Formulation and Evaluation of Flurbiprofen Loaded Emulgel.

1. Presented by,
Mr. Sumeet P. Sonaje
M. Pharm (IV Sem.)
(Pharmaceutics)
Seat No. 1035
Guided by,
Mr. S. B. Gondkar
M. Pharm
(Pharmaceutics)
R.G. SAPKAL COLLEGE OF PHARMACY, ANJANERI, NASHIK
FORMULATION AND EVALUATION OF
FLURBIPROFEN LOADED EMULGEL

2. Contents
2
Need and Objectives
Summary and Conclusion
Literature Survey
Plan of Work
References
Future Outcomes
Marketed Products
Drug and Polymer Profile
Material and Equipment's
Preformulation and Formulation
Evaluation
Introduction

3. Why Transdermal Drug Delivery System ?
Transdermal drug delivery system is recognized as one of the most important
and reliable alternative to the oral and parenteral drug delivery system. Skin act
as reservoir system for drug.
TDDS includes the patches, gels, microemulsion, nanoparticles, liposomes,
niosomes, emulgel etc.
The NSAID’s, antifungals, antivirals drugs can be given through the TDDS.
Advantages of TDDS:
 Avoidance of first pass metabolism.
 Convenient and easy to apply.
 Avoidance of gastro-intestinal incompatibility.
 A relatively large area of application in comparison with buccal or nasal
cavity.
3

4. Introduction
Anatomy and Physiology of Skin:
4
Fig. : Structure of skin

5. 5
Human skin consist of three layers,
(1) Epidermis
Epidermis has five layers,
 Stratum corneum (horny layer)
 Stratum lucidum
 Stratum granulosum (granular cell layer)
 Stratum spinosum (spinous or prickle cell layer)
 Stratum basale (basale or germinativum cell layer)
(2) Dermis
(3) Hypodermis

6. Skin as Permeability Barrier
An important element in transdermal drug delivery system is the skin itself. It act as permeability
barrier against the transdermal absorption of various chemicals and biologicals agents. Like all other
epithelium systems of the body, the prime function of the skin is to keep water and other vital
substances in the skin and restricted the entry of foreign substances.
The permeability barrier of skin is constituted of three major layers that include:
 Stratum corneum ( 10 µm thick)
 Viable epidermis (100 µm thick)
 Papillary epidermis (100-200 µm thick)
Components of stratum corneum:
6
Components % Gross biochemical
compositions
Cell membranes 5 Lipids and nonfibrous proteins
Cell contents 85 Lipids ( 20%)
α – proteins (50%)
β – proteins (20%)
Nonfibrous proteins (10%)
Intercellular materials 10 Lipids and nonfibrous proteins

7. Mechanism of Percutaneous Absorption
Fig. : Mechanism of percutaneous absorption
7

8. Methods of Drug Penetration
 Chemical enhancement :-
Eg. Sulfoxides, Azone, Fatty acids,
Alcohols.
 Physical enhancement :-
- Ultrasound
- Iontophoresis
8
Fig. :- Schematic presentation of emulgel penetration
through skin

9. Physiological factors
 - Skin thickness
 - Lipid content
 - Density of hair follicles
 - Density of sweat glands
 - Skin pH
 - Blood flow
 - Hydration of skin
 - Inflammation of skin
Physicochemical factors
 - Partition coefficient
 - Molecular wt. ( < 400 dalton )
 - Degree of ionization
 - Effect of vehicles.
9 Factors Affecting Topical Absorption

10. Rheumatoid Arthritis
 Inflammation is an important nonspecific defence reaction to tissue injury caused
by pathogen or wound.
 The five cardinal signs of inflammation are redness, swelling, heat, pain, loss of
function.
 Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation
of the joints.
10

11. Emulgel
Definition:-
When gel and emulsion are used in combined form the dosage form are referred as
‘Emulgel’.
11

12.  The use of transparent gel has expanded both in cosmetics and in pharmaceutical
preparations. Gels are relatively newer class of dosage form created by entrapment of
large amount of aqueous liquids in a network of colloidal solid particle.
 In spite of many advantages of gels a major limitation is in the delivery of
hydrophobic drugs. So to overcome this limitation emulgels are prepared and with
their use the hydrophobic drugs are delivered.
 The presence of gelling agent in the water phase converts a classical emulsion into an
emulgel.
 Both o/w and w/o emulsions are used as vehicles to deliver various drugs to the skin.
 Emulsion itself is a controlled release system where entrapped drug particles in
internal phase pass through the external phase to the skin and slowly get absorbed.
Internal phases act as reservoir of drug and slowly release drug in a controlled way
through the external phase to the skin. Gel forms cross linked network where it
captures small drug particles and provides its release in a controlled manner.
12

13.  Due to its bioadhesive property it prolongs the contact period of medication
over the skin. Since emulgel possesses the property of both emulsions and gel,
it acts as dual control release system.
 Depending on the type of emulsion used to prepare emulgel, they are referred
as macroemulgel, microemulgel, nanoemulgel.
 Various categories of drug such as NSAIDS, antifungal, antibacterial, antiviral
etc. are used for preparation of emulgel.
13

14. Ideal Properties of Emulgel
being greaseless,
easily spreadable,
easily removable,
emollient,
non-staining,
longer shelf life, bio-friendly,
pleasing appearance.
14

15. Advantages15
Hydrophobic drugs can be easily incorporated into gels using emulsions.
Better stability.
Better drug loading capacity.
No intensive sonication.
Controlled release, medication can be terminated when needed.
Avoidance of first pass metabolism.

