FORMULATION & EVALUATION OF ETORICOXIB …

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Yalavarthi et al. European Journal of Biomedical and Pharmaceutical Sciences

512

FORMULATION & EVALUATION OF ETORICOXIB TRANSFEROSOMAL GEL

Krishna Sai Yalavarthi*, Bala Tripura Sundari Ivatury

1 and Dr. M. Bhagavan Raju

2

*1,2Department of Pharmaceutics, Sri Venkateshwara College of Pharmacy, Madhapur, Hyderabad, Telangana, India -

500081.

Article Received on 02/11/2017 Article Revised on 23/11/2017 Article Accepted on 13/12/2017

INTRODUCTION Etoricoxib, a widely prescribed anti-inflammatory drug

belongs to class IΙ under BCS and exhibit low and

variable oral bioavailability due to its poor aqueous

solubility. It is practically in soluble in water. Etoricoxib

is a Non steroidal Anti-Inflammatory Drug (NSAID)

belonging to the class of cyclooxygenase 2 (COX-2)

inhibitors used in the treatment of relieving moderate

pain and swelling of joints associated with different

forms of arthritis. Etoricoxib is commercially available

as tablets. Oral treatment involves attainment and

maintenance of drug concentration in the body within a

therapeutically effective range by introduction of a fixed

dose at regular intervals, due to which the drug

concentration in the body follows a peak and trough

profile, leading to a greater chance of adverse effects or

therapeutic failure & large amount of drug is lost in the

vicinity of the target organ. Also oral administration of

etoricoxib causes Gastro-Intestinal (G.I) Irritation.

Transdermal drug delivery system appears to be most

promising delivery system over conventional delivery

systems in order to avoid “Hepatic first-pass effect”, to

overcome the problems associated with the oral

administration, to decrease the dosing frequency required

for oral treatment.

To reduce the side effects of oral administration and to

sustain the release transferosomal drug delivery was

selected. Transferosomes are specially optimized, ultra

deformable (ultra flexible) lipid supra molecular

aggregate, this high deformability gives better

penetration of intact vesicles. Transferosomes mainly

composed of phospholipids like phosphatidyl choline

which self assembles into lipid bilayer in aqueous

environment and closes to form a vesicle. The main

component in transferosome formulation is edge

activator. It consists of single chain surfactant that causes

destabilization of the lipid bilayer thereby increasing its

fluidity and elasticity. Due to their flexibility when

compared to other vesicles, transferosomes are well

suited for the skin penetration. Transferosomes overcome

the skin penetration difficulty by squeezing themselves

along the intracellular sealing lipid of the stratum

corneum.[1]

MATERIALS AND METHODS

Materials: Etoricoxib was obtained as a gift sample

from Cirex Pharmaceuticals Ltd., Medak Dist.,

SJIF Impact Factor 4.382 Research Article

ejbps, 2018, Volume 5, Issue 01 512-524.

European Journal of Biomedical AND Pharmaceutical sciences

http://www.ejbps.com

ISSN 2349-8870

Volume: 5

Issue: 01

512-524

Year: 2018

*Corresponding Author: Krishna Sai Yalavarthi

Department of Pharmaceutics, Sri Venkateshwara College of Pharmacy, Madhapur, Hyderabad, Telangana, India - 500081.

ABSTRACT

The aim of the research was to develop an Etoricoxib Transferosomal gel for better anti-inflammatory activity by

reducing the gastro-intestinal (G.I) related toxicities associated with oral administration & sustain the release.

Etoricoxib is a non steroidal anti-inflammatory drug (NSAID) which has shown many side effects when used

orally. Etoricoxib transferosomes were prepared by Thin Film Hydration method using Soya lecithin, Edge

Activators and Drug in different ratios. The edge activators used in the formulation are Span 80, Span 60 and

Tween 80. The prepared transferosomes were evaluated for particle size, entrapment efficiency, zeta potential and

in vitro drug release. The excipients compatibility was performed by using Fourier transform infrared

spectroscopy (FT-IR) and it was found compatible with each other. Optimized transferosomal formulation

exhibited an entrapment efficiency of 89.67% and drug release of 86.66% in 20hrs. The optimized formulation

was incorporated into gel using carbopol 934 of different concentrations. Optimized transferosomal gel showed

the Ex vivo drug release of 84.26 % in 12hrs. Stability studies indicated that optimized formulations were stable

for a period of 3months under normal room temperature conditions and refrigerated conditions. It is evident from

this study that transfersomes are a promising prolonged delivery system for etoricoxib and minimizing the G.I

toxicities associated with oral administration.

