TRANSDERMAL DRUG DELIVERY SYSTEM

PRESENTED BY – SHEETAL NAGAR M.PHARMDEPARTMENT OF PHARMACEUTICES

INTRTTTTTOD INTRODUCTION

INTRODUCTION UI BBBBCTIONWhat is TDDS ?The passage of substance from the outside of the skin

through its various layers into the bloodstream.

The primary objective is to ensure safety and efficacy of the drugs as well as patients compliance.

The future of transdermal drug delivery is the development of skin pre-treatment methods & combination devices

THE NEED FOR DEVELOPMENT OF TRANSDERMAL DELIVERY SYSTEM

• POOR BIOAVAILABILITY• FIRST PASS EFFECT• RAPID BLOOD SPIKES (HIGH or

LOW)

ADVANTAGES DISADVANTAGES

Avoidance of absorption and shortened metabolism of GIT.

Cause no Pain

No pitfalls of Enzymes & pH

Reduce dosing.

Constant dosing.

Multi-day therapy

Capacity to terminate drug effects

Drugs that require high blood levels cannot be administered.

Is not a means to achieve rapid bolus type drug input.

Adequate solubility of the drug in both lipo-phillic and aqueous environments, to reach and gain access to the systemic circulation.

The molecular size of the drug should be small.

Difficulty of permeation of the drug through human skin

SKIN ANATOMY

THE SKIN IS MULTILAYERED ORGAN COMPLEX IN BOTH STRUCTURE AND FUNCTION. CONSISTS OF THREE DISTINCT LAYERS

EPIDERSMIS

The stratum corneum consists of 10-15 layers of corneocytes and varies in thickness from approx 10-15 μm in the dry state to 40 μm when hydrated.

It comprises a multi-layered “brick and mortar” like structure of keratin-rich corneocytes(bricks) in an intercellular matrix (mortar).

It also Composed primarily of long chain ceramides, free fatty acids, triglycerides, cholesterol, cholesterol sulfate and sterol/wax esters .

In the initial layers of the stratum corneum material rearranges to form broad intercellular lipid lamellae which then associate into lipid bi-layers ,with the hydrocarbon chains aligned and polar head groups dissolved in an aqueous layer .

As a result of the lipid composition, the lipid phase behavior is different from that of other membranes.

The hydrocarbon chains are arranged into regions of crystalline, lamellar gel and lamellar liquid crystal phases creating various domains within the lipid bilayers .

The presence of intrinsic & extrinsic proteins, may also affect the lamellar structure of the corneum.

Also consists of Viable epidermis (150µm thick) Papillary layer of dermis (100-200)µm thick) DERMISIt is supplied by blood to convey nutrients, remove waste & regulate body temperature and drug is well absorbed by this route

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.

Transdermal Permeation

Skin is the most intensive and readily accessible organ of the body as only a fraction of millimeter of tissue separates its surface from the underlying capillary network. The various steps involved in transport of drug from patch to systemic circulation are as follows:Diffusion of drug from drug reservoir to the rate controlling membrane.Diffusion of drug from rate limiting membrane to stratum corneum. Sorption by stratum corneum and penetration through viable epidermis.Uptake of drug by capillary network in the dermal papillary layer.Effect on target organ.

PERMEABILITY COEFFICIENT IS THE CRITICAL PREDICTOR OF TRANSDERMAL DELIVERY

Transport = Flux = (mg/cm2/sec) = J=P x A x (Cd – Cr)

Permeability Coefficient = P = D x K (cm/sec) h

Where A = Surface area of patch D = Diffusivity of drug in membrane (skin) K = Partition coefficient (patch/skin) C = Concentration in donor or receptor patch

or skin) h = Thickness of membrane (skin)

MECHANISM OF DRUG PERMEATION THROUGH SKIN

A molecule traversing must partition into and diffuse through the keratinocyte, but in order to move to the next keratinocyte, the molecule must partition into and diffuses through the lipid lamellae between each keratinocyte.

