Download - Transdermal drug delivery system
A SEMINAR ON
TRANSDERMAL DRUG
DELIVERY SYSTEM
PRESENTED BY:
SHIRODE RAHUL A.M. Pharm.2nd sem.(2014-2015)
(Department of Pharmaceutics)
R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur
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CONTENTS Introduction
Advantages-Disadvantages
Comparison between IV, Oral and TDDS
Anatomy and Physiology of Skin
Permeation of Drug Molecule through Skin
Percutaneous Absorption
Classification of TDDS
Basic components of TDDS
Factors affecting Transdermal Permeation
Evaluation of TDDS
Application
Marketed Product
Conclusion
References.2
INTRODUCTION TDDS are topically administered medicaments in the
form of patches that deliver drugs for systemic effectsat predetermined and controlled rate.
Transdermal patch is an adhesive patch, that has acoating of medicine (drug), that is placed on the skinto deliver specific dose of the medicine, into theblood over a period of time.
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ADVANTAGES Avoidance of first-pass effect,
Long duration of action,
Comparable characteristics with IV infusion,
Ease of termination of drug action, if necessary,
No interference with gastric and intestinal fluids,
Suitable for administered of drug having-
Very short half-life, e.g. nitroglycerine.
Narrow therapeutic window.
Poor oral availability.
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DISADVANTAGES
Poor diffusion of large molecules,
Skin irritation,
Requires high drug load,
Unsuitable –If drug dose is large,
Absorption efficiency is vary with different sites of skin,
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COMPARISON BETWEEN IV,ORAL AND TDDSADVANTAGES IV ORAL TDD
Avoid hepatic
first-pass effects
YES NO YES
Constant drug levels
YES NO YES
Self-administration
NO YES YES
Termination of therapy
NO YES YES
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ANATOMY AND PHYSIOLOGY OF SKIN
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Skin is the part of Integrated system i.e. it helps tomaintain body temp and protect It fromsurrounding environment.
It covers an area of about 2m2 and 4.5-5 kg i.e. about16% of total body weight in adults.
Thickness is in range of 0.5mm (on eyelids ) to4.0mm ( on heels ).
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Skin has mainly 3 layers…
1)Epidermis
Stratum Cornium
Stratum Granulosm
Stratum Spinosum
Stratum Basal
2)Dermis
3)Subcutaneous layer
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EPIDERMIS Stratum Cornium- consists of 25 to 30 layers of
flattened dead keratinocytes. Which makes it waterrepellent.
Stratum Granulosm- consists of 3 to 5 layers andunder goes Apoptosis. It contains granules known asKeratohyalin. These granules release Lipid richsecretion, which acts as the water repellent.
Stratum Spinosum- contains 8 to 10 layers of cellsand it is closely arranged.
Stratum Basal- consists of single layer of cubical orcolumnar keratinocytes.
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DERMIS Composed of strong connective tissue containing
collagen and elastic fibres, hence it can easily stretchand recoil easily.
Blood vessel, nerves gland and hair follicles areembedded in this layer.
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SUBCUTANEOUS LAYER
It is also called as Hypodermis.
It is made up of loose connective tissue, includingAdipose tissue.
This helps to insulate the body by monitoring heatgain and heat loss.
The dermis is the layer of tissue that is Deeper andThicker than epidermis.
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PERMEATION OF DRUG MOLECULE THROUGH SKIN
It express by Fick’s first law of Diffusion-Drugmolecule diffuse from a region of higher conc. to oneof lower conc. until equilibrium is attained.
The process of Diffusion of molecule is driven bygradient between high concentration to lowconcentration.
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Fick’s First law of Diffusion-
dm/dt = J = D A K/h Where,
dm / dt =J= study state flux
D = diffusion coefficientA = surface areaK = partial coefficient between the Stratum
corneum and the vehicleh = diffusional path length or membrane
thickness
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PERCUTANEOUS ABSORPTION
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Percutaneous absorption done by 2-ways-
A. Transepidermal Absorption
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Stratum Corneum
Intracellular Pathway Intercellular Pathway
Viable Epidermis
Dermis
Microcirculation
B. Transfollicular Absorption
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Pilosebaceous unit Eccrine Gland
Hair Follicles Sebaceous Gland
Dermis
Microcirculation
CLASSIFICATION OF TDDS
A. Rate-Programmed Systems
Drug in Reservoir
Drug in Matrix
Drug in Adhesive
Drug in Microreservoir
B. Physical Stimuli-Activated Systems Structure-Based Systems Electrically-Based Systems
Iontophoresis Electroporation Sonophoresis
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1.Drug in Reservoir
2.Drug in Matrix
A.RATE-PROGRAMMED SYSTEMS-
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3.Drug in Adhesive
4.Drug in Microreservoir
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B. Physical Stimuli-Activated Systems-
1. Iontophoresis-
2. Electoporation-
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3. Sonophoresis-
4.Microneedles-
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BASIC COMPONENTS OF TDDS
Polymer matrix / Drug reservoir
Drug
Permeation enhancers
Pressure sensitive adhesive (PSA)
Backing laminate
Liner
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Polymer matrix / Drug reservoir-
Penetration Enhancers-
Chemical Enhancers-eg.- Azone, Pyrrolidone, Fattyacids, Essential oils, terpenes, organic solvents
Physical Enhancers-eg.- Iontophoresis, electroporation, Microneedles
Natural Polymer Synthetic Elastomer Synthetic Polymer
Gelatin Neoprene Polyethylene
Gum Arabic Silicone rubber Polystyrene
Starch Butyl rubber PVC
Shellac Chloroprene PVP
zein Polysiloxane Polyster
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Pressure Sensitive Adhesives (PSA)- A PSA is a material that helps in maintaining an intimate
contact between transdermal system and the skin surface.
