FORMULATION DESIGN AND EVALUATION OF FLURBIPROFEN … · infection which may result in death, for treating lung damage because of polluted air, use for killing household dust mites,

Pakistan Journal of Pharmacology ORIGINAL ARTICLE

Vol.35, No.1 & 2, January-July, 2018, pp.33-47

FORMULATION DESIGN AND EVALUATION OF

FLURBIPROFEN AND CLOVE OIL ORAL GEL

URVAH ASIF1*

, MOBINA MANZOOR2 AND FARAKH MUNIR

3

1Wilshire Laboratory Private Limited, Lahore, Pakistan 2Department of Pharmacy, Lahore College for Women University, Lahore, Pakistan

3Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan

ABSTRACT:

Tooth is considered to be one of the important organ of human body for oral administration

and main route of oral drug delivery system. Tooth Infections are one of the common buccal

problems. In this case, gels are well known candidates to deliver drugs locally.

Flurbiprofen belongs to non-steroidal anti-inflammatory drugs (NSAIDs) family. Its

indication includes pre-operative anti-miotic (in an ophthalmic solution) on the other side it

is useful for arthritis or dental pain. Flurbiprofen lies in Biopharmaceutics classification

system (BCS) class II system of drugs showing low solubility, so its oral administration

causes severe GIT irritation. Hence, to avoid this problem & to provide local effects to

different patients with periodontal diseases, oral gel of flurbiprofen with clove oil was

prepared. Ten different formulations namely F1, F2, F3, F4, F5, F6, F7, F8, F9, F10 by

varying the ratio of Polymer Carbopol (934), Propylene Glycol, Clove oil, Aspartame,

Glycerine and Preservatives, by varying concentration from 1% to 2% & by varying pH

from 6.34 to 7.1 were prepared. These formulations were tested for drug content, Viscosity,

Spread ability, Extrutability, Consistency, release profiles & subjected to DSC & FTIR

techniques. These FTIR & DSC results showed that carbopol 934 & other excipients showed

no significant shift in peak with active pharmaceutical ingredient. Whereas, F2 formulation

of 1% & F7 formulation of 2% showed best results for Viscosity, Extrutability, Spread

ability, Consistency & Drug content . When these best formulations namely F2 & F7 were

compared for their release profiles F2 formulation showed quick release profiles (with in

1hour) as compared to F7 formulation of 2% (within 2hour). Hence, clove oil showed best

good efficiency & release profile when used in ratio 1:2 (flurbiprofen:carbopol 934) Future

studies in this context may lead to more efficacious & suitable delivery system for

periodontal disease

Keywords: Periodontal diseases, flurbiprofen, clove oil, viscosity, extrutability, spread

ability, release profile.

INTRODUCTION

It is necessary to understand properties of

the Tooth. Tooth is actually the supporting

structure as well as provide surroundings to

mouth. It is considered the one important part

in contributing to digestive process. Most

significant role is to maintain healthy state of

teeth in order to provide complete nutrition &

digestion. Teeth also affect our speech and

appearance in addition to several other

functions. Infections of tooth are one of the

common buccal problems. Oral diseases are

most commonly (Angker et al., 2003).

According to WHO, peadtriatrics 60-90%

and 100% adults worldwide suffers with pain

of dental cavities. 15-20% of adults (middle

*Corresponding author: e-mail: [email protected]

Formulation design and evaluation of flurbiprofen and clove oil oral gel 34

aged 35-44 years) suffer from tooth loss

because of severe periodontal (gum) disease.

Worldwide older people are more likely to be

effected by complete loss of natural teeth. The

30% of people with age 65-74 globally claims

to have no natural teeth.

In many countries out of 100000 people one

to 10 cases suffers with oral cancer. Mainly

factors responsible for causing oral cancer

includes alcohol and tobacco. Whereas, men,

older people & illiterate people and those

having low income are more likely to suffer

from oral cancer as compared to others. 40-

50% of HIV Positive people are affected by

oral infections including bacterial, fungal &

viral infections (Petersen et al., 2010) Factors

mainly causing oral health problems includes

harmful use of tobacco which leads to oral

cancer, alcohol and unhealthy diet. Smoking is

responsible for half of the cases of gum

diseases in USA.

