etroxicab ethosome for transdermal delivery

1. SUBMITTED BY
Mr. Tanmay panigrahy
M. Pharm (Pharmaceutics)
OPTIMIZATION, FORMULATION &
EVALUATION OF ETORICOXIB LOADED
ETHOSOME FOR TRANSDERMAL DELIVERY
UNDER THE GUIDANCE OF
Dr. CH. NIRANJAN PATRA
M. Pharm, Ph.D., FIC
HOD PHARMACEUTICS

2. CONTENTS
• AIM & OBJECTIVE
• STANDARD CURVE
• FORMULATION TABLE
• METHOD OF PREPARATION
• EVALUATION METHOD
• RESULTS TABLES & GRAPHS
• CONCLUSIONS
• REFERENCES

3. AIM & OBJECTIVE
• Etoricoxib is a COX-2 inhibitor.
• Its low aqueous solubility, poor dissolution; delays absorption rate and onset of action via transdermal
delivery. Although, oral route is commonly used for inflammation; transdermal delivery of drug has
gathered more attention for systematic therapy of skin ailment.
• Ethosomes have (i) enhanced permeability, (ii) suitability for a wide range of API, (iii) non-invasive nature
and (iv) enhanced cellular uptake
• Hence the objective is to sustain the release etoricoxib for a prolonged period of time.

4. STANDARD CURVE
Absorption spectrum of
Etoricoxib (10mg/ml) in
PBS pH-7.4

5. FORMULATION TABLE
Formulation table for Ethosomal dispersion

6. METHOD OF PREPARATION
Cold method:(Organic & Aq. phase at 300C)—Non-uniform
liposomes. Storage (4-80C).

7. CONT…..
Freeze drying: 10ml of dispersion+ 500mg lactose. Deep
freeze at -180C for 24hr. Lyophilized at -500C, P=0.002mbar
until a free flowing powder form comes.

8. GEL PRPARATION
• Lyophilized optimized ethosomal formulation (E10) was formulated into gel.
Gels of different formulations A) F1, B) F3, C) F2

9. EVALUATION METHODS
Evaluation of Ethosomal dispersion
• EE
• PDI & Particle size
• Zeta potential
• In vitro Diffusion study
Evaluation of Ethosomal gel
• Physical appearance
• pH
• Viscosity
• In vitro Diffusion study
In-vitro diffusion A) Ethosome, B) Gel
Brookfield viscometer

10. RESULTS TABLES & GRAPHS
50.00 100.00 150.00 200.00
Temp [C]
-1.00
0.00
1.00
mW
DSC
128.96
x10
0
C
Onset
135.61
x10
0
C
Endset
124.11
x10
0
C
Start
138.41
x10
0
C
End
131.74
x10
0
C
Peak
-26.33
x10
0
mJ
-13.16
x10
0
J/g
Heat
File Name: ET ORICOXIB + CHOLEST EROL.tad
Detector: DSC-60
Acquisition Date
21/04/05
Acquisition T ime
13:04:00(+0530)
Sample Name:ET ORICOXIB + CHOLEST EROL
Sample W eight:
2.000[mg]
Annotation:
Thermal Analysis Result-CIR-RIPS
50.00 100.00 150.00 200.00
Temp [C]
-2.00
-1.00
0.00
1.00
mW
DSC
123.69
x10
0
C
Onset
134.38
x10
0
C
Endset
122.80
x10
0
C
Start
135.95
x10
0
C
End
129.60
x10
0
C
Peak
-18.75
x10
0
mJ
-9.38
x10
0
J/g
Heat
File Name: ET ORICOXIB +CARBOPOL 934.tad
Detector: DSC-60
Acquisition Date
21/04/05
Acquisition T ime
12:29:53(+0530)
Sample Name:ET ORICOXIB +CARBOPOL 934
Sample Weight:
2.000[mg]
Annotation:
Thermal Analysis Result-CIR-RIPS
50.00 100.00 150.00 200.00
Temp [C]
-1.00
0.00
1.00
mW
DSC
134.16
x10
0
C
Onset
153.10
x10
0
C
Endset
129.61
x10
0
C
Start
154.02
x10
0
C
End
147.56
x10
0
C
Peak
-23.30
x10
0
mJ
-11.65
x10
0
J/g
Heat
File Name: ET ORICOXIB FORM E10.tad
Detector: DSC-60
Acquisition Date
21/04/05
Acquisition T ime
14:17:13(+0530)
Sample Name:ET ORICOXIB FORM E10
Sample Weight:
2.000[mg]
Annotation:
Thermal Analysis Result-CIR-RIPS