Some widely used pressure sensitive adhesives are-
Eg- Polyisobutylenes, Polyacrylates, Silicones.
Backing Laminate:Hold and protect the drug reservoir from exposure to
atmosphere.Avoid loss of drugAccept printingHigh flexibilityEg- vinyl, polyethylene and polyester films, aluminium foil,
foam pad, metallic plastic laminate.
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Liner-
Protects the patch during storage. The liner is removedprior to use. Drug – Drug solution in direct contactwith release liner.
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FACTORS AFFECTING TRANSDERMAL PERMEATION
Physicochemical property of Drug molecule,
Partition co-efficient,
pH Condition,
Drug Concentration,
Molecular weight.
Physicochemical property of Drug DeliverySystem,
Release characteristics,
Use of permeation enhancer,
Composition of Drug Delivery System.27
Pathophysiological condition of Skin,
Reservoir effect of Horney Layer,
Hydration of skin,
Lipid Film,
Skin Temperature,
Pathological Injury to Skin,
Regional variation.
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Evaluation of TDDS
1. Evaluation of Adhesive
a. Peel Adhesion Properties- It is the force required to remove coating from a test substrate.
b. Tack Properties- It is the ability of polymer to adhere to a substrate with little contact pressure.
Thumb tack test
Rolling ball tack test
Quick-Stick test
Probe tack test
c. Shear Strength Properties- It is the measurement of the cohesive strength of an adhesive polymer.
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In vitro drug release evaluation
A. In vitro Permeation Studies-
In-Vitro skin Diffusion cells,
Skin-stripping,
Autoradiography.
B. In vitro Release Studies-
Paddle Over Disc Apparatus (USP Apparatus 5),
Reciprocating Disc (USP Apparatus 7).
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In vivo evaluation Animal models,
Skin-Stripping In vivo,
Microdialysis,
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APPLICATIONS For treatment of Angina Pectoris,
Smoking cessation(Nicotine Patch),
Contraceptive,
Antiemetic,
Anti-inflammatory,
Cosmetics.
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MARKETED PRODUCT
DRUG BRAND NAME MANUFACTURER
Nicotine Nicoderm gsk
Nicotine Habitraol Novartis
Nitroglycerine Transderm nitro Novartis
Insulin SonoDerm Imarx
Testosterone Testoderm Alza Corporation
Diclofenac diethyl amine NuPatch 100 Zudus Cadilla
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CONCLUSION
As we know, the basic functions of the skin isprotection and hence it is difficult to target the skinfor drug delivery. Because skin having numerouslayers. But using novel techniques in TDDS we havesuccessfully penetrate the drug into systemiccirculation.
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REFERENCES Brahmankar D. M., Jaiswal Sunil B.(2009)
Biopharmaceutics and Pharmacotherapeutics-ATreatise, 2nd edition, pp-495-501.
Chien Yie W.(2002), Novel Drug Delivery Systems,Marcel Dekkar, Inc Publication, volume-50, 2nd
edition, pp-301.
Walters Kenneth A.(2002), Dermatological andTransdermal Formulations, Marcel Dekkar, IncPublications, volume-119, pp-1,319.
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Robert’s Michael s., Walters Kenneth A.(2002),Dermal Absorption and Toxicity Assessment, MarcelDekker, Inc Publications, volume-91, pp-1, 189.
Dr. Patel Upendra, Bhavin Bhimani(2012)Transdermal Drug Delivery System As ProminentDosage Form For The Highly Lipophilic Drugs.International Journal Of Pharmaceutical ResearchAnd Bio-Science. Volume 1(3)42:65. pp- 1-6.
Jain, N.K. (1997) Controlled and novel drug delivery. 1st
ed. New Delhi: CBS publishers and distributors, pp.100- 127.
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