It also opened doors to

secondary disease such as cardiovascular

diseases, diabetes Mellitus, chronic diseases of

respiratory tract and cancer, oral diseases. Oral

disease is also caused by poor oral hygiene

(Sheiham et al., 2000). Healthy mouth has a

pH of 7.0 or above. When the pH goes below

neutral pH (at 6.5) tooth roots begin to

dissolve. When people sip drinks they are

more likely to be affected by erosion and

decay. When the mouth pH is alkaline i.e. 7.5

teeth becomes stronger and remineralize.

Basically, teeth damage occurs due to acidic

saliva. Food is one of the major component in

changing mouth pH 5 and 9 is considered to be

the resting pH of oral cavity which varies

because of number of factors (Akande et al.,

2004).

Fig. 1: Calibration curve of flurbiprofen

concentration against absorbance.

Gel

According to pharmacology, the term gel

was introduced as semisolid material. The gel

is defined in USP as a small inorganic particles

or large organic molecules dispersion that

forms a three dimensional semisolid system

interpenetrated by liquid. Gels are basically

made of two phase system in which inorganic

particles are only dispersed instead of

dissolving throughout the continuous phase

and large organic particles in the continuous

phase are dissolved completely. Gels can be

classified as based on colloidal phases, based

on nature of solvent used, based on physical

properties, and based on rheological

properties. Polymer is defined to be a

compound of repeating units. Preparations of

gels include polymers, which is responsible for

providing structural network to gels (Bhasha,

et al., 2013).

Advantages of gels over oral route

Gastrointestinal pH that results in

gastrointestinal drug absorption difficulties can

be avoided by use of gel. Avoiding drug

interaction and enzymatic activity is one of the

property of gels. When oral route is not

suitable then gels are considered to be the best

substitute. Gels are the way to avoid first pass

effect. Gels have minimum side effects

because of localized effects (Patel et al.,

2011).

Flurbiprofen

It belongs to non-steroidal anti-

inflammatory drugs (NSAIDs) family

(member of the phenyl alkanoic

acid derivative). It belongs to namely three

classes therapeutically it is Analgesic

Pharmacologically its NSAID & Chemically

its Class is Propionic Acid. Its indication

includes pre-operative anti-miotic (in

an ophthalmic solution) on the other side its

useful for arthritis and for tooth ache.

Flurbiprofen excreted poorly into human milk.

& flurbiprofen tablets cause premature closure

of the ductus arteriosus in pregnancy so tablets

must be avoided. Important route of eli-

mination for flurbiprofen metabolites is renal

clearance and minor is excreted less than 3%

Urvah asif et al 35

as unchanged in the urine and 70% of it is

eliminated as parent drug in the urine and

metabolites (Richy et al., 2007).

Essential oil extract

An essential oil extracted from clove plant

named syzygium aromaticum is known as

clove oil. It is naturally analgesic and

antiseptic containing eugenol which is used

primarily in dentistry.Other uses include home

remedy for dental pain relief and found in

aromatherapy, Eugenol extracted from clove

oil is used to relieve toothache. Clove oil is

used as an anaesthetic for toothaches,

headaches and joint pain and used as a food

flavoring agent worldwide and applied as a

topical analgesic and mouth sterilizer or

painkiller. Clove oil is antiseptic, majority use

in toothache, dental preparations, mouthwash,

local anesthetic (eugenol), as flavoring agent,

as stimulant, as local anesthetic, as spice, in oil

of perfumery, as carminative, as stimulant, in

diabetes and in temporary filling of dental

cavities along with ZnO, in skin cancer, use

for depression and on microscopic parasitic

infection which may result in death, for

treating lung damage because of polluted air,

use for killing household dust mites, use in

killing pathogenic yeast. It is used to provide

antiplague property in middle ages. Hence

clove oil can be used for oral infections as an

antimicrobial agent.

Clove contains 14-20%

of essential oil that has eugenol, acetyleugenol,

sesquiterpenes (α-and β-caryophyllenes) and

small quantities of esters, ketones and alcohol.

Clove conjointly contains tannins, sitosterol

and stigmosterol oils of clove are often rubbed

against the sore tooth or gums to alleviate

odontalgia, and whole clove are

often chewed to regulate unhealthy breath. The

name comes from the French name

“clou” which means nail. Since the

buds agree the form of nail it's been named in

such a way. The generic name comes from the

Greek word Syzygios (Redfern et al., 2014)

MATERIALS AND METHODS

Different mucoadhesive agents are available

in market. As oral gel of flurbiprofen with

clove oil is not formulated as oral drug

delivery form. Different formulations are

proposed and evaluated for their performance.