16. Disadvantages16
Drug of large particle size not easy to absorb through the skin.
Skin irritation or allergic reaction on contact dermatitis.
Occurrence of bubble during formation of emulgel.

17. Rational
 Because, many widely used topical agents like ointments, creams,
lotions have many disadvantages. They are sticky in nature causing
uneasiness to the patient when applied, have lesser spreading coefficient
so applied by rubbing and they also exhibit the problem of stability.
17

18. Need for Study
 Flurbiprofen belongs to the class II of the BCS system of drugs and oral
administration of Flurbiprofen is associated with severe gastric irritation
therefore to overcome this problem emulsion based gel form was formulated.
 Flurbiprofen is hydrophobic in nature therefore it reports a problem of
solubility in water this can be solved by adding drug in oil phase of emulsion.
 Emulgel overcomes the problems associated with emulsion (i.e. stability) and
gel (i.e. syneresis) alone.
 Emulgel are alternative to the solid dispersion gel.
18

19. 19
To overcome the limitation of conventional oral and parenteral route of
drug administration.
To improve the patient compliance..
To formulate Emulgel of Flurbiprofen for topical drug delivery system.
To eliminate the drawbacks of emulsion and gel
by formulating in an Emulgel.
In-vitro drug release permeation studies through the suitable membrane
models using modified Franz-Diffusion cell.
To predict stability of the formulation by
conducting stability studies.
Objectives

20. Plan of Work20
1. Literature survey
2. Selection of drug and polymer
3. Procurement of drug and polymer
4. Preformulation study of drug
 Organoleptic property
 Melting point
 Solubility
 UV spectroscopy
 FTIR
 Drug – Polymer compatibility study
5. Formulation development of emulgel
6. Optimization of emulgel

21. 7. Evaluation of Emulgel
 Appearance
 pH
 Viscosity
 Drug content
 Spreadability
 Swelling Index
 In- vitro diffusion study
 Ex- vivo diffusion study
 Skin irritation study
 Ex -vivo bioadhesive strength
 Stability study
8. Data Analysis
9. Result and Conclusion
21

22. Literature Survey
Sr .
No.
Author Topic Polymer
1 Khullar R et. al.
(Saudi Pharmaceutical
Journal, 20, 2012)
Formulation and evaluation Mefenamic
acid emulgel for topical drug delivery.
Carbopol 940 , liquid parrafin
,tween 20 ,span 20 , PG ,ethanol
, methyl paraben , ethyl paraben,
clove oil , mentha oil, water etc.
2 Jain A et. al. (Der
Pharmacia Sinica, 1(3),
2010)
Development and characterization of
Ketoconazole emulgel for topical drug
delivery.
Carbopol 940 carbopol 934 ,
liquid parrafin ,tween 20 ,span
20 , PG ,ethanol , methyl
paraben , propyl paraben,
Glutaraldehyde, water etc.
3 Bachav Y et. al.
(International Journal of
Pharmaceutics, 365,
2009)
Microemulsion based vaginal gel of
Clotrimazole : formulation , in -vitro
evaluation and stability studies.
Carbopol, cremophor ,
chlorocresol ,water, tween 20 ,
span 20, PG etc.
22

23. Sr.
no.
Author Topic Polymer
4 Patil P et. al.
(Indian Drugs,
49(11), 2012)
Evaluation of wound healing activity
of Silver Sulfadiazine emulgel (1%)
in the rat burn wound model and its
skin irritation study.
Poloxamer 407, Lecithin, Sepineo
P600, Tween 80, Span 60, calcium
hydroxide, methyl paraben, propyl
paraben, coconut oil, lavender oil etc.
5 Patil S et. al.
(WJPPS, 3(4),
2014)
Novel cosmeceutical herbal emulgel
for skin care.
Cucurbita pepo oil, carbopol 940,
liquid paraffin, tween 20, span 20,
propylene glycol, methyl paraben,
clove oil, water etc.
6 Varma VN et. al.
(Saudi
pharmaceutical
Journal, 2014)
Calcipotriol delivery into the skin as
emulgel for effective permeation.
Carbopol, Kollicream 3C, Kolliphor
CS, liquid paraffin, propylene glycol,
PEG, IPA, strong ammonia,
fragrance, water etc.
23 Literature Survey

