Formulation and evaluation of Tretinoin emulgel – an advanced approach for enhanced topical drug delivery This document discusses the formulation and evaluation of an emulgel containing the drug Tretinoin for topical delivery. Tretinoin emulgel was developed to improve the topical delivery and skin permeation of Tretinoin compared to conventional formulations. Various emulgel formulations with different concentrations of ingredients were prepared and evaluated based on parameters like physical appearance, pH, viscosity, drug content and diffusion studies. The results showed that formulations with optimal concentrations of surfactants and permeation enhancers demonstrated better properties for topical delivery of Tretinoin.

1. Formulation and evaluation of Tretinoin emulgel – an
advanced approach for enhanced topical drug delivery
ROLL NUMBER – 21, 22, 23, 24, 25
SEM - VIII
GUIDE NAME – Dr. Ankita J Patel
COLLEGE NAME – Smt. B. N. B. Swaminarayan Pharmacy College
PROJECT WORK
SUBJECT CODE: BP813PP
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2. CONTENT
• INTRODUCTION
• OBJECTIVES
• EMULGEL
• RATIONALE OF EMULGEL AS TOPICAL DRUG DELIVERY
• IDEAL PROPERTIES OF EMULGEL
• ADVANTAGES
• DISADVANTAGES
• EMULGEL PREPARATION
• DRUG PROFILE
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3. • PHARMACOKINETICS
• PREFORMULATION STUDY OF DRUG
• EXCIPIENT PROFILE
• PREPARATION OF FORMULATION
• FORMULA OF TRETINOIN EMULGEL
• EVALUATION PARAMETERS
• MARKETED FORMULATION
• CONCLUSION
• REFERENCES
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4. 4/6/2022 Dhruvi Machhi 4

5. ACNE
Everybody, who is suffering from Acne, is searching for the best and easy way to
follow the treatment
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6. OBJECTIVES
To develop
novel topical
drug delivery
system.
To compare
the various
activity of
drug with
conventional
dosage form.
To prevent
the first
pass
metabolis
m.
For sustain
release
medication.
To
eliminate
the
drawbacks
of
emulsion
and gel by
formulatin
g a Emulgel
Provides
targeted and
localized action
compare to
conventional
dosage form
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7. INTRODUCTION
EMULSION + GEL = EMUGEL
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8. EMULGEL
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9. RATIONALE OF EMULGEL ASTOPICAL DRUG
DELIVERY
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10. ADVANTAGES OF USING EMULGEL ASTOPICAL
DRUG DELIVERY SYSTEM
Avoidance of first pass metabolism.
Avoidance of gastrointestinal incompatibility.
More selective to a specific site.
Improve patient compliance.
Suitability for self-medication.
Providing utilization of drug with short biological half-life and narrow therapeutic
window.
Ability to easily terminate medication when needed.
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11. DISADVANTAGES
Skin irritation on contact dermatitis.
The possibility of allergenic reactions.
The poor permeability of some drug through the skin.
Drug of large particle size not easy to absorb through the skin.
The occurrence of the bubble during formation of emulgel.
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12. IDEAL PROPERTIES OF EMUGEL
Being
greaseless
Easily
spreadable
Easily
removable Emollient
Non-staining
Longer shelf
life Bio-friendly Pleasing
appearance.
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13. EMUGEL PREPRATION
Oil phase Aqueous phase
Emulsification
O/W or W/O Emulsion
Incorporation in to gel based
Emulgel
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14. PLAN OF WORK
1. Literature survey
2. Selection of drug and polymer
3. Procurement of drug and polymer
4. Preformulation study of drug
5. Formulation development of emulgel
6. Optimization of emulgel
7. Evaluation of emulgel
8. Data analysis
9. Result and conclusion
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15. LITERATURE SURVEY
SR. NO AUTHOR TOPIC
1. Zignani M, Tabatabay C, Gurny R Topical semi-solid drug delivery: kinetics and
tolerance of ophthalmic hydrogels.
2. Shokri J, Azarmi S, Fasihi Z Effect of various penetration enhancers on
percutaneous absorption of piroxicam from emulgel
3. Foldvari M: Non-invasive administration of drugs through the
skin: challenges in delivery system design
4 Kullar R, Saini S, Steth N, and Rana AC Emulgel a surrogate approach for topical used
hydrophobic drugs.
5 Single V, Saini S, Joshi B, Rana AC Emulgel: a new platform for topical drug delivery.
6. Zhang X, Zhao R, Qian W. Preparation of an emulgel for the treatment of
aphthous ulcer on the basis of Carbomers
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16. DRUG PROFILE
Sr.no Properties Tretinoin
1 IUPAC Name 3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic
acid
2 Molecular formula C20H28O2
3 Molecular weight 300.4
4 Description yellow to light-orange crystalline powder
5 Solubility Practically insoluble in water, soluble in methylene chloride, slightly
soluble in ethanol (96 per cent)
6 Melting point 180-181 °C
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17. Sr.No Properties Tretinoin
7 Dose 250 mg daily in divided doses.
8 UV 348.6 nm
10 Category Anti-acne, Antineoplastic and immunomodulation agents
11 Half Life 0.5-2 hours
12 Log P 0.6
13 Mode of Action ability to modify the abnormal follicular formation that comes from
excessive keratinization of epithelial cells.