Most commonly mucoadhesive agents are

carbopol 934, PAA, Carbophil, Hydroxy

metha acrylation.

Materials

Flurbiprofen, Carbopol-934, Propylene

Glycol, Clove oil, Glycerine, Methyl paraben

sodium, Propyl paraben sodium, NaOH

,distilled water, Aspartame. Clove oil was

obtained from Qadir chemicals. (Manufactured

by Qarshi Industry, Pakistan). According to

manufacturer information it was prepared by

steam distillation. Carbopol 934 was obtained

from sun chemicals, Methyl paraben sodium

and propyl paraben sodium was obtained from

Ayyub chemicals, Flurbiprofen (Hygro-

chemicals) Aspartame, Flavours and menthol

crystals were obtained as a gift sample from

OBSONS Pharmaceutical Lahore Pakistan

Glycerine and Propylene glycol were

purchased from market, Lahore, Pakistan.

Techniques applied Spectrophotometery, UV Visible

Spectrophotometery, FTIR (Fourier transform

infrared spectroscopy), Differential scanning

calorimetery (DSC), Dissolution testing.

Gel preparation The gel was prepared by varying the ratio of

carbopol and excipients by varying

concentrations and as 1% with five

formulations F1, F2, F3, F4 and F5. 2% with

five formulations F6, F7, F8 and F9 and F10.

having different PH 6.34-7.1. The two

concentrations of gel with various formu-

lations were prepared separately (quantity as

mentioned in formulation table for each 1%

and 2% formulations) by thoroughly mixing

carbopol 934 in distilled water for 1 hour as

mentioned in formulation. Flurbiprofen

possess low solubility in water. Hence to

enhance the solubility of this hydrophobic

compound it was mixed with propylene glycol

in another container. Weighed quantity of

propyl paraben sodium & methyl paraben

sodium were added to water before its addition


to carbopol mixture. Whereas known quantity

of Aspartame a sweetening agent was mixed

with propylene glycol in all formulations prior

it’s mixing to carbopol solution. After mixing

completely, add required quantity of glycerine,

flavor and color in this solution. Flurbiprofen

solution was then added to viscous carbpol

solution and mixing was done for about half an

hour. Finally clove oil was incorporated to the

mixture and was neutralized by using 0.1N

NaOH solution to different pH ranging from

6.34-7.1. Evaluation tests were applied to all

formulations which vary in ratio of carbopol

934 and other excipients and maintained at

different pH then the best was selected (Moon

et al., 2011). Due to presence of flurbiprofen

in this oral gel, 9.6 mg of eugenol (present in

clove oil) was used to provide combine effect.

UV visible spectrophotometry

Gel was analyzed by UV.

The amount of light which is absorbed by

the solution is proportional to its

concentration. Compound is determined by its

absorbance spectrum. While the visible range

of UV is from 200-400nm and that of visible is

from 400-700nm (Giusti et al., 2001)

FTIR (fourier transfiorm infrared

spectroscopy)

The spectrum was obtained by taking equal

amounts of active with excipients and peaks

were studied for functional groups (Li et al.,

2001)

DSC (Differential Scanning Calorimetery)

It is a measure of heat loss or heat gain by

the sample as a function of temperature or the

amount of heat require to elevate the

temperature of a sample & reference to be

measured as a function of temperature

(Hatakeyema et al., 2005)

Dissolution testing

Dissolution profile of a drug determines that

in specified time how much drug will be

available on the receptor site. Apparatus II,

USP was used with a dissolution medium of

PH 7.0 maintained at 37oC with specific RPM

(Murata et al., 2000). The Thermograms of

pure drug (flurbiprofen), pure polymer

(carbopol 934) and all other formulations were

observed. Results were recorded at different

time points as 5, 10, 15, 25, 30, 60, 120 min

(Murata et al., 2000).

Determination of pH

The pH of gel was determined by using

digital pH meter, the glass electrode immersed

into the gel system .The PH meter was

calibrated by using buffer solutions of 4 and 7

and 5 different pH were settled (6.34-7.1) for

each 1% & 2% formulations (Yuqing et al.,

2005). Results are shown in tables 3 and 4.

Determination of viscosity

Brookfield viscometer was used to

determine the viscosities of both 1% & 2%

gels with different pH using spindle No.4 at

50rpm. Reading displayed on digital

viscometer was noted (Al-Qadi et al., 2009).