KEYWORDS: Transferosomes, Etoricoxib, Soya Lecithin, Edge Activator, Carbopol 934, Spans and Tweens.

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Telangana, India. Soya Lecithin, Span 80, Span 60,

Tween 80, Chloroform amd Methanol were obtained

from commercial sources.

METHODS

Preformulation Studies

Drug - Excipient Studies

To investigate any possible interactions between the drug

and excipients, studies were carried out using Fourier

Transform Infrared (FTIR) spectrophotometer Shimadzu

8400S.

Solubility Studies

Solubility of Etoricoxib was determined using the shake

flask method. The solubility studies were performed by

adding an excess amount of Etoricoxib into different

ratios of Phosphate buffer (pH 7.4) and PEG 400

followed by sealing in vials. Sealed vials were kept on

Rota shaker (ELTEK®, India) for 72 hrs for attaining

equilibrium. Each vial was centrifuged at 15000 rpm

using a centrifuge (REMI®, Mumbai) followed by the

removal of undissolved drug by filtering using a

whatmann filter paper. Samples (0.1 ml) were suitably

diluted with respective media and drug concentration

was measured at 234 nm.

Preparation of Etoricoxib Transferosomes by Thin

Film Hydration.[1,2]

Step 1: Lipid Film Formation

The Lipid, Edge Activator and drug were dissolved

in 30ml of Chloroform and Methanol (3:1) in a

100ml round bottom flask.

The flask was attached to a rotary evaporator

(Superfit, India) immersed in 60ºC water bath and

rotated under vacuum.

This process was continued until all the solvent was

evaporated and lipid film was deposited on the walls

of the flask.

The flask was left in vacuum desiccators overnight

to ensure complete removal of the residual solvent.

Step 2: Hydration of the formed film

Phosphate Buffer pH 7.4 was added to the dried film

and rotated under similar conditions of Rotary

Vacuum Evaporation for another 30 minutes till the

lipid film was completely hydrated.

Step 3: Formation of small vesicles

The flask was removed and the transferosomes were

transferred to a container and subjected to sonication

at 50Hz in a bath sonicator for 15 minutes.

Table 1: Formulations of Transferosomes

Formulation Drug (mg) Soya Lecithin

(mg)

Span 80

(mg)

Tween 80

(mg)

Span 80

(mg) Solvent (ml)

F - 1 25 95 5 - - 30

F - 2 25 90 10 - - 30

F - 3 25 85 15 - - 30

F - 4 25 80 20 - - 30

F - 5 25 75 25 - - 30

F - 6 25 95 - 5 - 30

F - 7 25 90 - 10 - 30

F - 8 25 85 - 15 - 30

F - 9 25 80 - 20 - 30

F - 10 25 75 - 25 - 30

F - 11 25 95 - - 5 30

F - 12 25 90 - - 10 30

F - 13 25 85 - - 15 30

F - 14 25 80 - - 20 30

F - 15 25 75 - - 25 30

Characterization of Transferosomes[2,3,4]

Surface Morphology: The Surface Morphology was

determined using Scanning Electron Microscopy (SEM).

SEM gives a three dimensional (3-D) image of globules.

One drop of transferosomal suspension was mounted on

a clear glass stub. It was then air dried and gold coated

using sodium auro thiomalate to visualize under SEM.

Zeta Potential: Zeta potential was determined using

zetasizer (HORIBA SZ – 100). The Zeta potential is a

key indicator of stability of colloidal dispersions. The

magnitude of Zeta potential indicates the degree of

electrostatic repulsion between adjacent, similarly

charged particles in dispersion.

Entrapment Efficiency (EE): Entrapment Efficiency of

Etoricoxib transferosomal vesicles were determined by

centrifugation method. The vesicles were separated in a

high speed centrifuge at 19,000rpm for 90 minutes. The

sediment and supernatant liquids were separated.

