Slide 1: 1 1 TRANSDERMAL DRUG DELIVERY SYSTEM
(TDDS) BY:RASHMI SURVE
DEPARTMENT OF PHARMACEUTICS
KLE UNIVERSITY,BELGAUM.
Slide 2: 2 The NDDS may involve a new dosage form e.g., from thrice a day dosage to once a day dosage form or developing a patch form in place of injections.
Throughout the past 2 decades, the transdermal patch has become a proven technology that offers a variety of significant clinical benefits over other dosage forms. HISTORY OF TDDS:
Slide 3: 3 Transdermal drug delivery system was first introduced more than 20 years ago.
First transdermal patch was approved in 1981 to prevent nausea and vomiting associated with motion sickness.
The FDA has approved, more than 35 transdermal patch products. 3 Continued...,
Slide 4: 4 CONTENTS: Introduction.
Advantages & Disadvantages.
Structure of the skin.
Permeation through skin.
Factors affecting permeation.
Basic components of TDDS.
Advances in TDDS.
Slide 5: 5 INTRODUCTION: Definition:
Transdermal drug delivery is defined as a self contained discrete dosage form, which when applied to the intact skin, will deliver the drug at a controlled rate to the systemic circulation.
Slide 6: 6 ADVANTAGES:
Slide 7: 7 DISADVANTAGES:
Slide 8: 8 STRUCTURE OF SKIN: Epidermis:
Stratum corneum (Horny cell layer)
Stratum lucidum (Clear layer)
Stratum granulosum ( Granular Layer)
Stratum spinosum (Prickly layer)
Stratum germinativum
Dermis:
Hypodermis or Subcutaneous layer:
Slide 9: 9 CROSSECTION OF SKIN
Slide 10: 10
Slide 11: 11 STRUCTURE OF SKIN: Epidermis:
The outer layer of skin is made up of Stratified Squamous epithelial cells. Epidermis is thickest in palms and soles.
The stratum corneum forms the outer most layer (10-15µm thick ) which consists of many layers of compacted , flattened, dehydrated keratinized cells.
The stratum corneum is responsible for the barrier function of the skin and behaves as a primary barrier to the percutaneous absorption.
Slide 12: 12 Continued…
Water content of stratum corneum is around 20%.
The moisture required for stratum corneum is around 10% (w/w) to maintain flexibility and softness.
It consists of Cermides and neutral lipids such as Sterols, free fatty acids and triglycerides.
Slide 13: 13 Continued..
The composite structure of skin permeation barrier is represented by 3 layers:
Stratum corneum (15µm thick)
Viable epidermis (150µm thick)
Papillary layer of dermis (100-200µm thick)
Slide 14: 14 STRATUM CORNEUM VIABLE EPIDERMIS DERMIS CAPILLARY NETWORK
Slide 15: 15 DERMIS:
The dermis is made up of regular network of robust collagen fibers of fairly uniform thickness with regularly placed cross striations .
This network or the gel structure is responsible for the elastic properties of the skin.
It is supplied by blood to convey nutrients, remove waste & regulate body temp. Drug is well absorbed by this route.
Upper portion of the dermis is formed into ridges containing lymphatics and nerve endings.
Slide 16: 16 SUBCUTANEOUS TISSUE:
This is a sheet of the fat containing areolar tissue known as the superficial fascia, attaching the dermis to the underlying structures .
SKIN APPENDAGES:
Sweat glands produces sweat of pH 4-6.8 & absorbs drugs, secretes proteins, lipids and antibodies. Its function is to control heat.
HAIR FOLLICLES:
They have sebaceous glands which produces sebum and includes glycerides, cholesterol and squalene.
Slide 17: 17 MECHANISM OF ABSORPTION THROUGH SKIN Mechanism involved is passive diffusion
This can be expressed by FICK’s LAW of DIFFUSION
dq = D K A ( c1 – c2 )
dt h
dq /dt = rate of diffusion
D = diffusion co-efficient
K = partition co-efficient
A = surface area of membrane
H = thickness of membrane 17
Slide 18: 18 Routes of drug absorption through skin: Trans follicular route
Trans epidermal route 18
Slide 19: 19 TRANSFOLLICULAR ROUTE:
Fractional area available through this route is
0.1 %
Human skin contains 40-70 hair follicles, 200 to 250 sweat glands on every sq.cm. of skin area.
Mainly water soluble substance are diffused faster through appendages than that of other layers.
Sweat glands and hair follicles act as a shunt i.e. easy pathway for diffusion through rate limiting ST corneum.
Slide 20: 20 TRANS EPIDERMAL ROUTE
Epidermal barrier function mainly resides in horny layer
The viable layer may metabolize, inactivate or activate a prodrug.
Dermal capillary contains many capillaries so residence time of drug is only one minute.
Within stratum corneum molecule may penetrate either transcellularly or intercellularly.
Intracellular region is filled with lipid rich amorphous material.
Slide 21: 21 SCHEMATIC REPRESENTATION
Slide 22: 22 Process of transdermal permeation.
Slide 23: 23
Slide 24: 24 FACTORS AFFECTING TRANSDERMAL PERMEABILITY Physico chemical properties of parent molecule
Solubility and partition co- efficient
pH condition
Penetrant concentration
Physico chemical properties of drug delivery system
Release characteristic
Composition of drug delivery system
Permeation enhancer used
Slide 25: 25 Physiological and pathological condition of skin
Lipid film
Skin hydration
Skin temperature
Effect of vehicle
Pathological injury to skin
Biological factors
Skin age
Thickness of S. Corneum
Skin condition 25
Slide 26: 26 Solubility and partition co- efficient:
Solubility of a drug influences its ability to penetrate the skin.