11. DSC SUMMARY
Summary of DSC data:

12. FTIR

13. FTIR SUMMARY

14. EE,SIZE, PDI, ZETA POTENTIAL
Table was optimized by Box-Behnken method of CCD by DX-11 software

15. OPTIMIZATION
Design-Expert® Software
Factor Coding: Actual
EE
Design points above predicted value
Design points below predicted value
63.46
37.4
X1 = A: SPC
X2 = B: CHL
Actual Factor
C: ETH = 30.00
1.00
1.50
2.00
2.50
3.00
1.00
2.00
3.00
4.00
5.00
35
40
45
50
55
60
65
E
E
A: SPC
B: CHL
Design-Expert® Software
Factor Coding: Actual
PS
Design points above predicted value
Design points below predicted value
220
135
X1 = A: SPC
X2 = B: CHL
Actual Factor
C: ETH = 30.00
1.00
1.50
2.00
2.50
3.00
1.00
2.00
3.00
4.00
5.00
140
160
180
200
220
P
S
A: SPC
B: CHL
3D RESPONSE SURFACE PLOT: Influence of ethanol, Lipoid S100, Cholesterol on A) EE,
B) Particle Size

16. CONT….
Design-Expert® Software
Factor Coding: Actual
PDI
Design points above predicted value
Design points below predicted value
0.34
0.11
X1 = A: SPC
X2 = B: CHL
Actual Factor
C: ETH = 30.00
1.00
1.50
2.00
2.50
3.00
1.00
2.00
3.00
4.00
5.00
0.1
0.15
0.2
0.25
0.3
0.35
P
D
I
A: SPC
B: CHL
3D RESPONSE SURFACE PLOT: Influence of ethanol, Lipoid S100, Cholesterol on PDI

17. GEL: APPEARANCE, TEXTURE, VISCOSITY,
HOMOGENITY, PH
pH measurement

18. IN-VITRO DIFFUSION OF ETHOSOMAL DISPERSION
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30
CUMULATIVE
%
DRUG
RELEASE
TIME (in hr)
DIFFUSION STUDY DATA
E6
E10
E12
y = -0.0166x + 1.9633
R² = 0.9804
y = -0.0481x + 2.0257
R² = 0.9825
y = -0.0272x + 1.977
R² = 0.9895
0
0.5
1
1.5
2
2.5
0 5 10 15 20 25 30
CUMULATIVE
%
DRUG
REMAINED
TIME (in hr)
1st ORDER DATA
E6
E10
E12
y = 12.795x - 1.4694
R² = 0.9954
y = 20.996x - 8.4666
R² = 0.9511
y = 16.727x - 4.2044
R² = 0.9806
-20
0
20
40
60
80
100
0 1 2 3 4 5 6
CUMULATIVE
%
DRUG
RELEASE
√T (in hr)
HIGUCHI PLOT
E6
E10
E12
y = 0.5356x + 1.051
R² = 0.9889
y = 0.7576x + 0.9926
R² = 0.9822
y = 0.6084x + 1.0697
R² = 0.9872
0
0.5
1
1.5
2
2.5
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
Log
Cumulative
%
drug
release
Log T
KORSMEYER-PEPPAS PLOT
log E6
log E10
log E12

