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Premium member Presentation Transcript TOPICAL AND TRANSDERMAL DRUG DELIVERY : TOPICAL AND TRANSDERMAL DRUG DELIVERY BY MINYAHIL ALEBACHEW WOLDU ( Bpharm , Clinpharm MSc GC student, Jimma Uiversity ) Ethiopia 01/05/2012 1 Topical and Transdermal Drug DeliveryCONTENTS: CONTENTS OBJECTIVES INTRODUCTION DESIGN OF TOPICAL AND TD PRODUCTS ALTERNATIVE TECHNIQUES FOR TDD COUNSELING ISSUES RELATED TO TOPICAL PRODUCTS CONCLUSION REFERENCES 01/05/2012 2 Topical and Transdermal Drug DeliveryOBJECTIVES: OBJECTIVES Explain basic concepts of skin physiology Classify the different types of commonly used topical and transdermal delivery systems Compare and contrast the advantages and disadvantages of various topical and transdermal products Counsel patients and health care professionals to select the most appropriate delivery system for effective therapeutic applications 01/05/2012 3 Topical and Transdermal Drug Delivery‘’Topical and Transdermal Drug Delivery is a success through a deep understanding of the skin” : ‘’Topical and Transdermal Drug Delivery is a success through a deep understanding of the skin” Transpharma Medical www.ondrugdelivery.com 01/05/2012 4 Topical and Transdermal Drug DeliveryINTRODUCTION : INTRODUCTION The human skin 10-70 hair follicles and 200-250 sweat ducts/cm 2 one of the most readily accessible organs Skin of an average adult body covers a surface of approximately 2 m 2 and receives about one-third of the blood circulating through the body skin as the port of drug administration recognized for several decades but skin is a very difficult barrier to the ingress of drug materials 01/05/2012 5 Topical and Transdermal Drug DeliverySkin anatomy: Skin anatomy 01/05/2012 Topical and Transdermal Drug Delivery 6 The two major layers of the skin are the outer epidermis and the inner dermis. The epidermis stratiﬁed squamous keratinizing epithelial tissue Keratinocytes (abundant) no capillaries present The Dermis made of an irregular type of ﬁbrous connective tissueSkin anatomy…: Skin anatomy… Subcutaneous tissue mechanical cushion, thermal barrier, energy storage Appendages Sweat glands hair follicles Sebaceous glands Nails 01/05/2012 Topical and Transdermal Drug Delivery 7PowerPoint Presentation: 01/05/2012 Topical and Transdermal Drug Delivery 8Functions of skin: Functions of skin Mechanical function mainly from the dermis and s.c . tissues epidermis (minor) Protective function Microbiological barrier Chemical barrier Radiation barrier Heat barrier/temperature regulation Immune response 01/05/2012 Topical and Transdermal Drug Delivery 9Hx: Hx Over the past three decades, developing controlled drug delivery has become increasingly important in the pharmaceutical industry The first approved transdermal drug delivery system ( Transderm Scop ® Patch ),Novartis,1979, by FDA Which have opened the door to the current transdermal delivery systems TDD has evolved a successful alternative to systemic drug delivery 01/05/2012 10 Topical and Transdermal Drug DeliveryFactors Affecting the Extent and Rate of Topical and Percutaneous Drug Absorption and Transportation: Factors Affecting the Extent and Rate of Topical and Percutaneous D rug A bsorption and Transportation skin physiology , physicochemical properties of drugs and excipients , as well as fabrication and design of the delivery systems 01/05/2012 11 Topical and Transdermal Drug DeliveryTopical Vs Transdermal: Topical Vs Transdermal Both are intended for external use. Topical dermatologic products are intended for localized action on one or more layers of the skin unintentionally reach systemic circulation usually in sub-therapeutic conc . T ransdermal drug delivery systems use the percutaneous route for systemic drug delivery, but the skin is not the primary target organ 01/05/2012 12 Topical and Transdermal Drug DeliveryPowerPoint Presentation: Transdermal drug delivery means that a pharmaceutical compound is moved across the skin — the dermis—for subsequent systemic distribution. Hence, strictly semantically this does not only include the more commonly understood “patch”, but also traditional subcutaneous administration by means of a hypodermic needle and a syringe 01/05/2012 13 