24. Sr.
no.
Author Topic Polymer
7 Sushil Raut et. al.
(RJPT, 5(1), 2012)
Comparative evaluation of
Zidovudine loaded hydrogel and
emulgel.
AZT, Tween 20, Span 20, Carbopol 940,
Methyl paraben, Propyl paraben, Liquid
paraffin, PG, Ethanol, TEA etc.
8 Singla Vikas et. al.
(International
Pharmaceutica
Sciencia, 2(3), 2012)
Development and evaluation of
topical emulgel of Lornoxicam
using different polymer bases.
Lornoxicam, Carbopol 940 and 934,
HPMC K4M, Tween 20, Span 20,
Liquid paraffin, PG, Methyl paraben,
Propyl paraben, Mentha oil, Water etc.
9 Mahant Sheefali
et. al. (Scientia
Pharmaceutica, 80,
2012)
Formulation and characterization of
Benzoyl Peroxide gellified
emulsion.
Carbopol 940, Benzoyl Peroxide,
Almond oil, Wheat germ oil, Sesame
oil, Jojoba oil, tween 20, Span 60, PG,
MP, PP, Water, Disodim EDTA, BHT
etc.
24
Literature Survey

25. Sr.
no.
Author Topic Polymer
10 Ganapathi Jeevaprakash
et. al. (IJPIR, 2(1),
2012)
Efficient formulation and
evaluation of Flurbiprofen
transdemal gel compared with
marketed gel by using water
soluble polyacrylamide polymer.
Polyacrylamide polymer, Isopropyl
alcohol, Sodium metabisulphite,
Glycerine, Propylene glycol,
Cocodiethanolamide etc.
11 Charoo Naseem Ahmad
et. al. (Colloids and
Surfaces B:
Biointerfaces, 65, 2008)
Improvement in bioavailability
of transdermally applied
Flurbiprofen using tulsi and
turpentine oil.
Methocel, Tulsi oil, Turpentine oil,
PG, IPA etc.
12 Rajesh S. et. al.
(International Journal of
Pharmaceutics, 356,
2008)
Permeation of Flurbiprofen
polymeric films through human
cadaver skin.
PVP, PVA, PEG 400, DMSO,
Dimethyl formamide etc.
25 Literature Survey

26. Sr.
no.
Author Topic Polymer
13 Chandra Dinesh
et.al. (AJPR, 3(6),
2013)
Formulation and evaluation of
proniosomal gel of Flurbiprofen.
Lecithin, Brij 93, Cholesterol etc.
14 Idrees MA et.al.
(DARU, 19(6),
2011)
Enhance transdermal delivery of
Flurbiprofen via microemulsion:
effects of different types of
surfactants and cosurfactants.
Oleic acid, Tween 80, PG, Ethanol,
IPA, IPM, Tween 20 etc.
15 Perioli Luana et.al.
(International
Journal of
Pharmaceutics,
356, 2008)
Rheological and functional
characterization of new
antiinflammatory delivery
systems designed for buccal
administration.
Pemulen 1621, Compritol 888 ATO
etc.
26
Literature Survey

27. Drug Profile
Sr. No. Properties Flurbiprofen
1 IUPAC Name (2RS)-2-(2-Fluorobiphenyl-4-yl)propanoic acid
2 Molecular Formula C15H13FO2
3 Molecular Weight 244.3
4 Description White or almost white, crystalline powder.
5 Solubility Practically insoluble in water, freely soluble in
ethanol and in methylene chloride. Dissolves in
aqueous NaOH and Carbonates.
6 Melting Point 114°C - 117°C
27

28. Sr. No. Properties Flurbiprofen
7 Dose 150 – 200 mg daily in divided doses.
8 UV 247 nm
9 CAS Number 5104-49-4
10 Category Anti-inflammatory, Analgesics, Antipyretic.
11 Half life 4 – 5 hours
12 Log P 4.2
13 Mode of Action Flurbiprofen is a non-selective COX inhibitor and
inhibits the activity of both COX-1 and COX-2.
14 BCS Class II ( Low solubility, High permeability )
15 Storage condition Preserve in tight container.
28

29. Pharmacokinetics
Flurbiprofen
Absorbtion Flurbiprofen is rapidly and almost completely absorbed
following oral administration.
Bioavailability 96 %
Distribution 0.12 L/kg
Protein binding 99 %
Metabolism Hepatic (Hydroxylation, Conjugation)
Excretion Renal
29

30. Marketed Products of Flurbiprofen30
Brand Name Dosage Form Mfg. Company
Brugel Gel Abbott
Cadiflur Eye Drops Cadila (Le Sante)
Flurofen Tablet Sanofi Aventis
Froben SR Capsule Abbott
Relyonflurbi Transdermal Patch Indocoar