Drug solubility determines concentration presented to absorption site which will effect rate and extent of absorption.
Skin permeation can be enhanced by increasing lipophilic character of drug, so that drug penetrates through STC but not through epidermis due to decreased water solubility.
Drug which is lipid & water soluble is favored.
Slide 27: 27 pH & penetration concentration:
Moderate pH is favorable because if solutions with high or low pH will result in destruction to the skin.
Higher the concentration of the drug in vehicle faster the absorption.
At higher concentrations than solubility the excess solid drug will function as a reservoir and helps to maintain a constant drug constitution for prolonged period of time.
Slide 28: 28 28 Physico-chemical properties of drug delivery system
Release characteristic
Solubility of drug in vehicle determines the release rate.
Composition of drug delivery system
It not only effects the rate of drug release but also the permeability through STC.
Example methyl salicylate is more lipophilic than its parent acid (Salicylic acid). When applied to skin from fatty vehicle methylsalicylate yielded higher absorption.
Slide 29: 29 29 Physiological and pathological condition of skin
Lipid film:
It acts as protective layer to prevent removal of moisture from skin. Deffating of this film will decrease TD absorption.
Skin hydration:
It can be achieved by covering skin with plastic sheeting, which leads to accumulation of sweat, condensed water vapors, increase hydration and increase porosity.
Slide 30: 30 30 Effect of vehicle:
A vehicle can influence absorption by its effect on physical state of drug and skin. Example greases, paraffin bases are more occlusive while water in oil bases are less. Humectants in bases will dehydrate the skin and decrease percutaneous absorption.
Slide 31: 31 31 Biological factors:
Skin age:
Skin of foetus ,young ones and elders is more permeable than adult tissue.
Skin metabolism:
Viable epidermis is metabolically active than dermis. If topically applied drug is subjected to biotransformation during permeation local and systemic bioavailability is affected.
Basic components of Transdermal drug delivery : 32 32 Basic components of Transdermal drug delivery BACKING MEMBRANE DRUG ADHESIVE LINER
Slide 33: 33 33 LIST OF POLYMERS USED NATURAL POLYMERS:
Cellulose derivatives, Zein, Gelatin, Shellac, Waxes, Gums & Natural rubber
SYNTHETIC POLYMER
Poly vinyl alcohol, Poly vinyl chloride, Polyethylene, Poly propylene, Poly urea, Pvp
Slide 34: 34 34 DRUG For successful developing transdermal delivery, drug should be chosen with great care,
Physicochemical properties:
Mol. wt. less than 400 Daltons
2)Affinity for both lipophilic & hydrophilic phase
3)Drug should have low melting point
Slide 35: 35 Ideal properties of drug candidate
Schematic Skin absorption of drug : 36 Schematic Skin absorption of drug 36
Slide 37: 37 37 Hypothetical blood level pattern from a conventional
multiple dosing schedule, and an ideal pattern from a
transdermal delivery system.
Slide 38: 38 Fig. 3. Types of transdermal delivery devices.
Slide 39: 39 Polymer membrane permeation controlled tdds
Transderm scop
Transderm nitro
Catapres
Adhesive polymer dispersion tdds
Deponit
Frandol type
Nitro dur II Recent Developments
Slide 40: 40 Cont.., Non adhesive polymer dispersion tdds
Nitro-dur system
NTS system
Micro-reservoir dissolution controlled tdds
Nitro disc system
Transdermal contraceptive system
Slide 41: 41 Table 1 Transdermal Controlled-Release Products and Devices
Slide 42: 42 More than 35 TDD products have now been approved for sale in the US & approximately 16 active ingredients are approved for use in TDD products globally.
Slide 43: 43 43 DRUG APPLICATION Commercial success
Slide 44: 44 Review article from IJPS TDDS though expensive alternative to conventional formulation are becoming popular because of some unique advantages like :
controlled zero order absorption.
Simple administration mode.
Easy removal in case of adverse manifestations.
Slide 45: 45 Article from aaps Pharmsci Tech Comparison studies were carried out between oral carvedilol dosage form & carvedilol transdermal patch.
Oral carvedilol acted quickly & drastically but later its effect dropped off.
But the patches did not greatly decrease the BP in the initial phase when compared with the oral form.
The effect of oral carvedilol started declining after 6 hrs due to its short half life.
Since the administration of carvedilol through patches resulted in sustained and continued drug release for 24 hours, the patches were able to control the hypertension throughout the period.
Slide 46: 46 References Y. W. Chien, Novel drug delivery systems, 2nd edition, Revised & expanded, Marcel Dekker, Inc., New York, 1992.
N. K. Jain, Controlled & Novel drug delivery, CBS Publishers & Distributors, New Delhi, First edition, 1997.
Controlled drug delivery devices by Pravin Tyle, Marcel Dekker, Inc., New York, 1992, pg. no. 406 – 408.
Mechanisms of Transdermal drug delivery system by Y. W. Chien, Marcel Dekker, Inc., New York.
Journal of aaps pharmscitech, jan 19, 2007
Indian journal of pharmaceutical sciences september-october 2008 pg-556 to 560
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