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Presentation
A Study on Development of Liposomal
Drug Delivery of Miconazole Nitrate
Presented by:
Mahbub Alam
ID:201331222005
Department of Pharmacy Bangladesh University
Liposome
A liposome is a tiny bubble (vesicle), made out of the same
material as a cell membrane.
Liposomes were first described by British hematologist Dr. Alec.
LIPOSOME derives from two Greek words: lipo("fat") and
soma ("body"); it is so named because its composition is
primarily of phospholipid.
Structure of liposome
Advantages
 Non-toxic.
Biodegradable.
Lowers systemic toxicity.
Targeted delivery.
Protection of sensitive drug molecules.
Improved pharmacokinetic effects.
Disadvantages
Leakage of encapsulated drug during storage.
Short half-life.
Batch to batch variation.
Difficult in large scale manufacturing and sterilization.
Once administered, liposomes can not be removed.
Drug Profile: Miconazole
The antifungal agent used topically often in its nitrate
form, to treat candidiasis and other fungal infections.
Structure:
Miconazole Nitrate
Mechanism and indication of
Miconazole Nitrate
Miconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary
to convert lanosterol to ergosterol. As ergosterol is an essential component of the
fungal cell membrane, inhibition of its synthesis results in increased cellular
permeability causing leakage of cellular contents. Miconazole may also inhibit
endogenous respiration, interact with membrane phospholipids, inhibit the
transformation of yeasts to mycelial forms.
Indication
Treatment of skin Nail infection Vaginal infection
Methods of Formulation
Ether injection method
Thin film hydration technique
Sonication Method
Reverse Phase Evaporation Technique (REV)
Thin film hydration technique
Preparation steps:
Drug + lecithin + cholesterol + solvent
↓
Remove organic solvent at room temperature
↓
Thin layer formed on the walls of flask
↓
Film is rehydrated to form multilamellar liposome
Materials used for Formulation
Name of the Ingredient Purpose
Miconazole Nitrate API
Lecithin Vesicle Formation
Cholesterol Vesicle Formation
Chloroform & Methanol Solvent
Formulations
Formulation
Code
Drug (mg) Lecithin
(mg)
Cholesterol
(mg)
Ratio Chlorof
orm
(ml)
Methanol
(ml)
Total
(mg)
F1 100 577 323 1:5.7:3.2 37 23 1000
F2 100 635 265 1:6.3:2.6 31 29 1000
F3 100 700 200 1:7:2 25 35 1000
F4 100 760 140 1:7.6:1.4 18 42 1000
F5 100 815 085 1:8.1:0.9 13 47 1000
Optimization of Formulation of
Liposomes
 Physical appearance testing can be the most subjective tests performed
on drug substances. The color can be an indication of purity.
 The formulation F3, F4 and F5 are selected by physical appearance
determination.
 The formulation F3, F4, F5 are selected by determination of grittiness.
 The formulation F3, F4, F5 are selected by determination of uniformity
of content of active ingredient.
Photographic Visualization Of Miconazole
Nitrate Liposome
Entrapment Efficacy
Formulation No Drug : Lecithin :
Cholesterol
Ratio
Percentage
Entrapped Drug
F3 1:7:2 89.74%
F4 1:7.6:1.4 94.41%
F5 1:8.1:0.85 92.92%
Results and Discussion
Standard calibration curve data
Concentration (mcg/ml) Absorbance (nm)
2 0.004
4 0.0015
6 0.019
8 0.024
10 0.030
Standard calibration curve
y = 0.0031x + 1E-04
R² = 0.966
0
0.005
0.01
0.015
0.02
0.025
0.03
0.035
0 2 4 6 8 10 12
Series1 Linear (Series1)
First order release kinetics of miconazole
nitrate
0
20
40
60
80
100
120
0 10 20 30 40 50 60 70
Cumulative%drugrelease
Time (min)
Standard F3 F4 F5
Higuchi release kinetics of
miconazole nitrate
0
20
40
60
80
100
120
0 1 2 3 4 5 6 7 8 9
Cumulative%drugrelease
Square Route of Time (min)
Standard F3 F4 F5
Korsmeyer release kinetics of
miconazole nitrate
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 1.8 2
LogCumulative%drugrelease
Log Time (min)
Standard F3 F4 F5
Stability analysis of F3, F4, F5 formulation
Properties 1st month 3rd month 6th month
F3 F4 F5 F3 F4 F5
Entrapment
Efficiency
89.74% 94.41% 92.92% 79.55% 93.23% 90.50% Under observation
Grittiness No No No No No No Under observation
Visual aspect Moderate Good Good
Modera
te
Good Good Under observation
Conclusion
From the present study, it can be concluded that
Drug release rate and extent were increased.
