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SSJ COLLEGE OF PHARMACY(Approved by AICTE & PCI & Affiliated to JNTU

University, Hyderabad)VattinagulaPally, Gandipet, Hyderabad – 500 075.

GUIDANCE: S.RAMYA LATHAPRESENTIED BY,

B.RUTHU10FJ1R0001

TRANSDERMAL DRUG DELIVERY SYSTEM

INTRODUCTION ADVANTAGES AND LIMITATIONS SKIN AND EPIDERMIS STRUCTURE COMPONENTS OF TRANSDERMAL PATCH TYPES OF TRANSDERMAL PATCH FACTORS AFFECTING TRANSDERMAL PERMEABILITY POLYMERS THERAPIES THAT USE TRANSDERMAL DELIVERY OF

DRUGS CLASSIFICATION OF TDDS BASIC COMPONENTS OF TDDS EVALUATION CONCLUSION REFERENCE

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Transdermal delivery represents an attractive alternative to oral delivery of drugs and is poised to provide an alternative to hypodermic injection too.

For thousands of years, people have placed substances on the skin for therapeutic effects.

Definition: Transdermal drug delivery systems (patches) are

dosage forms designed to deliver a therapeutically effective amount of drug across a patient’s skin also defined as Medicated adhesive patch that is placed on the skin to deliver a specific dose of Medication through the skin and into the blood stream.

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Reduces first-pass metabolism effect and GI incompatibility

Sustains therapeutic drug levels Permits self-administration Non-invasive (no needles or injections) Improves patient compliance Reduces side effects Allows removal of drug source Long acting drug delivery

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Poor diffusion of large molecules

Skin irritation

Only suitable for very potent drugs

More expensive than oral drugs

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EPIDERMIS STRUCTURE

1. Liner - Protects the patch during storage.2. Drug - Drug solution in direct contact with

release liner.3. Adhesive - Serves to adhere the

components of the patch together along with adhering the patch to the skin.

4. Membrane - Controls the release of the drug.

5. Backing - Protects the patch.

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(1) Single-layer Drug-in- Adhesive: The adhesive layer of this system also contains the drug.

(2) multi-layer drug in adhesive: One of the layers is for immediate release of the drug and other layer is for control release of drug from the reservior.

(3) Reservoir:

(4) Matrix: The Matrix system has a drug layer of a semisolid matrix containing a drug solution or suspension.

(5) vapour patch: In this type of patch the adhesive layer not only serves to adhere the various layers together but also to release vapour.

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The drug layer is a liquid compartment containing a drug solution or suspension separated by the adhesive layer

(A) Physicochemical properties of the penetrants:1. Partition coefficient.2. PH conditions.3 . Penetrant concentration.(B) Physicochemical properties of drug delivery systems:1. Release characteristics.2. Composition of drug delivery systems-3. Enhancement of transdermal penetration.(C) Physiological and pathological conditions of the skin 1. Reservoir effect of horny layer2. Lipid film

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Polymers are the backbone of a transdermal drug delivery system. Systems for transdermal delivery are fabricated as multi-layered polymeric laminates in which a drug reservoir or a drug polymer matrix is sandwiched between two polymer layers an outer impervious backing layer that prevents the loss of drug through the backing surface. Examples :HPMC 100, CMC, Polyethylene glycol, polycarbonate, PVA, Polycarbonate, Sodium alginate

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Therapy Drug Delivered by TDDS

Motion Sickness ScopolamineAnti-angina NitroglycerineHypertension ClonidineSmoking Cessation NicotineHormone Replacement Therapy

EstradiolEstradiol/ProgestinTestosterone

Pain Management FentanylLidocaine

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1. Polymer membrane permeation-controlled.

2. Polymer matrix diffusion- controlled

3. Drug reservoir gradient-controlled

4. Micro reservoir dissolution-controlled

(1) Solution in matrix(2) Suspension in continuous matrix(3) Suspension in porous matrix(4) Solution upstream of membrane(5) Suspension upstream of membrane(6) Laminated membrane downstream

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1) Iontophoresis:

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It is an electrochemical method that enhances the transport of some solute molecules by creating a potential gradient through the skin with an applied electrical current or voltage.