Viscosities of all pH formulation for both 1%

and 2 % were noted and shown in tables 3 and

4.

Determination of extrutability The tube of gel with 5mm opening was used

to test the extutability. The amount of gel that

came out of tube by applying pressure was

used to determine extrutability and shown in

table results 3 and 4 (Tripathi et al., 2012)

Determination of spread ability

Glass slide & wooden block apparatus was

used to calculate spread ability. Flurbiprofen

gel was added to sterile pan. The time taken

for the upper slide to separate from fixed lower

slide was noted and spread ability was

determined by following formulae:

T

LMS

..=

S=Spreadability g-cm

/sec, M=Mass required to

move to upper slide in gm, L=Glass slide

length in cm, T=Time taken in seconds to

separate the two slides completely. The results

were calculated for each pH formulation and

were shown in table 3 and 4 (Prabhu et al.,

2007).

Urvah asif et al 37

Determination of consistency

The rod holding a cone was used to check

consistency of gel. The cone was dropped into

a gel by the help of rod from 10cm distance in

such a way that it will fall down in glass cup

full of gel at center point. The cone will

penetrate inside gel. This penetration of cone

was measured from the surface of gel to the tip

of cone that is inside the gel. After 10sec the

distance travelled by cone was noted. Results

are noted and shown in tables 3 and 4 (Ship et

al., 2007).

Determination of drug content

Assay of flurbiprofen gel was performed.

All formulations were evaluated for physical

properties. All formulations have characteristic

odor of clove oil & were lake blue in color.

The pH for all formulation was ranged from

6.34 to 7.1 which was well in normal pH range

of buccal cavity i.e. 6 to 7 in table 3 and 4

(Manosroi, A et al., 2008)

Drug release kinetic studies

These are following (Ahuja et al., 2007).

Zero order (cumulative percent drug released

v/s time)

L = KO.t

First order (log cumulative percent drug

released v/s time) Log L = Log LO – KI t/2.303

Higuchi (cumulative percent released v/s

time)

L = KH t1/2

Hixon Crowell’s cube root model (percentage

retained) 1/3 v/s time

LO – Lt1/3

=KHC t

Korsmeyer peppas Model (log cumulative

percent drug released v/s time) L = K t

n

RESULTS AND DISCUSSION

Tooth is actually the supporting structure as

well as provide surroundings to mouth .It is

considered the one important part in

contributing to digestive process. Infections of

tooth are one of the common buccal problems.

Oral diseases most commonly includes dental

cavities, oral cancer, periodontal (gum)

disease, trauma from injuries & oral infectious

diseases gastrointestinal pH that results in

gastrointestinal Drug absorption difficulties

can be avoided by use of gel. Carbopol 934

shows excellent stability has short flow

properties. Flurbiprofen is excreted poorly into

human milk and flurbiprofen tablets causes’

premature closure of the ductus arteriosus in

pregnancy so tablets must be avoided.

Flurbiprofen with clove oil was not present in

market hence the gel was prepared to ease

patients with different periodontal diseases.

Different formulations having different pH

v/s Viscosity with 1% flurbiprofen

Viscosity for five formulations having 1%

flurbiprofen with different PH was found to be

within 257 to 338 which indicate that F5

having PH 6.34 shows the maximum viscosity

&F1 having PH 7.1 with viscosity 295 shows

the decreasing trend towards F2 having PH of

7 .0 and viscosity of 257 where as F3 with PH

6.9 with viscosity of 289 shows the increasing

trends towards F4. Having PH 6.7 with

viscosity of 310, whereas F2 is best

formulation as viscosity is less which indicate

it will have good extrutability.


v/s Viscosity with 2% flurbiprofen

Viscosity for five formulations having 2%

flurbiprofen with different PH was found to be

within 249 to 309 which indicate that F6

having pH 7.1 with viscosity 289 shows

decreasing trend towards F7 having pH 7.0

with viscosity 249.whereas F7 with pH 7.0

shows the increasing trend towards F8 with pH

6.9 and viscosity of 261.F8 then shows

increasing trend towards F9 having pH 6.7

with viscosity of 309 and F9 formulation leads

decreasing trend towards F10 with pH 6.34 &

viscosity of 255, whereas F7 shows the

minimum viscosity which indicate it will have

good extrutability.


