Topical Drug Delivery 1-7 Flashcards
(96 cards)
1
Q
State the functions of the skin
A
- Largely they act as a protective barrier against external forces; protects against loss of moisture, microbial infection etc.
- Stabilises blood pressure and temperature (site of heat loss for the body)
- Mediates sensitisation of
- Temperature, touch and pain
2
Q
State the three main layers of the skin
A
Epidermis - Dermis - Subcutaneous tissue
3
Q
What is the hypodermis, What are its thickness factors dependent on?
A
The hypodermis (the subcutaneous tissue) is a structured fatty layer that exists almost over the whole body. The purpose of this layer is partially to provide protection to the body and also serves as a source of energy
Thickness depends on:
- Sex
- Age
- Endocrine and nutritional status of the person
4
Q
Describe the dermis
A
Composed of a matrix of connective tissue, formed of fibrous protein (around 80% collagen and elastin) and also glycosaminoglycan gel (20%), As this is a relatively hydrophilic layer, this is a potential barrier to the absorption of some lipophilic molecules.
It is the site of:
- Blood vessels
- Some Sweat glands
- Hair follicles
5
Q
What sweat glands are found in the dermis
A
Eccrine sweat glands
Apocrine sweat glands
Sebacious glands
6
Q
What does the Eccrine glands secrete?
A
- These glands secrete a watery fluid with a pH of 4-7 and can secrete roughly 1L per day of fluid.
7
Q
What do Apocrine glands release?
A
The apocrine sweat glands secrete a different fluid; milky fluid in nature and is responsible for the “sweat odour”.
8
Q
Talk to me about the sebaceuous gland
A
Found around Forehead/face/ear and Middle of the back. Releases Sebum. The sebaceous glands are the site at which acne generally develops. This could potentially be a site for drug delivery into the skin for treating acne conditions. Sebum is a complex mixture of lipids of which lubricate the skin surface and maintains the skin at pH around 5
9
Q
What is the epidermis?
A
It’s the top layer of the skin - A major barrier to drug absorption through the skin.
- This thickness of this layer varies depending on the site on the body:
- 0.06mm(eyelids) – 0.8mm(soles of feet)
formed of four distinct layers, and by the time we get to the top layer of the skin, the cells found on the stratum corneum become non-viable/dead cells by the time they are at the top of the skin surface.
10
Q
Describe the basement membrane
A
Found at the very base of the stratum corneum. The basement membrane is connected to the rest of the epidermis via hemi-desmosomes. Above the basement membrane is the viable epidermis
11
Q
describe the viable epidermis
A
- Formed of: 75-50µm thick, stratified, squamous epithelium; a major component of the stratum corneum being the keratinocytes.
- There are four distinctive strata of which are responsible for keratinocyte differentiation; keratinocytes differentiate as they move up this epidermis layer until they reach the stratum corneum, at which we have non-viable cells.
12
Q
Name the last of the 4 strata, and explain what is it composed of
A
stratum basale (just above BM). Consists of 4 viable, active dividing cells
- Keratinocytes - the dominant cell type in the skin structure. At this point, its a viable cell. Later migrates upwards
- Melanocytes (synthesis of melanin free radical scavengers and absorb UV radiation),
- Langerhans cells, capable of antigen binding. So plays an immune role to alert body of foreign species
- Merkel cells involved with skin sensation because associated with nerve endings
13
Q
Describe the stratum corneum!
A
(“Horny layer” - Uppermost layer)
This layer forms the main barrier to absorption through the skin; the part of the skin of which is mainly responsible for its barrier properties.
- It is this layer of the skin which prevents water loss or terrestrial animals as well as preventing entry of microorganisms/dirt into the skin.
- Formed of 10µm layer of thick, dead, flattened keratinocytes
In this layer, once the keratinocytes have differentiated up to the upper layer and become fully flattened, with their contents fully extruded – we refer to them as corneocytes. These are very dry cells of which have very low water content compared to other areas of the body
14
Q
Talk about the Stratum Corneum on a cellular level
A
- Dead, flattened cells with insoluble keratin bundles in them.
- The intracellular region between the flattened corneocytes is formed of a lipid domain (formed of mostly lipid and some desmosomes which aid cohesion between corneocytes)
15
Q
what distinguishing feature makes the stratum corneum impenetratable
A
In terms of a drug passing through the skin it is not as simple as a lipophilic drug being able to cross through three lipidic domains. It will have to move through structured rigid layers of lipids, providing three different layers of differing hydrophobicity. This is the main reason of which the stratum corneum is a principle barrier to penetration and thus drug delivery.
