Term
| What is the primary purpose of the skin, and what are the two main layers? |
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Definition
The skin is used for temperature regulation, primary defense, and protection. The two layers of the skin are the Epidermis and Dermis. |
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Term
| What is the Epidermis made up of? |
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Definition
| The epidermis is made of Stratified Epithelium, 95% Keratinocytes, Melanocytes, Langerhans Cells, and Merkel cells |
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Term
| What is the Stratum Corneum and what is it made of? |
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Definition
| The Stratum Corneum is the top-most layer of the epidermis, and is made of dead cells (filled with keratin) embedded in a highly organized lipid matrix. It is the main barrier, and is approximately 20 um. |
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Term
| What is the viable epidermis and what is it made of? |
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Definition
| The viable epidermis is right underneath the SC and is made of 4 distinct layers: the Stratum Basale, Spinosum, Granulosa, and Lucidum. |
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Term
| What is the dermis, the inner layer of the skin, made of? |
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Definition
| Connective tissue (collagen, elastin, glycosaminoglycans) as well as sweat glands, pilosebaceous units (pappila of hair in subcutaneous), infiltrating leukocytes, blood vessels. |
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Term
| What is the main barrier and limiting step in the absorption of trandermal delivery drugs? |
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Definition
| The Stratum Corneum is the main barrier and limiting step, as it is made of hydrophillic cells in a lipophilic matrix. |
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Term
| What are some local surface effects of transdermal drugs? |
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Definition
| Hydration, action against surface microorganisms |
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Term
| What are some local Stratum Corneum effects of transdermal drugs? |
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Definition
| Sunscreens, Keratolytic agents |
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Term
| What are some local epidermis/dermis effects of transdermal drugs? |
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Definition
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Term
| What are some systemic effects of transdermal drugs? |
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Definition
| Drug delivery across skin - drugs must reach the blood vessels. |
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Term
| What are some advantages of topical and transdermal delivery? |
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Definition
Local or system effect (Topical vs. transdermal) Reduction in adverse effects Avoidance of first-pass heptatic metabolism by absorbing through skin Consistent number of blood vessels in skin Substitute oral route when vomiting and diarrhea occurs Patient Convenience |
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Term
| What are some Disadvantages of topical and transdermal deliver? |
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Definition
500 Da Rule: Molecules that are over 500 Daltons will not be able to penetrate the skin effectively, only a few drugs meet this requirement. Irritation |
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Term
| What are some types of Semi-Solid topical/transdermal systems? |
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Definition
Semi-Solid Formulations: Creams, Gels, Ointments, Testosterone Gel for transdermal delivery is Androgel and Testim Diclofenac Gel for local action is Voltaren Cosmetics |
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Term
| What are some examples of Topical Sprays? |
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Definition
Benzocaine: Endocaine Sunblock |
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Term
| What else can be applied topical besides ointment, creams, sprays, and lotions? |
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Definition
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Term
| What are some factors of the drug that control skin penetration? |
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Definition
Molecular Weight Suitable Logp: Affinity for oil and water Unionized vs. Ionized forms Concentration |
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Term
| What are some factors of the vehicle that control skin penetration? |
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Definition
| Dissolve the drug but retain it |
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Term
| What are some factors of the skin that control skin penetration? |
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Definition
Increasing the surface increases absorption Site: Stratum Corneum thickness Integrity (how nice your skin is?!) Increasing hydration increases absorption Age and Ethnicity Drug Metabolism in the skin |
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Term
What is the equation for Fick's First Law?