Amount of the drug in the supernatant was determined. It

was then diluted appropriately and estimated using UV -

Visible Spectrophotometer at 234nm. From this, the

entrapment efficiency was determined using following

formula.

% Entrapment Efficiency = x 100

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In-Vitro drug release studies: In-vitro drug release

studies were performed using modified diffusion cell.

The In-vitro diffusion of the drug was performed through

semi permeable membrane which was previously soaked

in a buffer for 3 - 4 hrs. It was clamped to one end of the

hallow glass tube of 17mm (area 2.01cm2). This acts as a

donor compartment. 50ml of Phosphate Buffer pH 7.4 :

PEG 400 (80:20) was taken in a beaker which was used

as receptor compartment. 50ml of the medium was taken

to maintain the sink conditions. The known quantity of

transferosomal suspension was spread uniformly on the

membrane. The donor compartment was kept in contact

with the receptor compartment and the temperature was

maintained at 37 ± 0.5ºC. The solutions of the receptor

side were stirred by externally driven Teflon coated

magnetic beads. At predetermined time intervals, 5ml of

aliquot was withdrawn and replaced by 5ml of the

respective media. The drug concentrations of the aliquots

were analyzed using UV-Visible Spectrophotometer at

234nm against appropriate blank.

Preparation of Transferosomal Gel: The gels were

prepared by dispersion method using Carbopol 934 in

different ratios as shown in the table. Gels were prepared

by dispersing the gelling agent in the transferosomal

suspension. Then the mixture was allowed to swell

overnight.

Table 2: Formulations of Transferosomal Gel using Carbopol 934.

Formulation Transferosomal

Suspension (ml)

Carbopol

concentration (%)

Propylene

Glycol (ml)

Triethanolamine

(% v/v)

TG - 1 10 0.5 5 0.5

TG - 2 10 1 5 0.5

TG - 3 10 1.5 5 0.5

Evaluation of Transferosomal Gel

pH: pH was checked using pH meter (Systronics digital

pH meter). The electrode was submersed into the

formulation at room temperature and the readings were

noted.

Viscosity: Viscosity determinations of the prepared

formulations were carried out by Brookfield

Synchroelectric viscometer (LV-DV Pro II), Spindle S64

(Small sample adapter) and the angular velocity

increased from 5, 10, 50, and 100rpm and results were

noted.

Drug Content: Drug content was estimated

spectrometrically where 100mg of formulation was taken

and dissolved in methanol and filtered. The volume was

made to 100ml with methanol. The resultant solution was

suitably diluted with methanol and absorbance was

measured at 234nm.

Spreadability: The spreadability of the gel formulation

was determined by measuring diameter of 1gm of gel

between horizontal plates (20 x 20 cm2) after 1 minute.

The standard weight tied on upper plate was 125grams.

Stability Studies: The physical stability of the

developed transferosomal formulations were performed

according to the ICH guidelines. The Optimized

formulations were stored at two different temperature

ranges for 3 months i.e., refrigerator conditions (2-8 ±

2ºC) and room temperature (25 ± 2ºC). Samples were

withdrawn at 30, 60, 90 day time interval and checked

for the percentage drug entrapment.

Ex - vivo skin permeation studies

The skin permeation study was performed by using rat

skin. The animal was sacrificed by cervical dislocation of

the spinal cord and superficial hair on the abdominal skin

was removed with adhesive tape taking extreme

precaution not to damage skin and examined under

microscope for cuts and wounds. Then the skin was

mounted on the receptor compartment such that the

dermis side faces the receptor compartment and the

stratum corneum faces the donor compartment. The

Etoricoxib transferosomal gel formulation was placed on

the stratum corneum in the donor compartment and the

experiment will be run for permeation studies.

RESULTS AND DISCUSSION

Drug - Excipient Compatibility studies

Drug - Excipient compatibility studies were carried out

by Fourier Transform Infrared Spectroscopy analysis

(Shimadzu 8400S). The IR spectrum of the pure drug

was compared with IR spectrum of combination of drug

and all excipients and it was found that there were no

specific interactions between the drug and excipients.

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Fig 1: IR Spectrum of Etoricoxib drug.

Fig 2: IR Spectrum of Drug and Excipients.

