TRANSDERMAL DRUG DELIVERY SYSTEMS

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TRANSDERMALDRUG DELIVERYA S Adebayo PhD INTRODUCTION Transdermal drug delivery.
systems TDDS are dosageforms designed to facilitate thepassage of therapeuticquantities of drug substancesthrough the skin and into the.
general circulation for systemic SKIN STRUCTURE The epidermis almost impermeable deadlayer of cells It controls the percutaneousabsorption of drugs and other chemical.
The dermis matrix of connective tissuemade up of fibrous proteins collagen elastin reticulin embedded in mucopolysaccharide It also contains nerves blood vessels andlymphatic vessels and appendages such as.
sweat glands Branches from arterial plexus deliver blood tosweat glands hair follicles subcutaneous fatand the dermis DRUG TRANSPORT.
THROUGH THE SKIN The epidermis is very selective and itprovides major control for the permeationof the skin Drug entry into the skin can occur through.
three possible routes Through the hair follicles Via the sweat duct Across the stratum corneum FACTORS AFFECTING.
PERCUTANEOUS DRUG ABSORPTION Concentration of drug The amount of drugabsorbed per unit surface area per time increases withincrease in concentration of drug in the TDDS Surface area of application More drug is.
absorbed from TDDS with larger size Affinity of drug for skin and for the base Physicochemical attraction of drug should be higher forthe skin than for the base PC should be adequate Molecular weight of the drug Drugs of molecular.
weight MW between 100 800 can permeate the skinprovided the lipid solubility is adequate The idealmolecular size of drugs for TDDS is 100 400 PARTITION COEFFICIENT Compounds with.
partition coefficientsindicating an ability todissolve in both oil andwater i e log P of 1 3 would permeate the skin.
relatively rapidly 6 29 20 7 FACTORS AFFECTINGPERCUTANEOUS DRUG ABSORPTION Hydration of the skin The skin should.
be adequately hydrated for efficientdrug absorption from TDDS Site of application Better delivery isachieved when TDDS is applied to sitewith thin horny layer see below .
Duration of application The longer themedicated application remains on thegreater the total drug absorbed VARYING SKIN THICKNESSESAT DIFFERENT BODY REGIONS .
Rushmer R F Buettner K J K Short J M Odland G F The skin Science 1966 154 343 348 FORMULATION OFThe main components of TDDS The drug.
The base delivery device The Percutaneous absorptionenhancers 6 29 20 10 DRUGS IN TDDS.
Examples of drugs meeting the criteria fordelivery in TDDS are 1 Clonidine Catapress TTS Four layeredpatch for antihypertensive delivery of clonidineover 7 days.
2 Estradiol Estraderm Norvatis Four layered patch and Vivelle Norvatis three layered patch Both are designed to release 17 estradiol continuously 3 Nicotine Habitrol Norvatis consumer .
Multilayered patch for controlling nicotinedependence 6 29 20 11 DELIVERY DEVICES These are also known as transdermal.
patches Designed to support the passage of drugsubstances from the surface of the skinthrough its various layers into the systemiccirculation .
The two most common types are the monolithic systems membrane controlled TDS 6 29 20 12 MONOLITHIC SYSTEMS.
Monolithic systems The designincorporates a drug matrix layerbetween the device backing andthe frontal layers The polymer matrix controls the.
rate at which the drug is releasedfor percutaneous absorption 6 29 20 13 MEMBRANE CONTROLLED Membrane controlled systems .
Designed to contain adrug reservoir or pouch usually in liquid or gel form a rate controlling membrane abacking adhesive and.
protecting layers 6 29 20 14 MEMBRANE CONTROLLEDSYSTEMS CONT These systems may be prepared.
pre constructing the delivery unit filling in the drug reservoir and aprocess of lamination whichinvolves a continuous process ofconstruction dosing and sealing .
6 29 20 15 ADVANTAGES OF TDDS Avoidance of gastrointestinal absorptiondifficulties caused by pH enzyme and druginteraction with food etc .
Suitable in cases where oral route is notappropriate as in vomiting diarrhea Avoidance of the first pass metabolism in the Avoidance of the inconveniences of parenteral therapy Improved patient compliance due to the lower frequency.
of dosing 6 29 20 16 DISADVANTAGES OF TDDS Onlyrelatively potent drugscan be so formulated.
Incidence of contactdermatitis has beenreported in some patients6 29 20 17 PERCUTANEOUS.