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Definition
J = Dm x C x K L J = Flux across membrane Dm = Diffusion coefficient of the compound in the membrane L = Length of the barrier C = Concentration of compound in the donor formulation |
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Term
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Definition
K is the Partition Coefficient K = Solubility of the compound in the membrane Solubility of the compound in the donor formulation |
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Term
| In terms of enhances penetration enhancement, would would you have to do to increase Dm? |
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Definition
| Modify the drug, or modify the Stratum Corneum barrier |
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Term
| In terms of enhances penetration enhancement, would would you have to do to increase K? |
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Definition
| Increase the drug partition in the membrane: modify drug solubility in the SC or in the formulation |
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Term
| In terms of enhancing penetration enhancement, would would you have to do to increase L? |
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Definition
| Create a direct/short pathway across the skin |
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Term
| In the calculation of the flux for infinite dose in donor solution, what is the slope of the line? |
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Definition
Y = ax + b a = J J = ug/cm2/h |
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Term
| What are some strategies to improve drug penetration? |
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Definition
Chemical penetration enhancers Electrically assisted methods Methods that bypass or remove High velocity particles: jet injectors Drug Delivery Systems Pro-drugs |
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Term
| What are characteristics of good chemical penetration enhancers? |
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Definition
Non-toxic, non-irritant, not pharmacologically active Act rapidly and reversibly Compatible with drug and formulation |
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Term
| How do chemical penetration enhancers work? |
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Definition
Alter Stratum Corneum characteristics and barrier function Change drug affinity with the vehicle: Increase partition and thermodynamic activity |
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Term
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Definition
Application of small electrical current to the skin to increase the delivery of charged molecules. Used in physcial therapy for delivery of NSAIDS. |
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Term
| What is the mechanism of drug penetration for iontoporesis? |
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Definition
Repulsion of similar charges Skin appendages are the main route SC disruption Increase water content in Stratum Corneum |
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Term
| Can iontophoresis increase transport of polar but uncharged compounds? If so, how, and what is this called? |
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Definition
| Yes it can. This is by way of electroosmotic flow, which is an electromigration of ions that creates a solvent motion that drags uncharged compounds. This process is called iontophoresis. |
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Term
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Definition
| Intense electric charge that creates transient small pores in the Stratum Corneum |
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Term
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Definition
| Application of ultrasound energy to deliver drugs. Done so by Cavitation which is the formation of hydrophilic channels. Frequency is 1 MHz |
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Term
| What does heat do for enhancing penetration? |
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Definition
Heat increases microcirculation and blood vessel permeability. Increases drug solubility in the skin. |
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Term
| There are a couple different methods of drug penetratoin that involve bypassing or removing the Stratum Corneum, Dermabrasion is one, but what is it? |
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Definition
Exfoliation of skin using aluminum oxide crystals Done by laser |
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Term
| Microneedles are another way to bypass the Stratum Corneum. How do they work? |
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Definition
Microprojections between 100 and 1,000 um long combined in a piece of polymer that works as a ptch. Needles penetrate the top layers of skin and allow the drug to pass through the skin easily. Needles can be solid or hollow |
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Term
| Using high velocity particles, such as in jet injectors, is a way to enhance drug penetration. What are jet injectors? |
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Definition
Combine transdermal and parenteral drug delivery methods. Fires fine, solid particles through the stratum corneum using high-pressure helium gas. - No pain - Overcomes "needle phobia" - Decrease risk of infections associated with needles - Accurate dosing - Target different skin layers - Vaccines, insulin |
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Term
| Different drug delivery systems can act as penetration enhancers, what are some examples of these? |
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Definition
Lipid vesicles - Liposomes, etosomes Microemulsions Liquid-crystalline phases - Cubic phase, hexagonal phase |
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Term
| Different drug delivery systems can act as penetration enhancers, how do they act? |
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Definition
Contain chemical penetration enhancers in their structure This leads to a more effective interaction with the skin |
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Term
| What are products and how do they work? |
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Definition
Have the presence of esterases and other enzymes. Prodrug can be cleaved in the active compound The advantage of this is that prodrugs can have different characteristics, which leads to increased penetration. |
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Term
| For determining penetration, what are some analytical methods for quantification? |
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Definition
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Term
| What are some methods to track drug penetration in the skin or endpoints? |
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Definition
Infrared Spectroscopy Differential Scanning calorimetry Fluorescence spectroscopy: Optical Fiber probe Draw blood |
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Term
| What is a way to evaluate skin penetration and percutaneous delivery? |
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Definition
| Penetration assay using Franz diffusion cells |
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Term
| Penetration assay using Franz diffusion (picture) |
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Definition
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Term
| What are some different skin models, as well as advantages and disadvantages for each, that could be used in a Franz penetration assay? |
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Definition
Human - Good because it's what the drug will be used on Rabbit - Higher permeability and has hair Rat and Mouse: Higher permeability and has hair |
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Term
| What is the BEST model of skin for a Franz penetration assay? |
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Definition
Pig: Most relevant model, histological and biochemical properties similar to human, similar permeability. Also, Bioengineered human tissue works very well. |
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Term
| What is characteristic of human models for penetration assays? |
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Definition
No Invasive Methods Tape stripping Blood samples Fluorescence spectroscopy: optical fiber probe Microdialysis |
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Term
| What are the characteristics of an animal model that is used in penetration assays? |
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Definition
Tape Stripping Blood Samples Fluorescence spectroscopy: Optical Fiber Probe Microdialysis Skin Homogenization Efficacy Tests Skin Irritation (Cell Cultures or artifical skin) |
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