19. IN-VITRO DIFFUSION OF ETHOSOMAL GEL
•
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30
Cumulative
%
drug
release
Time (in hr)
DIFFUSION STUDY DATA
E10
F1
F2
F3
y = -0.0481x + 2.0257
R² = 0.9825
y = -0.0439x + 2.0409
R² = 0.9809
y = -0.0319x + 2.0313
R² = 0.9905
y = -0.0173x + 1.9938
R² = 0.989
0
0.5
1
1.5
2
2.5
0 5 10 15 20 25 30
log
%
drug
remainED
Time (in hr)
1st ORDER PLOT Log E10
Log F1
Log F2
Log F3
y = 23.088x - 15.069
R² = 0.9585
y = 23.798x - 21.902
R² = 0.9565
y = 20.849x - 20.881
R² = 0.9874
y = 15.418x - 13.661
R² = 0.9927
-20
0
20
40
60
80
100
120
0 1 2 3 4 5 6
CUMULATIVE
%
DRUG
RELEASE
√Time (in hr)
HIGUCHI PLOT E10
F1
F2
F3
y = 0.7523x + 0.9941
R² = 0.9807
y = 0.918x + 0.7704
R² = 0.975
y = 0.9675x + 0.6477
R² = 0.9898
y = 0.9771x + 0.5436
R² = 0.9727
0
0.5
1
1.5
2
2.5
0 0.5 1 1.5
Log
cumulative
%
drug
release
Log t (in hr)
KORSMEYER-PEPPAS PLOT Log E10
Log F1
Log F2
Log F3

20. SUMMARY OF DIFFUSION DATA
• Initial: Higher release due to the presence of unentrapped drug. At higher
concentration of lipoid S100, the initial burst release ↓ due to more EE.
-SR: Due to drug solubilize slowly through bilayer & indicates major amount of
drug was entrapped within ethanolic core.
-In vitro release kinetic study: E10 followed 1st order. E6 & E12 followed zero
order.
-Higuchi equation: Good value of 3 means diffusion was the prime
mechanism of drug release. All the above 3 formulations (E6, E10 & E12)
showed Non-Fickian diffusion controlled release mechanism.
Gel:-
• Drug release study suggests further SR from gels due to the presence of
Carbopol 934. Release kinetic study for gel suggests zero order release
kinetics. The drug mechanism is Non-Fickian diffusion controlled release
mechanism. (0.89< x<1)

21. CONCLUSIONS
• FTIR: Drug-excipient compatible.
• Dm of optimized ethosome: 207nm
• PDI: homogeneity in particle size distribution.
• EE & Release rate: Affected by cholesterol & ethanol %.
• z-potential: Higher, indicates the stability.
• In-vitro release studies for a period of 24 h: (62.08%, 92.3% & 77.82%) Drug has been released in a
sustained manner by following Non–Fickian approach.
• Gel showed SR like ethosomal dispersion.
It was concluded that developed ethosomal gel of Etoricoxib holds promise for prolonged availability of
drug in the systemic circulation and can be used for better management of inflammatory conditions.

22. REFERENCES
1. Siddhodhan SB, Sameer K, Meghana SK, Chaudhari PD (2013), A study on ethosome as mode for
transdermal delivery of an repaglinide, Drug Delivery, 20:1 (40-46), Available from:
www.tandfonline.com/loi/idrd20
2. Padmanabha RA, Samed N, Kumar A, Madhusudhan A, Jin Chul Kim (2020), Enhancement and extended
release of the antihypertensive drug carvedilol using optimized ethosomal gel via transdermal route.
Available from: https://www.researchgate.net/publication/347294830
3. Sony V. Soba, Babu M, Rajitha P(2020), Ethosomal gel formulation of a-phellandrene for the transdermal
delivery in gout, Adv Pharm Bull, 11:1 (137-149), Available from: https:// apb.tbzmed.ac.ir
4. Chourasia MK, Kang L, Chan SY (2011), Nanosized ethosomes bearing ketoprofen for improved
transdermal delivery, Pharma Sciences, 1 (60–67), Available from: www.elsevier. com/locate/rinphs
5. Rakesh R, Pooja M, Alpana R (2018), Nanosized ethanol based malleable liposomes of cytarabine to
accentuate transdermal delivery: formulation, optimization, in vitro skin permeation and in vivo
bioavailability; Artificial Cells, Nanomedicine and Biotechnology, 46:2 (951-963), DOI:
10.1080/21691401.2018.1473414, Available from: https://www.tandf online.com/toc/ianb20/current

23. THANK
YOU