MDM: Tablets Flashcards
What are tablets?
A solid preparation manufactured by compressing uniform volumes of particles which contain a single dose of one of more active ingredients and excipients.
What are advantages of tablets?
- Convient - to carry/ store
- Good patinet compliance
- Acurate dosing
- chemical, physical and microbial stability
- Generally cheap, robust and elegent
Disadvantages of tablets
- Generally systemic delivery
- poor bioavailability
- must be swallowed
- local irritation - GI mucosa
- Extensive developmental work
What are the basic steps taken when forming a tablet?
When forming a tablet what are the ideal properties for a powder blend?
- Homogenous - doesn’t segregate
- Free flowing - freely flows through tablet machinary
- Adheres and coheres
- doesnt adhere to tablet tooling
What are examples of excipents included in tablets?
- Binder
- Distigrant
- Lubricant
- Diluent
- Glidant
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What is the role of a diluent and some examples?
Increases tablets bulk density and acheive required strength
Lactose, sucrose, mannitol, glucose, Calcium hydrogen phosphate, MCC
What are examples of lubricants and their role
Reduce friction between tablet and machinary during manufacture
Magnesium sterate and sodium steryl fumarate
What are examples of binders and their roles
Improves mechanical strength by binding particles
PVP, gelatine, sucrose
What is the role of distigrants and some examples
Promote rapid tablet distigrant
Starch, cellulose, PVP,
What are example of glidants and their roles?
Improves powder flow by reducing intra-particular friction
silica, magnesuim sterate, talc
What are methods used to determine powder flow?
What do these methods tell you?
- Flow through an orfice - flow rate
- Angle of response - inter particular cohesion
- Bulk density - percentage compressability and friction
What is powder flow dependent upon?
- Particle size, shape and density
A powder has poor flow characteristics. What could be done to sort this?
- Increase particle size and reduce size distribution
- Change particle size and texture e.g. during spray drying, cyrstallisation
- Change surface forces - e.g. add glidant
- Alter process conditions e.g. vibration assisted hoppers
What are examples of equipments used to mix powders?
- tumbling
- high speed mixer granulators
- fluidised bed mixers
- agitator mixers
What is powder mixing depent on?
- shape
- size
- density of particles
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What improvement could be done to improve powder mixing?
- Granulation
- Reduce particle size distribution - e.g. sieving or milling
- controlled crystilisation - particular shape and sized crystals
- Choose excipents with similar density to API
- Reduce blending movement
- Equipment - reduce time in hoppers, reduce transfer
When forming tablets what are the 2 methods that can be used?
Describe breifely these
Direct compression - drug and excipents mixed
or granulation - primary powder particles adhere to form granules
What are advantages and disadvantages of direct compression?
Advantages:
- Faster drug dissolution
- Reduction in manufactuing time and costs
Disadvantages:
- powder segregation
- poor compaction properties
- poor colour uniformity
- specialist fillers and binders required
- powder must have good flow properties
Advantages and disadvantages of granulation
Advantages:
- increases compactiabilty
- improved colour uniformity
- improves powder flow
- increases bulk density
- improves homogeneity and prevent segregation
Disadvantages:
- increases in production time and costs
- may cause hydrolysis of drug
Describe 2 other granulating methods
- Fluidised bed drier - spray drying using a binder solution
- Dry granulating - using pressure to form compacts
What are the benefits/ negatives of spray drying and dry granulating?
Spray drying - produces high quality granules - good homeogenity, flow and compactability. Time consusing
Dry granulation - no hydrolysis of drug
What is powder compression?
Pushing particles into close proximaty to each other by using confined compression
What are the 3 stages involved in powder compression to form a tablet?
- Die filling
- Tablet formation (compression of tablet from upper and lower die)
- Tablet ejection
How does a tablet pressor work?
What are the differences between both?
What are they used for?
- Hopper filed with powder and and fills dies which are then compressed by upper and lower dies before being ejected
- Single punch tablet press - one set of tools and small output.
- rotary tablet press - multiple sets of tools and high out put
- Single tablet punch used to produce tablets for clinical trials and during formulation development
Why would we coat a tablet?
- Protect the drug
- mask taste
- ease of swallowing
- improves appearance
- rapid idnetificartion
- increases bulk
- modified release characteristics
- ease of handling
What are examples of types of tablet coatings?
