Tabletting and Associated Technologies (OSD 1-5) 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
What does sugar coating allow you to do?
- formulate immediate release drugs
- mask taste
- use combination of film and sugar
- alter drug profile
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 does the 1st compression allow you to do?
Make the core
What does the 2nd compression allow you to do?
Make the coating
What does compression coating allow you to do?
Formulate 2 drugs, 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
What are the 3 stages for determining drug stability?
- Drug in native form
- Drug in formulation / in presence of excipients
- Drug when stored
Which drug becomes toxic in the presence of water?
Flucytosine - formulate in absence of water
What does aspirin convert to in the presence of water?
Salicylic acid
What is chloramphenicol converted to in the presence of water?
a non-active compound
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 is dimerisation?
Joining together of 2 molecules
What happens if a drug undergoes isomeric changes?
It can convert between stereoisomers which can have toxic effects or no effects
What catalyses photodegradation?
UV at wavelength 300-400nm
What can lead to conformation changes?
Changes in physical conditions which can damage biological molecules
Give examples of degradation due to chemical incompatibility
Presence of another drug
Presence of an excipient
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
How can drugs be stabilised?
- Temp : store at 2 - 8 degrees C or RT
- Solvent : replace aq with non-aq
- Stability at pH : control with buffer
- Limit exposure to light and O2
What is forced stability testing?
Exposing material to harsh conditions
What can forced stability testing determine?
- Formulation approach
- Excipient types
- Protective additives
- Packaging considerations
What properties should analytical methods used have?
- Sensitive to pick up small amounts
- Selective to pick up all degradation
- Reproducible
What should drug analysis identify?
- Weight
- Purity
- Chemical structure
- Impurities
- Degradation products
- Solubility
- pKa
- Partition coefficient
What is the method for analysis?
- Prepare calibration plot / linear response graph for drug and breakdown or degradation products
- Extract drug from formulation or biological sample into solvent
- Analyse standards and extraction samples using analytical methods
- Calculate conc in the sample
For HPLC analysis - look at different retention times
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 advantages of oral drug delivery to a pharmacist?
- Easy to store
- Easy to dispense
What are the advantages of oral drug delivery to the manufacturer?
- Better chemical and physical stability
- Low cost
- Modify release
- Masking of appearance and taste
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
Give examples of types of tablets
Effervescent, chewable, buccal / sublingual, lozenge, controlled release, dispersible, rectal / vaginal
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 should tablet size be proportional to?
Amount of drug present present
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 physiochemical properties of a drug governed by?
- Solubility, Log P, stability of the drug, pH, pKa
- Manufacturing process
- Type of tablet
What is the site of absorption governed by?
Dissociation constant, lipid solubility and pH
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 & 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
What is tensile strength determined by?
Tilting table method
Define angle of repose
The angle ont eh ode of the cone - the higher the angle the greater the cohesive forces
When would a powder slide?
When the inclination angle is larger than friction
When would a powder stop sliding?
when friction is greater than the inclination angle
What contributes to bulk flow?
Particle: size, shape, density and packing geometry
How can bulk flow be measured?
Measure a volume of powder
Determine the weight of powder
Subject powder to taps
Determine tapped volume
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’s / 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 are the advantages of dry granulation?
- Doesn’t involve solvents
- Fewer pieces of equipment
- Useful for temp and moisture sensitive material
- Economical
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
What is a dissolution test?
The cumulative amount of drug that passes into solution over a given period of time
Why are dissolution tests performed?
Performed to evaluate potential effect of formulation and process variables on drug bioavailability
What is the stirred vessel method for dissolution testing?
SDF is dropped in dissolution medium using a basket or paddle
Dissolution is dependent on temperature or on the dissolution media
What is the continuous flow method for dissolution testing?
SDF is held in a cell and dissolution is pumped at a controlled rate
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 happens in a tablet fails a crushing test?
It fails - got to split in 2 to pass
What is chipping an indicator of?
Friability failure
Machine related issues
Powder compaction problems
