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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
April 15, 2023
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.April 15, 2023
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 routeApril 15, 2023
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
April 15, 2023
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
8
Composition of Mucus Layer
Water -95%
Glycoprotein and lipids – 0.5-3.00%
Mineral salts – 1%
Free proteins – 0.5-1.0%
April 15, 2023
9
General structure of mucous layer
April 15, 2023
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
April 15, 2023
11Penetration enhancer
Substances that facilitate the permeation through
mucosa are referred as permeation enhancers .
What is penetration enhancer ?
April 15, 2023
12Mode of permeation
Mode of permeation
Passive diffusion Carrier mediated Endocytosis
April 15, 2023
13
Passive diffusion:
Transcellular (intracellular)
Paracellular (intercellular)
April 15, 2023
14►Carrier mediated transport
April 15, 2023
15
Pinocytosis
►Endocytosis :
Phagocytosis
April 15, 2023
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
April 15, 2023
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
April 15, 2023
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
20
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.
April 15, 2023
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
Ap
ril 15
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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
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.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
April 15, 2023
285. Chelating agents
E.g. EDTA , Citric acid, Salicylates
Mechanism of action
Interfere with calcium ion
Acts by transcellular and paracellular route
April 15, 2023
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
April 15, 2023
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
April 15, 2023
32Cyclodextrin
E.g. β-Cyclodextrin
Mechanism of action
It disturbs intercellular lipids
Affect protein integrity
April 15, 2023
33Case study - 1
April 15, 2023
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……
April 15, 2023
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
April 15, 2023
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
April 15, 2023
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
April 15, 2023
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.
April 15, 2023
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.
April 15, 2023
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Thank you
April 15, 2023
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