Tretinoin promotes cornified cell detachment and enhances
shedding
14 BCS Class Class II (Low solubility , High permeability )
15 Storage Condition Keep container tightly closed in a dry and well-ventilated place.
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18. PHARMACOKINETICS
Tretinoin
Absorption 1-31 % (Topical )
Bioavailability 96%
Distribution 500 ng/mL.
Protein binding 95%
Metabolism Hepatic (hydroxylation , conjugation)
Excretion 60% renal & 30% feaces
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19. PREFORMULATION STUDIES OF DRUG
Calibration Curve of Tretinoin in Phosphate Buffer pH 7.4 at λmax 348.6 nm:
• Tretinoin exhibits maximum absorbance at 346.8 nm in phosphate buffer pH-7.4 and obeyed Beer’s law in the
range of 10-80 μg/ml.
Sr.
No.
Concentration(μg/ml) Absorbance mean at 348.6nm
(mean ± SD) (n=3)
1 0 0
2 10 0.103
3 20 0.220
4 30 0.337
5 40 0.462
6 50 0.586
7 60 0.645
8 70 0.732
9 80 0.822
y = 0.0105x + 0.0158
R² = 0.9927
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0 20 40 60 80 100
Absorbance
Concentration (μg/ml)
Absorbance Mean at 348.6 nm
Absorbance
Linear (Absorbance)
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20. IDENTIFICATION OF DRUG
• 1. APPEARANCE – Yellow crystalline powder
• Reported standard – yellow to light orange crystalline powder
• 2. COLOUR – Yellow
• Reported Standard – Yellow to light orange
• 3. MELTING POINT – 180 °C
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21. SOLUBILITY OF TRETENOIN IN DIFFERENT VEHICLES
Excipient Solubility (mg/ml) (Mean ± S.D.) (n = 3)
Liquid paraffin 8.02 ± 0.02
Span 20 2.49 ± 0.03
Tween 20 4.27 ± 0.12
Propylene Glycol 7.93 ± 0.06
Ethanol 2.7 ± 0.02
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22. EXCIPIENT PROFILE
EXCIPIENT USES
Carbopol 940 Gelling agent
Liquid paraffin Oil phase
Tween 20 Emulsifier
Span 20 Emulsifier
Propylene glycol Oil phase
ethanol Aqueous phase
Methyl paraben Preservative
Propyl paraben Preservative
Mentha oil Permeation enhancers
Water Aqueous vehicle
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23. PREPARATION OF FORMULATION
Step 1: Preparation of Gel:
The required quantity of Carbopol was accurately weighed on electronic balance and to
specific quantity of purified water and stirrer continuously on Magnetic Stirrer at moderate
speed.
Step 2: Preparation of Emulsion:
Oil phase was prepared by dissolving certain amount of Span 20 in Liquid Paraffin.
The aqueous phase was prepared by dissolving amount of Tween 20 in purified water.
Tretinoin is accurately weighed and dissolved in Propylene Glycol and ethanol, while Methyl
Paraben and Ethyl Paraben were dissolved in aqueous phase.
Both Oily phase and aqueous phase were separately heated to 70-80 C. Then oily phase was
added to the aqueous phase with continuous stirring until cooled to temperature.
Step 3: Tretinoin Emulgel:
The Tretinoin Emulgel was prepared by dispersing the emulsion into gel in 1:1 ratio with
gentle stirring until homogenous emulgel was obtained.
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24. Step 1 – Preparation of gel
Carbopol 940
Formation of gel
Step 2 - Preparation of emulsion
Oil phase –
addition of span
in liquid
paraffin
Aqueous phase –
tween in water
and add
preservative
Dissolved drug in
Propylene glycol and
ethanol
Formation of emulsion
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25. EXPERIMENTALWORK
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26. FORMULA OF TRETINOIN EMULGEL
INGREDIENT% F1 F2 F3 F4 F5 F6
Tretinoin 0.2 0.2 0.2 0.2 0.2 0.2
Carbapol 2 2 2 2 2 2
Liquid Paraffin 8 8 8 8 8 8
Tween 20 0.5 1 1.5 1 1 1
Span 20 1 1 1 1 1 1
Propylene Glycol 3 3 3 3 3 3
Methyl Paraben 0.03 0.03 0.03 0.03 0.03 0.03
Mentha Oil 0 0 0 2 3 4
Water Q.S. Q.S. Q.S. Q.S. Q.S. Q.S.
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27. EVALUTION PARAMETERS
Physical Appearance
Spreading Coefficient
Extrudability Study
Globule Size & Its Distribution
Rheological Study
Swelling Index
Drug diffusion study
Drug Content Determination
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28. PHYSICAL EXAMINATION
• The prepared emulsions were were inspected visually for for their colour ,
homogeneity ,consistency and pH.
