L1 3D Printing Solid Dosage Forms Flashcards
An example of an approved additive manufacturing
This makes solid dosage and targeted drug delivery devices.
E.g. Triasteks’s T19 is a melt extrusion 3DP tablet in 2021 and was approved ijnto clinical studies.
What is additive manufacturing and different types?
- Generate 3D model via CAD.
- Printer software slices it into many layers.
- Use 3D printer to print structure layer by layer thus it is cross sections of it.
Stereolithography
Inkjet printing
Powder bed-based 3D printing
Extrusion-based
Already discussed in 3D prinitng a tool for making a new tissue.
Subtractive vs additive.
Advantages of additive:
* Complex structures with no additonal costs.
* Custom geometries
* Spatial control of multiple materials
Disadvantages
* Slow so not suitable for mass production
* Objects have lower quality(rough surface)
* Hard to get quality assurance.
Additive (3D) you end up having less waste material and you use material to start which doesnt need to be broken down.
Whereas subtractive you have a block of material which needs to be broken down then you get the 3d object and have more waste.
3D printed vs OTC fast melt
OTC is significantly slower
Inside of 3d printed tablet, you can see the granules and excipients of the durgs, blue belts are where the particles bind together. Very porus structure which is better than the OTC tablet.
3D tablets had= glidant (lubrication-powder flowing), disintegrant (tablet to dissolve into smaller particles increasing SA) , binder and surfactant.
Powder based 3D printing process.
Spreading bar to spread the thin layer of powder onto the platform (why you need glidant).
Jet tiny droplets (binder droplets=PVP,solvent(water/ethan),surfactant (Tween 20))
Excipient in the powder bed.
- Good wetting and penetratation of the binder solution through the powder bed.
- If you place a water droplet on the surface and surrounds the tablet like a ball, it means that its bad wetting and hydrophobic
- Whereas when water completely spreads on the surface, this shows hydrophilicity.
- But it is different wetting of each excipients.
As researchers found out, that the use of solvent as a water/ethanol mixture and surfactant, not matter what excipients there is good spreading of water allowing successful delivery of the binder.
Powder bed based medical devices
3D printed metal cage for spinal fusion which is used to treat lower back pain.
This then expects the bones to grow into porus structure then both of the bones fuse together.
How these powder based 3d printed devices are made?
A thin and even layer of powder is placed on the fabrication piston by a roller/blade
You can use a high energy laser (HEL) beam to scan the powder, to scan where you want to bind the powders together.
The powders partially melt via the (HEL) laser and this allows them to bind the powders together.
Polypill
Extrusion based 3D printing.
5 drugs including; ramipril, pravastatin, atenolol, aspirin, hydrocglorothiazide.
These complex regiemns can be combined in a single personalised tbalet.
Multiple drugs in one pill may improve patient adherence.
How extrusion based 3D printing works?
Need a low viscosity from the cartridge (resistance to flowww)
Need the V to increase when it comes out otherwise its hard to form a 3D structure from droplets.
3D structure needs to withstand its own weight which requires that increase in VIS.
Linking back to pollypill they need barriers for each different drug, the formulations are:
Cellulose acetate (acts as hydrophobic membrane between the compartments)
D-mannitol (filler-bulking agent)
Polyethyleneglycol PG6000 (platiciser to increase flow of paste/ink)
Acetone and DMSO= Acetone has low bpt, therefore will evaporate when coming out of the cartride causing visocisty to increase, DMSO has higher bpt and tunes the organic solvent on how fast it evaporates
Like printers at home
Inkjet printing
They questioned how can you use different geometries of tablets to control different rate of releas of drugs.
Higher surface area means faster release
How inkjet works?
Ink comes out of printed nozzle.
Piezoelectric actuator, when applying a volatge to it either shrinks or expands(causes nozzle to squeeze or expand).
To make 3d printed objects you have to consider the spacing of the droplets.
Solidify the droplets by exposing to UV thus causing crosslinking and then another layer can then be printed on top of the solidifed ink.
Ink crosslinking which involves solidification
NVP, polyethylene glycocl and Irgacure 2959
Irgacure 2959= activated by UV which then forms radicals.
Radicals will attack carbin double binnd in PEGDA to from crosslinked network structure.
Red dots-carbon DB
Blue line is cross link.
Once crosslinked turns from liquid to solid.
Photon based 3D printing
Drug load can be a hollow space sphere.
Travels in the intestine, particles are magentic, so can use external magnetci field to open the seal where the drugs are loaded inside to release.
Use light based technology called two photon micro fabrication to make the spheres which have a cavity inside. Sphere is made of polymer and they coat magnetic metals such as titanium and nickel and apply seel material on top. (NIR responsive sealing layer.
Stereolithography
UV light source, then use digital micromirror device to reflect light onto those resin tank.
Resin tank is liquid, when the UV light is exposed this then solidfied using the crosslinked method from earlier.
You can choose where to shine the UV light, if you do that layer by layer you can then make the 3D structure.
DMD is made up of an array of micromirrors, each mirrors can be tilted independently.
If you want 3d shape of pyramid, you need to slice in to 3 layers for example. You can tell the projector where to shine the screen to, if the screen is photo sensible and crosslinakable, this will form the shape, but the ones that are not still stay as a resin liquid. This is then repeated.