Fig. 2: FTIR chromatogram of pure flurbiprofen sample with reference standard

Fig. 3: FTIR chromatogram of clove oil sample with reference standard

Fig. 4: FTIR chromatogram of formulation that’s contains 1% flurbiprofen

Urvah asif et al 39

Fig. 5: FTIR chromatogram of formulation that’s contains 2% flurbiprofen

Fig. 6: DSC study of pure flurbiprofen sample used in toothache formulations

Fig. 7: DSC study of clove oil sample used in toothache formulations


Fig. 8: DSC result of clove oil with flurbiprofen

Fig. 9: Formulation of 1% gel shows Weibull Model

Fig. 10: Formulation of 2% gel shows Weibull Model

Urvah asif et al 41

Table 1

Formulation of gel preparation at 1% flurbiprofen

Ingredients F1(PH=7.1) F2(PH=7.0) F3(PH=6.9) F4(PH=6.7) F5(PH=6.34)

Flurbiprofen(g) 1 1 1 1 1

Carbopol 934(g) 2.2 2 2.5 2.7 2.9

Propylene glycol (ml) 18 20 22 19 21

Methyl paraben sodium (g) 0.04 0.03 0.02 0.05 0.01

Propyl paraben sodium (g) 0.02 0.01 0.009 0.03 0.008

Apartame (g) 0.1 0.1 0.1 0.1 0.1

Distilled water 70 70 70 70 70

Glycerine (ml) 5.1 5 5.3 5.6 5.8

NaOH Pellets(g) 0.1 0.1 0.1 0.1 0.1

Clove oil 2-3 drops 3-4 drops 1-2 drops 2-3 drops 3-4 drops

Menthol crystals Pinch Pinch Pinch Pinch Pinch

Banana and strawberry flavour

Pinch Pinch Pinch Pinch Pinch

Colour Pinch Pinch Pinch Pinch Pinch

Distilled water q.s q.s q.s q.s q.s

Table 2

Formulation of gel preparation at 2% flurbiprofen

Ingredients F6(PH=7.1) F7(PH=7.0) F8(PH=6.9) F9(PH=6.7) F10(PH=6.34)

Flurbiprofen(g) 2 2 2 2 2

Carbopol 934(g) 1.8 1.5 1.7 1.9 1.6

Propylene glycol(ml) 18 20 22 19 21

Methyl paraben sodium (g) 0.04 0.03 0.02 0.05 0.01

Propyl paraben sodium (g) 0.02 0.01 0.009 0.03 0.008

Apartame (g) 0.1 0.1 0.1 0.1 0.1

Distilled water 70 70 70 70 70

Glycerine (ml) 5.1 5 5.3 5.6 5.8

NaOH Pellets(g) 0.1 0.1 0.1 0.1 0.1

Clove oil 2-3drops 3-4 drops 1-2 drops 2-3 drops 3-4 drops

Menthol crystals Pinch Pinch Pinch Pinch Pinch

Banana & strawberry flavour

Pinch Pinch Pinch Pinch Pinch

Colour Pinch Pinch Pinch Pinch Pinch

Distilled water q.s q.s q.s q.s q.s

Table 3

Results of 1% flurbiprofen formulations pH, Viscosity, extrutability, spreadability,

consistency and drug contents

Code pH Viscosity

(cps)

Extrutability

(%)

Spreadability

(g-cm

/sec)

Consistency (mm)

Drug content (%)

F1 7.10 295 93.00 5.20 6.10 102.60

F2 7.00 257 96.60 4.16 5.00 103.24

F3 6.90 289 95.00 3.90 3.00 100.00

F4 6.70 310 91.60 4.46 5.80 101.60

F5 6.34 338 89.30 5.00 6.20 101.00


Table 4

Results of 1% flurbiprofen formulations pH, viscosity, extrutability, spreadability, consistency

and drug contents

Code

pH viscosity

(cps)

Extrutability

(%)

Spreadability

(g-cm/sec)

Consistency

(mm)

Drug content

(%)

F6 7.10 289 93.30 5.73 6.00 102.35

F7 7.00 249 98.60 3.28 5.10 103.09

F8 6.90 261 95.30 5.68 7.00 103.50

F9 6.70 309 92.00 3.78 4.60 104.00

F10 6.34 255 97.30 4.80 5.80 102.00

Table 5

Reading of calibration curve of flurbiprofen with dissolution media at 247nm

Concentrations Absorbance

0.00125 0.109

0.0025 0.213

0.005 0.427

0.0075 0.636

0.01 0.813

Table 6

Dissolution study and release profile of flurbiprofen with 1% and 2% clove oil

Duration

(Limits)