 To be used efficiently for enhancing absorption.
Ease of application.
Thank You

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advanced drug delivery system of miconazole nitrate

  • 2. A Study on Development of Liposomal Drug Delivery of Miconazole Nitrate Presented by: Mahbub Alam ID:201331222005 Department of Pharmacy Bangladesh University
  • 3. Liposome A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes were first described by British hematologist Dr. Alec. LIPOSOME derives from two Greek words: lipo("fat") and soma ("body"); it is so named because its composition is primarily of phospholipid.
  • 5.
  • 6. Advantages  Non-toxic. Biodegradable. Lowers systemic toxicity. Targeted delivery. Protection of sensitive drug molecules. Improved pharmacokinetic effects.
  • 7. Disadvantages Leakage of encapsulated drug during storage. Short half-life. Batch to batch variation. Difficult in large scale manufacturing and sterilization. Once administered, liposomes can not be removed.
  • 8. Drug Profile: Miconazole The antifungal agent used topically often in its nitrate form, to treat candidiasis and other fungal infections. Structure: Miconazole Nitrate
  • 9. Mechanism and indication of Miconazole Nitrate Miconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Miconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms. Indication Treatment of skin Nail infection Vaginal infection
  • 10. Methods of Formulation Ether injection method Thin film hydration technique Sonication Method Reverse Phase Evaporation Technique (REV)
  • 11. Thin film hydration technique Preparation steps: Drug + lecithin + cholesterol + solvent ↓ Remove organic solvent at room temperature ↓ Thin layer formed on the walls of flask ↓ Film is rehydrated to form multilamellar liposome
  • 12. Materials used for Formulation Name of the Ingredient Purpose Miconazole Nitrate API Lecithin Vesicle Formation Cholesterol Vesicle Formation Chloroform & Methanol Solvent
  • 13. Formulations Formulation Code Drug (mg) Lecithin (mg) Cholesterol (mg) Ratio Chlorof orm (ml) Methanol (ml) Total (mg) F1 100 577 323 1:5.7:3.2 37 23 1000 F2 100 635 265 1:6.3:2.6 31 29 1000 F3 100 700 200 1:7:2 25 35 1000 F4 100 760 140 1:7.6:1.4 18 42 1000 F5 100 815 085 1:8.1:0.9 13 47 1000
  • 14. Optimization of Formulation of Liposomes  Physical appearance testing can be the most subjective tests performed on drug substances. The color can be an indication of purity.  The formulation F3, F4 and F5 are selected by physical appearance determination.  The formulation F3, F4, F5 are selected by determination of grittiness.  The formulation F3, F4, F5 are selected by determination of uniformity of content of active ingredient.
  • 15. Photographic Visualization Of Miconazole Nitrate Liposome
  • 16. Entrapment Efficacy Formulation No Drug : Lecithin : Cholesterol Ratio Percentage Entrapped Drug F3 1:7:2 89.74% F4 1:7.6:1.4 94.41% F5 1:8.1:0.85 92.92%
  • 17. Results and Discussion Standard calibration curve data Concentration (mcg/ml) Absorbance (nm) 2 0.004 4 0.0015 6 0.019 8 0.024 10 0.030
  • 18. Standard calibration curve y = 0.0031x + 1E-04 R² = 0.966 0 0.005 0.01 0.015 0.02 0.025 0.03 0.035 0 2 4 6 8 10 12 Series1 Linear (Series1)
  • 19. First order release kinetics of miconazole nitrate 0 20 40 60 80 100 120 0 10 20 30 40 50 60 70 Cumulative%drugrelease Time (min) Standard F3 F4 F5
  • 20. Higuchi release kinetics of miconazole nitrate 0 20 40 60 80 100 120 0 1 2 3 4 5 6 7 8 9 Cumulative%drugrelease Square Route of Time (min) Standard F3 F4 F5
  • 21. Korsmeyer release kinetics of miconazole nitrate 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 1.8 2 LogCumulative%drugrelease Log Time (min) Standard F3 F4 F5
  • 22. Stability analysis of F3, F4, F5 formulation Properties 1st month 3rd month 6th month F3 F4 F5 F3 F4 F5 Entrapment Efficiency 89.74% 94.41% 92.92% 79.55% 93.23% 90.50% Under observation Grittiness No No No No No No Under observation Visual aspect Moderate Good Good Modera te Good Good Under observation
  • 23. Conclusion From the present study, it can be concluded that Drug release rate and extent were increased.  To be used efficiently for enhancing absorption. Ease of application.