D5 Making tablets Flashcards
what does oral administration of medicines restrict, particularly tablets?
- formulation size and appearance
- tablet has to be of a reasonable size for patients to take or a liquid for children
- eg. size to swallow, taste and palatability
how fast must disintegration of tablets occur and how does this happen in terms of excipients and technology?
- formulation must disintegrate in GIT in appropriate time
- use of optimised excipients (disintegrants)
- use of fabrication technology (coating)
explain how formulations make drug available for absorption
- drug needs to be in dissolved state during its transit through the GIT for absorption to occur
- consider appropriate drug solubilisation approaches
what balance must drugs have?
- right balance of hydrophilicity and hydrophobicity
- too hydrophilic means it will stay in GIT and can’t cross membranes
- too hydrophobic means it will precipitate and not be in solution to be absorbed
what 2 things do medicine formulations need to address? give examples
- drug sensitivity to environment in GIT (eg. protection be enteric coating, local pH buffering or enzyme inactivation)
- drug absorption properties from GIT (use of absorption enhancers and gastroretentive formulations to overcome absorption window issues)
roughly, what percent of medicines are taken orally?
90%
what are the requirement for an ideal oral solid dosage form? give 6
- uniform drug content (reproducible dose)
- drug must remain stable during production and storage
- drug must be bioavailable (formulation reliably releases drug in GIT)
- formulation is robust during handling (by patient as well)
- easy and cost effective to mass produce
- pleasant to take (appropriate to patient group)
what can be achieved by tablets? give 6 things
- accuracy in dosing
- stability (in comparison to liquid formulations)
- release of drug in GIT
- robust on handling
- ease of manufacture (‘mature’ technology in pharmaceutical industry)
- convenient administration and high patient compliance
after drug discovery, what use occur in order to make tablets?
- drug powder needs to be made into a medicine
- powder must be compressed into a tablet that can then quickly disintegrated again
why do we bother making drug powders into tablets?
- easier to dose a tablet than a spoonful of powder (accuracy in dosing)
- most drugs are not very nice tasting or palatable
- tablets are much more convenient
why are fine particles needed for making tablets?
- fine powder dissolves faster and therefore absorption occurs faster
- molecules of the drugs are absorbed, not particles of drug
describe and explain this schematic of the tableting process
- powder you want to compress into a tablet is put through the hopper and flows into the die cavities
- each die must be filled equally
- upper punch compresses the tablet
- lower punch ejects the tablet
what excipient is important in the ejecting of tablets from the die cavities?
lubricant
why must each die be filled equally in the tableting process?
- the weight of the tablets are determined according to the volume of powder used in the die then compressed
- powder always equally and uniformly fills the die
why must powder mixes for tablets be homogenous?
so that all the tablets contain the same amount of active ingredient and excipients
5 requirements for tabletting process
- uniform flow of the powder
- no powder segregation
- die cavity uniformly filled
- powder compressibility
- lubricability
from the 5 requirements for the tabletting process, which is a prerequisite for uniform tablet weight?
uniform flow of the powder
from the 5 requirements for the tabletting process, which TWO are prerequisites for uniform drug content?
- no powder segregation
- die cavity uniformly filled
in the 5 requirements for the tabletting process, what is meant by powder compressibility?
for tablets to remain as tablets once the pressure is removed
in the 5 requirements for the tabletting process, what is meant by lubricability?
no sticking to the die cavity and punches under pressure
what determines the tablets weight and drug dose of tablets?
volume of powder filling die cavity
can all powders be compressed into tablets? explain
- no
- they do not possess the required properties (compressibility)
- after they are compressed they will just turn back into powder if they don’t possess compressibility properties
- excipients with compressibility properties are needed
what are the 3 methods of forming tablets?
- wet granulation
- dry granulation
- direct compression into tablet
what kinds of particles will have the best flow?
- larger particles
- this is because they have a smaller surface area to volume ratio
which particles have the best dissolution rate?
smaller particles
which 2 properties contradict and lead to the requirement for granulation when making tablets?
- dissolution (smaller particles best)
- flow (larger particles best)
what is granulation? what does it eliminate?
- build up of small particles into a larger aggregates with the aid of a binding agent or mechanical force
- eliminates problem of segregation
benefits of granulation when making tablets
- spherical and free-flowing granular particles
- more uniform size distribution
- improved flow due to larger particle size
- reduced segregation
- allows volume dispensing
- improved compression
- binder introduction
how can improved strength of granules be achieved?
- improved strength of final granule can be achieved by addition of binding agent
- eg. binder excipient
advantages of spray granulation / fluid bed wet granulation
- one step procedure
- includes granulation and drying, control of spraying and drying rate critical
describe spray granulation / fluid bed wet granulation
- container has hot air blowing underneath and the powders are inside
- powders flow depending on density and size meaning that larger particles can segregate
describe the compaction of powder in dry granulation
- powder blend is compacted by applying mechanical force onto the powder
- powder is poured through the 2 drums and they make the powder into bricks
- these bricks are not homogenous because the drug and excipients do not flow the same
- these bricks are then broken up again
how is the compaction force applied in dry granulation?
by specialised tableting machine (‘slugging’)
OR
by roller compaction equipment
what is dry granulation used for?
- moisture sensitive materials (drugs prone to hydrolysis)
- heat sensitive materials
disadvantages of dry granulation
- can result in granules with low porosity
- dust creation
- special equipment required
what is the direct compression process based on?
- availability of an excipient that has physicochemical properties required for tableting called ‘direct compression excipients’
what happens during the direct compression process?
- mix drug powder straight with direct compression excipients and compress
- no need for dry or wet granulation, just mix together and compress
there are some desired properties of direct compression excipients. what requirements do these properties satisfy?
- good flow
- good compression properties
- particle size similar to the active drug
- high bulk density
- physically and chemically stable in contact with moisture, heat and air
- chemically inert
why do particles of excipients in direct compression need to be similar to that of the active drug?
to avoid segregation during processing (this is usually the trickiest requirement to satisfy for direct compression)
why is high bulk density required for direct compression excipients?
thin tablet will be produced otherwise
what is the use of direct compression dependent on for making tablets?
the development and availability of direct compressible excipients
describe how many drug powders are suitable for compressibility and what happens if they are not
- most drug powders can’t be compressed into tablet, they don’t possess the required properties
- typically 20-30% of poorly compressible drugs can be incorporated into tablets made by using direct compressible excipient
describe some directly compressible excipients
- commercially available, specialty ingredients developed by supplier (by patented processes)
- eg. Ludipress, Embed, Avicel, Tablettose
- different forms of lactose, cellulose or starch (modified through processing to acquire required properties for direct compression)