Absorbance/

Assay (%)

Standard After

05min

After

10min

After

15min

After

25min

After

30min

After

1hour

After

2hours

Absorbance 0.164 0.193 0.239 0.257 0.283 0.416 0.415 For 1%

% age

0.413

39.7 46.73 57.8 62.29 68.61 100.7 100.48

Absorbance 0.372 0.372 0.463 0.502 0.574 0.735 0.829

For 2% % age

0.811

33.6 45.86 57 61.8 70.7 90.6 102.2

Table 7

Kinetics release study of oral gel with 1% and 2% formulations of flurbiprofen with clove oil

Results of F2 Formulation of 1%

oral gel

Results of F7 Formulation of 2% oral gel Model

R2 AIC R2 AIC

Zero Order -1.4544 65.4715 -1.2016 64.6312

First Order 0.8379 46.4479 0.8978 43.1388

Higuchi 0.6330 52.1696 0.7356 49.7954

0.9233 43.2117 0.9738 35.6169 Korsmeyer Peppas

n=0.311 Quasi Fickian n=0.325 Quasi Fickian

Hixon 0.7181 50.3229 0.7891 48.2130

Hopfenberg 0.8379 48.4501 0.8976 45.1528

Weibull (α ,β, Ti) 0.9784 36.3272 0.9854 33.5213

It follows the Weibull model of drug release and shows Fickain release

Urvah asif et al 43


v/s Viscosity for both 1% and 2% flurbiprofen

This indicates that F1 having pH 7.1 shows

viscosity 295, whereas, F7 formulations

having pH 7.0 shows viscosity 249 which is

the minimum viscosity, while F2 formulation

having pH 7.0 of shows increasing trend

towards F3 having pH of 6.9 and F7

formulation having pH 7.0 of shows increasing

trend towards F8 having pH of 6.9 with

viscosities as 289 and 261. Then F3 shows

increasing trend towards F4 and F7 shows

increasing trend towards F8. Finally F4 shows

increasing behavior towards F5 however F9

shows decreasing trend towards F10

formulation. F2 formulation of 1% and F7

formulation of 2% is considered to be the best

as it shows minimum viscosity with greater

extrutability.


v/s extrutability for 1% flurbiprofen

F5 with PH 6.34 shows minimum

Extrutability i.e. 89.30% .F1 formulation with

PH 7.1 shows extrutability 93 %.F4

formulation with pH 7.0 shows extrutability

91.6% that lies in between F1 and F5

formulation extrutability whereas F3

formulation with pH 6.9 shows extrutability of

95% i.e. slightly less than F2, F3, F4 and F5

shows decreasing trends. F2 formulation with

pH 7 shows maximum extrutability of 96.6%

which shows it is less viscous and easy to

apply.


v/s extrutability for 2% flurbiprofen F9 formulation with pH 6.7 shows

minimum extrutability i.e. 92% whereas F7

with PH 7.0 shows maximum Extrutability i.e.

98.6% so it’s the best formulation having less

viscosity. F6 formulation with pH 7.1 shows

extrutability 93.3 %.F8 formulation with pH

6.9 shows extrutability 95.3% that lies in

between F6 and F7 formulation extrutability.

Whereas F10 formulation with pH 6.34 having

extrutability of 97.3 % that is slightly less than

F7.


v/s extrutability for both 1% and 2%

flurbiprofen F1 & F6 formulation having PH of 7.1 of

both 1% and 2 % shows almost same but F6 is

a bit higher as compared to F1 extrutability. F7

formulation is slightly higher than F2. F3 and

F8 formulation shows same results as above.

F9 formulation shows higher extrutability as

compared to F4 formulation and finally F10 is

much higher as compared to F5.


v/s spread ability for 1% flurbiprofen F1 with PH 7.1 Shows maximum spread

ability i.e., 5.20, F2 with pH 7.0 shows spread

ability of 4.16 that shows further decreasing

trend towards F3 having spread ability value

of 3.90. F3 slightly shows Increasing behavior.

