TRANSDERMAL DRUG DELIVERY SYSTEM

PRESENTED BY h SHEETAL NAGAR M.PHARM DEPARTMENT OF PHARMACEUTICES

INTRTTTTTOD INTRODUCTION

INTRODUCTION
WhatBBBBCTION UI 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

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THE NEED FOR DEVELOPMENT OF TRANSDERMAL DELIVERY SYSTEM ‡ ‡ ‡ POOR BIOAVAILABILITY FIRST PASS EFFECT RAPID BLOOD SPIKES (HIGH or LOW) .

The molecular size of the drug should be small. Cause no Pain No pitfalls of Enzymes & pH Reduce dosing. Multi-day therapy Capacity to terminate drug effects Drugs that require high blood levels cannot be administered. Difficulty of permeation of the drug through human skin           . Is not a means to achieve rapid bolus type drug input. to reach and gain access to the systemic circulation. Constant dosing. Adequate solubility of the drug in both lipo-phillic and aqueous environments.ADVANTAGES  DISADVANTAGES  Avoidance of absorption and shortened metabolism of GIT.

SKIN ANATOMY .

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

 It comprises a multi-layered ´brick and mortarµ like structure of keratin-rich corneocytes(bricks) in an intercellular matrix (mortar). cholesterol sulfate and sterol/wax esters .with the hydrocarbon chains aligned and polar head groups dissolved in an aqueous layer . free fatty acids. It also Composed primarily of long chain ceramides. . triglycerides. In the initial layers of the stratum corneum material rearranges to form broad intercellular lipid lamellae which then associate into lipid bi-layers .The stratum corneum consists of 10-15 layers of corneocytes and varies in thickness from approx 10-15 m in the dry state to 40 m when hydrated. cholesterol.

As a result of the lipid composition. lamellar gel and lamellar liquid crystal phases creating various domains within the lipid bilayers . Also consists of Viable epidermis (150µm thick) Papillary layer of dermis (100-200)µm thick) DERMIS It is supplied by blood to convey nutrients. remove waste & regulate body temperature and drug is well absorbed by this route . the lipid phase behavior is different from that of other membranes. The presence of intrinsic & extrinsic proteins. may also affect the lamellar structure of the corneum. The hydrocarbon chains are arranged into regions of crystalline.

lipids and antibodies. attaching the dermis to the underlying structures.8 & absorbs drugs. HAIR FOLLICLES: They have sebaceous glands which produces sebum and includes glycerides. . secretes proteins.SUBCUTANEOUS TISSUE: This is a sheet of the fat containing areolar tissue known as the superficial fascia. cholesterol and squalene. Its function is to control heat. SKIN APPENDAGES: Sweat glands produces sweat of pH 4-6.

Effect on target organ. Uptake of drug by capillary network in the dermal papillary layer. Sorption by stratum corneum and penetration through viable epidermis. Diffusion of drug from rate limiting membrane to stratum corneum. 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.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. .

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) ´ ´ ´ ´ ´ ´ ´ .

the molecule must partition into and diffuses through the lipid lamellae between each keratinocyte. .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.

´ Percutaneous Absorption: Percutaneous Absorption involves passive diffusion of substances through the skin. Trans-appandageal . Mechanism of permeation can be : 1. Trans-epidermal 2.

Climara. Nicoderm. Duragesic. Exelon Matrix diffusion controlled TDDSNitroDur  ´  ´ Microreservoir dissolution controlled TDDSAndroderm  . Habitrol. Clonidine-TTS Drug in adhesive-type TDDS Daytrana.DIFFERENT APPROACHES OF TDDS SYSTEMS  ´ Membrane permeation-controlled TDDS Transderm-Scop.

Starch Synthetic Polymers Eg.Polyamide :: Drug . PVC.Basic Components of TDDS Polymer Matrix ‡ Natural Polymers Eg. Cellulose.

Acrylic based ‡ Backing laminates Eg.Calciumthioglycolate ´ ‡ Pressure sensitive adhesive (PSA) Eg. Permeation enhancers (i) Solvents² Eg. Methanol.. Silicon based . Flexible Polyurethane .Sodium deoxycholate (iii) Miscellaneous-. Sodium Lauryl Sulphate. Propyleneglycol (ii) Surfactants³Eg. Aluminium foil.BASIC COMPONENTS OF TDDS CONT«.

FACTORS CONSIDERATION FOR TDS DEVELOPMENT Skin Characteristics ´ Bioactivity of drug ´ Formulation ´ Adhesion ´ System design ´ .