Percutaneous Absorption:

Percutaneous Absorption involves passive diffusion of substances through the skin.

Mechanism of permeation can be :

1. Trans-epidermal

2. Trans-appandageal

DIFFERENT APPROACHES OF TDDS SYSTEMS Membrane permeation-controlled TDDS - Transderm-Scop, Duragesic, Clonidine-TTS

Drug in adhesive-type TDDS - Daytrana, Climara, Habitrol, Nicoderm, Exelon

Matrix diffusion controlled TDDS- NitroDur

Microreservoir dissolution controlled TDDS- Androderm

Basic Components of TDDS

•

:: Drug

Polymer Matrix

Synthetic Polymers

Eg. PVC,Polyamide

Natural PolymersEg.

Cellulose,Starch

BASIC COMPONENTS OF TDDS CONT…..

Permeation enhancers

(i) Solvents– Eg. Methanol, Propyleneglycol(ii) Surfactants—Eg. Sodium Lauryl Sulphate,Sodium

deoxycholate(iii) Miscellaneous-- Calciumthioglycolate

• Pressure sensitive adhesive (PSA)

Eg. Silicon based ,Acrylic based

• Backing laminates

Eg. Aluminium foil, Flexible Polyurethane

FACTORS CONSIDERATION FOR TDS DEVELOPMENT

Skin Characteristics Bioactivity of drug Formulation Adhesion System design

POLYMER MEMBRANE PERMEATION-CONTROLLED TDDS

•TransdermScop (Scopolamine) for 3 days protection of motion sickness and TransdermNitr(Nitroglycerine) for once a day medication of angina pectoris.

ADHESIVE DIFFUSION CONTROLLED TDDS

Deponit (Nitroglycerine) for once a day medication ofangina pectoris.

MATRIX DIFFUSION CONTROLLED TDDS

Nitro Dur (Nitroglycerine) used for once a day medication of angina pectoris.

MICRORESERVOIR CONTROLLED

Nitro- dur® System (Nitroglycerin) for once a daytreatment of angina pectoris.

DRUG IN ADHESIVE PATCHES

A system in which the drug is incorporated

directly into the adhesive, rather than into a separate layer. Usually used for smaller molecular weight compounds.

These can be either a single layer or multi-layer.Sometimes referred to as the “matrix type

patch”

SCHEMATIC DRAWING OF THE MATRIX (DRUG-IN-ADHESIVE) TYPE OF PATCH.

Film Backing

Drug/Adhesive Layer

Protective Liner (removed prior to use)

skin

RESERVOIR PATCHES

The reservoir system has a drug layer that is separate from the adhesive

SCHEMATIC DRAWING OF THE RESERVOIR TYPE OF PATCH.

Film Backing

Drug Layer

Protective Peel Strip (removed prior to use)

Rate-controlling Membrane

Contact Adhesive

FACTOR INFLUENCE THE TRANSDERMAL ROUTE

Time scale of permeation (steady-state vs. transient diffusion)

Physicochemical properties of penetrant (pKa, molecular size, stability, binding affinity, solubility, partition coefficient)

Integrity and thickness of stratum corneum Density of sweat glands and folicles Skin hydration Metabolism Vehicle effects

These studies are predictive of transdermal dosage forms and can be classified into following types:• Physicochemical evaluation• In vitro evaluation• In vivo evaluation

Physicochemical Evaluation: Thickness:

Uniformity of weight Drug content determination:

Moisture content:

Flatness:

Folding Endurance:

Tensile Strength:

Water vapour transmission studies (WVT): Microscopic studies:

Thickness of the patch

The thickness of the drug prepared patch is measured by using a digital micrometer at different point of patch and determines the average thickness and standard deviation for the same to ensure the thickness of the prepared patch