F4 with pH 6.7 shows slightly increasing trend

towards F5 wit spread ability value of 5.0


v/s spread ability for 2% flurbiprofen F6 with pH 7.1 Shows maximum spread

ability i.e., 5.73 ,F7 with PH 7.0 shows spread

ability of 3.28 that shows increasing trend

towards F8 having spread ability value of 5.68

.F8 shows decreasing behavior. F9 with pH 6.7

shows slightly increasing trend towards F10

with spread ability value of 4.80


v/s spread ability for both 1% and 2%

flurbiprofen

F1 formulation having pH 7.1 shows

decreasing trend towards F2 and F6 towards

F7 with pH 7.0 Whereas F2 shows decreasing

trend towards F3 with pH 6.9 and F7 shows

Increasing trend towards F8 with same pH. F3

of 1% formulation increases towards F4

having pH of 6.7 However F8 formulation

shows decreasing trend towards F9 with same

pH. F4 increases towards F5 and F9 increases

towards F10.


v/s consistency for 1% flurbiprofen

F5 with pH 6.34 has max consistency where

as F1 formulation with pH 7.1 shows

consistency slightly less than F5. F3 with PH


6.9 shows the minimum consistency. F2 with

pH 7.0 and F4 with pH 6.7 show consistency

in between.


v/s consistency for 2% flurbiprofen

F8 with pH 6.9 has max consistency where

as F6 formulation with pH 7.1 shows

consistency s less than F8 of pH 6.9. F9 with

pH 6.7 shows the minimum consistency. F10

with PH 6.34 shows consistency in between F8

and F6 and F7 with pH 7.0 shows consistency

slightly more than F9 but less than F10


v/s consistency for both 1% and 2%

flurbiprofen

F5 formulation with pH 6.34 shows max

consistency for 1% i.e. 6.2 whereas for 2% F8

formulation having pH 6.9 shows maximum

consistency.F3 with pH 6.9 of 1% shows the

minimum consistency i.e.3 where as F9 with

pH of 6.7 shows consistency of 4.6.F1 of 1%

with pH 7.1 has consistency 6.1 which is

slightly more as compared to F6 of 2%

formulation with same PH of 7.1. i.e., 6.0. F7

of 2% with pH 7.0 shows consistency 5.1

whereas F2 of 1% shows 5.1


v/s drug content for 1% flurbiprofen

F2 formulation shows maximum drug

content of 103.24% having pH of 7.0. F1

formulation having pH 7.1 shows drug content

102.6% which is slightly less as compared to

F2 formulation.F4, F5 and F3 shows drug

contents as, 101.6%, 101% and 100% which

lies with in limit.


v/s drug content for 2% flurbiprofen

F9 formulation shows max drug content of

104%.where as F7 which is best formulation

shows drug content of 103.09% with pH 7.0

F6 and F10 shows almost same. Whereas F8

shows 103.5%

Calibration curve

Calibration curve of flurbiprofen in solvent

shows straight line. And calibration curve of

flurbiprofen in dissolution medium shows a

straight line.

FTIR study of flurbiprofen

FTIR spectra of pure drug Flurbiprofen was

obtained at the wavelengths between 600 to

1800 cm-1.

Positions of peak in IR spectra of

drug showed its characteristic bands. The

absorption peaks shows strong bending

vibrations at 696.52 cm -1

which indicate the

presence of =C-H bond .C-F shows stretch

vibrations at 1216 cm -1

having strong

intensity. Whereas C-H stretch bond is at 1461

cm-1

and C=O stretch band exist at1697cm-1.

In

this FTIR Spectra all the mentioned positions

do not show any remarkable shift in wave

number of peaks.

In-vitro drug release

The assay value taken at 247nm.2hrs

dissolution study was performed. pH 7.0

buffer was made. USP Apparatus 2 was used.

Rpm were 50.Gel was dissolved and drug

content assay was calculated using analytical

method.

Drug release kinetics

Dissolution data of best formulations was

fitted to zero order, first order, and Higuchi,

Hixon-crowell and peppas equation to

determine the mechanism of drug release. The

data was comparatively fitted in weibul model

and indicated fickian (0.45<n>0.89) for best

formulation.

