Tabletting technologies Flashcards
What are some disadvantages of tablets?
manufacture requires a series of unit processes – product loss at each stage, drug absorption is dependent on gastric emptying rate, compression difficulties due to powder physical properties
What is the definition of excipient?
an inert substance that is used as a diluent or vehicle for preparing a drug product
What are some advantages of tablets?
Improves patient compliance
- Convenient and safe way of administration
- Easy to carry multiple doses
- Accurate and reproducible doses
- Aesthetically pleasing
- Easy to store and dispense
- Solid dosage forms have better chemical and physical stability
- Ease of low cost mass production
- Possible to modify release and performance characteristics
- Possible to mask unpleasant taste and appearance
- Different tablet forms available
What is the minimum and maximum tablet weight?
< 800 mg max
50mg min
High dose tablets require a filler. True or false?
false
low dose - <5mg tablets
The filler used in tablets should be hygroscopic, True or false?
false, non-hygroscopic as you don’t want it to absorb water as they make bulk of tablet
Why is a filler needed in a low dose tablet?
For ease of manufacturing and handling
What is the need for a disintegrant in a tablet?
to ensure the tablet breaks up into smaller fragments (it’s primary particles)
What is the role of a binder in a tablet?
added to ensure that the tablet can be formed with the required mechanical strength
What is the role of a glidant in a tablet
to improve flowability of the powder – either for direct compaction of for granulation
What is the role of a lubricant in a tablet?
to ensure that tablet formation and ejection can occur with low friction between the tablet and the die
Why would you want to minimise the amount of lubricant in a tablet, although it helps with tablet formulation?
because they are usually lipophilic and so will hinder the dissolution and disintegration of the tablet if too much is used
What is the role of an antiadherent in tablet?
to reduce the adhesion between the powder and the punches which could otherwise lead to uneven tablet surface
What is tensile strength used to measure?
Adhesive/cohesive properties
What is meant by tensile strength?
how easy it is to introduce a breakage in the tablet
What does a high angle of repose indicate?
High cohesive forces
When the angle of inclination is greater than the frictional force, does the powder slide or stop sliding?
Slide
How can powder flow be improved?
increase the particle size eg by granulation, alter surface forces – controlled temp, humidity etc. Formulation additives eg glidants, lubricants, change process conditions – vibration assisted hoppers, force feeders
What is granulation?
primary powder particles are made to adhere to form larger multi-particle entities called granules
Why use granulation?
granules flow better than powder, prevent segregation of ingredients, improve compaction, ease of transport as they are less dense than powder and so occupy less vol/unit weight
What is the mechanism of granulation?
3 steps
Nucleation, transition (nuclei growth), granule growth
Wet granulation is suitable for temperature and moisture sensitive material. True or false?
False
Dry granulation is
What are some advantages of dry granulation?
Economical - less energy costs, low equipment costs, easy to scale up
Bulk density affects die filling. True or false?
True
How many tablets should be tested for uniformity of content?
More than 5 to be representative
What are the accepted % limit for API in uniformity of content test?
90-110%
There is a direct correlation between uniformity of content and tablet weight. True or false?
True
In tablet weight testing, no more than 2 tablets should have a mass difference of more than 20%. True or false?
10%
What happens to a tablet that is ingested but doesn’t disintegrate in the body?
Excreted
How many tablets need to fail the disintegration test for it to be repeated on a second full batch?
2 tablets
What is the definition of dissolution?
the transfer of molecules or ions from the solid state into solution
If a reaction is exothermic, will dissolution be favoured by an increase in temperature?
No
What are the two methods of conducting dissolution tests?
stirred vessel method, continuous flow method
What are the 2 possible apparatus for dissolution in the stirred vessel method?
Basket and paddle
Which dissolution method is a better mimic of GIT conditions?
Continuous flow
The mechanical strength of a tablet is associated with resistance of the solid specimen to what 2 things?
fracturing and attrition
What are friability tests used to mimic?
forces that are present in production, storage and administration
In the friability test you are looking for less than 5% weight loss in the tablet. True or false?
False
Less than 1% weight loss
In the friability test, how many tablets are tested?
20 in a revolving cycle
When testing the tablet’s resistance to crushing, if the tablet splits in two, does it pass the test?
Yes
What are the gastro- retentive tablets designed for?
To be retained in upper GIT
What are the 3 types of coating?
Film
Sugar
Compression
What is titanium dioxide used as in coating?
A Colourant
Are tablets more evenly coated if a horizontal spray is used or a tilted spray is used?
Tilted
What are some problems that are associated with coating?
erosion, peeling and breakage, poor mechanical strength, uneven coat, tablet peeling
Sugar coating involves successive applications of what solution?
Sucrose
- What are the characteristics of tablets that are coated with a sugar coating?
immediate release of drug – as sugar is very soluble in water, masked taste of tablet
How much weight does sugar coating add to a tablet?
30-50%
Main reason for using a sugar coating is for masking taste rather than functionality. True or false?
True, would still need a film coat eg. enteric if you want functionality
How long is the sugar coating process?
Takes over 8 hours
What are the 6 steps involved in sugar coating process?
sealing, subcoating, smoothing, colouring, polishing & printing
Compression coating allows for 2 drugs to be present in one tablet. True or false?
True
One in coating, one in core
Soft gelatin capsules cannot be filled with liquid. True or false?
false, can be filled with liquid – helps to increase solubility or permeability of drug across cell membrane
Soft gel capsules are not suitable for potent drugs. True or false?
False
Why is there no risk of leakage in a soft gel capsule?
because it is the one piece that is sealed
Why is it harder to have al liquid in a hard capsule?
Risk of leakage
Capsule made of two halves
Hard capsules are filled with liquid. True or false?
false, powder or more pellets usually
The hard capsule shell doesn’t give any controlled release properties. True or false?
true, if you want controlled release, this has to be done at the granulation stage of process
Hydrolysis only occurs in the presence of water. True or false?
False - water, acid or base
Most Ibuprofen is supplied as a racemic mixture. Unusually, this drug is converted to the R form in the body. True or false?
False
Converted to S form
What does a maillard reaction occur between?
lactose and an amide containing drug, resulting in a glycosamine
How can a maillard reaction be prevented?
by using an alternative diluent to lactose such as mannitol
Replacing an aqueous solvent with a non-aqueous solvent will maximize the stability of the drug. Why?
Because it will be less prone to hydrolysis
Magnesium stearate only acts as a lubricant. True or false?
false, lubricant, glidant, anti-adherent
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
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
What are the 3 stages at which you determine drug stability?
- Drug in native form
- Drug in formulation / in presence of excipients
- Drug when stored
What modes of degradation can a drug undergo?
Hydrolysis Oxidation Dimerisation Isomeric changes Photodegradation Conformational changes
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
What are transacetylation reactions?
The moving of a functional group to another - this can remove functionality
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 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 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?
What properties do particles <100µm have?
What is tensile strength determined by?
Tilting table method
Describe the process of wet granulation
Spray with binder
Bridges are formed between particles
Evaporate and remove solvent leaving granules
Create solid bridges
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