16
Q
summarise the regions drug penetrate the skin through
A
17
Q
what is able to permeate through all levels of skin?
A
nicotine patch, hormones, fentanyl etc. Able to permeate through all layers of the skin and successfully reach the blood.
18
Q
Appendages (hair follicles + sweat glands) are sites of delivery for what drugs?
A
antimicrobials, depilatories, acne treatment/infection of the follicle
19
Q
what kind of drugs exhibit a local effect?
A
corticosteroids, cytotoxics, antiviral, antihistamines, anaesthetics (interested in permeating through one layer) – They’re not systemic
20
Q
What type of drugs are targeted at the Stratum Corneum?
A
Barriers/repellants, sunscreens, antimicrobials for infections on the surface of skin, antiseptics (e.g. targeting wounds)
21
Q
For drugs to be delivered successfully to the skin, they need…
A
Low molecular weight: <500 Da
LogP (octanol/water partition coefficient): 1-3
Low melting point <200˚C
Relatively high solubility
(Need high concentration of drug to maintain the concentration gradient)
>1mg/mL
In order to create a diffusion gradient to encourage transport of the drug through the skin (through this impermeable barrier – the creation of a concentration gradient is extremely important as a driving force to get drugs into the skin)
22
Q
Advantages of drug delivery to the skin:
A
- It is a non-invasive dosing mechanism
- Unlike oral dosage forms we can bypass the GI tract and first-pass metabolism
- Allows lower drug doses for topical delivery as we are targeting our site of action
- Minimises any side effects that may occur from systemic administration
- Easy, simple to apply – increase patient compliance, preferred over routes such as injection
- Dosing regimen can easily and promptly be interrupted – we can easily instantly stop the delivery of the drug to the patient if needed
- This type of drug delivery is flexible and versatile – there is a possibility of use as controlled/sustained systemic (e.g. transdermal patches) or localised (dermal) drug delivery.
23
Q
State the three mechanisms of drug transport to the skin
A
Shunt (transappendageal) route
Paracellular route
Transcellular route (intracellular)
24
Q
With the transcellular route, drugs must be able to..
A
For this route, the drug is going to diffuse through, into the keratinised cell and then diffuse back out again going through the cell layer – in and out of the cells one by one.
25
Whats special about the Transappendageal route, and what drug properties must be like?
This route provides a direct route into the dermis, bypassing the stratum corneum
**water soluble molecules** that they may have relatively **high diffusion coefficient** for passing through this route into the lower layers of the skin.
26
With the paracellular (**inter**cellular) route - how does the drug move?
Is it a simple route?
* Around the **outside** of the keratinised cells (through the lipid matrix that is surrounding these flattened cells).
* This is not a simple passage through one lipid phase – this is a highly torturous multiple structure layer. The drug **needs to pass between different lipid layers** through the structure and this **may retard the passage** through this layer.
27
Whhat route is the shortest path length?
Transcellular, as it travelling directly through the stratum corneum and so it has a higher rate of mass transfer through the skin.
28
Patient factors affecting drug transport across the skin:
* Affected by **hydration of the skin** (the transcellular route; travelling through the cells is going to be more challenging if we have dehydrated skin as we are relying on this hydration to help the diffusion of drugs through the skin layer)
* **Presence of hair follicles** – going to have an effect on the transappendageal route
* **Age of patient**
* Hydration and blood flow to the skin decreases with age – need to create a diffusion gradient which powers mass transport across the skin
* **Anatomical site of skin** (varied thickness)
29
what three things does our formulation need to do effectively?
* Need to ensure that our **drug is effectively released from formulation –** this is important as we need to maintain a high diffusion coefficient as the driving force for transdermal and topical drug delivery.
* Need to ensure that the drug **can penetrate into the skin to the site of action**
* Need to tell that the drug is **able to activate a pharmacological response –** needs to remain stable, cannot be metabolically damaged during its delivery
30
Explain this: (fick's law of diffusion)
**J**= flux of permeant
**D**= Diffusion coefficient
**Dc/dx** = concentration gradient
The minus sign tells us that the diffusion is going **_down_** a concentration gradient (from high concentration to low concentration). Diffusion coefficient is inversely proportional to the molecular weight/size and viscosity; smaller compound = the greater the diffusion coefficient + greater rate of mass transfer per unit of time.