Topical and Transdermal Drug DeliveryTopical DFs: Topical DFs Topical dosage forms include solutions (for which release testing is not indicated), collodion , suspensions, emulsions (e.g., lotions), semisolids (e.g., foams, ointments, pastes, creams, and gels), solids (e.g., powders and aerosols), and sprays. The physical characteristics of these dosage forms vary widely 01/05/2012 Topical and Transdermal Drug Delivery 14Five Main Target Regions In Dermatology: Five Main Target Regions In Dermatology Surface treatment Camouflage, Protective Layer, Insect Repellent, Antimicrobial/Antifungal, Sunscreen Stratum corneum Emollient , keratosis Skin appendage Acne , Antibiotics, Depilatory , Antiperspirant, Viable epidermis/dermis Antiinflammation , Anesthetics, Antihistamine, Antipruritic Systemic treatment Transdermal 01/05/2012 Topical and Transdermal Drug Delivery 15Percutaneous Drug Absorption: Percutaneous Drug Absorption The epidermis has morphologically distinct regions; basal layer, spiny layer, stratum granulosum and upper most stratum corneum 01/05/2012 16 Topical and Transdermal Drug DeliveryPercutaneous Drug Absorption…: Percutaneous Drug Absorption… The stratum corneum / keratin ranges from 10-20 µm is the rate-limiting barrier to percutaneous drug transport Transport of hydrophilic or charged molecules is especially difficult attributable to the lipid-rich nature of the stratum corneum and its low water content; 40% lipids, 40% protein, and only 20% water 01/05/2012 Topical and Transdermal Drug Delivery 17Percutaneous Drug Absorption…: Percutaneous Drug Absorption… Transport of lipophilic drug molecules is facilitated by their dissolution into intercellular lipids around the cells of the stratum corneum . Absorption of hydrophilic molecules into skin can occur through ‘pores’ or openings of the hair follicles and sebaceous glands , but the relative surface area of these openings is barely 1% of the total skin surface. This small surface area limits the amount of drug absorption 01/05/2012 Topical and Transdermal Drug Delivery 18Percutaneous Drug Absorption…: Percutaneous Drug Absorption… The stratum corneum is a remarkably more formidable barrier compared to GI and other mucosal Delivery In general, once drug molecules cross the stratum corneal barrier, passage into deeper dermal layers and systemic uptake occurs relatively quickly and easily. Topical drug delivery is generally used for local drug effects. Drug may be applied as an ointment or cream to the skin or various mucous membranes 01/05/2012 Topical and Transdermal Drug Delivery 19Fick’s law: Fick’s law 01/05/2012 Topical and Transdermal Drug Delivery 20 Drug absorption into the skin occurs by passive diffusion. The rate of drug transport across the stratum corneum follows Fick’s Law of DiffusionFick’s law of diffusion: Fick’s law of diffusion The rate of drug transport depends directly aqueous solubility and/or oil/water partition coefficient concentration in the formulation vehicle, the surface area of the skin to which it is exposed; inversely proportional to the thickness of the stratum corneum . The stratum corneum is thickest in the plantar (soles) and palmar regions and thinnest in the postauricular , axillary , and scalp regions of the body 01/05/2012 21 Topical and Transdermal Drug DeliveryPowerPoint Presentation: Optimum therapeutic outcomes require not only proper drug selection but also effective drug delivery . The human skin is a readily accessible surface for drug delivery. The pharmacological response , both the desired therapeutic effect and the undesired adverse effect, of a drug is dependent on the concentration of the drug at the site of action, which in turn depends upon the dosage form and the extent of absorption of the drug at the site of action 01/05/2012 22 Topical and Transdermal Drug DeliveryAdvantages of TDD: Advantages of TDD consistent serum drug levels as IV non invasive The lack of peaks in plasma concentration Drugs that require relatively consistent plasma levels are very good candidates Convenience and high adherence non invasive Usually once weekly application Removal of the patch in case of toxicity Avoids FPM, and GI irritation great advantage in patients who are nauseated or unconscious