Table 4: Characteristic IR peaks of Etoricoxib plain drug

Functional Group Reported Frequency (cm-1

) Observed Frequency (cm-1

)

C-Cl 800 – 600 781

C-CH3 1470 – 1430 1433

N=C 1750 – 1550 1599

S=O 1500 – 1000 1240

Table 5: Characteristic IR peaks of Etoricoxib drug and excipients

Functional Group Reported Frequency (cm-1

) Observed Frequency (cm-1

)

C-Cl 800 – 600 781

C-CH3 1470 – 1430 1433

N=C 1750 – 1550 1710

S=O 1500 – 1000 1086

Solubility Studies

The mixture of 7.4pH phosphate buffer and PEG 400 in

the ratio 80:20 respectively was selected as a diffusion

medium for drug release studies.

Table 6: Solubility Study data

Buffer : PEG 400 Solubility (mg/ml)

90:10 1.6

80:20 2.7

Surface Morphology: The surface morphology of the

formulated transferosomes was determined using

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Scanning Electron Microscopy (SEM). The images

indicated that the transferosomes were in a spherical

shape. The images of the globules shown in below

figure.

Fig 3: SEM image of Etoricoxib Transferosomes.

Globule Size & Zeta Potential: Globule size and zeta

potential were measured using Horiba Scientific

nanopartica. The mean Globule size for the optimized

formulation was found to be 382.0 nm. The zeta potential

of the transferosomes was found to be -33.4 mV which

indicates that the transferosomes possess good stability.

Fig 4: Particle size analysis of Etoricoxib Transferosomes.

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Fig 5: Zeta Potential of Etoricoxib Transferosomes.

From Fig 4 it was observed that the diameter of the

transferosomes was found to be in the range of 100 to

1000 nm. The average size of the transferosomes was

found to be 382nm.

Entrapment Efficiency

The maximum entrapment efficiency obtained was

88.62% for the formulation F - 3. The entrapment

efficiency in transferosomes is reported to depend on the

edge activator concentration in the bilayer.[6,7]

Proportion

of the edge activator was varied from 5 – 25mg of the

phospholipid concentration. Initially, with the increase in

edge activator concentration, there was an increase in the

entrapment efficiency. However, after a threshold level

(above 15mg for Span 80 & Span 60, above 20mg for

Tween 80), further increase in surfactant concentration

led to a decrease in entrapment efficiency. This may be

due to the formation of the mixed micelles in bilayer

resulting in pore formation in vesicle membranes and

complete conversion of vesicle membranes into mixed

micelles. Large numbers of mixed micelles can be

observed, if the concentration of edge activator exceeds

15% - 20% of the phospholipid. These mixed micelles

are reported to have a lower drug carrying capacity and

poor skin permeation.[6,7]

Fig 6: Entrapment Efficiency of formulations F - 1 to F – 15.

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In-vitro Drug release studies

In-vitro drug release studies were performed for all

formulations using modified diffusion cell. 50ml of the

diffusion medium was placed in the receptor

compartment in order to maintain the sink conditions.

Percentage drug release from F - 1 to F - 15 are shown in

the table 7 to 9 and the release profiles of the

formulations are represented in the figures 7 to 9.

Drug release studies were performed using Modified

diffusion cell.

Temperature - 37 + 0.5◦C

Diffusion medium - Phosphate buffer

pH 7.4 : PEG 400

(80:20)

Volume of Diffusion medium - 50ml

Aliquot withdrawn - 3ml

Aliquot replaced - 3ml

Table 7: Percentage drug release of the formulations F - 1 to F – 5.

Time

(Hrs)