.POLYMER MEMBRANE PERMEATIONCONTROLLED 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 of angina pectoris.

MATRIX DIFFUSION CONTROLLED TDDS Nitro Dur (Nitroglycerine) used for once a day medication of angina pectoris. .

dur® System (Nitroglycerin) for once a day treatment of angina pectoris. .MICRORESERVOIR CONTROLLED Nitro.

These can be either a single layer or multi-layer.DRUG IN ADHESIVE PATCHES A system in which the drug is incorporated directly into the adhesive. Usually used for smaller molecular weight compounds. rather than into a separate layer. Sometimes referred to as the ´matrix type patchµ .

Film Backing Drug/Adhesive Layer Protective Liner (removed prior to use) skin .SCHEMATIC DRAWING OF THE MATRIX (DRUG-IN-ADHESIVE) TYPE OF PATCH.

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 Rate-controlling Membrane Contact Adhesive Protective Peel Strip (removed prior to use) .

solubility. molecular size. transient diffusion) Physicochemical properties of penetrant (pKa.FACTOR INFLUENCE THE TRANSDERMAL ROUTE ´ ´ ´ ´ ´ ´ ´ Time scale of permeation (steady-state vs. partition coefficient) Integrity and thickness of stratum corneum Density of sweat glands and folicles Skin hydration Metabolism Vehicle effects . binding affinity. stability.

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:  Tensile Strength:  Folding Endurance:  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 .

But if 3 patches have content in the range of 75% to 125%. 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 . Content uniformity test 10 patches are selected and content is determined for individual patches. then the transdermal patches pass the test . If these 20 patches have range from 85% to 115%.then additional 20 patches are tested for drug content. then transdermal patches pass the test of content uniformity.

drug in solution is estimated spectrophotometrically by appropriate dilution . After sonication and subsequent filtration.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.

The films are weighed again after a specified interval until they show a constant weight. Moisture content: The prepared films are weighed individually and kept in a desiccators containing calcium chloride at room temperature for 24 h. Initial weight ² Final weight % Moisture content = ---------------------------------X100 Final weight . The percent moisture content is calculated using following formula.

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

The length of each strip is measured and variation in length is measured by determining percent constriction.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. Zero percent constriction is equivalent to 100 percent . one strip is cut from the centre and two from each side of patches.

Folding endurance is determined by repeatedly folding the film at the same place until it break. 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 . polymeric films are sandwiched separately by corked linear iron plates.  Tensile Strength: To determine tensile strength.Folding Endurance: Evaluation of folding endurance involves determining the folding capacity of the films subjected to frequent extreme conditions of folding . The number of times the films could be folded at the same place without breaking is folding endurance value.

b is thickness of film.Tensile strength=F/a . .  Water vapour transmission studies (WVT): For the determination of WVT. b (1+L/l) (2) F is the force required to break. L is length of film. l is elongation of film at break point. a is width of film. weighed one gram of calcium chloride and placed it in previously dried empty vials having equal diameter.

Adhesive studies: Peel Adhesion properties Tack properties Thumb tack test Rolling ball test Quick stick (Peel tack) test Probe tack test Shear strength properties or creep resistance .

Molecular weight of adhesive polymer. the type and amount of additives are the variables that determined the peel adhesion properties.Peel Adhesion test: ‡In this test. and the force required for tape removed is measured . the force required to remove an adhesive coating form a test substrate is referred to as peel adhesion. 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.

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

The distance the ball travels along the adhesive provides the measurement of tack. 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. which is expressed in inch .In this test. upward facing adhesive (Figure-2).

which is expressed in ounces or grams per inch width . . 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.Quick stick (peel-tack) test In this test.

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

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 .Probe Tack test In this test.

In vitro release studies 
The 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 Studies 
Animal models Human volunteers

RECENT ADVANCES IN TDDS

´ Microneedles

´ Microchannel

based Rf

´ Ionotopheresis

Smaller the hypodermic needle. hollow) . glass . Various types of needles have been fabricated ex: solid (straight. Microneedles have been fabricated with various materials such as: metals.INTRODUCTION TO MICRONEEDLES ´ They are one micron in diameter and range from 1100 microns in length. bent filtered. silicon. silicon dioxide. polymers.

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

MAJOR DIFFERENCE TRANSDERMAL PATCH TRANSDERMAL MICRONEEDLES .

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

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 .

