Term
| What are the local effects of drugs applied to the surface of the skin? What are the local effects on the stratum corneum? What about the epidermis and dermis? |
|
Definition
| Local effects on the surface of the skin include hydration, action against surface microorganisms, and prevention of mosquito bites. Local effects on the stratum corneum include sunscreens and keratolytic agents. Local effects on the epirdermis and dermis include treatment of infections. |
|
|
Term
| For systemic effects to be achieved, what type of delivery is necessary? Where must the drugs reach? |
|
Definition
| Transdermal delivery is necessary. The drug molecules must reach the blood capillaries in the dermis. |
|
|
Term
| What are the advantages of transdermal systemic delivery? |
|
Definition
The drugs do not have to first pass the hepatic metabolism.
Blood levels are consistent for a long-term delivery.
You can substitute it for an oral route when vomiting and diarrhea occur.
It is convenient for the patient. |
|
|
Term
| What are the disadvantages of transdermal systemic delivery? |
|
Definition
You are limited to drugs with good permeability.
Possibly skin irritation could occur. |
|
|
Term
The epidermis is ___a___ thick.
The dermis is __b___ thick.
A synonym for topical is ___c___.
A synonym for transdermal is __d__. |
|
Definition
(a) 100micrometers
(b) 1000 micrometers
(c) epicutaneous
(d) percutaneous |
|
|
Term
| What is the epidermis composed of? The dermis? |
|
Definition
| The epidermis is avascular. The dermis is composed of connective tissue with vasculature. |
|
|
Term
| What must the drug molecules cross in transdermal delivery? |
|
Definition
| Entire epidermis, portion of the dermis, and wall of the capillary. |
|
|
Term
| What is the main barrier to transport? |
|
Definition
| Stratum corneum - top layer |
|
|
Term
| What does the stratum corneum consist of? |
|
Definition
| Flat keratinized envelopes embedded in a highly organized lipid matrix. The envelopes are mostly impermeable to drug molecules. Drugs mostly diffuse through the lipid matrix. |
|
|
Term
| Viable epidermis contains how many layers of viable cells? What are they? What are they made of? |
|
Definition
4: Stratum lucidum, granulosum, spinosum, and basale.
Their composition is 95% keratinocytes, melanocytes, Langerhans, and Merkel cells. |
|
|
Term
| The stratum corneum consists of flat keratinized envelopes embedded in a lipid matrix. It is visualized as a ____. |
|
Definition
|
|
Term
| How many layers of flat, keratinized envelopes are in the SC? Where are there more? |
|
Definition
| About 5. There are more at the bottom of the feet, palms, and fingers. |
|
|
Term
| Describe the contents of the envelopes of the SC. |
|
Definition
| They contain covalently bound lipids on the surface and are filled with dead corneocytes containing keratin and water. |
|
|
Term
| Describe the content of the lipid matrix. |
|
Definition
| It consists of cholesterol, free fatty acids, ceramides, and phospholipids (about 5%). It has a multilamellar structure composed of interacting bilayers. |
|
|
Term
| Drugs mostly diffuse through which part of the SC? How? |
|
Definition
| Drugs mostly diffuse through the lipid matrix of the SC, utilizing trans-bilayer transport. |
|
|
Term
| What are the four types of transdermal transport mechanisms? What is the main form of transport? |
|
Definition
(a) paracellular transport through lipids of SC - most preferred
(b) through a hair follicle
(c) through sweat ducts
(d) transcellular transport through dead keratinocytes of SC |
|
|
Term
| What is Dm? How could you increase it? What would this do? |
|
Definition
| Dm is the diffusion coefficient in the lipids. If you increased it you would enhance transdermal permeation. You could do this by modifying the drug to achieve intermediate lipo, amphi, and cephalophilicity. You could also do this by modifying the stratum corneum using chemical enhancers. |
|
|
Term
| What is Pm? How could you increase it? |
|
Definition
| Pm is the partition coefficient (lipids/vehicle). You could increase it by modifying the drug to achieve intermediate lipophilicity. You could also modify the vehicle. |
|
|
Term
| What is the cD and how could you increase it? What is the h and how could you decrease it? |
|
Definition
| cD is the concentration of the drug in the donor compartment. You could modify the vehicle to increase it. THe h is the thickness of the barrier. Two ways you could decrease it would be abrasion and micro-needle devices. |