Drugs that are degraded by the enzymes and acids in the gastrointestinal system 01/05/2012 23 Topical and Transdermal Drug DeliveryDisadvantages of TDD: Disadvantages of TDD local irritation rotation can minimize irritation severe allergic reactions –DC skin's low permeability limits the number of drugs that can be delivered after removal, most patches contain at least 95% of the total amount of drug initially in the patch patients must exercise care when disposing of patches Damage to a transdermal patch Patients should be advised to discard a patch if the outer packaging or the patch itself appears damaged or altered in any way 01/05/2012 24 Topical and Transdermal Drug DeliveryRoutes of Traditional TDD: Routes of Traditional TDD 01/05/2012 25 Topical and Transdermal Drug DeliveryPowerPoint Presentation: Transcellular pathway path of shortest distance, the drugs encounter significant resistance to permeation Few drugs have the properties to cross via this method I ntercellular route more tortuous 20X longer Appendageal route follicular route(hair follicles) Eccrine pathway (sweat ducts) sebaceous glands ROUTES OF TRADITIONAL TDD 01/05/2012 26 Topical and Transdermal Drug DeliveryDESIGN OF TD PRODUCTS: DESIGN OF TD PRODUCTS Patch design is among the first considerations in developing a transdermal drug. Properties of the drug, the desired delivery profile, and the target patient group determine which design is best for a given application Transdermal delivery provides a leading edge over injectables and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. 01/05/2012 27 Topical and Transdermal Drug DeliveryDESIGN OF TD PRODUCTS: DESIGN OF TD PRODUCTS Transdermal delivery not only provides controlled, constant administration of the drug, but also allows continuous input of drugs with short biological half-lives and eliminates pulsed entry into systemic circulation Systemic absorption of transdermal is better with low dose, low molecular weight, lipid soluble drugs 01/05/2012 Topical and Transdermal Drug Delivery 28DESIGN OF TD PRODUCTS: DESIGN OF TD PRODUCTS Every design incorporates four elements: a backing, adhesive , a release liner, and the drug. In addition, the reservoir and multilaminate designs include a membrane film that controls the rate of delivery from the patch 01/05/2012 29 Topical and Transdermal Drug DeliveryPowerPoint Presentation: 01/05/2012 30 Topical and Transdermal Drug DeliveryTypes of Transdermal Patches: Types of Transdermal Patches Single layer drug in adhesive Multi -layer drug in adhesive immediate drug release layer Vapour patch for releasing of essential oils in decongestion Reservoir system the drug reservoir is embedded between an impervious backing layer and a rate controlling membran Matrix system 01/05/2012 31 Topical and Transdermal Drug DeliveryPowerPoint Presentation: 01/05/2012 32 Topical and Transdermal Drug DeliveryMatrix Vs Reservoir system: Matrix Vs Reservoir system In the reservoir-type design , the drug solution is in a liquid reservoir compartment, separated from the release liner by a semipermeable membrane and an adhesive. The matrix design is similar to that of the reservoir, but the drug is instead provided as a semisolid formulation , and there is no membrane layer 01/05/2012 Topical and Transdermal Drug Delivery 33ALTERNATIVE TECHNIQUES FOR TDD: ALTERNATIVE TECHNIQUES FOR TDD Jet injectors Jet injectors are hand-held devices that deliver a high-pressure liquid stream through a small nozzle oriﬁce . Eg . Bioject , Injex , Intraject , and J-Tip Iontophoresis refers to the delivery of drugs across the skin by means of an electric ﬁeld. Limitations: Hair follicle damage is possible. Voltage aided drug delivery Ultrasound ( Phonophoresis / Sonophoresis ) skin is made permeable under inﬂuence of ultrasonic waves . The ultrasonic energy (at low frequency) disturbs the lipid packing in stratum corneum by cavitation Chemical penetration enhancers The simplest form of penetration enhancement is the use of water Skin ablation doubling of the TEWL (Trans Epidermal Water Loss) using surgical tapes to aid skin permeation Microneedles – A Recent advancement! 