% DR of

F-1 ± SD

% DR of

F-2 ± SD

% DR of

F-3 ± SD

% DR of

F-4 ± SD

% DR of

F-5 ± SD

0 0 0 0 0 0

1 3.66 ± 0.17 5.29 ± 0.25 8.12 ± 0.18 6.89 ± 0.32 4.62 ± 0.42

2 6.16 ± 0.54 9.73 ± 0.12 14.36 ± 0.29 11.18 ± 0.25 8.28 ± 0.23

3 8.91 ± 0.26 14.28 ± 0.31 19.83 ± 0.23 16.82 ± 0.11 11.79 ± 0.16

4 11.76 ± 0.24 18.61 ± 0.26 25.44 ± 0.51 22.41 ± 0.53 15.26 ± 0.51

5 14.64 ± 0.32 22.27 ± 0.21 31.17 ± 0.43 27.74 ± 0.47 18.64 ± 0.43

6 17.45 ± 0.42 26.91 ± 0.47 37.38 ± 0.31 33.27 ± 0.62 22.36 ± 0.38

7 21.18 ± 0.37 31.26 ± 0.54 42.71 ± 0.64 38.79 ± 0.45 25.81 ± 0.63

8 24.72 ± 0.24 35.69 ± 0.19 48.87 ± 0.35 44.52 ± 0.73 29.37 ± 0.78

10 30.61 ± 0.57 44.76 ± 0.26 59.34 ± 0.47 53.87 ± 0.67 37.15 ± 0.24

12 36.73 ± 0.43 53.52 ± 0.57 68.46 ± 0.38 64.36 ± 0.26 45.28 ± 0.46

Fig 7: Drug release profiles of formulations F - 1 to F – 5.

Table 8: Percentage drug release of the formulations F - 6 to F - 10

Time

(Hrs)

% DR of

F-6 ± SD

% DR of

F-7 ± SD

% DR of

F-8 ± SD

% DR of

F-9 ± SD

% DR of

F-10 ± SD

0 0 0 0 0 0

1 1.08 ± 0.30 2.87 ± 0.14 3.26 ± 0.26 4.10 ± 0.22 1.66 ± 0.18

2 2.47 ± 0.11 5.28 ± 0.32 6.82 ± 0.15 7.61 ± 0.30 3.47 ± 0.31

3 4.12 ± 0.47 7.71 ± 0.25 9.19 ± 0.30 10.49 ± 0.15 5.64 ± 0.29

4 5.96 ± 0.23 9.37 ± 0.30 10.81 ± 0.26 14.35 ± 0.12 7.72 ± 0.14

5 7.13 ± 0.52 11.22 ± 0.62 13.19 ± 0.49 17.87 ± 0.25 9.44 ± 0.42

6 8.62 ± 0.18 13.64 ± 0.44 16.87 ± 0.32 20.38 ± 0.37 11.16 ± 0.61

7 10.47 ± 0.26 15.38 ± 0.51 20.12 ± 0.55 23.94 ± 0.49 13.74 ± 0.17

8 12.16 ± 0.19 17.74 ± 0.23 23.77 ± 0.31 27.73 ± 0.34 15.27 ± 0.54

10 15.74 ± 0.47 22.24 ± 0.16 27.41 ± 0.27 35.17 ± 0.21 19.62 ± 0.35

12 19.25 ± 0.62 25.83 ± 0.38 31.13 ± 0.19 42.69 ± 0.23 23.26 ± 0.27

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Table 9: Percentage drug release of the formulations F - 11 to F – 15.

Time

(Hrs)