|
|
Term
| What are some electrically assisted methods used to improve penetration? |
|
Definition
| Iontophoresis and electroporation. |
|
|
Term
| What are some methods use to bypass or remove the stratum corneum to improve penetration? |
|
Definition
| High velocity particles such as jet injectors, micro-needles, dermabrasion using aluminum oxide crystal or laser. |
|
|
Term
| What are 4 mechanisms of chemical penetration enhancers? |
|
Definition
| Inserting a PE into the SC, Creation of pools, lipid extraction, and keratin denaturation. |
|
|
Term
| What does PE insertion do to the membrane? |
|
Definition
| It provides disorganization, fluidization, and alters the solubility in the SC. |
|
|
Term
| What does the creation of pools in the SC do to the membrane? |
|
Definition
| It provides phase separation and increases hydration. |
|
|
Term
| What does keratin denaturation do to the membrane? |
|
Definition
| It provides swelling and is effective on desmosomes. |
|
|
Term
| What does lipid extraction do to the membrane? |
|
Definition
| Provides disorganization. |
|
|
Term
List examples of each of the following:
PE insertion, keratin denaturation, creation of pools, and lipid extraction. |
|
Definition
PE insertion: azone, terpenes, ethanol, DMSO
Creation of pools: azone, oleic acid, and water
Keratin denaturation: poly-arginine
Lipid extraction: monoolein, ethanol |
|
|
Term
| To have intermediate lipophilicity, what must your logP value be. |
|
Definition
|
|
Term
| What is a good molecular weight for a drug to have good trans-bilayer permeability? |
|
Definition
|
|
Term
| For a drug to have good trans-bilayer permeability, it must have a significant fraction of ___ molecules. |
|
Definition
|
|
Term
| What are the 2 characteristics of a good vehicle for skin permeation? |
|
Definition
Must dissolve the drug but not retain it.
Must lead to the appropriate ionization of the drug. |
|
|
Term
| For skin, what improves absorption? |
|
Definition
| Hydration improves absorption. |
|
|
Term
| What are 3 advantages for transdermal patches? |
|
Definition
(1) steady flux - extended therapy with a single application
(2) skip (hepatic) first-pass metabolism and GI problems
(3) convenience and comfort |
|
|
Term
| List the disadvantages of transdermal patches. |
|
Definition
| Possibly skin irritation, very small number of drugs are suitable for a patch. |
|
|
Term
| For a patch with a membrane, the rate of drug delivery is __a__. Drug diffusion in the liquid matrix is fast and drug delivery follows __b__ kinetics. |
|
Definition
(a) lower than the absorption capacity of the skin.
(b) pseudo-first order |
|
|
Term
| For a patch with contact (semisolid matrix), if the diffusion rate in the matrix does not limit release, the rate is __. |
|
Definition
| higher than the absorption capacity of the skin, which becomes a reservoir for the drug. |
|
|
Term
| In a patch with contact, the delivery from the patch follows ____ kinetics. |
|
Definition
|
|
Term
| For a patch with contact, if the diffusion in the matrix DOES affect release, the _a__ zone originates in the matrix and __b__ diffusion --> the time has a __c__ n. |
|
Definition
(a) depeletion
(b) slows down
(c) diffusional exponenet, n |
|
|
Term
| Name the 2 locations adhesive can be found on a patch. |
|
Definition
|
|
Term
| Name 5 qualities of adhesive. |
|
Definition
(1) not irritate or sensitize skin
(2) allow fast adherence with minimum pressure
(3) support the patch holding in place for the intended time period but allow easy peel-off
(4) be compatibly with other components
(5) not influence drug release, when covering the face of the patch |
|
|
Term
| List 3 main characteristics of backing film. |
|
Definition
(1) occlusive / impermeable
(a) retain skin hydration /moisture - increase skin penetration
(b) avoid evaporation of vehicleand changes in drug concentration in the reservoir
(c) not allow drug diffusion through backing
(d) protect product during use
(2) flexible
(3) transparent or pigmented |
|
|
Term
| List examples of backing film (2). |
|
Definition
| polyethylene and polypropylene. |
|
|
Term
| Name a potential problem in a Drug-in-adhesive patch. |
|
Definition
| Drug may affect stickiness of the patch. |
|
|
Term
| Name 2 examples of drug-in-adhesive patches. What are they / what do they do? |
|
Definition
Climara and Berlex.
