Tabletting Flashcards
What is a coat?
A dry, outer layer of material applied to the surface of a dosage form to improve different properties such as the release of the drug
What are the types of coating?
- Film coating
- Sugar coating
- Compression coating
What methods of bed coating are used?
Fluidised or pan bed coating
What is an immediate release film coat used for?
Non-biological properties such as appearance
What is a modified release film coat used for?
Delaying or controlling drug release
Give examples of film coating compounds.
- Polymers : HMPC / MC or EC / cellulose acetate for modified release
- Plasticisers : PEG, PG or diethyl phthalate
- Colourants : iron oxide or titanium dioxide
- Solvated compounds : organic polymer solutions
What will affect the properties of the coat?
The methods and conditions of the coating process
What are some problems with coating?
- Erosion
- Peeling - due to excess moisture inside
- Breakage - due to poor mechanical strength
How long can sugar coating take?
> 8 hours
What is the process of sugar coating?
- Seal porous core with : shellac, PVAP or CAP
- Sub-coat with bulking agents, anti-adherents and binders
- Smoothing : adding a coat to sub-coat
- Colouring
- Polish with wax
- Print with edible ink (if necessary)
What is compression coating?
A novel drug development process - it is a dry process that requires specialist equipment
What is the 1st compression stage for?
Making the core
What is the 2nd compression stage for?
Making the coating
What does compression coating allow you to do?
Formulate 2 drugs together, one in the core and the other in the coat
What are soft gels good for?
Poorly soluble drugs
Potent drug
Liquid formulations
What is the process of manufacturing soft gels?
- Gelatin preparation
- Material preparation
- Encapsulation
- Drying
- Inspection
- Polishing
- Packaging
How are hard capsules supplied?
As closed units which have to be filled
What is the process of manufacturing hard capsules?
- Capsules are separated by a vacuum
- Check if they open
- Eject unopened ones
- Fill with pellet/granule/powder for injection
- Recover unused powder
- Rejoin and eject capsules
- Clean any residue left behind and repeat the process again
Define drug stability
Length of time a drug retains its chemical and physical properties without any loss of potency
Which drug becomes toxic in the presence of water?
Flucytosine - formulate in absence of water
What modes of degradation can a drug undergo?
Hydrolysis Oxidation Dimerisation Isomeric changes Photodegradation Photodegradation Conformational changes
What happens to ascorbic acid when oxidised?
Converts to dehydroascorbic acid - reversible reaction in the body. But it can irreversibly convert to 2,3-diketogluoinc acid
What catalyses photodegradation?
UV at wavelength 300-400nm
What are transacetylation reactions?
The moving of a functional group to another - this can remove functionality
What is the Maillard reaction?
This react occurs between lactose and amides. A glucosamine is formed.
What can be avoided by use of mannitol as a diluent?
Maillard reaction
glycoamination
What is forced stability testing?
Exposing material to harsh conditions
What properties should analytical methods used have?
- Sensitive to pick up small amounts
- Selective to pick up all degradation
- Reproducible
What are the advantages of oral drug delivery to the patient?
- Improved compliance
- Convenient
- Safe and easy to use
- Carry multiple doses
- Accurate
- Reproducible doses
What are the disadvantages of oral drug delivery?
- Needs a serious of unit processes
- Drug absorption is dependent on gastric emptying
- Compression difficulties
- Certain patient groups can’t take tablets
What API weight range should be in a tablet?
5 - 500mg
What is considered to be a high API dose?
> 50% of the tablet weight
What is considered to a low API dose?
<5% of the tablet weight
What is the ideal total tablet weight?
<800mg
Give examples of diluents.
Lactose, sucrose, glucose and mannitol
What is the purpose of a disintegrant?
Give examples
Ensures the tablet breaks up
E.g. starch, cellulose, calcium carbonate
What is the purpose of a binder?
Give examples
Ensures tables are formed with required mechanical strength
E.g. gelatin, PVP, HPMC, PEG, sucrose, starch
What is the purpose of a glidant?
Give examples
Improves flowability for direct compaction or granulation
E.g. Talc, colloidal silicon, magnesium stearate
What is the purpose of an anti-adherent?
Give examples
Reduce adhesion
E.g. magnesium stearate, talc, starch
What is the purpose of a lubricant?
Give examples
Ensure tablet formation and ejection can occur with low friction
E.g. magnesium stearate, stearic acid, PEG, SLS, liquid paraffin
What are the unit processes of tableting?
Weighing Mixing Tablet manufacture Quality assurance checks Dissolution Coating Quality control checks
What does uneven powder flow result in?
Air trapped in the powder, capping and lamination, excess fine powder and dust contamination
What properties do particles <100µm have?
They have greater cohesion and so will need a glidant or lubricant to increase surface area
Define tensile strength.
How easy it is to introduce breakage - the stronger the cohesive & adhesive forces the less likely it is that breakage will occur
Define angle of repose
The angle ont eh ode of the cone - the higher the angle the greater the cohesive forces
What is tensile strength determined by?
Tilting table method
What contributes to bulk flow?
Particle: size, shape, density and packing geometry
What effect does high bulk density have on bulk flow?
There is no change in density after tapping as the particles are already tightly packed
What is the ideal Carr/ compressibility index?
0 - 10%
How can powder flow be improved?
- Changing particle size
- Alter surface forces
- Formulation additives
- Change process conditions
What is the process of wet granulation?
Spray with binder
Bridges are formed between particles
Evaporate and remove solvent leaving granules
Create solid bridges
What are the advantages of wet granulation?
- Improves flow
- Prevents segregation
- Improves compaction
- Reduces fine powder particles
- Reduces water uptake
- Less dense granules
What is dry granulation useful for?
Moisture sensitive material
What does variation in uniformity content suggest?
- Non-homogeniety
- Segregation of powders
- Problems with compression
How can tablet weight be checked?
- Weigh 20 at random
- No more than 2% should be >10% of tablet weight
- None should be >20% of tablet weight
Describe the method used to check disintegration
Test 6 tablets
- Drop tablet and agitate it
- Monitor time taken to disintegrate
- Repeat if 2 tablets fail
Why does mechanical strength need to be determined?
To assess importance of formulation and production variables for the resistance of a tablet to fracture and attrition during design, development and production.
What is chipping an indicator of?
Friability failure
Machine related issues
Powder compaction problems