 ‡ . cutting speed of 2mm/s .MICRONEEDLE FABRICA MICRONEEDLE FABRICAMICRONEEDLE FABRICATION N TION MICRONEEDLE FABRICATION  ‡ ‡ Laser cutting : Stainless steel sheets using Infrared laser.air purge at 140KPa. 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 ²plane) were pushed out manually by using forceps or Hypodermic needle and then bent at 90 degrees with aid of a single ²edged razor blade. Prepared either by individual rows (¶in-plane·) or two dimensional array into plane and bent at 90 degrees (¶out of -plane·). shapes were obtained from AUTOCAD software and three phases are required.

2% 10-um latex beads .then dried and stored Coating solution : composed of 1% carboxy-methylcellulose sodium salt+0.10% barium sulfate .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 . . 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 .Electro polishing : In a solution of Glycerin.microneedles as anode and vibrated at 10Hz to remove bubbles with a current density of 1.1% bovine serum .0. ortho-phosporic acid(85%) and water (6:3:1).01% sulforhodamine calcein .5% 20um latez beads .8. A copper plate was used as cathode .5%(w/v) Lutrol F-68 NF + mode l drug Model drugs used are 0.in a 300ml glass beaker at 700 at a stirring rate 150 rpm.05% luciferase plasmid DNA .

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 outof-plane microneedles.

Multiple out-of-plane rows of microneedle. . A patch of 50 microneedles are taken . single-sided polyethylene medical foam tape using a co 2 laser and then manually inserted into each slit from the nonadhesive side of the foam tape and glued to the foam tape using a medical grade adhesive. In the middle of this disc.8-mm thick. 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.MICRONEEDLE PATCH ASSEMBLY: Multiple In-plane rows of microneedles. The stainless steel microneedle array was then attached to this exposed adhesive. A double-sided. 7mm long were laser cut into a 1.8 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. A polyethylene medical foam tape (0. 1st ten slits each 75um wide &7. singlesided medical foam tape using the CO2 laser.6mm thick. The tape is then slipped over the microneedles . A circular disc of 20mmdiameter was first cut from a 0. polyethylene-phthalate carrier tape is attached.

especially in the case of out-of-plane microneedle arrays.MICRONEEDLE ARRAY PATCHES ‡The adhesive layer was periodically disrupted via small holes or slits to allow the microneedles to stick out for penetration. 4B) ‡out-of-plane microneedles (Fig. . ‡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. 4D). ‡Microneedle arrays prepared on the basis of this design are shown for patches of in-plane microneedles (Fig.

‡ Improved coating uniformity and elimination of base-substrate contamination after addition of coatingsolution excipients and use of a microdip-coating device for (C) a single microneedle. . non-uniform coatings with base-substrate contamination on: (A)a single microneedle and (B) a 50.(E2) 25% coated. ‡ Poor. (D) a 50-microneedle outof-plane array.MICRO-DIP-COATING OF MICRONEEDLES: ‡ Poor and good microneedle coatings via bright field micrographs of vitamin B coated microneedles. (E3) 50% coated . (E1) uncoated. ‡ (E) an in-plane microneedle row.(E5) 100% coated.(E4) 75% coated .microneedle out-of-plane array.

COATING A LARGE RANGE OF COMPOUNDS ‡Breadth of molecules and micro particles coated onto microneedles. . (C) Bovine serum albumin conjugated (BSA) With Texas Red. ‡Fluorescent or bright field micrographs of single microneedles coated with: (A) Calcein (B) Vitamin B. (D) plasmid DNA conjugated with YOYO1.m diameter barium sulfate Particles.m diameter latex particles. (G) 10. (E) modified vaccinia virus ³ Ankara conjugated with YOYO-1. (F) 1.

Storage . Eliminate coldchain storage. Vaccine delivery potent immune response 4. Increased bioavailability 3.DELIVERY FROM COATED MICRONEEDLES 1.antigen stability 5. No residue on skin surface 2. .

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

IONTOPHORETIC PATCHES .

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IONTOPHORETIC PATCHES .

.A convenient.MICRO CHANNEL BASED TRANS DELIVERY SYSTEM USING RF ´ ´ A novel system for active transdermal drug delivery.Efficient delivery of a wide range of molecular sizes including proteins and other macromolecules. . This novel and unique approach provides various advantages such as. .A predicted and precisely controlled drug delivery rate. . based on creating microchannels in the skin using radiofrequency (RF) electrical current. 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 wellknown 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
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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.