31. Justification for Selection of Drug
 Nature of Flurbiprofen is hydrophobic.
 Flurbiprofen possess analgesic-anti-inflammatory effect in addition to antipyretic
action.
 Suitable for formulation of emulgel.
 Molecular mass of Flurbiprofen is less than 600 Daltons i.e. 244.3
 Solubility of Flurbiprofen in water is less and oil solubility is high.
 Log P of Flurbiprofen is 4.2
 Half life is 3-4 hrs. so required frequent dosing i.e. patient incompliance.
31

32. Excipients Profile
(1) Transcutol – P
Definition Highly purified diethylene glycol monoethyl ether.
CAS 111-90-0
Synonyms Carbitol, Solvolsol, Dioxitol, Transcutol.
Chemical formula C6H14O3
IUPAC Name 2-(2-ethoxyethoxy) ethanol
Molecular weight 134.17356
Appearance Colourless limpid liquid.
32

33. Odour Faint
Description Transcutol–P is a hydrophilic/lipophilic high purity solubilizer,
with broad API compatibility and a broad spectrum of use in
creams and lotions to aqueous gels.
Use  Dermal drug delivery: Solvent, oil.
 Dermal drug delivery: Solubilizer for actives.
 Dermal drug delivery: Absorption enhancer for cutaneous
application.
Storage Store the product in its original packaging sealed tightly,
protected from light and moisture. Special temperature storage
conditions are not required.
33

34. (2) Sepineo P 600
INCI Name Acrylamide/ Sodium Aryloyldimethyl taurate copolymer and
Isohexadecane and Polysorbate 80.
Physical State Liquid (Emulsion)
Colour Opaque, White, Yellow tint
Odour Faint odour
pH 5 to 7 (Conc. (% w/w) 2%)
Solubility Dispersible in cold water
Viscosity Dynamic (1500 to 5000 cp) at 250C
Description Thickening power
Emulsifying power
Stabilizing power
34

35. Sepineo P 600
Benefits
 Ready to use fluid form.
 Very easy to handle at room temperature
 Thickens over a large pH range
 Stabilizes and thickens O/W emulsions
 Gel-Cream texture
 Good skin tolerance
Sepineo P 600 Doses  Gel application = thickening power up to 5 %
 Cream application = stabilizing power 0.5 % to 2 %
 Gel- Cream application = emulsifying power up to 5 %
35

36. Material and Equipment's
36
Sr.
No.
Instruments Manufacturer
1 UV- visible Spectrophotometer Jasco- V630, Japan.
2 FTIR Spectrometer Cary 630, Agilent Technologies,
USA.
3 Brookfield Viscometer DV II+ pro, Brookfield Engineering
Laboratories, Inc, USA.
4 Digital pH Meter Systronics, Ahmadabad.
5 Magnetic Stirrer DBK Instruments, Mumbai.
6 Franz Diffusion Cell Lab. made assembly
7 Melting point apparatus Analab Scientific Instruments Pvt.
Ltd. India.

37. Sr. No. Instruments Manufacturer
8 Assembly for Bioadhesive strength
measurement
Lab. made assembly
9 Sonicator PCI Analytics 1.5 L
10 Centrifuge Eltek
11 Spreadability apparatus Lab. made assembly
12 Electronic analytical balance AY220 Shimadzu corporation
Kyoco, Japan.
37

38. Experimental Work
38
Organoleptic Properties
Properties Observation Reported Standards
Appearance Crystalline powder Crystalline powder
Color White White or almost white
Melting Point Determination
Sr. No. Observation Reported Standards
1 114-119 0C 114-117 0C
Preformulation Study of Drug

39. Solvents Solubility
Distilled Water Practically insoluble
Dichloromethane soluble
0.1 N NaOH soluble
Methanol soluble
0.1 N HCL soluble
Acetone soluble
Ethanol soluble
Phosphate buffer pH 6.8 soluble
Phosphate buffer pH 7.0 soluble
Phosphate buffer pH 7.4 soluble
39
Solubility Determination in Solvents

40. Oils Solubility (mg/ml)
Castor oil 72.91
Oleic acid 78.71
Propylene glycol 148.36
Transcutol - P 341.33
40 Solubility Determination in Oils
78.71 72.91
148.36
341.33
0
50
100
150
200
250
300
350
400
Oleic acid Castor oil Propylene glycol Transcutol - P
Solubility(mg/ml)
Oils
Solubility

41. 41
Determination of λ max
Media λ max observed
Methanol 247 nm
Sr. no. Conc. (ppm) Abs.
1 2 0.1858
2 4 0.3595
3 6 0.4966
4 8 0.6566
5 10 0.7979
y = 0.0819x - 0.0428
R² = 0.999
0
0.2
0.4
0.6
0.8
1
0 2 4 6 8 10 12
Absorbances
Concentration (ppm)
CC of Flurbiprofen in Methanol
UV Analysis