Estradiol in polyacrylate glue.
-Treats symptoms from deficiency of estrogen production
-transdermal delivery helps avoid rapid and extensive hepatic metabolism of estradiol
-patch applied once or twice a week |
|
|
Term
| What is another name for a matrix controlled device? |
|
Definition
|
|
Term
| Name an example of a matrix-controlled device. What does it do? |
|
Definition
Testoderm (Alza)
-testosterone in matrix of ethylene-vinyl acetate copolymer
-treatment of testosterone deficiency
-applied daily to scrotal skin |
|
|
Term
| What's another name for a membrane controlled device? |
|
Definition
|
|
Term
| When is the release rate constant in a membrane-controlled patch? |
|
Definition
| When the reservoir is saturated. |
|
|
Term
|
Definition
| A small amount of drug added to the adhesive layer to initate prompt absorption and therapeutic effect. |
|
|
Term
| What are 2 example of membrane-controlled devices? What are the contents of their reservoirs? |
|
Definition
Estraderm / Novartis for delivery of 17beta-estradiol
-reservoir: hydroxypropyl cellulose and alcohol
Trandserm Scop (Novartis) for scopolamine to treat motion sickness
-reservoir: mineral oil, polyisobutylene and loading dose |
|
|
Term
| What is the average electrical current used in iontrophoresis? What does it do? |
|
Definition
0.5mA/cm2
Small electrical current applied to the skin to increase the delivery of charged molecules. |
|
|
Term
| Iontrophoresis is used in physical therapy for delivery of ____. |
|
Definition
|
|
Term
| What are the 3 mechanisms used in iontrophoresis? |
|
Definition
(1) repulsion of like charges
(2) disruption of SC
(3) increase hydration in SC |
|
|
Term
| What does the drag in electrosmotic flow do? |
|
Definition
| Increase the permeation of uncharged, polar molecules. |
|
|
Term
| What is electroporation and what does it do? |
|
Definition
| Short, strong pules of electric current. Creates transitional small pores in SC. |
|
|
Term
| What is sonophoresis? What does it do? |
|
Definition
| It is the application of ultrasound energy to change the SC. It provides cavitation, or the formation of a hydrophilic channels in the SC. Typical frequency - 1Mhz. |
|
|
Term
| How does heat affect the stratum corneum? |
|
Definition
| Increases blood vessel permeability and circulation. It also increases drug solubility in skin. |
|
|
Term
| What are microneedles and how do the work? Are the needles solid or hollow? |
|
Definition
| Microprojections between 100micrometers and 1000micrometers long combined in a piece of polymer that works as a patch. The needles penetrate the top layers of skin and allow the drug to pass through the skin easily. The needles can be solid or hollow. |
|
|
Term
| List 8 characteristics of high velocity particles or jet injections. |
|
Definition
(1) Combine parenteral and transdermal drug delivery methods
(2) overcome needle phobia
(3) no pain
(4) fire fine, solid particles through SC using high-pressure helium gas
(5) decrease the risk of infections associated with needles
(6) accurate dosing
(7) target different skin layers
(8) planned for vaccines and insulin |
|
|
Term
| What are the 3 steps to measuring skin permeation? |
|
Definition
(1) Measure transport across skin
(2) Track drug in penetration in the skin
(3) Measure relevant endpoints |
|
|
Term
| How can you measure transport in excised skin? |
|
Definition
| HPLC, Fluorimetry (in vitro) |
|
|
Term
| How do you track the drug penetration into the skin? |
|
Definition
| infrared spectroscopy, differential scanning, calorimetry, fluorescence spectroscopy, blood analysis (in vitro and in vivo) |
|
|
Term
| How do you measure relevant endpoints? |
|
Definition
| Efficacy studies (in vivo) |
|
|
Term
| How do you measure the transport across excised skin using a penetration assay? What type of skin can be used? Which is the best animal surrogate? |
|
Definition
Use the Franz diffusion cell.