Content uniformity test 10 patches are selected and content is determined for individual patches. If 9 out of 10 patches have content between 85% to 115% of the specified value and one has content not less than 75% to 125% of the specified value , then transdermal patches pass the test of content uniformity. But if 3 patches have content in the range of 75% to 125%,then additional 20 patches are tested for drug content. If these 20 patches have range from 85% to 115%, then the transdermal patches pass the test

Drug content determination

An accurately weighed portion of film (above 100 mg) is dissolved in 100 mL of suitable solvent in which drug is soluble and then the solution is shaken continuously for 24 h in shaker incubator. Then the wholesolution is sonicated. After sonication and subsequent filtration, drug in solution is estimated spectrophotometrically byappropriate dilution

Moisture content:

The prepared films are weighed individually and kept in a desiccators containing calcium chloride at room temperature for 24 h. The films are weighed again after a specified interval until they show a constant weight. The percent moisture content is calculated using following formula. Initial weight – Final weight % Moisture content = ---------------------------------X100 Final weight

Moisture Uptake:

Weighed film sare kept in a desiccator at room temperature for 24 h. These are then taken out and exposed to 84% relative humidityusing saturated solution of Potassium chloride in a desiccator until a constantweight is achieved. % moisture uptake is calculated as given below. Final weight – Initial weight% moisture uptake =---------------------------------- X 100 Initial weight

Flatness:

A transdermal patch should possess a smooth surface and should not constrict with time. This can be demonstrated with flatness study. For flatness determination, one strip is cut from the centre and two from each side of patches. The length of each strip is measured and variation in length is measured by determining percent constriction. Zero percent constriction is equivalent to 100 percent

Folding Endurance: Evaluation of folding endurance involves determining the folding capacity of the films subjected to frequent extreme conditions of folding . Folding endurance is determined by repeatedly folding the film at the same place until it break. The number of times the films could be folded at the same place without breaking is folding endurance value. Tensile Strength: To determine tensile strength, polymeric films are sandwiched separately by corked linear iron plates. One end of the films is kept fixed with the help of an iron screen and other end is connected to a freely movable thread over

Tensile strength=F/a . b (1+L/l) (2)

F is the force required to break; a is width of film; b is thickness of film; L is length of film; l is elongation of film at break point. Water vapour transmission studies (WVT):

For the determination of WVT, weighed one gram of calcium chloride and placed it in previously dried empty vials having equal diameter.

Peel Adhesion propertiesTack properties Thumb tack test Rolling ball test Quick stick (Peel tack) test Probe tack testShear strength properties or creep resistance

Adhesive studies:

•In this test, the force required to remove an adhesive coating form a test substrate is referred to as peel adhesion. Molecular weight of adhesive polymer, the type and amount of additives are the variables that determined the peel adhesion properties. A single tape is applied to a stainless steel plate or a backing membrane of choice and then tape is pulled from the substrate at a 180°C angle, and the force required for tape removed is measured

Peel Adhesion test:

Tack properties: It is the ability of the polymer to adhere to substrate with little contact pressure. Tack is dependent on molecular weight and composition of polymer as well as on the use of tackifying resins in polymer Thumb tack testThe force required to remove thumb from adhesive is a measure of tack.

Rolling ball tack testThis test measures the softness of a polymer

In this test, stainless steel ball of 7/16 inches in diameter is released on an inclined track so that it rolls down and comes into contact with horizontal, upward facing adhesive (Figure-2). The distance the ball travels along the adhesive provides the measurement of tack, which is expressed in inch

Quick stick (peel-tack) test

In this test, the tape is pulled away from the substrate at 90ºC at a speed of 12 inches/min. The peel force required breaking the bond between adhesive and substrate is measured (Figure-3) and recorded as tack value, which is expressed in ounces or grams per inch width .