01/05/2012 34 Topical and Transdermal Drug DeliveryPowerPoint Presentation: iontophoretic transdermal patch jet injector Microneedle 01/05/2012 35 Topical and Transdermal Drug DeliveryPowerPoint Presentation: 01/05/2012 Topical and Transdermal Drug Delivery 36PowerPoint Presentation: FDA-approved transdermal patches 01/05/2012 37 Topical and Transdermal Drug DeliveryTopical Bioadhesive Formulations: Topical Bioadhesive Formulations The drug delivery systems used in this case are required to adhere to the skin for the purpose of: Collecting body fluids Protecting the skin Providing local or systemic drug delivery Adhesion can be described as the formation of a new mechanical bond between the skin and the adhesive agent. 01/05/2012 Topical and Transdermal Drug Delivery 38Topical Bioadhesive…: Topical Bioadhesive … Bioadhesive products targeted to the skin are formulated into different dosage forms which include liquids, powders and semi-solids such as ointments and transdermal patches. Transdermal patches are sustained-release devices that release a specific amount of drug whilst firmly attached to the skin. They must provide a firm, soft contact with the skin but also allow the patch to be easily removed with minor effort. 01/05/2012 Topical and Transdermal Drug Delivery 39COUNSELING ISSUES: COUNSELING ISSUES Greasy products vs water-soluble bases (PEGs) Greasy products are less acceptable to patients, as these are greasy, may stain clothing, or are difficult to wash off, but are superior to water-soluble bases like polyethylene glycol in their emollient action PEGs are attractive in term of ease of use, but are capable of irritating traumatized or broken skin Creams Vs oleaginous ointments Creams provide an excellent emollient effect, have superior spreadability , and are less staining than oleaginous ointments. However, one needs to consider the skin condition and environmental factors when selecting a medicated or non-medicated cream or ointment. 01/05/2012 40 Topical and Transdermal Drug DeliveryCOUNSELING ISSUES…: COUNSELING ISSUES… While both Creams and oleaginous ointments provide very good emollient effects, oleaginous ointments are preferred for dry, chapped skin in an environment of low humidity because of its occlusive properties Creams are preferred for use over normal, healthy skin in more humid environments, as these permit some moisture evaporation from the skin and allow skin to ‘breathe.’ 01/05/2012 Topical and Transdermal Drug Delivery 41COUNSELING ISSUES…: COUNSELING ISSUES… When drug penetration into deeper skin layers is desired, oleaginous bases have proven superior to creams and water-soluble bases, which are attributable to their skin-hydrating properties. Steroids have been more effective topically when applied in a petrolatum base than when applied in a cream (o/w) vehicle Gel formulations generally provide faster drug release compared with ointments and creams, and may be suggested when available 01/05/2012 Topical and Transdermal Drug Delivery 42COUNSELING ISSUES…: The presence or absence of serous discharges from skin lesions will also dictate the best-suited formulation for a dermatologic application Certain ointments and creams may be available in jars as well as tubes . In such cases, the pharmacist may want to evaluate the situation and discuss the pros and cons of using either packaging While jars are economical when larger quantities are needed, a product is better protected from the environment and contamination when packaged in a tube. Besides, it may be more convenient for the patient to carry a tube rather than a jar. 01/05/2012 Topical and Transdermal Drug Delivery 43 COUNSELING ISSUES…COUNSELING ISSUES…: Special precautions should be used in handling products that contain inflammable ingredients ( collodions , tinctures), and these should be stored in original containers with tight closures, away from heat and light. Direct skin contact with the collodion should be avoided except to the region of application, and it should be applied carefully with an applicator brush that is usually provided with the container. 