Penetration enhancers are used to increase the penetration of the drug into the body through the skin and mucus also. These enhancers having different category having special effect on the mucus and skin as well. In this presentation enlighten those points of penetration enhancers which are related to the mucoadhesive drug delivery system. this presentation covers types of penetration enhancers, their mechanism of action, route of penetration and their examples.
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Penetration enhancer in MDDS
1. PENETRATION ENHNACER IN
MUCOADHESIVE DRUG DELIVERY SYSTEM
SINHGAD TECHNICAL EDUCATION SOCIETY’S
SINHGAD INSTITUTE OF PHARMACY, NARHE
1
Aragade Prity S.
( M. Pharm Sem -II )
Dr. C.R. Kokare
( HOD Pharmaceutics Dept.)
2. 2Contents
► Introduction
► Penetration enhancer
► Mode of permeation
► Ideal characteristics
► Factors affecting on permeation
► Mechanisms of action of permeation
► Classification
► Case study
► References
3. Introduction 3
Mucoadhesive drug delivery systems
► Utilized the property of bioadhesion of certain
polymers
► Adhesive on hydration
► Targeting a drug to particular region of the body
4. Advantages
Easy of administration
Significant reduction in dose can be achieved, there by
reducing dose, dose dependent side effects.
Drug release for prolonged period of time.
Maximized absorption rate due to close contact with the
absorbing membrane.
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5. Limitations
Drugs which irritate the mucosa cannot be
administered by this route
Only those drugs which are absorbed by passive
diffusion can be administered by this route
Drugs which are unstable at mucosal pH cannot be
administered by this route
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6. What is mucus ?
Mucus is a translucent and viscid secretion
Secreted by the globet cells lining the epithelia or by
special exoesive glands with mucus cell acini
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7. The mucoadhesive drug delivery system
includes
Buccal drug delivery system
Sublingual drug delivery system
Vaginal drug delivery system
Rectal drug delivery system
Nasal drug delivery system
Ocular drug delivery system
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8. Composition of Mucus Layer
Water -95%
Glycoprotein and lipids – 0.5-3.00%
Mineral salts – 1%
Free proteins – 0.5-1.0%
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10. Functions of mucus
Protective : Particularly from its hydrophobicity
Barrier : In tissue absorption of the drugs and influence
the bioavailability.
Adhesion : Mucus has strong cohesion properties
Lubrication : Digestion
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11. Penetration enhancer
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Substances that facilitate the permeation through
mucosa are referred as permeation enhancers .
What is penetration enhancer ?
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12. Mode of permeation
Mode of
permeation
Passive
diffusion
Carrier
mediated
Endocytosis
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16. Ideal characteristics
Safe and non toxic, non irritating and non allergenic
Pharmacologically and chemically inert
They should have no pharmacological activity within
the body
The penetration enhancers should be compatible with
both excipients and drugs
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17. Factors affecting on permeation
Physicochemical properties of the drug
Site of administration
Nature of the vehicle
Other excipients
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18. Mechanisms of action of permeation
► Changing mucus rheology
By reducing the viscosity of the mucus.
► Increasing the fluidity of lipid bilayer membrane
Disturb the intracellular lipid packing by interaction with
either lipid or protein components
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19. Cont…..
Acting on the components at tight junctions
Act on desmosomes, a foremost component at the tight junctions
by this means enhances drug absorption.
Increasing the thermodynamic activity of drugs
Some enhancers increase the solubility of drug there by alters
the partition coefficient
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21. 1.Surfactants
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Anionic
E.g. Sodium lauryl sulfate, Sodium dodecyl sulfate
Nonionic
E.g. Tween80, Sodium glycocholate
Cationic
E.g. Cetylpyridinium chloride, Chitosan, Trimethyl
chitosan
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22. Mechanism of action
► Perturbation of intercellular lipids
► Ionic interaction with negative charge on the mucosal
surface
► Surfactant act by protein denaturation or by swelling of
tissue and extraction of lipids component.
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23. 2. Fatty acids and derivatives
E.g. Oleic acid, Caprylic acid, Lauric acid, Linoleic acid,
Acylcholines, Acylcarnitine, Sodium caprate,
Mechanism of action
► Fatty acid are act by paracellular and transcellular
route
► Increase fluidity of phospholipids domains
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25. 3. Bile salts and derivatives
E.g. Sodium deoxycholate, Sodium taurocholate, Sodium
glycocholate
Mechanism of action
Bile salts are widely used for buccal route.
