Drug Delivery to the Skin - 5 - Flashcards in University Pharmacy

Describe features of iontophoresis (1)

Electrical current (0.5 mA/cm2) results in electromigration, electroosmosis and liquid disruption. Small DC through drug containing electrode in contact within, grounding electrode completes circuit (easier to delivery cationic drugs)

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Describe features of iontophoresis (2)

Charged species driven by electrorepulsion (electrophoresis) from driving electrode. Electroosmosis affects uncharged large polar molecules (convective flow of water due to ion movement at pH of skin)

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Describe features of iontophoresis (3)

Current increases permeability of skin. Apply charge in liquid containing ions, conducts electricity, body is able to conduct electricity, apply charge using patch/machine, able to pass drugs through the skin (use of electrodes to generate charge)

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What are the issues with using iontophoresis? (1)

Can cause erythema. Lots of electrolytes in the body, electrolytes try to balance out ions, electrolytes move out, diminishes effect (may push charged ion into the skin but pull out Na/K/Cl to balance out ions)

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What are the issues with using iontophoresis? (2)

Current usually increases permeability of the skin – current takes path of least resistance (current surge in particular area, current not spread evenly) – current passes through hair follicles

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What are the issues with using iontophoresis? (3)

Drugs must be in ionised form. Buffer salts should be avoided in vehicle to avoid competition. Drugs will take route of least resistance thus damage can occur to follicles and hair damage. High currents may irreversibly compromise skin integrity

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What are the issues with using iontophoresis? (4)

Failed to significantly improve delivery of macromolecules >7000Da

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Describe features of the GlucoWatch (1)

Reverse iontophoresis has also been used to monitor glucose in extracellular fluid e.g. GlucoWatch. Skin (movement of ions into and out of the skin), watch strapped to arm, apply charge, glucose removed from the skin (measure glucose concentration)

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Describe features of the GlucoWatch (2)

But takes time to be calibrated, accuracy not as effective as a blood test, patient’s constantly checking measurements. GlucoWatch improved – focuses on hair follicles. Skin – portal for diagnosis (e.g. detection of melanoma, skin cancer)

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Describe features of Vyteris and E-TRANS

E-TRANS – iontophoresis applied to fentanyl patches, maximum concentration achieved within a shorter time period (issue – cost)

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Describe the use of iontophoresis in hyperhidrosis

Hyperhidrosis - sweating that occurs at inappropriate times, far in excess of the amount necessary to maintain normal body temperature. Iontophoresis (effective but there are S/E, safety issues, online products)

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Describe features of electroporation (1)

Short (μ-ms) electrical pulses (100-1000V/cm) creating pores in the lipid bilayers. Transport through the pores can occur by via iontophoresis (during the pulse), electro-osmosis or simple diffusion

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Describe features of electroporation (2)

Concerns raised over use of such high voltages and the reversibility of process. However devices are under development e.g. E-TRANS and Genetronics, often in combination with patches, iontophoresis or penetration enhancers

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Describe features of phonophoresis/sonophoresis (1)

Low frequency ultrasound 20-100 kHz. Ultrasound perturbs stratum corneum by cavitation. Increases free volume space by the formation and oscillation of small gaseous inclusions which collapse.

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Describe features of phonophoresis/sonophoresis (2)

Reported benefit for macromolecules up to 48kDa. Reversibility and effect on skin enzymes still under debate. However, the SonoPrep device (Sontra) has been used to reduce the onset of dermal anaesthesia form 60 min to 5 min

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Describe features of laser (photomechanical ablation)

Removal of Stratum corneum and hence barrier properties. No damage to viable epidermis. New laser generation to create ultra-precise micropores

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Describe features of magnetophoresis

Magnetic field applied acting as an external driving force to enhance diamagnetic solute across the skin

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Describe features of thermophoresis (1)

Concept - patches with iron oxide, heat up, used for pain. Heating up the skin can enhance drug penetration. Diffusion of molecules – important for drug delivery. • Apply heat – diffusion increases (membrane doesn’t change)

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Describe features of thermophoresis (2)

High permeation due to the molecules moving faster. Silicone – has diffusion and partition (diffusion and partition increases with temperature), silicone becomes more fluid

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Describe features of thermophoresis (3)

Applied to skin – after a particular temperature, the skin opens up for drug delivery, transition temperature (~ 41 degrees, more penetrable), cool skin (returns to normal). Thermophoresis – failed during observations (CHADD).

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Describe features of thermophoresis (4)

Sodium acetate, supersaturation, crystallisation, generation of heat (not harmful). Issue – long time periods.

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Describe features of thermophoresis (5)

Thermophoresis – worked in experimental/theoretical practice. Issue – administration (not stable enough, crystallisation in pump of the spray)

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Describe features of needless injections (1)

Vaccination – site of action (into dermis, to get into the blood/systemic circulation). Issue – depth of injection into the skin. Needless injection – use of liquids, powder/liquid fired through S.corneum at supersonic speed

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Describe features of needless injections (2)

Compressed gas (He) is often the driving force. Avoids issue of needles e.g. needle stick injury, needle phobia. But often a low dose was delivered, can vary significantly. Long term effect unknown. Issue- damage to injection site

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Describe features of micro-needle array/imprinting (1)

100s of needles insert drug just below Stratum corneum avoiding nerves in underlying tissue. Needles (50-100μm) either coated or contain the drug. As such causes no pain

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Describe features of micro-needle array/imprinting (2)

Can be combined with a patch e.g. Macroflux and iontophoresis e.g. Microelectromechanical systems (MEMS) for programmable and controllable drug delivery. However issues have arisen on the breakage of the tips of the microneedles

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Describe features of micro-needle array/imprinting (3)

Short needles (don’t touch neurones/don’t hurt), potential for one-off vaccinations. Four different modes of delivery (solid MN - make holes, apply cream, coated MN - on skin, molecules attracted to skin, dissolving MN, hollow MN)

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Describe features of micro-needle array/imprinting (4)

Delivery/diagnostic purposes. Polymers – dissolve when reaching dermis. Tip of MN dissolve with drug (doesn’t remain on patch).

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Describe features of micro-needle array/imprinting (5)

Good for the delivery of large molecules – potential for injections for psoriasis. Consequence of not having regular injections for psoriasis – drug becomes less effective (need to enforce compliance during patient counselling)

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Give examples of devices which promote physical enhancement

Phoresor, Lidosite, E-TRANS, Glucowatch, Iontopath, EES (Electrode Scanning System), Acyclovir Direct, Accuresis, Lectro Patch, ActiPatch (some devices FDA approved, some under development/in clinical trials)

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Drug Delivery to the Skin - 5

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Other cards in this set

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Card 5

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