42. UV Analysis
42
Determination of λ max
Media λ max observed
0.1 N NaOH 247 nm
Sr. no. Conc. (ppm) Abs.
1 2 0.2514
2 4 0.4101
3 6 0.5497
4 8 0.6825
5 10 0.8463
y = 0.0731x + 0.1093
R² = 0.9988
0
0.2
0.4
0.6
0.8
1
0 2 4 6 8 10 12
Absorbances
Concentration
CC of Flurbiprofen in 0.1 N NaOH

43. UV Analysis
43
Determination of λ max
Media λ max observed
PBS pH 7.0 247 nm
Sr. no. Conc. (ppm) Abs.
1 2 0.1929
2 4 0.341
3 6 0.5129
4 8 0.691
5 10 0.8798
y = 0.0862x + 0.0064
R² = 0.9981
0
0.2
0.4
0.6
0.8
1
0 5 10 15
Absorbances
Concentration (ppm)
CC of Flurbiprofen in PBS pH 7
Series1
Linear (Series1)

44. IR Analysis44
40060080010001200140016001800200024002800320036004000
1/cm
25
30
35
40
45
50
55
%T
3070.78
3010.98
2928.04
2717.79
2623.28
2536.48
2337.80
1898.02
1838.22
1695.49
1622.19
1572.04
1465.95
1415.80
1315.50
1265.35
1217.12
1136.11
1072.46
960.58
866.07
839.06
765.77
688.61
623.03
580.59
453.29
f lurbiprof en
Sr.
No
.
Functional Groups Observed
Ranges (cm-1)
Standard
Ranges (cm-1)
1. Aromatic C-H
stretch
3070.78 3150-3050
2. C-X Fluoride (F) 1217.12 1400-1000
3. C=O Carboxylic
acid
1695.49 1725-1700
4. CH3 Bend of Alkane 1465.95 1450 and 1375
5. C=C Alkene 1622.19 1680-1600

45. 45
Sr.
No
.
Functional
Group
Pure
Drug
Physical
mixture
Standard
Value
1 Aromatic C-H
stretch
Yes Yes 3150-3050
2 C-X Fluoride (F) Yes Yes 1400-1000
3 C=O Carboxylic
acid
Yes Yes 1725-1700
4 CH3 Bend of
Alkane
Yes Yes 1450 and
1375
5 C=C Alkane Yes Yes 1680-1600
Drug- Excipients Compatibility Study

46. Formulation
Ingrediants Property
Flurbiprofen Active Pharmaceutical Ingredient
Transcutol – P As Oil and Penetration Enhancer
Sepineo P600 As Gelling agent, Emulsifying agent and
Stabilising agent
Propylene Glycol Cosolvent, Humectant
Methyl Paraben Antimicrobial Preservative
Propyl Paraben Antimicrobial Preservative
BHT Antioxidant
Distilled Water Vehicle
46

47. Method of Preparation
 Step 1: Preparation of gel using gelling agent and water by constant stirring.
 Step 2: Preparation of emulsion.
 Step 3: Incorporation of emulsion into gel.
Flow diagram showing emulgel preparation,
47

48. 48
Emulsion
Preparation
of Gel

49. 32 Factorial Design
Independent Variables
Levels
Low Medium High
X1 = Transcutol – P 1.5 2.5 5.0
X2 = Sepineo P 600 0.25 0.5 1.0
Dependent Variables Goal
Y1 = % CDR 100 %
Y2 = Viscosity _
49

50. Composition of 32 Factorial Design for Emulsion
50

51. Preparation of Gel
Ingrediants ( % w/w ) Quantity
Sepineo P 600 0.35
Distilled Water q.s. 50
51
Fig. : Emulgel formulations

52. Evaluation of Formulations52
Batch code Colour Phase separation Homogeneity
F1 White No Homogenous
F2 White No Homogenous
F3 White No Homogenous
F4 White No Homogenous
F5 White No Homogenous
F6 White No Homogenous
F7 White No Homogenous
F8 White No Homogenous
F9 White No Homogenous
Physical Parameters

53. Viscosity (cp)
Batch Spindle RPM Viscosity
(cp)
F1 LV 4 20 503.9
LV 4 40 422.9
LV 4 60 399.2
LV 4 100 387.5
F2 LV 4 20 2519
LV 4 40 1815
LV 4 60 1490
LV 4 100 1200
53
Batch Spindle RPM Viscosity
(cp)
F3 LV 4 20 6599
LV 4 40 4274
LV 4 60 3469
LV 4 100 2543
F4 LV 4 20 1500
LV 4 40 975
LV 4 60 659.9
LV 4 100 407

54. Viscosity (cp)
Batch Spindle RPM Viscosity
(cp)
F5 LV 4 20 7558
LV 4 40 4274
LV 4 60 3529
LV 4 100 2471
F6 LV 4 20 12357
LV 4 40 7453
LV 4 60 5649
LV 4 100 3875
54
Batch Spindle RPM Viscosity
(cp)
F7 LV 4 20 3749
LV 4 40 2624
LV 4 60 2050
LV 4 100 1530
F8 LV 4 20 6209
LV 4 40 3809
LV 4 60 2589
LV 4 100 1686

