1PENETRATION ENHNACER IN

MUCOADHESIVE DRUG DELIVERY SYSTEM

SINHGAD TECHNICAL EDUCATION SOCIETY’S

SINHGAD INSTITUTE OF PHARMACY, NARHE

Presented by Guide

Aragade Prity S.( M. Pharm Sem -II )

Dr. C.R. Kokare( HOD Pharmaceutics Dept.)

2Contents► Introduction► Penetration enhancer► Mode of permeation► Ideal characteristics► Factors affecting on permeation► Mechanisms of action of permeation► Classification► Case study► References April 15, 2023

3Introduction

Mucoadhesive drug delivery systems

► Utilized the property of bioadhesion of certain

polymers

► Adhesive on hydration

► Targeting a drug to particular region of the body

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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.April 15, 2023

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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 routeApril 15, 2023

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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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7The 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 April 15, 2023

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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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General structure of mucous layer

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10Functions 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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11Penetration enhancer

Substances that facilitate the permeation through

mucosa are referred as permeation enhancers .

What is penetration enhancer ?

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12Mode of permeation

Mode of permeation

Passive diffusion Carrier mediated Endocytosis

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Passive diffusion:

Transcellular (intracellular)

Paracellular (intercellular)

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14►Carrier mediated transport

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Pinocytosis

►Endocytosis :

Phagocytosis

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16Ideal 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 April 15, 2023

17Factors affecting on permeation

Physicochemical properties of the drug

Site of administration

Nature of the vehicle

Other excipients

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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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19Cont…..

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 coefficientApril 15, 2023

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Classification

Penetration enhancers

Surfactants

Fatty acids and derivatives

Bile salts and derivatives

SulfoxidesChelating agents

Monohydric alcohols

Polyols

Others (non-surfactant)

April 15, 2023

211.Surfactants

AnionicE.g. Sodium lauryl sulfate, Sodium dodecyl sulfate

Nonionic

E.g. Tween80, Sodium glycocholate

Cationic

E.g. Cetylpyridinium chloride, Chitosan, Trimethyl chitosan

April 15, 2023

22Mechanism 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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232. 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 April 15, 2023

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253. 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 upApril 15, 2023

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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.April 15, 2023

274. 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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285. 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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296. 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

April 15, 2023

307. Polyols

E.g. Propylene glycol, Polyethylene glycol, Glycerol,

Propanediol

Mechanism of action

► Acts by paracellular route

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31Azone

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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32Cyclodextrin

E.g. β-Cyclodextrin

Mechanism of action

It disturbs intercellular lipids

Affect protein integrity

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33Case study - 1

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34Purposes 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 ratsApril 15, 2023

35Preparation of the homogenates of sublingual

mucosa

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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36Cont…

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 readyApril 15, 2023

37Effect on the fluidity of sublingual lipid

mucosa

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38Result

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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39Conclusion

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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40References

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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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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Thank you

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