Human, pig, rat, nude mice, rabbit
Pig is best animal surrogate. |
|
|
Term
| How does confocal fluorescence microscopy work? |
|
Definition
| The fluorescent permeants absorb light and emit it at a longer wavelength. The wavelength is longer in nonpolar lipid environment, so the permeant moelcules in lipids fluoresce differently from those in water. |
|
|
Term
| What 5 things must you do for in vivo assays? |
|
Definition
(1) evaluate transdermal percutaneous availability
(2) evaluate systemic bioavailability
(3) establish bioequivalence between different formulations
(4) evaluate efficacy
(5) evaluate skin irritation - options: cell and tissue culture |
|
|
Term
| If there is not drug content in an ointment, what can it be used as? |
|
Definition
|
|
Term
| What is the key component determining the character of an ointment? |
|
Definition
|
|
Term
| Name the 4 types of ointment bases. |
|
Definition
Hydrocarbon / oligeanous / fatty
Absorption
Water-soluble
Water-removable |
|
|
Term
| Name the 8 characteristics of an ointment base. |
|
Definition
| Water content, Affinity for water, Spreadability, Washability, occlusiveness, drug incorporation potential, uses, disadvantages. |
|
|
Term
| What is the water content for an oleaginous base? |
|
Definition
| Anyhydrous - practically water-free |
|
|
Term
| What is an oligeanous base's affinity for water? |
|
Definition
| minimal - hydrophobic material |
|
|
Term
| What is the spreadability and washability of an ointment made with a fatty base? |
|
Definition
|
|
Term
| What is the drug incorporation potential of an ointment made with a fatty base? |
|
Definition
Solids (hydrophobic) or oils
incorporation of very small volumes of aqueous solutions or hydrophilic agents. |
|
|
Term
| Is a hydrocarbon base occlusive? |
|
Definition
|
|
Term
| What are the uses of a hydrocarbon base? |
|
Definition
Emollients (skin softening), moisturizers
Retention on the skin for long time
vehicles for hydrolyzable drugs, slow release |
|
|
Term
| What are the disadvantages of hydrocarbon bases? |
|
Definition
| greasy, difficult to wash off, may stain clothes |
|
|
Term
| What are some examples of hydrocarbon ointments? |
|
Definition
| petrolatum, diaper rash ointments, yellow and white ointment |
|
|
Term
| What is white petrolatum? |
|
Definition
Decolorized, more esthetically pleasing.
Mixture of semisolid hydrocarbons obtained from petroleum.
Mixed with mineral oil to change consistency. |
|
|
Term
| What is soft petrolatum base? |
|
Definition
It contain 10% oil.
Minral oils acts also as a levigating agent - facilitating smooth, homogenous consistency. |
|
|
Term
|
Definition
| MIxture of petrolatum (95%) and purified yellow wax (5%, extracted from bee honeycomb) |
|
|
Term
|
Definition
| Mixture of white petrolatum and bleached / purified wax. |
|
|
Term
| What are absorption bases? |
|
Definition
They are made for slow drug release.
They are anhydrous hydrophilic bases that allow incorporation of water to form water-in-oil (w/o) emulsions.
Fatty compounds + w/o surfactant as emulsifier.
Emulsion formed when aqueous solution (with or without drug) is added. |
|
|
Term
| What is an example of an absorption base? |
|
Definition
Hydrophilic petrolatum (Aquaphor - OTC - diaper rash)
Cholesterol, stearyl alcohol, white wax, white petrolatum.
The stearyl alcohol acts as an adjuvant emulsifier, aiding in firmness and heat stability. |
|
|
Term
| (absorption base) What is an example of a hydrous base that are w/o emulsions? |
|
Definition
| Hydrous Lanolin - isolated from sheep wool (allergenic), viscous, contains 0.25% water and dissolves more. |
|
|
Term
| Describe 8 characteristics of anhydrous absoprtion bases. How are hydrous absorption bases different? |
|
Definition
Water content - Anhydrous
Affinity for water - Hydrophilic - absorb water after agitation
Spreadability - moderate
Washability - poorly washable
Drug incorporation potential - solids or oils
Allow incorp. of low volume of aqueous solutions or hydrophilic agents.
Occlusiveness: intermediate
Uses: emollients, vehicles for drugs instable in water, aqueous solutions, and non-hydrolyzable drugs
Disadvantages: Greasy, difficult to remove, may stain clothes
Hydrous:
contains water, moderate to easy spreadability, |
|
|
Term
| Describe water-removable bases. |
|
Definition
o/w emulsions.
oil coponent + water + o/w surfactants
HLB 8-18
Water content >45%
Drug release from the ointment is generally fast.
Most common ointment base used. |
|
|
Term
|
Definition
Contain water, hydrophilic and lipophilic components, easy spreadability and washability (resembles creams).