Shear strength properties or creep resistanceShear strength is the measurement of the cohesive strength of an adhesive polymer i.e., device should not slip on application determined by measuring the time ittakes to pull an adhesive coated tape off a stainless plate

Probe Tack testIn this test, the tip of a clean probe with a defined surface roughness is brought into contact with adhesive, and when a bond is formed between probe and adhesive. The subsequent removal of the probe mechanically breaks it (Figure-4). The force required to pull the probe away from the adhesive at fixed rate is recorded as tack and it is expressed in grams

In vitro release studiesThe Paddle over Disc:The Cylinder modified USP Basket:The reciprocating disc: Keshary- Chien Cell:

In vitro permeation studies:Preparation of skin for permeation

studies:

Intact full thickness skin:

Separation of epidermis from full thickness skin

In vivo StudiesAnimal modelsHuman volunteers

RECENT ADVANCES IN TDDS

Microneedles

Microchannel based Rf

Ionotopheresis

INTRODUCTION TO MICRONEEDLES

They are one micron in diameter and range from 1-100 microns in length.

Microneedles have been fabricated with various materials such as: metals, silicon, silicon dioxide, polymers, glass .Smaller the hypodermic needle, Various types of needles have been fabricated ex: solid (straight, bent filtered, hollow)

The hollow needle designs include tapered and beveled tips, and could be used to deliver micro liter quantities of drugs to very specific locations.

MAJOR DIFFERENCE TRANSDERMAL PATCH TRANSDERMAL MICRONEEDLES

MECHANISM

Is not based on diffusion as it is in other transdermal drug delivery products. Instead, it is based on the temporary mechanical disruption of the skin and the placement of the drug within the epidermis, where it can more readily reach its site of action.

MODELS OF DELIVERY Piercing microneedle + application of drug

patches Coated microneedle Encapsulated biodegradable microneedle Injecting drug through hollow

microneedles

ESSENTIAL CHARACTERS OF COATING PROCESS Uniform coating Limit deposition onto microneedle Avoid high temperature High drug loading Good adhesion of coating solution Aqueous coating solution Rapid or controlled – dissolution kinetics Coating processes

dip coating – micron scale-used

roll coating not used

spray coating

MICRONEEDLE FABRICA MICRONEEDLE FABRICAMICRONEEDLE FABRICATION N TION MICRONEEDLE FABRICATION

Laser cutting : Stainless steel sheets using Infrared laser, shapes were obtained from AUTOCAD software and three phases are required.

• cutting speed of 2mm/s ,air purge at 140KPa.• Prepared either by individual rows (‘in-plane’) or two

dimensional array into plane and bent at 90 degrees (‘out of -plane’).

Cleaning and Bending microneedles: Manually cleaned with detergents (Alconox, White plains) to de-grease the surface an remove slag and oxides and rinsed with running water

• (out of –plane) were pushed out manually by using forceps or Hypodermic needle and then bent at 90 degrees with aid of a single –edged razor blade.

Electro polishing : In a solution of Glycerin, ortho-phosporic acid(85%) and water (6:3:1),in a 300ml glass beaker at 700 at a stirring rate 150 rpm. A copper plate was used as cathode ,microneedles as anode and vibrated at 10Hz to remove bubbles with a current density of 1.8mA/mm2 and then cleaned in de-ionized water and 25% nitric acid for 30s each then again in hot running water and a final wash in running de-ionized water by this thickness recedes to 50micro meter ,then dried and storedCoating solution : composed of 1% carboxy-methylcellulose sodium salt+0.5%(w/v) Lutrol F-68 NF + mode

l drug

Model drugs used are 0.01% sulforhodamine calcein ,0.05% luciferase plasmid DNA ,1% bovine serum ,10% barium sulfate , 1.2% 10-um latex beads ,8.5% 20um latez beads.DNA and viruses are made fluorescent by incubating with YOYO-1 at a dye:basepair/virus ratio 1:5 for 1 hr at room temperature in dark .

MICRONEEDLE PATCH ASSEMBLY:

Coated Microneedles array are assembled into transdermal patch containing pressure sensitive adhesive to adhere to the skin.They are fabricated in plane rows or individual arrays of out-of-plane microneedles.