Sr. no Formulation
code
Colour Phase
seperation
Grittiness Homogenicity Consistency
1 F1 YellowishWhite None - Good Good
2 F2 YellowishWhite None - Good Good
3 F3 YellowishWhite None - Good Good
4 F4 YellowishWhite None - Good Good
5 F5 YellowishWhite None - Excellent Good
6 F6 Yellowish white None - Excellent Good
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29. MEASUREMENT OF PH
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30. RHEOLOGICAL STUDY
The tests were performed by using Brook – field Viscometer. Results are given in Table
highest viscosity was found in formulation F6. It may be due to high level of penetration
enhancer. F5 Batch shows Accepted viscosity due to optimum concentration of Surfactant
and penetration enhancer.
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31. DIFFUSION STUDY
Franz diffusion cell was used to determine the release profile of drug from topical Emulgel. The cell
consisted of two chambers, the donor and the receptor compartment between which a diffusion
membrane (egg membrane) was mounted. The donor compartment, with inner diameter 24 mm,
was open i.e. exposed to the atmosphere at one end and the receptor compartment was such that it
permitted sampling. The diffusion medium used was phosphate buffer solution pH 6.8 (PBS).
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32. EXTRUDABILITY STUDY
The Extrudability study shows Good Extrudability in Batch Number F4, F5, and F6 due to
optimum concentration of surfactant and penetration enhancer. Where, Batch No. F1, F2, and
F3 show very high Extrudability due to low Concentration of surfactant.
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33. SPREADING CO-EFFICIENT
Spreadability is determined by apparatus, which is suitably modified in the laboratory and
used for the study. It consists of a two glass slide, above glass slide provided by a pulley at
one end. By this method, spreadability is measured on the basis of ‘Slip’ and ‘Drag’
characteristics of Emulgel. A ground glass slide is fixed. An excess of emulgel (about 2gm)
under study is placed on this ground slide.
The emulgel is then sandwiched between this slide and another glass slide having the
dimension of fixed ground slide and provided with the hook. A 1kg weight is placed on the
top of the two slides for 5 minutes to expel air and to provide a uniform film of the emulgel
between the slides.
S = M * L
T
Where, S = Spreadability,
M = Weight tied to upper slide,
L = Length of glass slide;
T = Time taken to separate the slides completely from each other.
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34. GLOBULE SIZE DETERMINATION
effect of various concentration of surfactant on Globule size. F2- batch shows good globule
size due to use of optimum amount of surfactant
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35. MARKETED FORMULATION OFTRETINOIN
Brand Name Dosage form Mfg. company
CA ATRA – IO Soft gelatin capsule JENOME BIOPHARM
Renova Cream Ortho Pharmaceutical
Atranza Capsules Melon Global care
acnon gel Kavya pharma
Acretin Cream Jamjoom Pharma
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36. CONCLUSION
• It had been compare by various marketed formulation and following parameters
has been concluded.
• Topical drug deliver system will be extensively to impart better patient compliance.
• Emulgel is helpful in enhancing spreadabillity, adhesion, viscosity and extrusion.
• Its become solution for loading hydrophobic drugs in water soluble gel bases for
the long term stability
• Topical Tretinoin emulgel was prepared by using liquid paraffin as oil phase and
Carbopol 940 showed acceptable physical properties, pH, drug content, viscosity
and % drug diffusion.
• When emulgel was compared with the marketed gel, drug released from the
emulgel was found to be increased and prolonged. Additionally its permeation and
appearance was found to be more acceptable.
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37. FUTURE OUTCOMES
• The future trends in innovation 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 Nano sponges, micro emulsion, and Nano emulsion in emulgel for
enhancing the performance of emulgels
• Selection of packaging material for emulgels.
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38. REFERENCE
• HP Gollnick, CC Zouboulis, Akamatsu H, Kurokawa I, Schulte A," Pathogenesis and Pathogenesis related treatment of acne” Journal of Dermatol
1991.
• Zi P , Yang X, Kuang H, Yang Y, Yu L: Effect of HPbeta CD on solubility and transdermal delivery of capsaicin through rat skin. Int. J. Pharm. 2008; 358:
151–158.
• Elsayed MM, Abdallah OY, Naggar VF, and Khalafallah NM: Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int. J.
Pharm.2007; 332: 1–16.
• RutterN. Drug absorption through the skin: a mixed blessing. Arch Dis Child 1987; 62:220-1.
• Jacob SW, Francone CA. Structure and function of man. WB Saunders Co. Philadelphia; 1970. p. 55-60.
• Chandira RM, Pradeep, Pasupathi A, Bhowmik D, Chiranjib, Jayakar B, Tripathi K , “Sampath Kumar KP. Design, Development and Formulation of
Antiacne Dermatological Gel”.Journal of Chemical and Pharmaceutical Research 2010, 2(1): 401-414.
• Sanjay Jain, B. D., Padsalg, A., Patel, K., &Mokale, V. (2007). Formulation, development and evaluation of Fluconazole gel in various polymer bases,
ASI. J. Pharm., 1, 63-68.
• Asian Journal of Pharmaceutical and Clinical Research, anti-acne gel of Tretinoin, Vol. 10 Issue 11 2017.
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