31
How do we express and relate parition coefficient, Diffusion coefficient and thickeness of the skin?
.
32
Two things particularly crucial for drug delivery across the skin:
* The **concentration** of the drug in the **vehicle** (CV)
* The **THERMODYNAMIC ACTIVITY** of the drug
33
what is "thermodynamic activity" of a drug mean? what does it mean if it =1 or is below 1?
Thermodynamic activity is a measure of the **escaping tendency** of the drug from the **formulation** (how *likely* is this drug to leave the formulation).
The thermodynamic activity **= 1** when we have a **saturated solution. I**t is very likely for the drug to escape the solution and enter the skin.
If the thermodynamic activity is LESS than 1, this suggests we do **not have a sufficient driving force** for the drug to leave the vehicle and therefore decrease the rate of mass transport.
34
What does it mean when a drug is 'Super Saturated'
If we use a SUPERSATURATED solution, then the thermodynamic activity is **above** 1 and thus there is a much higher tendency of the drug to escape from the vehicle. e.g ethanol based vehicles.
35
In topical formulation, define a solution.
Solutions are a **single phase**, comprised of a solvent (can be aqueous/oil) which may also be formulated with some miscible co-solvents.
36
what is generally added to solutions for topical administration and explain why?
Miscible co-solvents. They can increase the concentration of the drug. It can be used to modify drug solutbility and get greater concentrations into the solution. E.g with ethanol there is an increase in **thermodynamic** activity, hence greater flux.
37
disadvantages of using solution
low viscosity and so poor residence time.
38
In Topical administration, describe what a lotion is. Do they have any benefits over solutions?
1. They are formed of oil-in-water or water-in-oil emulsions
2. More common, **especially when one phase is volatile resulting in a cooling** **effect** and the formation of a film on top of the skin (e.g. calamine lotion)
3. have slightly increased viscosity in comparison to solutions, therefore slight increase in skin residence time.
39
What is a gel system
A gel system is a liquid continuous phase with a polymer of which is crosslinked in a mesh-like network in order to create a more viscous matrix.
The liquid phase (solvent) in which is used to create the gel can be a **polar, non-polar or a blend of different solvents** (e.g. could use miscible co-solvents in order to increase drug concentration and thermodynamic activity)
The gelling agent (thickener) will **depend upon the drug** and the **continuous phase** (the type of liquid used to make the gel). Need to ensure that the drug and the excipients such as gelling agent are compatible.
40
Define an ointment
Ointments are greasy/fatty (**oleaginous**) semi-solid formulations which contain a dissolved drug. Ointments form an *occlusive* layer over the skin (form a barrier layer) which can result in a limited permeation due to such high viscosity. However the drug permeation can be enhanced in broken skin.
41
which topical formulation do i give to maximise time on skin residency? How does this help?
ointments have a longer residency time on the skin - maximises drug penetration
42
Types of Ointment?
Absorption ointments - Emulsifying ointments - Water-soluble ointment
43
describe adsorption ointments
These types of ointments contain an emulsifying agent in order to soak up water or aqueous secretions (e.g from the skin) into the ointment
e.g vegetable oils with sorbitan monocleate
44
Emusifying ointments?
Similar to absorption ointments but form an oil-in-water system when water is added.
(E.g. mixture of paraffin waxes, containing cetostearyl alcohol and surfactants)
This mixture is able to be “self-emulsifying” and so is miscible with water – this means that is it easily washed off from the skin.
45
water-soluble ointments?
These are ointments which contain different macrogols (PEGs) – different mixtures of these can be used to create ointments which have different properties (ranging from liquid to semi-solid).
pros: As these are water soluble they blend very easily with skin secretions. Can incorporate water from the skin + can be washed off easily
cons: Not able to contrain as much water as some of the other systems
46
what is a cream?
A cream is an emulsion formed of one liquid phase dispersed within the other (two miscible phases) as fine globules (internal phase) surrounded by the external phase. Creams can be oil-in-water or water-in-oil emulsion. (Can also be formed with three phases e.g. w/o/w)
47
Emulsions are generally unstable. How do we improve this?
Improve through the use of emulsifying agents to improve stability e.g Surfactants and Polymers + viscosity enhancers can also help by immobilising globules and prevent coalescence of droplets
48
differences between creams and ointments?
Creams in general are **less** occlusive than ointments and wont stay on the skin as long as ointments.