MICRONEEDLE PATCH ASSEMBLY: Multiple In-plane

rows of

microneedles. A patch of 50 microneedles are taken .

1st ten slits each 75um wide &7. 7mm long were laser cut into a 1.6mm thick, single-sided polyethylene medical

foam tape using a co 2 laser and

then manually inserted into each slit from the non-adhesive side of the foam tape and glued to the foam tape using a medical grade adhesive.

A polyethylene medical foam tape (0.8 mm thick) was then cut into a disc of 16 mm diameter and affixed onto the dried glue area to provide a cushioned backing to facilitate pressing the patch during insertion.

Multiple out-of-plane rows of microneedle.A circular disc of

20mmdiameter was first cut from a 0.8-mm thick, single-sided medical foam tape using the CO2 laser. In the middle of this disc, a rectangular piece of the adhesive release liner equal in dimensions to the periphery of the array (12 ×12mm) was cut out using the CO2 laser and peeled off.

The stainless steel microneedle array was then attached to this exposed adhesive. A double-sided, poly-ethylene-phthalate carrier tape is attached.

The tape is then slipped over the microneedles .

MICRONEEDLE ARRAY PATCHES•The adhesive layer was periodically disrupted via small holes or slits to allow the microneedles to stick out for penetration.

•The adhesive served to hold microneedles firmly against the skin by compensating for the mechanical mismatch between the flexible skin tissue and the rigid microneedle substrate, especially in the case of out-of-plane microneedle arrays.

•Microneedle arrays prepared on the basis ofthis design are shown for patches of in-plane microneedles (Fig. 4B)

•out-of-plane microneedles (Fig. 4D).

MICRO-DIP-COATING OF MICRONEEDLES:

• Poor and good microneedle coatings via bright field micrographs of vitamin B coated microneedles.

• Poor, non-uniform coatings withbase-substrate contamination on: (A)a single microneedle and (B) a 50- microneedle out-of-plane

array.

• Improved coating uniformity and elimination of base-substrate contamination after addition of coating-solution excipients and use of a micro-dip-coating device for (C) a single microneedle, (D) a 50-microneedle out-of-plane array.

• (E) an in-plane microneedle row. (E1) uncoated,(E2) 25% coated, (E3)

50% coated ,(E4) 75% coated ,(E5) 100% coated.

COATING A LARGE RANGE OF COMPOUNDS

•Breadth of molecules and micro particles coated onto microneedles.•Fluorescent or bright field micrographs of single microneedles coated with:(A)Calcein(B)Vitamin B,(C)Bovine serum albumin

conjugated (BSA) With Texas Red.

(D) plasmid DNA conjugated with YOYO1, (E) modified vaccinia virus — Ankara conjugated with YOYO-1. (F) 1-μm diameter barium sulfate Particles.(G) 10-μm diameter latex particles.

DELIVERY FROM COATED MICRONEEDLES

1. No residue on skin surface

2. Increased bioavailability

3. Vaccine delivery – potent immune response

4. Storage - antigen stability

5. Eliminate cold-chain storage.

IONTOPHORETIC PATCHES

Iontophoretic patches use a tiny electrical current to promote flow of the drug (usually charged) through the skin.

IONTOPHORETIC PATCHES

IONTOPHORETIC PATCHES

MICRO CHANNEL BASED TRANS DELIVERY SYSTEM USING RF

A novel system for active transdermal drug delivery, based on creating microchannels in the skin using radio-frequency (RF) electrical current.

This novel and unique approach provides various advantages such as;

- A predicted and precisely controlled drug delivery rate,

- Efficient delivery of a wide range of molecular sizes including proteins and other macromolecules,

- A convenient, pain-free system suitable for self application at home.