ABSORPTION ENHANCERS Chemical dimethyl acetamideenhancers dimethyl formamideAgents which.
reversibly alter dimethyl sulfoxidethe physico Ethanolnature of the oleic acidstratum polyethylene glycolscorneum to.
reduce its propylene glycol sodium laurylsulphate diffusionalresistance 6 29 20 18 NEW ENHANCERS.
Over the past 2 decades several chemical skinpermeation enhancers have been designed synthesized and evaluated Azone 1 dodecylazacycloheptan 2 one... SEPA 2 n nonyl 1 3 dioxolane .
1 2 decylthio ethyl azacyclope... HPE 101 4 decyloxazolid 2 one DermacTM SR 38 dodecyl N N dimethylamino isopropionate DDAIP NexACT 88 6 29 20 19.
STRUCTURES OF THE SKINPERMEATION ENHANCERS HPE 101 DERMAC SR 386 29 20 20 ADVERSE LOCAL REACTIONS AND.
STRATEGIES FOR REDUCTION Adverse skin responses tochemical exposure are variable may be immediate or delayed Long or short duration .
Irritant or allergic 6 29 20 21 ADVERSE LOCAL REACTIONS ANDSTRATEGIES FOR REDUCTION Dermatologicaland transdermal formulations.
contain a complex mixture of active and inactiveingredients adverse reactions may be due to a formulation additive excipient and not necessarily an active compound it is well known that the pressure sensitive adhesive.
used to produce intimate contact with the skin is moreoften the source of cutaneous reactivity not the drug many of the inactive ingredients used in topicalpharmaceutical dosage forms have the ability to alterthe barrier function of the skin.
6 29 20 22 MITIGATING ADVERSELOCAL REACTION Plant extracts reputed to possess anti irritant propertiesand have been recommended for use in cosmetic.
formulations Tea tree oil Borage seed oil Paraguay tea extract Kola nut extract.
Oil of rosemary Lavender oil 6 29 20 23 MITIGATING ADVERSELOCAL REACTION .
Strontium nitrate Cosmederm 7TM reduce the sensory irritation and erythemaproduced following application of a 70 freeglycolic acid peel histamine induced itch A combination of compounds oleic acid .
a short chain length alcohol and aglycol all gelled with a carbomer has been found to reduce chemical induced inflammation associated with thetopical application of several CELLEDIRM .
Cellegy Pharmaceuticals Inc 6 29 20 24 PERCUTANEOUS ABSORPTIONENHANCERS CONT Ionophoresis Delivery of charged compounds.
across the skin membrane using appliedelectrical field E g Lindocaine Dexamethasone Insulin.
verapamil propranolol 6 29 20 25 PERCUTANEOUS ABSORPTIONENHANCERS CONT .
Sonophoresis Use of High frequencyultrasound to enhance transdermaldrug delivery Therapeutic frequency ultrasound 1 3MHz is most commonly used at intensity.
in the range of 0 2W cm2 Therapeutic ultrasound has been attempted toenhance transdermal transport of more than6 29 20 26 MECHANISMS OF.
SONOPHORETIC TRANSPORT Cavitation Acoustic streaming around Electroporation Thermoporation.
6 29 20 27 MECHANISMS OFSONOPHORETIC Ultrasound exposure in the therapeutic rangecauses cavitation in the keratinocytes of the.
stratum corneum Oscillations of the ultrasound inducedcavitation bubbles near the keratinocyte lipidbilayer interfaces may in turn causeoscillations in the lipid bilayers causing.
structural disorder of the SC lipids Shock waves generated by the collapse ofcavitation bubbles at the interfaces may alsocontribute to the structure disordering effect 6 29 20 28.
ULTRASOUND INDUCEDCAVITATION BUBBLES INSTRATUM CORNEUM MITRAGOTRI 6 29 20 29 HUMAN SKIN PERMEABILITY.
TO INSULIN6 29 20 30 AGENTS FOR APPLICATIONOF SONOPHORESIS steroidal anti inflammatory drugs.
hydrocortisone dexamethasone non steroidal anti inflammatory drugssuch as salicylates and ibuprofen anesthetic agents such as lidocaine.
proteins such as insulin 6 29 20 31 EXPERIMENTAL SET UP FORSONOPHORESIS DELIVERY6 29 20 32.
TRANSDERMAL DRUGDELIVERY SYSTEMSTHANK YOU FOR YOUR ATTENTION6 29 20 33.
adverse reactions may be due to a formulation additive (excipient) and not necessarily an active compound. it is well known that the pressure sensitive adhesive used to produce intimate contact with the skin is more often the source of cutaneous reactivity & not the drug.

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