2)Electroporation: It is a method where high voltage

electrical pulses supplied to the skin.

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Non-invasive, needle-free

Rapid onset and cessation kinetics

Controlled, programmable and titratable drug delivery capabilities

Ability to provide smooth, variable or bolus plasma levels, singly or in combination, all in a single delivery system

Enhanced transdermal delivery for a broad range of compounds, including large drug molecules such as peptides and oligonucleotides

Minimal variability in the delivery profiles among patients and body sites

Potential for enhanced patient compliance and control

SCIENTIFIC BASIS OF IONTOPHORESIS The Nernst-Planck equation, seen below, is the traditional relationship accepted for describing transport of an ionic species across a membrane:

J = DzVFC/kT+ Cu - D(dC/dx)

where J = molar flux

D = diffusivity coefficient

C = the concentration (molar)

u = the convective flow of water

T = temperature

k = Boltzman's constant

z = charge on the species

V = electric field

F = Faraday's constant

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Phonophoresis is the introduction of substances into the body by ultrasonic energy. Unlike iontophoresis which involves the transfer of ions into the tissue, phonophoresis transmits molecules a different process although similar in concept.

Some of the common chemicals compounded for phonophoresis include:

Betamethasone DipropionateDexamethasone Dexamethasone / Lidocaine Fluocinonide Hydrocortisone Hydrocortisone /LidocaineKetoprofen / Naproxen Piroxicam / Sodium Salicylate

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Matrix

Reservoir

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Matrix ReservoirSimplified patch construction

Complicated patch construction

Complex formulation

Simplified formulation

Skin controlled delivery

Membrane moderated delivery

Thinner construction

Multiple layers

Excellent skin conformability

Poor skin conformability

Efficient utilization of size

Requires extended size

Low dose dumping potential

Dose dumping potential

The patches were prepared by solvent casting method . The polymer (Carbopol/HPMC) was taken in a beaker with

aminimum quantity of the solvent Then 2/3rd of the solvent was mixed with the other polymers (Eudragit L 100) and was added with stirring at lower rpm initially and later at a higher speed.

The plasticizer was added and uniformly mixed and the drug was incorporated with continuing agitation and the volume was made up.

The films were cast onto a suitably designed and fabricated glass mould and then dried in oven at 40oC.

The films were removed by using sharp blade by inserting along the edges of the film.

The dried films were wrapped in butter paper and stored in a closed container away from light and in cool place .

Permeability coefficient is the velocity of drug passage through the membrane in cm/h.

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Clinical evaluation Formulation and manufacturing scale-up Stability studies Analytical evaluation Regulatory submission and approval

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1.Weight uniformity.2.Thickness.3.Folding endurance.4.% moisture content.5.Moisture uptake.6.% Elongation break test.7.Drug content.8.In-vitro drug release studies.9.Skin irritation studies.

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Due to the recent advances in technology and the incorporation of the drug to the site of action without rupturing the skin membrane transdermal route is becoming the most widely accepted route of drug administration.

It promises to eliminate needles for administration of a wide variety of drugs in the future.

To optimize this drug delivery system, greater understanding of different mechanism of biological interactions, and polymers are required.

TDDS a realistic practical application as the next generation of drug delivery system.

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1..Williams A. London: Pharmaceutical Press; 2003. Transdermal and Topical Drug Delivery.

2. Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery.t Rev Drug Discov. 2004;3:115–124.

3. Bronaugh RL, Maibach HI, editors. Edn. 4th. New York: Marcel Dekker; 2005. Percutaneous Absorption.

4. Miller MA, Pisani E. The cost of unsafe injections. Bull World Health Organ. 1999;77:808–811.

5. Aulton.M.E, Pharmaceutics; The science of dosage form design, second edition, Churchill Livingston, Harcourt publishers-2002.

6. Ansel.H.C, Loyd.A.V, Popovich.N.G, Pharmaceutical dosage forms and drug delivery systems, Seventh edition, Lippincott Williams and Willkins publication.

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