Creams do **not** hydrate the stratum corneum as well as ointments
creams **more** versatile as a delivery system
49
list all **formulation** reqiurements with topical drug delivery (not API)
- stability / compatibility of drug
- must not support microbial growth
- must be non-toxic, non-sensitising and well tolerated
- must remain at site of action so that a [high] gradient is maintained for as long as possible to increase the flux.
- must be easily removed
50
how the drug from a transdermal patch partitions through the skin barrier will be a mixture of three main routes:
paracellular, transcellular, shunt
51
what features must all patches have?
1. Essential covering on the back
2. Adhesive that prevents escape of volatile components from patch
3. All other components are fully **compatible** with skin
52
describe an adhesive patch system
drug inside an adhesive. In these devices there is **no rate controlling membrane** – we just have the adhesive in contact *with* the skin. This means that the *rate* of diffusion/partition of the drug out of the adhesive into the skin is *determined* by the rate of **partition of drug from the skin surface** through the deeper layers of the skin
53
Describe a matrix/layered patch system
Multi layered strategies within this type of patch system aim to slightly reduce the rate of drug diffusion through the patch; this is going to give us slightly different release kinetics compared to a simple adhesive system
54
Elicit the structure of a patch, from start to back. Go!
Liner, Adhesive, semi-permeable release membranes, Matrix, backing.
55
what does PSA stand for and what types exist? What are the key features?
Pressure sensitive adhesives. Exist to make patch stick to skin surface. e.g
* Alkyl acrylates, low irritancy as single component system, very sticky – Must be retained on the skin for a sufficiently long time.
* Should be compatible with all other components
* non-toxic
* leave no tacky residue on the skin.
56
describe the key features of a backing layer. any examples of material?
Usually occlusive – designed to totally protect the layer to provide a complete barrier between the drug, skin, and outside environment. Helps reduce chances of microbial contamination
Made from different polymers e.g. **polyethylene, polyester**
In order for the patch to remain on the skin for a long time – they must be able to *conform* to the skin i.e must be flexible
57
what is the 'matrix' of the patch and describe its typical features
1. Matrix is the system in which we have dispersed the drug.
2. Can dictate the drug release if it is the site of drug incorporation.
3. Usually made from simple polymer mixtures of PVP and PVA
We can modify the composition of polymers, cross-linking and the incorporation of a plasticiser (e.g. glycerol) in order to modify the nature of the gel – affecting the release of drug from the matrix.
58
key features of a semi-permeable release membrane and examples?
**Creates a barrier** between the reservoir of **drug** and the **site** where it is able to access to the skin.
Often a co-polymer of **ethyl acetate** and vinyl acetate with a **plasticiser**
59
state the different types of **chemical strategies** to enhance drug delivery across the skin
Penetration enhancers
Pro-drugs
Ion pairing
Eutectic mixtures
Changing the thermodynamic activity of drug (super saturated systems), vesicles
60
state the different physical strategies to enhance penetration across the skin. What makes this different from chemical methods?
Iontophoresis
Electroporation
Phonophoresis, magnetophoresis
Needleless injection/microneedle arrays/imprinting
we are **not** using the chemical composition of the formulation but applying an “**external force/field**” which is going to affect the **rate** of transdermal drug delivery.
61
what actually *are* penetration enhancers?
They have **no pharmacological effect**, but they improve the penetration of the drug through the stratum corneum.
Components partition into the stratum corneum – most of them work by **disrupting/reducing the barrier properties** of the membrane (*stratum corneum*).
This must be a *temporarry* effect and the barrier properties must return to normal after use. It should **not damage underlying** skin cells
62
What factors of this equation are affected by the presence of penetration enhancers?
**_Factors affected (increased):_**
**D** = **Diffusion coefficient** (Ease of diffusion through skin) – affected if we make the barrier more permeable)
**P** = **Partition coefficient** (partitioning/permeation from vehicle into the skin)
63
Ideal properties of chemical penetration enhancers must display:
* Must be **pharmacologically inert**
* **Non-irritating/non-allergenic** – a lot of possibility for skin irritation
* **Onset and duration should be predictable and controllable** (should have a reliable ad predictable effect)
* **Full recovery of skin following removal**
* **Unidirectional** (should be enhancing penetration through the skin and not causing an efflux of drug back out of the skin)
* **Pharmaceutically compatible and acceptable** – should not be degrading/breaking down of device causing loss of pharmacological action of drug
* **Good solvent** – we want to keep our drug concentration high, drug should dissolve well in the solvent
64
what are the three broad ways that penetration enhancers work?