% DR of

F-11 ± SD

% DR of

F-12 ± SD

% DR of

F-13 ± SD

% DR of

F-14 ± SD

% DR of

F-15 ± SD

0 0 0 0 0 0

1 3.04 ± 0.22 3.81 ± 0.37 4.48 ± 0.31 3.51 ± 0.26 2.44 ± 0.20

2 5.80 ± 0.50 7.27 ± 0.24 8.27 ± 0.18 6.88 ± 0.34 4.11 ± 0.33

3 8.12 ± 0.36 9.83 ± 0.19 11.86 ± 0.46 8.65 ± 0.37 6.87 ± 0.19

4 10.77 ± 0.26 13.52 ± 0.44 15.43 ± 0.35 12.11 ± 0.14 8.05 ± 0.41

5 13.21 ± 0.47 16.44 ± 0.15 19.62 ± 0.61 15.70 ± 0.48 10.36 ± 0.28

6 15.94 ± 0.21 19.67 ± 0.27 23.58 ± 0.39 19.24 ± 0.31 12.45 ± 0.53

7 19.20 ± 0.65 23.51 ± 0.59 27.39 ± 0.25 22.49 ± 0.75 14.60 ± 0.36

8 22.72 ± 0.36 26.73± 0.43 31.26 ± 0.58 26.18 ± 0.46 16.92 ± 0.24

10 28.81 ± 0.40 32.38 ± 0.12 39.73 ± 0.74 31.82 ± 0.81 21.36 ± 0.47

12 34.28 ± 0.15 39.14 ± 0.67 45.66 ± 0.33 38.62 ± 0.45 24.57 ± 0.31


Initially the drug release for the formulations was

increased with the increase in the concentration of edge

activator. At high concentrations, vesicles lack their

vesicular structure and forms rigid mixed micelle which

results in low drug release. Out of all the formulations,

formulation F - 3 exhibited more drug release than the

other formulations. The Formulation F - 3 containing

Phospholipid (Soya Lecithin) 85mg and Edge Activator

(Span 80) 15mg, showed 68.46% drug release in 12 hrs.

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EVALUATION OF TRANSFEROSOMAL GEL[5]

Appearance: All the formulations were opaque and

white in colour, odorless, semisolid in nature and had

smooth appearance.

pH: The pH of Transferosomal gels TG-1, TG-2 & TG-3

were found to be 6.67, 6.85 & 7.04 respectively. At this

pH the gel will not produce any irritation to the skin.

Table 10: pH of the Transferosomal Gels.

FORMULATION pH

TG - 1 6.67

TG - 2 6.85

TG - 3 7.04

Spreadability: The transferosomal gel TG - 1 showed a

better Spreadability than the other transferosomal gels.

Spreadability of the gel formulation was decreased with

the increase in polymer concentration. The results are

shown in the table 11.

Table 11: Spreadability of the Transferosomal Gels

Transferosomal

Gel

Spreadability

(cm)

TG - 1 3.1 ± 0.21

TG - 2 2.8 ± 0.14

TG - 3 2.6 ± 0.35

Viscosity: Viscosity determinations of the prepared

formulations were carried out by Brookfield

Synchroelectric viscometer (LV-DV Pro II), Spindle S64

(Small sample adapter) and the angular velocity

increased from 5, 10, 50, and 100rpm and values were

noted and represented in the table 12.

Table 12: Viscosity of the Transferosomal Gels.

Transferosomal

Gel

At 5 rpm

(cps)

At 10 rpm

(cps)

At 50

rpm (cps)

At 100

rpm (cps)

TG - 1 6953 4183 1172 439

TG - 2 8651 5019 1404 834

TG - 3 9838 5962 1829 1081

The viscosities of all the gel formulations were ranged

from 9838 cps to 439 cps. The viscosity of formulations

decreased on increasing the shear rate.

Drug Content: The Etoricoxib content was found from

97.36 % to 98.87 %. These results indicate the uniform

Etoricoxib distribution in the gel formulation. The results

are shown in the below table.

Table 13: Drug Content of the Transferosomal Gels

Transferosomal

Gel

% Drug

Content

TG – 1 98.28

TG – 2 98.87

TG - 3 97.36

In-vitro Drug release studies: In-vitro drug release

studies were performed using cellophane membrane.

Drug release studies were performed using Modified

diffusion cell.

Temperature - 37 + 0.5ºC

Diffusion medium - Phosphate buffer

pH 7.4 : PEG 400 (80:20)

Volume of Diffusion medium - 50ml

Aliquot withdrawn - 3ml

Aliquot replaced - 3ml

Table 14: Percentage Drug Release of the Transferosomal Gels.

Time

(Hrs)

% DR of

TG - 1 ± SD

% DR of

TG - 2 ± SD

% DR of

TG - 3 ± SD

0 0 0 0

1 5.68 ± 0.26 7.41 ± 0.19 6.37 ± 0.23

2 9.77 ± 0.15 12.68 ± 0.31 10.52 ± 0.42

3 14.58 ± 0.54 18.73 ± 0.27 15.36 ± 0.33

4 18.27 ± 0.26 23.66 ± 0.21 20.14 ± 0.15

5 23.81 ± 0.19 29.46 ± 0.35 25.78 ± 0.20

6 27.56 ± 0.35 35.74 ± 0.16 30.49 ± 0.53

7 31.48 ± 0.41 40.27 ± 0.38 34.96 ± 0.21

8 35.92 ± 0.28 46.39 ± 0.32 39.18 ± 0.32

10 39.73 ± 0.33 54.73 ± 0.14 45.32 ± 0.47

12 45.19 ± 0.24 60.24 ± 0.36 51.32 ± 0.27

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Fig 10: Drug Release profiles of Transferosomal Gels.