55. Viscosity (cp)
Batch Spindle RPM Viscosity (cp)
F9 LV 4 20 13715
LV 4 40 8293
LV 4 60 6359
LV 4 100 5359
Marketed LV 4 20 18530
gel LV 4 40 11814
LV 4 60 8750
LV 4 100 4990
55
0
5000
10000
15000
20000
0 20 40 60 80 100 120
Viscosity(cps)
RPM
F1 F2 F3 F4
F5 F6 F7 F8
F9 Marketed Gel

56. pH Determination
Sr. No. Formulation Observed pH ( ± S.D.)
1 F1 6.67 ± 0.085
2 F2 6.53 ± 0.170
3 F3 6.81 ± 0.066
4 F4 6.33 ± 0.052
5 F5 6.55 ± 0.1014
6 F6 6.80 ± 0.05
7 F7 6.74 ± 0.070
8 F8 6.45 ± 0.096
9 F9 6.92 ± 0.0503
10 Marketed Product 6.3 ± 0.085
56

57. Spreadability
Batch Code Spreadability ( gm.cm/sec)
F1 14.33 ± 0.050
F2 16.65 ± 0.315
F3 18.78 ± 0.130
F4 15.20 ± 0.075
F5 17.86 ± 0.2968
F6 32.26 ± 0.1101
F7 22.14 ± 0.1662
F8 31.01 ± 0.1205
F9 38.49 ± 0.1417
Marketed Product
57 It is calculated by the following formula,
S = M × L / T
Where, M = wt. tied to upper slide
L = length of glass slides
T = time taken to separate the slides

58. Swelling Index
Formulation code Time (Min.) Swelling Index (%)
At 30 min. 113.33
F1 At 60 min. 119.33
At 90 min. 121.56
At 30 min. 88.88
F2 At 60 min. 100.0
At 90 min. 111.0
At 30 min. 77.77
F3 At 60 min. 86.66
At 90 min. 102.22
At 30 min. 91.11
F4 At 60 min. 100
At 90 min. 120
58

59. Swelling Index
Formulation code Time (Min.) Swelling Index (%)
At 30 min. 106.66
F5 At 60 min. 113.33
At 90 min. 113.33
At 30 min. 80
F6 At 60 min. 88.88
At 90 min. 95.55
At 30 min. 108.88
F7 At 60 min. 113.33
At 90 min. 115.55
At 30 min. 88.88
F8 At 60 min. 97.77
At 90 min. 113.33
59

60. Swelling Index
Formulation code Time (Min.) Swelling Index (%)
At 30 min. 73.33
F9 At 60 min. 80
At 90 min. 86.66
At 30 min. 70.88
Marketed Gel At 60 min. 82.15
At 90 min. 87.22
60

61. Drug Content
Batch Code
Drug Content ( % )
in methanol at 247 λmax.
F1 99.87 ± 0.1167
F2 99.20 ± 0.1026
F3 98.12 ± 0.1609
F4 100.24 ± 0.1250
F5 98.45 ± 0.1001
F6 98.35 ± 0.0655
F7 100.77 ± 0.1026
F8 98.33 ± 0.0953
F9 99.55 ± 0.07
Marketed Product 100.4 ± 0.1532
61

62. In–vitro Drug Release
Time
(hrs)
F1(%) F2(%) F3(%) F4(%) F5(%) F6(%) F7(%) F8(%) F9(%) Marketed
Product
0 min 0 0 0 0 0 0 0 0 0 0
0.25 6.10±0.0025 1.58±0.0015 4.88±0.020 3.49±0.015 2.06±0.05 2.069±0.015 4.63±0.0034 1.58±0.019 1.56±0.0025 6.32±0.05
0.5 17.59±0.0025 3.55±0.002 7.33±0.026 10.72±0.020 10.70±0.020 10.70±0.020 10.41±0.0024 4.84±0.022 2.70±0.0020 20.07±0.019
0.75 30.44±0.0020 8.57±0.055 10.86±0.025 28.94±0.015 28.93±0.015 20.92±0.020 20.57±0.052 6.14±0.025 5.65±0.0025 41.31±0.020
1 51.46±0.0025 27.86±0.0020 27.95±0.057 35.97±0.010 34.34±0.020 26.13±0.020 26.15±0.019 10.82±0.031 10.53±0.026 59.63±0.0047
2 68.13±0.057 40.79±0.025 40.88±0.020 45.82±0.030 41.25±0.020 35.69±0.020 34.31±0.026 20.24±0.036 16.86±0.034 78.63±0.072
3 81.01±0.007 57.94±0.020 58.03±0.020 63.77±0.015 55.95±0.015 38.78±0.020 58.07±0.025 36.66±0.025 28.04±0.035 90.72±0.042
4 94.35±0.003 67.03±0.0025 65.71±0.020 66.09±0.079 60.43±0.015 52.52±0.021 70.37±0.035 41.94±0.028 36.80±0.015 95.53±0.022
5 96.89±0.03 77.46±0.013 70.18±0.010 77.79±0.020 64.77±0.020 54.70±0.029 81.48±0.072 62.25±0.022 46.15±0.042 96.31±0.024
6 98.88±0.0025 84.29±0.0030 74.66±0.0047 95.43±0.015 69.75±0.025 56.14±0.036 90.02±0.032 78.44±0.062 52.38±0.028 98.06±0.035
7 99.76±0.0025 94.44±0.025 80.06±0.025 97.54±0.020 75.00±0.020 59.78±0.032 96.84±0.018 85.65±0.032 57.54±0.068 99.65±0.020
8 99.80±0.0020 98.07±0.015 84.92±0.0020 99.49±0.015 77.92±0.015 62.13±0.018 97.79±0.032 92.86±0.052 57.58±0.020 99.71±0.015
62

