Transdermal Systems CH4106 PDF

Transdermal Systems 11. Transdermal Drug Delivery systems (TDDS) 1 In this section you will learn…. Terminology Advantages/disadvantages of TDDSs Factor affecting drug passage though skin Percutaneous absorption enhancers: iontophoresis...

Transdermal Systems 11. Transdermal Drug Delivery systems (TDDS) 1 In this section you will learn…. Terminology Advantages/disadvantages of TDDSs Factor affecting drug passage though skin Percutaneous absorption enhancers: iontophoresis and sonophoresis Types of transdermal systems Examples of transdermal drugs 2 Terminology Percutaneous: passed, done, or effected through the skin Transdermal: delivery into/ through skin TDDSs: facilitate passage of drug through the skin into the general circulation for systemic effects. Skin is not being the target. Ideally, drug should pass to the blood without buildup in the dermal layers 3 Transdermal Drug Delivery: Advantages/Benefits Variation associated with oral therapy are avoided (GI variations) By-passes the first-pass metabolism Continuity / ability to terminate medication Multiday therapy with single application Avoids risk & inconvenience of parenteral therapy Extends activity of drugs with short half lives May provide an alternative when oral route is unsuitable Better patient compliance 4 Transdermal Drug Delivery: Disadvantages/Limitation Only potent drugs are suitable due to skin impermeability Lipophilic (moderately) uncharged drugs with low MW only Some patients develop contact dermatitis Components, formulation & drug must be non-irritating & non-sensitizing 5 Structure of the Skin Skin is divided:  Epidermis: stratum corneum  Dermis  Fatty subcutaneous tissue  Skin appendages Stratum corneum: outer layer, 10-15 µm thick layer of flat partially desiccated dead epidermal cells. The film that covers the corneum behave like a semipermeable membrane 6 Pathways of Transdermal Permeation 7 Transdermal Absorption: Resistance The skin can be considered a membrane: m = D k A (Cs - Cb) t m = mass of drug diffusing in time t D = Drug’s diffusion coefficient d K = partition coefficient (SC and Sebum) A = area for absorption through skin thickness d Cs = concentration of drug in sebum Cb = concentration of drug in systemic circulation Resistance has many components:  Vehicle, stratum corneum, epidermis and dermis  The resistances occur one after another ‘in series’  Rtotal = Rvehicle+ Rstratum corneum+ Repidermis+ Rdermis Factors That Determine The Rate of Drug Passage Through Skin The factors are:  Drug  Delivery system (formulation)  Physiological conditions in skin Drug factors:  Hydrophilic or lipophilic (penetrate better)  pKa - ionization reduces penetration  Drugs with Mw 100-800 permeate skin, ideal Mw is 400  Particle size: small molecules penetrate faster 10 µm remain on skin 3-10 µm concentrate in hair follicle 9