Can incorporate solids: hydrophilic or small amounts of hydrophobic compounds allow dilution with water.
They are not occlusive.
Can be used as emollient, vehicles for solids, aqueous solutions, or non-hydrolyzable drugs. |
|
|
Term
| Water-removable base examples. (2) |
|
Definition
| Hydrophilic ointments and vanishing cream. |
|
|
Term
| Water-soluble bases are polymers of ___ with varying number of monomer units. These are called ___. |
|
Definition
Polymers of ethylene oxide.
Polyethylene glycols (PEG). |
|
|
Term
| Water-Soluble bases have a wide range of molecular weights. Describe their appearances at these different weights. |
|
Definition
<600 - clear, colorless liquids
600>1000 - white, wax-like materials
Viscosity increases with increasing molecular weight. |
|
|
Term
| What is the affinity for water, spreadability, washability, drug incorporation potential, and occlusiveness of water-soluble bases? |
|
Definition
hydrophilic - cannot incorporate large amounts of water - loss of viscosity
Easy spreadability and washability
Can incorporate mostly solids.
No occlusiveness. |
|
|
Term
|
Definition
| A thin, vascularized mucous membrane. |
|
|
Term
|
Definition
| Made up of mucopolysaccharides and collagen. |
|
|
Term
| How many membranes does the cornea have? |
|
Definition
|
|
Term
| What is opthalmic delivery limited by? |
|
Definition
structure, permeability, and small surface area of cornea
short residence time of drug on the surface of the eye |
|
|
Term
| What tissues does the drug diffuse through in vaginal absorption? |
|
Definition
| Mucosa, submucosa (vasculature connective tissue with no glands), and smooth muscle |
|
|
Term
| Name the 4 main types of gelling agents. |
|
Definition
| cellulose derivatives, carbomers, poloxomers, sodium alginate |
|
|
Term
| Name the 4 types of cellulose derivatives. |
|
Definition
| Carboxymethylcellulose, methylcellulose, hydroxy ethyl celulose, hydroxy propylcellulose |
|
|
Term
| Which is the only anionic cellulose derivative? |
|
Definition
|
|
Term
| What is the ideal pH for CMC? |
|
Definition
|
|
Term
| Describe the hydration of each cellulose derivative? |
|
Definition
CMC - hydrates in cold water under stirring
MC - hydrates in hot water under stirring
HEC - hydrates in cold and hot water under stirring
HPC - INsoluble in cold water, above 45, no stirring, hydration for 8-12 hours |
|
|
Term
| Name the additives/special characteristics for each cellulose derivative. |
|
Definition
CMC - none
MC - propylene glycol or alcohol to wet
HEC - provides occlusion
HPC - organic solvent - less hydrophilic drugs |
|
|
Term
| name the incompatibilities for the cellulose derivatives. |
|
Definition
CMC - ethanol and other organic solvents, inrease salt and pH - decrease viscosity
MC - increase salt - precipitation
HEC - alcohol
HPC - none |
|
|
Term
| Name the organic solvents for each cellulose derivative. |
|
Definition
CMC - none
MC - alcohol
HEC - none
HPC - ethanol and other organic solvents |
|
|
Term
| What is carbomer 910 used for? What about carbomer 940? |
|
Definition
| 910 is used for low viscosity formulationg. 940 is used for hydroalcoholic gel. |
|
|
Term
| When does a carbomer achieve its maximum viscosity and clarity? |
|
Definition
|
|
Term
| What are carbomers incompatible with? |
|
Definition
| salt - formation of rubbery mass |
|
|
Term
| How is aqueous solubilty related to temperature in poloxamers? |
|
Definition
| Decrease aqueous solubility with increasing temperature. |
|
|
Term
| What is the most common type of poloxmer? |
|
Definition
|
|
Term
| Where is alginic acid obtained from? |
|
Definition
|
|
Term
|
Definition
| Tasteless, odorless, white to yellowish. |
|
|
Term
| What are the concentrations of alginic acid and poloxamers? |
|
Definition
alginic acid - 10%
carbomer - 50% |
|
|
Term
| What pH are gels stable at in an alginic acid? |
|
Definition
|
|
Term
| What are calcium salts used for in alginic acid? |
|
Definition
| To cross-link alginic acid and increase viscosity |
|
|
Term
| What happens if the pH is less than 3 in a alginic acid? |
|
Definition
|
|