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EFFECT OF PATCH TECHNOLOGY ON PHARMACOKINETIC PROFILES:
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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.

can be easily delivered. size can be increased significantly by pretreatment & for macromolecules. It is help in increasing the drug concentration on the skin in the vicinity of the microchannels will result in a higher delivery rate. Water-insoluble drugs can be delivered by increasing the water solubility through a suitable formulation. like peptides and proteins. also help in delivering them systemically through the skin by this technology.FACTORS INFLUENCES THIS SYSTEM ´ Molecular size: In case of small-molecule drugs. ´ ´ . Concentration: In contrast to any passive delivery. Water solubility: Water-soluble molecules.

depending on the type of patch technology used ´ ´ ´ . Beside this.FACTORS INFLUENCES THIS SYSTEM ´ Microchannel density: By increasing the microchannel density (MCs/cm2 ). a higher amount of drug can be delivered in efficient manner. Drug profile: The result of the transdermal delivery using RF cell ablation can be a peak-plasma profile or a constant blood level. gels. Creams & the other semisolid dosage forms can be used. 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.

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.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. Lack of reservoir in the skin: In contrast to passive delivery. the use of a printed patch is advisable for stability purposes. No issue of reservoir formation exists. ´ .

Main Application For protein delivery For hydrophilic drug & hydrophobic drug For macromolecules .

leaving a dry and thin layer of formulated protein on top of the liner. The manufacturing method involves dispensing very small droplets of a concentrated protein solution on a transdermal liner in a predetermined pattern. The highly water-soluble proteins are dissolved by the interstitial fluid that is secreted from the skin through the RF microchannels. .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 liquid is dried. 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. control of patch size and shape. This manufacturing method enables complete and flexible control of the drug load on the patch. In addition. and high manufacturing yield with minimal protein losses. this method fully retains the stability and biological activity of the protein drug. This process brings about a high delivery rate and a peak-blood profile of the drug resembling that of a subcutaneous injection.

such as drug-cyclodextrin complexes or dissolving the drug in a water-alcohol mixture. the drugs are also able to permeate the skin ´ ´ . By increasing solubility using various formulation approaches. Drugs that exhibit insufficient solubility in water can still benefit from the technology.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.

The delivery rate increased linearly with the concentration of the loaded compound. ´ ´ . 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).PATCH TECHNOLOGY FOR HYDROPLILIC DRUG & HYDROPHOBIC DRUG ´ The results show enhanced transdermal delivery with the hydrophilic compounds²granisetron hydrogen chloride (HCl) and lidocaine HCl.

PATCH TECHNOLOGY FOR MACROMOLECULES ´ The delivery of these macromolecules through a fullthickness 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.

In contrast to micro needle . a common method for administering large proteins and peptides in low manufacturing cost. this avoid first pass effect and offers the benefit of immediate cessation of drug administration in case of an adverse effect or overdose. this is use for long time There is also no molecular size limitation. In contrast to passive delivery . and less invasive alternative to injection. the more extended release the delivery system . no molecular electrical charge requirement. painless. Microchannel over other Advantage based Trans Delivery System by using Radio Frequency ( RF) is conventional techniques a Novel Approch for Drug delivery system In contrast to Iontophoresis . this allow for the delivery of watersoluble drugs So. In contrast to oral delivery . and no specific formulation pH constraint. this is use for potent & less potent drug.A convenient.

OR IN DEVELOPMENT INCLUDE ´ ´ ´ ´ Clonidine Works as an agonist of adrenaline at the presynaptic E2 adrenergic Product name = Catapres-TTS® used to treat hypertension .PRODUCTS ON THE MARKET.

ETHINYLESTRADIOL (EO) AND NORELGESTROMIN (N) Product name = Ortho-Evra® ´ Used for Contraception ´ Type of patch = Drug-in-Adhesive ´ Frequency of application = weekly ´ .

Fentanyl Product Name = Duragesic® Used for: Analgesia Type of Patch = Drug-in-Adhesive Frequency of Application = Weekly .

Nicotrol®.Nicotine Product name = Habitrol®. Prostep® Used for: Smoking cessation Frequency of administration = Daily . Nicoderm ² CQ®.

Nitroglycerin Works by producing nitric oxide (NO). Transderm-Nitro® Used for: Angina Type of Patch = Nitro-Dur is Drug-in-adhesive Nitrodisc is reservoir Frequency of administration = Daily . which then acts as a vasodilator Product Names = Nitro-Dur®.

Climara®. Vivelle-DOT® Used for: Hormone replacement Type of Patch: Drug-in-adhesive Frequency of application = weekly . FemPatch®. Esclim®. Vivelle®.Estradiol Product Name = Alora®. Estraderm®.

Scopolamine Works as competitive antagonist of acetylcholine at the muscarinic receptor Product Name = Transderm Scop® Used for: Motion Sickness .

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