Lipid distruption (major way)
Protien modification
Partitioning promotion
65
describe how Penetration enhancer's lipid disruptors opperate. What is the consequence? give examples of lipid disruptors
* Major way in which penetration enhancers work is by disrupting this lipid structure – they **disrupt the organisation of the lipids within the** ***stratum corneum*** and make the barrier more permeable to drug molecules
* This produces an **increase in the diffusion coefficient, D,** of a drug across the skin barrier
eg: azone, fatty acids (oleic acid). DMSO/Ethanol
66
Protein Modifyers - how do these work? What are the consequences? State examples
They're able to **enter into and denature the dense protein structure** of the top layer in the stratum corneum.
* These work by **interacting with the keratin** in order to open up the structure thus enhancing the permeability of drug through the skin
* Enhances/increases diffusion coefficient, D
Ionic surfactants, DMSO, Urea
67
How do Penetration enhancing 'partitioning promoters' work. Example?
* partitioning promoters enter into the stratum corneum and **change its solubility properties**
* Examples: hydration (water) or *any kind of occlusive barrier* which causes the skin to become more hydrated/increase the water content within the skin
68
what is the **most common penetration enhancer,** and why?
WATER (most simple type):
simplest and most effective penetration enhancer and this works by **hydrating the stratum corneum.**
Keratin is non-hydrated, dry – causing a dry environment in the stratum corneum. If we increase the water content/hydration this can make the bilayer more fluid.
* Also by increasing the fluidity, we also increase the **lipophilic drug transport** through the membrane
* Least toxic
69
how do surfactants enhance drug penetration? and what examples are there?
1. **Extraction of lipids** from the stratum corneum (densely packed lipid bilayer)
* Disrupts the structure of the lipid bilayer and increases drug transport
2. **Interacts with keratin** protein – by interacting with the protein folding and denaturing the protein in order to increase the fluidity of the membrane and rate of drug transport
70
what is the preferred type of surfactant and what is the drawback of long term use?
Generally, **_anionic_** surfactants are better than cationic which in turn are more effective than non-ionic surfactants.
Long term use of surfactant is often harmful, and surfactants may *reduce* drug delivery by increasing the _solubility and stability of the formulation_
71
How does urea work as a penetratrion enhancer. What is it also used for?
* Hydrating agent used to treat scaling conditions e.g. psoriasis
* _Promotes hydration of the skin_ (usually delivered in a formulation with water and *it can double the capacity to absorb water*) and may exert keratolytic activity (disrupt keratinised cell membrane structure)
72
How do fatty acids work as
work as penetration enhancers.
* Able to **partition into** the stratum corneum.
* Disrupts liipid structure
73
How does ethanol work as a penetration enhancer?
1. Believed to be able to **partially extract lipids** from the stratum corneum
2. **Alter the solubility properties** of the stratum corneum by promoting its hydration
3. **Can transport drugs via “solvent drag”**
4. Ethanol is volatile and increases the thermodynamic activity on the skin upon evaporation
74
How do pro-drugs work as a chemical enhancer? e.g
In terms of skin drug delivery we want our drug to be as **lipophilic as possible**, so the process of delivering prodrugs is to introduce *lipophilic moieties* into the structure of the drug and thus increase the absorption by affecting the *partition coefficient, P*
Prodrug can then be enzymatically converted into its active form in skin's lower layers or when in systemic circulation
e.g Clindamycin phosphate
75
What are Iron pairs and how do they work as chemical enhancers
drug molecules delivered as Salt form
* Use of **counter ions**. E.g. salicylates with amines, and Lidocaine HCl
(Rather than having a specific one-to-one salt, a counter ion can be added i.e. something that **forms a complex** together of which is able to go across the stratum corneum. It is often delivered in high excess.)
76
Tell me about supersaturated systems in regards to chemical enhancers, mentioning beclomethasone and ethanol
If a drug beclomethasone has a solubility of 1mg / ml in ethanol and we therefore make a topical solution of 1 mg / ml it will have a thermodynamic activity of 1 because thermodynamic activity = drug concentration / maximum saturable concentration in a vehicle.
After 10 minutes if 20 % of the ethanol has evaporated then there will only be 0.8 ml left in the solution and hence the concentration will have increased the thermodynamic activity to 1.25 due to 1/0.8 = 1.25.
77
what is a major disadvantage of a supersaturated system
supersaturated systems are _unstable_ – and require anti-nucleating polymers (stabilising agents to ensure it does not start precipitating) such as HPMC.