01/05/2012 Topical and Transdermal Drug Delivery 44 COUNSELING ISSUES…COUNSELING ISSUES…: Emulsions (creams, lotions) may break down if exposed to excessive heat or sudden changes in temperature. Lotions should be shaken well prior to each use. While lotions are easier to apply, these do not remain on the skin as well and are generally less convenient to carry around compared with ointments, creams, or gels A topical product should never be applied over open wounds or broken skin unless it is labeled as a sterile product . Besides the risk of infection, such an application is often associated with problems of significant systemic drug absorption. 01/05/2012 45 Topical and Transdermal Drug Delivery COUNSELING ISSUES…COUNSELING ISSUES…: The patient should be counselled on proper handling and storage of topical products, so as to avoid contaminating the product during use. Care should also be used in applying any drug to inflamed skin. The integrity of inflamed skin is generally compromised, resulting in increased percutaneous migration and systemic absorption of most drugs The presence or absence of serous discharges from skin lesions will also dictate the best-suited formulation for a dermatologic application 01/05/2012 Topical and Transdermal Drug Delivery 46 COUNSELING ISSUES…COUNSELING ISSUES…: COUNSELING ISSUES… The post-auricular region is best suited for small-sized patches Most often, larger patches are applied on the forearm, inner thigh, lower back, or chest. The patch should be worn only for the designated period. For repeated use of transdermal patches, application sites should be rotated Transdermal patches should be stored in original sealed pouches until the time of use 01/05/2012 Topical and Transdermal Drug Delivery 47COUNSELING ISSUES…: Handling of the patch during removal from its package and its application is especially important. Care should be taken to avoid touching or damaging the adhesive surface When applying a patch to the skin, it should be firmly pressed against the skin with the heel of the hand for about 10 seconds to ensure uniform contact and adhesion Upon removal , a used patch should be folded into half with the adhesive layers sticking together, so that it cannot be reused 01/05/2012 Topical and Transdermal Drug Delivery 48 COUNSELING ISSUES…RECENT ADVANCEMENTS AND STUDIES ON TRANSDERMAL THERAPY: RECENT ADVANCEMENTS AND STUDIES ON TRANSDERMAL THERAPY TransPharma has modified and implemented the use of radio frequency (RF) ablation and developed the RF- MicroChannel technology to create passages through the skin that allow a novel and unique approach for transdermal drug delivery TransPharma uses its unique printed-patch technology for transdermal delivery of proteins thereby complementing its ViaDerm delivery technology 01/05/2012 49 Topical and Transdermal Drug DeliveryRECENT ADVANCEMENTS AND STUDIES ON TRANSDERMAL THERAPY: RECENT ADVANCEMENTS AND STUDIES ON TRANSDERMAL THERAPY Altea Therapeutics is currently developing transdermal skin patch ( PassPort ™ Apomorphine HCL) to provide continuous delivery of apomorphine for the prevention of ‘off’ periods and provide an improved option for the symptomatic management of Parkinson’s disease . 01/05/2012 50 Topical and Transdermal Drug DeliveryCONCLUSION: CONCLUSION The current statuses of Transdermal Drug Delivery Systems (TDDS) have great potentials , since it can be used for both hydrophobic and hydrophilic active substance into promising deliverable drugs. TDDS is a realistic practical application as the next generation of drug delivery system 01/05/2012 51 Topical and Transdermal Drug DeliveryReferences: References Eseldin Keleb1, R.K.S., Esmaeil B mosa2,Abd-alkadar Z aljahwi2. Transdermal Drug Delivery System- Design and Evaluation. International Journal of Advances in Pharmaceutical Sciences , 201-11 (2010). Ratna Mehta, P.D.A.P.P.S.C.o.P . Topical and Transdermal Drug Delivery: What a Pharmacist Needs to Know (2004). Roxhed , N. A Fully Integrated Microneedle -based Transdermal Drug Delivery System. (2007). Leon Shargel , P., RPh . Applied Biopharmaceutics and Pharmacokinetics . 5th edn . (Mc graw Hill's: 2004). Benson*, H.A.E. Transdermal Drug Delivery: Penetration Enhancement Techniques. In: Current Drug Delivery, 1 edn ., Vol. 2 (Bentham Science Publishers Ltd., 2005) Kris Derdzinski , G.E., Gordon Flynn, Howard Maibach , MargarethMarques (USP Scientific Liaison). 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