 0.148 40 89.25± 0.420 90.39± 0.289 91.47 ± 0.283 28.09 ± 0.129 50 90.20± 0.396 93.18± 0.356 95.45 ± 0.372 30.23 ± 0.167 60 91.77± 0.278 94.47± 0.239 96.72 ± 0.277 32.69 ± 0.134

Time % Cumulative Drug Release of batches F1-F6 F1 F2 F3 F4 F5 F6 0 0.0 0.0 0.0 0.0 0.0 0.0 5 64.55±0.341 63.63±0.420 61.51±0.314 65.76±0.369 66.98±0.413 79.14±0.124 10 74.28±0.256 71.23±0.314 70.05±0.367 74.28±0.278 77.92 ±0.225 83.70±0.187 15 80.22±0.145 76.87±0.360 78.59±0.410 80.52±0.247 82.69 ±0.376 88.53 ± .210 20 86.57±0.358 81.62±0.287 86.22±0.329 83.23±0.249 86.64 ±0.187 92.85±0.319 30 91.46±0.257 86.45±0.197 91.19±0.294 86.26±0.348 90.01 ±0.146 94.46±0.147 40 93.06±0.412 91.38±0.245 92.24±0.189 91.14±0.127 92.50 ±0.357 96.69±0.264 50 94.65±0.373 93.85±0.384 95.51±0.334 94.54±0.196 95.00 ±0.327 98.33±0.371 60 95.96±0.246 95.11±0.215 96.41±0.276 96.15±0.324 97.83 ±0.278 99.36±0.259



Fig. 1e : %Cumulative Release of Fast Dissolving Tablets of Flurbiprofen Batches F1-F6

020

4060

80

100120

0 20 40 60 80

% cu

mul

ativ

e dr

ug re

leas

e

Time (min.)

% cumulative Drug release of batches F1- F6 %

cumulative Drug release F1

% cumulative Drug release F2



Fig. 1f : % Cumulative Release of Fast Dissolving Tablets of Flurbiprofen Batches F7-

F9&F

CONCLUSION Fast dissolving tablets of flurbiprofen were

prepared by forming inclusion complex with

β-cyclodextrin by direct compression

method using super disintegrants. All the

evaluation parameters shows that results

show that after forming inclusion complex

the dissolution is further enhanced and super



disintegrants make them suitable for fast

dissolving.

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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.

development and evaluation of fast dissolving tablets of flurbiprofen

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