Out of these three formulations, formulation TG - 3

exhibited a better drug release. From this result, the

formulation TG - 3 was optimized.

Ex-Vivo Skin permeation studies: The optimized gel

formulation TG - 3 was selected for the skin permeation

studies using excised skin of the rat. The results of the

Ex-Vivo skin permeation studies are table 15.

Table 15: Percentage of drug release through the skin

Time (Hrs)

% DR of Optimized

transferosomal gel (TG - 3)

± SD

0 0

1 8.38 ± 0.34

2 15.69 ± 0.19

3 20.18 ± 0.42

4 26.93 ± 0.53

5 32.71 ± 0.24

6 40.19 ± 0.37

7 47.52 ± 0.53

8 54.64 ± 0.29

10 71.47 ± 0.38

12 84.26 ± 0.27

Fig 11: Drug release profile of TG - 3 through the skin.

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Fig 12: Drug Permeation profile of Transferosomal gel.

In the Ex-vivo drug permeation studies, it was found that

the drug released from the skin was higher than the drug

released from the cellophane membrane. The increase in

the drug release may be due to the action of permeation

enhancers (Propylene Glycol) on the intercellular lipids

of stratum corneum, by weakening the stratum corneum

and raising the fluidity. The Phospholipids also have

high affinity for biological membranes. The presence of

unsaturated fatty acids in Phosphatidyl choline may be

responsible for the enhanced permeation.

Permeability parameters Steady-State flux (Jss) &

Permeability Coefficient (Kp) were determined. The

results are shown in the table 16.

Table 16: Permeation Data Analysis.

Formulation Jss ± SD

(µg/cm2/h)

Kp ± SD

(cm/h) *10-

2

Transferosomal gel 354.8 ± 1.6 11.08 ± 0.31

Stability Studies

Stability studies were performed as per ICH guidelines at

two different temperatures for 3 months i.e., refrigerator

conditions (2-8ºC ± 2ºC) and room temperature (25ºC ±

2ºC). The drug content of the optimized formulations

was monitored for a period of 90days.

Table 17: Stability study data

Time

Period

(Days)

% Drug Content at

Refrigerator conditions

(2- 8ºC ± 2ºC)

% Drug Content at Room

temperature conditions

(25ºC ± 2ºC)

0 98.87 98.87

30 98.69 98.41

60 98.36 98.08

90 98.19 97.72

The formulations were analyzed for the drug content and

from the obtained results it can be observed that the

transferosomal formulations were found to be stable at

different temperature conditions.

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LIST OF ABBREVIATIONS

Abbreviations Full-form

%

nm

cm

mm

mg

μg

ml

UV

Vis

IR

FTIR

rpm

cps

mV

min

h (or) Hrs

F

TG oC

SD

PEG

SEM

GI

DR

Percentage

Nanometer

Centimeter

Millimeter

Milligram

Microgram

Millilitre

Ultra-violet

Visible

Infrared

Fourier Transform Infrared

Rotations Per Minute

Centipoise

Millivolt

Minutes

Hour

Transferosomal formulation

Transferosomal Gel formulation

Degree Celsius

Standard Deviation

Poly Ethylene Glycol

Scanning Electron Microscopy

Gastro Intestinal

Drug Release

CONCLUSION

This transdermal delivery of etoricoxib can bypass the

first pass metabolism and overcome the problems

associated with oral administration. The Drug - Excipient

compatibility results indicated that there was no

interaction between the drug and excipients. The

formulation F - 3 consisting of soya lecithin (85mg) and

span 80 (15mg) was optimized on basis of evaluation

parameters such as Entrapment Efficiency & In-vitro

drug release. The SEM images revealed that the vesicles

have a spherical shape and the size was in the nanometer

(nm) range. This size enables easy permeability of

vesicles through the skin. Optimized transferosomal gel

showed the Ex-vivo drug release of 84.26 % in 12hrs.

From the stability studies, it was found that there is no

significant change in the drug content. From the results

of the present study it can be concluded that

transferosomal gel sustains the drug release. Hence,

Transferosomes proves to be a promising delivery of

etoricoxib.

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