Drug Delivery Devices (D3) Flashcards
Das lecture 3 of 5
How do microneedles work?
They are a method of transdermal delivery, which overcome the natural barrier of the stratum corneum by piercing through it
What 2 types of microneedle designs are there?
Hollow
coated/solid microneedles
Describe how hollow microneedles work
- The needles pierce the SC and stop in the viable skin zone
- The drug reservoir feeds drugs through the hollow needles slowly naturally injecting the drug into the skin
How do solid/coated microneedles deliver drugs?
- The needles are coated in the drug
- Once pierced in the skin, tissue fluid dissolves the drug dispersing it
What other types of microneedles exist? (bonus)
What are the potential uses or applications of microneedles?
- Immunisation
- Treatment of diabetes
- Cosmetic - wrinkle treatment
What is the process called in which solid microneedles are coating in drug
Dip coating
Explain the process of dip coating
- A bottom plate filled with coating solution + drug is filled with a cover plate
- The microneedles are dipped into the solution and withdrawn
How can dip coating be improved?
- The drug can be charged and the needle oppositely charged so that the molecules stick to the needle better
What are the steps in microfabricating microneedles using photolithography
1) Expose a silicon wafer to steam at temps of 900-1500 creating a thin surface layer of silicon oxide
2) Add a thin layer of photoresist (positive or negative) by spin coating (which is pouring it onto the surface and spinning rapidly to produce a thin even layer)
3) The wafer is then soft baked to remove excess photoresist solvent and improve adherence of layers
4) Exposure of the photoresist to UV through the mask causes a chemical change in the photoresist that is exposed to the light because of the mask
5) Developer washes away the photoresist that becomes changed (positive photoresist becomes soluble and washes away when light is shone on it)
6) Etching is then used to to break down the silicon oxide that is not protected by the photoresist, producing microneedles
7) Remove the photoresist layer
Talk through microfabrication quickly using this model to guide
1) Expose a silicon wafer to steam at temps of 900-1500 creating a thin surface layer of silicon oxide
2) Add a thin layer of photoresist (positive or negative) by spin coating (which is pouring it onto the surface and spinning rapidly to produce a thin even layer)
3) The wafer is then soft baked to remove excess photoresist solvent and improve adherence of layers
4) Exposure of the photoresist to UV through the mask causes a chemical change in the photoresist that is exposed to the light because of the mask
5) Developer washes away the photoresist that becomes changed. (Left is positive photoresist, right is negative)
6) Etching is then used to to break down the silicon oxide that is not protected by the photoresist, producing microneedles
7) Remove the photoresist layer
Compared to hypodermic needles, how do microneedles perform in:
Transport
Sustained delivery
Pain level
Cost
Microneedles transport less drug
The delivery is more sustained over a longer period
Far less pain and irritation
Much higher cost and complexity
In the optimisation of microneedles, what factors need to be looked at?
- Needle geometry
- Needle distribution (space between)
- How the needles are coated or hole dimension
- The extra width of the needle when solid coated needs to be accounted for
What does g mean in this equation built to optimise conical microneedles?
the permeability factor, the higher g the higher the permeability
What does this graph show us?
g is the permeability function of microneedles, a higher g value indicates higher permeability and a better microneedle design
- This shows that a small patch with hollow rectangular microneedles produce the highest permeability profile (faster and more drug diffusion)
- As patch SA increased, permeability function reduces
Some geometries of microneedles coated in solid drug produce back diffusion, what is this?
When drug diffuses back up away from the blood vessels due to the concentration gradient
What effect does having a high elimination rate constant have on the blood conc vs time graphs
A high elimination rate constant means that the rate at which the drug is metabolised by the patient is greater
- A greater change in gradient, the graph flattens faster
- A graph with a smaller area under curve
What effect does having a high volume of blood have on the blood conc vs time graphs
A higher volume of blood means that with a set dosage the concentration is less influenced
- Less steep initial gradient
- Lower SA under the curve
How are flux and permeability linked via equation?
Flux = drug permeability constant * Conc. of drug in the blood
What does this graph tell us? And what trade off may apply?
1) As microneedle tip radius increases, so does diffusive flux almost linearly
2) The wider the bulk microneedle is the greater the diffusive flux
More pain from larger needles, less of them in a set area if they are larger
What issue arises from having needles too geometrically compact?
- Needles too geometrically close require a lot of friction to insert
- There is an optimal spacing where friction is minimal while the geometric compaction of the needles isnt too sparse resulting in larger patches or less drug delivery (roughly 150um here)