63. In-vitro Drug Release Profile of the Formulations63
0
20
40
60
80
100
120
0 1 2 3 4 5 6 7 8 9
%CDR
Time (Hrs.)
In-vitro drug release
%CDR f1
%CDR f2
%CDR f3
%CDR f4
%CDR f5
%CDR f6
%CDR f7
%CDR f8
%CDR f9
% CDR Mktd. Gel

64. Data Analysis : Layout of Design
Formulation
Factor 1
A: Transcutol- P
(%)
Factor 2
B: Sepineo P 600
(%)
Response1:
%Drug Release
(%)
Response2:
Viscosity (cp)
F1 1.5 0.25 99.80 587.9
F2 1.5 0.5 98.07 1692
F3 1.5 1.0 84.92 3755
F4 2.5 0.25 99.49 755.8
F5 2.5 0.5 77.92 3839
F6 2.5 1.0 62.13 6371
F7 5.0 0.25 97.79 2363
F8 5.0 0.5 92.86 3143
F9 5.0 1.0 57.58 7222
64

65. (1) % CDR
Final Equation in Terms of Actual Factors :
% drug release = +117.03692 – 2.43564 * Transcutol-P – 41.33524 * Sepineo P600
ANOVA for % drug release
65
Source Sum of
Square
df Mean
square
F value P- value
Prob > F
S. D. R2
Model 1610.71 2 805.35 9.01 0.0156 9.45 0.7503 Signific
ant
A –
Transcutol P
115.68 1 115.35 1.29 0.2986
B- Sepineo
P600
1495.03 1 1495.03 16.73 0.0064

66. Counter Plot (% CDR)
66
Perturbation Plot

67. 3-D Response Surface Plot (% CDR)
67

68. (2) Viscosity
Final Equation in Terms of Actual Factors
Viscosity = -1890.21238 + 560.03846 * Transcutol-P + 6022.78095 * Sepineo P600
ANOVA for Viscosity
ANOVA for Viscosity:
68
Source Sum of
Squares
df Mean
Square
F Value p- Value
Prob> F
S. D. R2
Model 3.786E+007 2 1.893E+007 23.80 0.0014 891.78 0.8881 Signific
ant
A –Transcutol-
P
6.116E+006 1 6.116E+006 7.69 0.0323
B- Sepineo
P600
3.174E+007 1 3.174E+007 39.91 0.0007

69. Countor Plot (viscosity)
69
Perturbation Plot

70. 3-D Response Surface Plot (viscosity)
70

71. Solution for Optimized Batch
Sr. No. Conc. of Transcutol-
P (%w/w)
Conc. of Sepineo
P 600 (%w/w)
%CDR viscosity
(cps)
Desirability
1. 2.5 0.25 99.49 755.8 1
71
Composition of Optimized Batch
Sr. No. Ingrediants Quantity (%)
1 Flurbiprofen 1
2 Transcutol – P 2.5
3 Sepineo P 600 0.25
4 Propylene glycol 2.5
5 Methyl paraben 0.015
6 Propyl paraben 0.005
7 BHT 0.05
8 Distilled water q.s. 50

72. Ex-vivo Drug Release
Time
(hrs.)
Optimized Batch Marketed Product
0 0 0
0.25 1.58 ± 0.2650 5.30 ± 0.3611
0.5 9.20 ± 0.1053 11.02 ± 0.2032
0.75 24.18 ± 0.2122 19.89 ± 0.1056
1 38.56 ± 0.7856 25.61 ± 0.4122
2 44.23 ± 0.4306 32.60 ± 0.2581
3 53.06 ± 0.5029 43.09 ± 0.1326
4 58.98 ± 0.3092 57.96 ± 0.5941
5 61.31 ± 0.2389 62.91 ± 0.1152
6 65.20 ± 0.3579 67.13 ± 0.096
7 69.55 ± 0.1966 75.03 ± 0.1020
8 71.59 ± 0.1128 81.33 ± 0.08599
72