78
for maximum penetration, the drug should be at its
highest thermodynamic activity
79
why are vesicles good for topical drug delivery?
* Liposomes can be used to encapsulate **both hydrophilic and hydrophobic drug molecules**; **hydrophilic molecules can be encapsulated within the core** of the liposomes, and **hydrophobic molecules can be trapped within the lipidic “shell”** of the liposome.
80
How does iontophoresis work as a physical enhancer?
* **Charged drug species** can be driven into the skin by **electrorepulsion** (electrophoresis) from the driving electrode
* It can also affect the larger, **uncharged** molecules due to the convective flow of water of which occurs as well
81
How does electroporation work?
This method uses shorter (µ-ms) bursts or electrical pulses of higher voltage (100-1000V/cm) can actually **create pores in the structure** of the lipid bilayer.
This is believed to happen via “*heat phase transition of lipids*”; by **heating the lipids** we are causing a **temporary phase transition** to occur with the application of current, thus increasing the permeation of the stratum corneum structure, therefore increasing the rate of drug delivery through the skin.
_There is a risk of long term damage_
82
How does phonophoresis work?
* Involves the **application of low frequency ultrasound** (*20-100 kHz*) to the skin.
By applying ultrasound to the skin structure we can create “cavities” or “free volume spaces”
83
how does magnetophoresis work in skin delivery?
A magnetic field is applied to the skin, acting as an external driving force to enhance diamagnetic solute across the skin.
84
How does Thermophoresis work?
The temperature of the skin is **increased to above 32 degrees Celsius** by application of heat, to potentially increase drug delivery. Elevating **temperature** in turn can elevate **diffusion**, and the physical processes of which are contributing to the drug delivery across the skin.
85
Novel device strategies for skin permeation
Needleless injection**:** A driving force of a **compressed gas** is used as an alternative to the conventional injection needle. This is used to push fine droplets/streams of the drug out of the device at supersonic speed.
86
State all the methods for measuring drug transport across the skin
Punch Biopsies
Tape Stripping
Skin blanching
ATR-FITR
Confocal Microscopy
Microdialysis
87
How does punch biopsies work. what they useful for?
* **Sample taken of all layers of skin** with circular blade
* Sections of the is skin removed using a circular blade (fairly invasive process)
**you can** Quantify drugs in SC, viable epidermis, dermis and subcutaneous tissue
88
how does tape stripping work?
* Removes layers of the stratum corneum sequentially
* Concentration-depth profiles can be derived
* Can see how many layers (depth) the drug has permeated
89
how does skin blanching work?
* assesses **how white the skin has become** – correlated to success of transport into skin but **only applicable to drugs that cause vasoconstriction** and thus whitening
* Used for **topically applied corticosteroids** because **Steroid leads to vasoconstriction** thus the skin whitening effect – skin becomes whiter around areas of application – indicating the steroid has been successful
90
how does confocal microsopy work?
* Used to visualise where the drug has permeated to in the skin sample*
* Labelled drug (e.g. Fluorescently labelled drug) can be visualised in skin layers
91
how does Microdialysis in drug transport
* Semi permeable **tube is inserted under skin** then quantify how much drug that can permeate through the skin and enter into the membrane and be collected by the tube
* Collects the permeant (drug)
* Minimally invasive, but can induce inflammation
92
give an experimental outline to how Franz Cell Studies work
1. Vehicle/drug is **applied** to the surface
2. Cell is left stirring for up to **48 hours at 37˚C**
1. Donor solvent in the donor compartment of the Franz cell is stirred. Then **wait to see how much drug can penetrate the membrane** and enter into the receptor solvent.
2. Samples are removed from the side arm (receptor fluid) during this time we leave it stirring in contact with the drug
3. Drug content is measured on the skin **surface**, In skin **layers** and in **receptor fluid.**
93
what type of franz cell systems exist?
* Air-Liquid (in which case you apply cream or semi-solid forulation)
* Liquid-Liquid: (apply loition/liquid formulation)
* Static
* flow-through (maintains the **[**gradient**]** by recieving fluid through the reciever compartment)
* finite or infinite dose
94
what does a franz cell structure look like?
95
what skin is most acceptable for use in franz cell studies? But which one is most equivalent to us?
Synthetic membrane. But obciously human skin is more similar, given that is has the S*tratum cornum*
96
how do we express flux results in franz cell system?
normally expressed as either J (e.g. mg/cm2 /h), Kp (cm2 /h) or Q (amount at any given time)