Release profiles

F1 formulation of 1% showed release of

38.7% at 05 min, 45.7% at 10 min, 57% at

15min, whereas at 25 min it showed the

release profile of 61%, at 30 min 68.2% &

after 1 hr it showed release at101.2 however it

showed 100.7% after 2 hours. F2 formulation

showed the release profile at time point 05, 10,

15, 25, 30, 60 and 120 min as 40.6%, 47.6%,

58.3%, 62.7%, 69.24%, 99.5% and 101.4%

Similarly F3 showed the increasing trend from

5min to 1h i.e. 05 min indicated the release at

39.4% 10 min at 46.7%, 15 min at 57.8%, 25

min showed at 61.98% whereas after half an

hour it goes to 68.5% with no significant

Urvah asif et al 45

change. But after 30 min it shows abrupt

increase at 60 min. I e. 100.4%, while after 2

hours it was 99.7% F4 formulation showed the

release at 10 min of 39.2% at 5 min where as

46.2 % and 15 min showed the value of 57%

.25 min at 61.98%. After half hour it indicates

increasing trends with release at 68.5%. 60

min indicate release at 100.4 % and finally

after 2 hrs it showed 99.7%. F5 formulation

showed release profile of 39.9%, 47.2%,

58.1%, 63.4%, 68%, 99.7% and 101.45% at

different time points i.e., 5, 10, 15, 25, 30, 60

and 120 min. F6 formulation of 2% showed

release profile behavior on 5, 10, 15, 25, 30,

60 and 120 min as 33.1%, 45.8%, 57%, 61%,

70.7%, 90% and 102%. Whereas F7

formulation indicate release profile of 34.4%,

46.5%, 57.7%, 63.5%, 71.3%, 91.49% and

102.9% at time points as mentioned above. F8

formulation at 5 min was 33.5%, 46.2%,

57.3%, 61.5%, 71%, 90.5% and 102.2% F9

formulation showed release profile as follow

33.9% at 5 min, 45.6% at 10min, 56.9% at 15

min, 62.6% at 25min, 70.4% at 30min and

91.3% after 1 hour where as 102.7 % after 2

hours. F10 formulation also showed same

trends as rest 5min showed release of 33.9%,

45.4% at 10min, 15 min showed 56.8% then

62.5% at 25 min. whereas after 30 min it

released about 71.39%. 1 hour indicated the

release amount to be 91.1% and finally after

2hours it showed 102.3%. All above release

profiles indicated that F2 formulation of 1%

was best among all.

Differential scanning calorometery

DSC of carbopol 934 and other excipient

was performed with active and thermograms

were shown in graphs. Carbopol 934 showed

no difference in thermogram of DSC with

flurbiprofen. Whereas aspartame showed little

difference in peak so best formulation doesn’t

contain aspartame.

Antimicrobial activity

Oral gel was checked for microbial growth.

It showed no microbial growth on agar media.

The presence of clove oil showed that it inhibit

the growth of microbes in gel.

CONCLUSION

Flurbiprofen with clove oil oral gel was

formulated with ten different formulations by

varying the ratio of Polymer Carbopol (934),

Propylene Glycol, Clove oil , Aspartame ,

Glycerine and Preservatives & by varying

concentration from 1% to 2% and pH from

6.34-7.1. It was inferred from research study

that F2 formulation of 1% and F7 formulation

of 2% showed good results. F2 (1%)

formulation demonstrates drug content of

103.24 and F7 of 103.09%. Whereas F2 has

minimum viscosity of 257cp and F7 indicates

viscosity value of 249cp which determine that

these have good extrutability of 96.6% and

98.6%. Both possess good spread ability and

consistency results which made them suitable

for applicable and help them to retain at

surface applied. DSC and FTIR revealed that

there is no chemical interaction of the drug

with the excipients used. Dissolution studies of

best formulations were performed F2

formulation displayed the best release profiles

as compared to F7. Carbopol 934 was

considered better to provide best efficiency &

release profile as well as clinical efficacy

when used with flurbiprofen in ratio

(flurbiprofen:carbopol 934) (1:2). Anti-

microbial activity test of best formulation

showed that oral gel is free of any microbes.

Promising results are obtained on small scale

clinical studies. Further studies in this

direction could lead to effective drug delivery

system for treatment of periodontal diseases.

Significance

Aches are classified on the behalf of degree

of intensity of pain. Tooth ache is considered

in severe category and flurbiprofen tablets are

mostly prescribed for this purpose.

However no flurbiprofen with clove oil oral

gel is available, therefore present study was

conducted to produce fast relief gel in pain in

periodontal diseases that not only has benefit

of reducing the dose of the drug but has the

advantage of specific buccal delivery system

.This formulation may prove useful to provide

local effects in pregnant ladies and nursing


mothers, because flurbiprofen oral tablets are

contraindicated in expecting mothers.

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