73. Ex-vivo Drug Release Profile73
0
10
20
30
40
50
60
70
80
90
0 1 2 3 4 5 6 7 8 9
%drugrelease
Time (hrs.)
Optimized Batch Marketed Product

74. Drug Release Kinetics of Formulation
Formulation
Code
Zero order First order Higuchi
Korsmeyer
Peppas
R2 R2 R2 R2 n
F4 0.9415 0.9866 0.9487 0.9514 0.8591
74
Parameters for Korsmeyer – Peppas Equation
n 0.8591
k 0.5648
It was performed by using the PCP Disso V3. Software

75.  This study approved by IAEC no. 06 under the guidelines of CPCSEA.
 The skin irritation study was performed on female albino wister rats weight between 145 to 185 gm.
 The study was carried out by using 9 rats.
Control Standard Marketed Formulation
75
Skin Irritation Study
Groups Parameters No. of rats
Group I Control -
Group II Standard (Formalin) 3
Group III Test 3
Group IV Marketed formulation 3

76. Skin Irritation Study (continue)
76
Marking of
Rats
Hours Erythema Edema
1 (Head) 48 0 0
2 (Middle) 48 0 0
3 (Tail) 48 0 0
M
H
T
Results after 48 hrs.

77. Bioadhesive Strength Determination
Bioadhesion strength is performed to evaluate the ability of emulgel
formulation to adhere onto skin for longer duration of time where it can release
medicament for prolonged period and thus provide sustained release type of
drug release.
77
Formulation
code
Bioadhesion strength
(Newton))
F4 0.044 N

78. Stability Study
From the stability studies of the optimized batch, it was found that the formulation did not
show any change in physical appearance, clarity and other parameters were also found to be
within limits.
78
Sr. No. Observations
Stability testing interval days
Before stability
testing
3 month 6 month
1 Appearance White cream like White cream like White cream like
2 pH 6.72 6.49 6.55
3 Drug content 99.49 99.95 98.56
4
Viscosity
At 20 rpm
At 40 rpm
At 60 rpm
At 100 rpm
1520 cp
960 cp
721 cp
466 cp
1535 cp
986 cp
768 cp
490 cp
1565 cp
1012 cp
787 cp
531 cp

79. Marketed Comparison
Brand Name Drug Manufacturer Quantity ( gm )
BRUGEL Flurbiprofen Abbott 30 gm
79

80. Marketed Products
Product Name Drug Manufacturer
 Voltaren emulgel™ Diclofenac diethyl
ammonium
Novartis Pharma
 Miconaz-H-emulgel™ Miconazole nitrate,
Hydrocortisone
Medical Union
Pharmaceuticals
 Diclomax Emulgel™ Diclofenac diethyl amine Torrent Pharma
80

81. Conclusion
Following conclusions can be came forward after performing present study:
1) Amongst all formulations, emulgel prepared with Transcutol-P (2.5%), Sepineo P600 (0.25%) was
better with respect to overall product qualities.
2) Emulsion system provides solubalization of hydrophobic drug, thus imparts in enhancing availability of drug in
the formulation.
3) When emulgel was compared with the marketed gel, drug release from the emulgel was found to be increased
and prolonged. Additionally its permeation and appearance was found to be more acceptable.
4) The formulation followed Korsmeyer-Peppas kinetic model of drug release.
5) In-vitro diffusion studies showed good percent drug release for more than 8 hrs.
6) The formulated emulgel showed no irritation after performing skin irritation study using wistar albino female
rat is model.
Thus, results of the current study clearly indicate that Flurbiprofen emulgel can be a good alternative to the
conventional dosage form. However, further clinical studies are needed to assess the utility of this system. By
considering all above points it was concluded that, the objective of the present research study were achieved
successfully.
81

82. Future Outcomes
 The future trends in innovations of drug delivery systems will continue to bring together different
technological disciplines and formulation aspects to create novel technologies.
 The futuristic disciplines for emulgel may be,
 Use of natural polymers as gelling agents for emulgel preparation.
 Accessing the stability study for natural polymers.
 Emulgels can be used in case of drugs which are having short half-life.
 The use of nanosponges, microemulsion and nanoemulsion in emulgel for enhancing the
performance of emulgels.
 Selection of packaging material for emulgels.
82

83. Papers Communicated
Review Paper
1) Gellified emulsion: A new born formulation for topical delivery of hydrophobic
drugs. WJPPS, Vol. 3, Issue 1, 2013, 233-251.
2) A review on Atrigel by using Biodegradable Polymers: A Depot and Innovative
system for Controlled and Sustained release drug delivery system. Inventi Rapid:
NDDS, Vol. 2014, Issue 4, 2014, 1-9.
83

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88. 88