MICRO CHANNEL BASED TRANS DELIVERY SYSTEM USING RF

PRINCIPLE

It is based on principle of RF ablation, a well-known medical technology to eliminate living cells which used to cut through tissues in minimally invasive operations or to destroy small tumors in the kidney and liver by passing an alternating electrical current at a frequency above 100 KHz (radio frequency) through the area.

METHOD

Application of RF device by placing a closely spaced array of tiny electrodes with very precise dimensions against the skin

Alternating electrical current is transferred through each of the microelectrodes

Cell ablation and Cell ablation and form the microscopic passage

passage

Application of transdermal patch and microchannels serve as aquatic channels into the inner layers of the skin

Formation of RF microchannels with consistent, well-controlled depths

ELECTRODE

DRUG DELIVERY DEVICE The system consists of the device, which is used to pretreat the

skin and form the RF microchannels in the outer layers of the skin, and a patch containing the drug, which is placed on top of the pretreated skin.

(a) THE DEVICE(b) THE MICROELECTRODE ARRAY(c) THE PATCH

EFFECT OF PATCH TECHNOLOGY ON PHARMACOKINETIC PROFILES:

For drug delivery, the microchannels may last up to 24 h. At 36 h, the delivery through treated skin returns to the values of intact skin.

To achieve a sustained drug flux for 24 h, incorporating the active material into a moist matrix such as a hydrogel that serves as an infinite reservoir.

The study was conducted on six healthy adult volunteers in each test group by Galit Levin. The results revealed differences in the plasma-drug levels and profiles between the treatments.

FACTORS INFLUENCES THIS SYSTEM

Molecular size: In case of small-molecule drugs, size can be increased significantly by pretreatment & for macromolecules, like peptides and proteins, also help in delivering them systemically through the skin by this technology.

Water solubility: Water-soluble molecules, can be easily delivered. Water-insoluble drugs can be delivered by increasing the water solubility through a suitable formulation.

Concentration: In contrast to any passive delivery, It is help in increasing the drug concentration on the skin in the vicinity of the microchannels will result in a higher delivery rate.

FACTORS INFLUENCES THIS SYSTEM Microchannel density: By increasing the microchannel

density (MCs/cm2 ), a higher amount of drug can be delivered in efficient manner.

Duration of delivery: The drug delivery can be enhanced up to 24 h using this technology

Dosage forms: A patch is the most convenient dosage form for drug delivery. Beside this, gels, Creams & the other semisolid dosage forms can be used.

Drug profile: The result of the transdermal delivery using RF cell ablation can be a peak-plasma profile or a constant blood level, depending on the type of patch technology used

FACTORS INFLUENCES THIS SYSTEM

Type of patches: A reservoir patch, usually a water-based hydrogel, can be used to incorporate small or large molecules and apply them on the skin. For proteins, the use of a printed patch is advisable for stability purposes.

Lack of reservoir in the skin: In contrast to passive delivery, the microelectronic system based on RF cell ablation used in this study delivered water-soluble drugs that cannot be accumulated in the lipidic stratum corneum. No issue of reservoir formation exists.

Main Application

For protein delivery

For hydrophilic

drug & hydrophobic

drug

For macromole-

cules

PATCH TECHNOLOGY FOR PROTEIN DELIVERY:

Transdermal delivery of large proteins is a novel and exciting method because no commercial technology currently available incorporates proteins into transdermal patches.

The manufacturing method involves dispensing very small droplets of a concentrated protein solution on a transdermal liner in a predetermined pattern.

The liquid is dried, leaving a dry and thin layer of formulated protein on top of the liner.

The highly water-soluble proteins are dissolved by the interstitial fluid that is secreted from the skin through the RF microchannels, thus forming a highly concentrated protein solution in situ.

PATCH TECHNOLOGY FOR PROTEIN DELIVERY:

PATCH TECHNOLOGY FOR PROTEIN DELIVERY:

The diffusion of the dissolved molecules occurs through the RF microchannels into the viable tissues of the skin across a steep concentration gradient.

This process brings about a high delivery rate and a peak-blood profile of the drug resembling that of a subcutaneous injection.