Act by modifying the cell membrane integrity in such
a way that the intracellular domain is open up
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26. At a high concentration increase absorption of drug
through intestinal membrane disruption caused by the
solubilization of phospholipids.
At low concentration absorption of drug increase by
formation of reverse micelles and calcium
complexation without membrane disruption.
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27. 4. Sulfoxide
E.g. Dimethyl sulfoxide (DMSO), Declmethyl sulfoxide
Mechanism of action
► Increase fluidity of lipid bilayer and disturb protein
component from mucus
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28. 5. Chelating agents
E.g. EDTA , Citric acid, Salicylates
Mechanism of action
Interfere with calcium ion
Acts by transcellular and paracellular route
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29. 6. Monohydric alcohols
E.g. Ethanol, Isopropanol, methanol
Mechanism of action
► Increase the partition coefficient of a drug by
facilitating the transcellular pathway in a
concentration independent manner
► Disrupt arrangement of intercellular lipids
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30. 7. Polyols
E.g. Propylene glycol, Polyethylene glycol, Glycerol,
Propanediol
Mechanism of action
► Acts by paracellular route
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31. Azone
Mechanism of action
► Azone primarily enhances the transport of lipophilic
drug across the keratinized oral mucosa.
► It forms an ion pair with anionic drug thereby
promoting their penetration
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34. Purposes of this study
To evaluate the effects of
Enhancers for sublingual delivering insulin on the
mucosal
Lipid fluidity and protein conformation
Transport pathway
In vivo hypoglycemic activity in normal rats
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35. Preparation of the homogenates of sublingual
mucosa
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Male Sprague–
Dawley rats
After sacrificed sublingual
membrane was removed
Washed for 3 times
using cold D-Hanks
solution
Sample homogenized in cold
physiological saline
(mucosa:saline 1:3, w/w) at 4 °C
Cont……
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36. Cont…
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Filtrate was centrifuged
(300 rpm) for 1hr at 4 °C
Filtered (3-layer
sterilized gauze)
Slightly homogenized at 4°C,
sonicated (1 min) and centrifuged
(30000 rpm) for 1 hr
Supernatant was
collected
Mucosa is ready
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37. Effect on the fluidity of sublingual lipid
mucosa
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38. Result
Chitosan was the most significant factor which affected the
fluidity of cellular membrane lipid
The influencing extent was as follows:
chitosan >polyethylene–polypropylene glycol > polyoxyethylene
lauryl ether > egg lecithin > oleic acid > HP-β-CD
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39. Conclusion
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HP-β-CD, chitosan, polyethylene–polypropylene glycol,
polysorbate 80, polyoxyethylene lauryl ether, egg lecithin,
and oleic acid could significantly increase the mucosal
lipid fluidity, affect the conformation of mucosal protein,
and increase the transport amount of insulin
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40. References
Sevda S. Hıncal A., Drug permeation enhancement via buccal route: possibilities
and limitations. Journal of Controlled Release. Issues 1–3,2001(72),133–144
Choudhary A. et al, A Review on Novelty and Potentiality of Vaginal Drug
Delivery. International Journal of Pharm Tech Research.2011,(3),1033-1044.
Cui C. Y. et al, Sublingual Delivery Of Insulin: Effects Of Enhancers On The
Mucosal Lipid Fluidity And Protein Conformation, Transport, And In Vivo
Hypoglycemic Activity. Pharma Society of Japan.2005, (28),2279-2288.
Dobaria N. et al. Vaginal Drug Delivery Systems: A Review Of Current Status.
East and Central African Journal of Pharmaceutical Sciences .2010,(7), 3-13.
Dodla S., velmurugan S. Buccal Penetration Enhancers-an Overview. Asian
Journal of Pharmaceutics and Clinical Research.2013,(6),39-47.
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41. Gandhi P. A. et al. A Review Article On Mucoadhesive Buccal Drug Delivery
System. International Journal of Pharmaceutical Research and Development
2011,(3),159-173.
Gandhi S. D. et al, Mucoadhesive Drug Delivery Systems-an Unusual
Maneuver For Site Specific Drug Delivery System. Pharma Science Monitor
an International Journal of Pharmaceutical Sciences .2011,851-871
Madan J., et al. Mucosal Drug Delivery System. International Journal of
Research in Ayurveda & Pharmacy. 2010,(1), 63-70.
Prasanna I. P. et al. Effect Of Permeation Of Buccal Patches Of Propranolol
Hydrochloride For Buccal Drug Delivery. International Journal of Innovative
Pharmaceutical Sciences and Research.2013, (1), 117-131.
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