This manufacturing method enables complete and flexible control of the drug load on the patch, control of patch size and shape, and high manufacturing yield with minimal protein losses.

In addition, this method fully retains the stability and biological activity of the protein drug.

PATCH TECHNOLOGY FOR HYDROPLILIC DRUG & HYDROPHOBIC DRUG Under this technique, pretreating the skin allows

aquatic channels to form across the stratum corneum, which provides significant enhancement in the permeability of water-soluble compounds.

Drugs that exhibit insufficient solubility in water can still benefit from the technology.

By increasing solubility using various formulation approaches, such as drug-cyclodextrin complexes or dissolving the drug in a water-alcohol mixture, the drugs are also able to permeate the skin

PATCH TECHNOLOGY FOR HYDROPLILIC DRUG & HYDROPHOBIC DRUG

The results show enhanced transdermal delivery with the hydrophilic compounds—granisetron hydrogen chloride (HCl) and lidocaine HCl. Lidocaine HCl is more water-soluble than diclofenac sodium and had higher delivery rates.

The effect of the compound concentration on its delivery rate was shown with testosterone (2% versus 6% in aqueous solution) and lidocaine HCl (2% versus 5% in aqueous solution).

The delivery rate increased linearly with the concentration of the loaded compound.

PATCH TECHNOLOGY FOR MACROMOLECULES

The delivery of these macromolecules through a full-thickness porcine skin that had been pretreated with the device. An increase in molecular size brought about a decrease in delivery rate.

The largest 70-kDa molecule was successfully delivered transdermally through the RF microchannels.

Advantage over other conventional techniques

A convenient, painless, and less invasive alternative to injection, a common method for administering large proteins and peptides in low manufacturing cost.

In contrast to oral delivery , this avoid first pass effect and offers the benefit of immediate cessation of drug administration in case of an adverse effect or overdose.

In contrast to passive delivery , this allow for the delivery of water-soluble drugs

In contrast to Iontophoresis , this is use for long time There is also no molecular size limitation, no molecular electrical charge requirement, and no specific formulation pH constraint.

In contrast to micro needle , this is use for potent & less potent drug, the more extended release the delivery system

So, Microchannel based Trans Delivery System by using Radio Frequency ( RF) is a Novel Approch for Drug delivery system

PRODUCTS ON THE MARKET, OR IN DEVELOPMENT INCLUDE

Clonidine Works as an agonist of adrenaline at the

presynaptic a2 adrenergic Product name = Catapres-TTS®

used to treat hypertension

ETHINYLESTRADIOL (EO) AND NORELGESTROMIN (N)

Product name = Ortho-Evra®

Used for Contraception Type of patch = Drug-in-Adhesive Frequency of application = weekly

OH

H

H H

Ethinylestradiol (an estrogen)

HON

OH

H H

HO

H H

Norelgestromin (a progestin)

FentanylProduct Name = Duragesic®

Used for: AnalgesiaType of Patch = Drug-in-AdhesiveFrequency of Application = Weekly

N

O

N

NicotineProduct name = Habitrol®, Nicoderm – CQ®, Nicotrol®, Prostep®

Used for: Smoking cessationFrequency of administration = Daily

NitroglycerinWorks by producing nitric oxide (NO), which then acts as a vasodilatorProduct Names = Nitro-Dur®, Transderm-Nitro®

Used for: AnginaType of Patch = Nitro-Dur is Drug-in-adhesive Nitrodisc is reservoirFrequency of administration = Daily

EstradiolProduct Name = Alora®, Climara®, Esclim®, Estraderm®, FemPatch®, Vivelle®, Vivelle-DOT®

Used for: Hormone replacementType of Patch: Drug-in-adhesiveFrequency of application = weekly

ScopolamineWorks as competitive antagonist of acetylcholine at the muscarinic receptorProduct Name = Transderm Scop®

Used for: Motion Sickness

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