- film
- sugar
- compression
Describe film coating
- most common
- ploymers, platisticizers, colourants
- sprayed onto rotating tablet
- immediate (non functional) - water soluble
- functional - modified - PH 5 -6
Describe sugar coating
- sucrose based syrup
- sugar coating pan (6 stages - sealing, subcoating, smoothing, colouring, polishing, printing)
- readily water soluble - distigrant
- generally immediate release
Describe compression coating
compatction of granular particles around tablet core
What are the desired attributes of a tablet?
- contains correct dose
- consistant size, weight and appearance
- drug release controlled and reproducable
- sufficent mechanical strength
- physical, chemiacal and microbiologically stable
- formulated for patient acceptance
- packaged appropriately
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Why is tablet testing required?
- To ensure the patient receives a tablet which contains the required amount of drug substance in a form in which it can exert its full pharmacological action.
- to ensure it is microbiologically stable
- to ensure the AI is released over a specified time
- ensure mechanical strenght is sufficent to avoid it crumbling/ breaking on handling
What are examples of drug tests carried out?
- Uniformity of weight
Describe uniformity of weight testing
- equal to or greater than 25mg or 25% drug coc
- individually weigh 20 tablets and determine the mean
- Not more than 2 tablets should deviate from the mean by particular % and no tablets should deviate by twice the %
- More acurate with higher drug conc
- ≤ 80mg - 10%
- > 80mg /< 250mg - 7.5%
- ≥250mg - 5%
Describe uniformity of content
- Done if less than 25mg or less than 25% drug content
- using appropriate analytical technique determine drug content of 20 tablets
- Drug content of each tablet should fall between 85% - 115% of average content
- One tablet allowed to be between 75% - 125% of avergae content
- if one tablet falls out with limits re test another 20
Describe friability testing
- Friabilitor used - Mimics forces encountered during handling
- tablets must resist friability to ensure appearance and dose is maintained
- if less or equal to 650mg - 6.5g of whole tablets tested
- if more than 650mg - 10 tablets tested
- No more thn 1% mass loss allowed and no chips or cracks allowed
Describe fracture resistance testing
- The resistance to crush tablet - measured by force.
- Tablet placed against platen, load applied along diameter by movable platen. Tablet cracks along diameter into two pieces of similar size and force recorded.
- Record mean, minimum and maximum forces (Newtons). RGU: Mean force - 40 – 100 Newtons
Describe distigratin testing
- Determines if tablets disintigrate in prescribed time
- 6 tablets in purified water at 37°C +/- 2 for 15 mins
- if 1 or 1 fail test further 12. 16/ 18 must distigrate in required time
- depends on type of tablet e.g. coated - 60 mins
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Describe dissolution testing
- Tablet placed in dissolution medium in stirred vessle at 37 +/- 0.5
- more than 70/ 75% of drug released after 45 mins
What are problems that can occur during tableting?
- low mechanical strength
- weight/ dose variations (granulate?)
- capping - top of tablet fractures/ breaks
- lamination - tablet breaks into more than 2 distinict horizontal layers
- sticking - powder sticks to punch
- picking - particular sticking where powder sticks wihtin letters/ logos of punch
- chipping - breaking of edge of tablet
What tablet classes is there?
- immediate release: rapid drug release
- modified release: slower/ varied drug release
- prolonged release: released slowly over a long period of time
- Pulsatile release: Released in two or more pulses
- Delayed release: Released some time after administration
What are types of immediate release tablets?
- distigrating
- chewable
- effervescent
- compressed lozingers
- sublingual and buccal tablets
Describe distigratning tablets
- Most common tablet type - intended for swallowing whole.
- Drug release: disintegration -> dissolution -> absorption
- Disintegration rate: dependant on several formulation and production factors.
- Dissolution rate: limited by drug factors such as solubility and particle size.
- Absorption rate: lipophilicity
- Examples: Paracetamol, Ibuprofen.
Describe chewable tablets
- Mechanical disintegration – no disintegrant
- Drug dissolves in stomach
- Rapid effect, no water required, for patients with difficulty swallowing
- Flavourings and colourings commonly used
- Vitamins, Gaviscon
Describe effervscengt tablets
- Releases carbon dioxide – facilitating disintegration and dissolution (reaction between carbonate / bicarbonate and acid such as citric or tartaric acids)
- Rapid drug action
- Analgesics, vitamins
Describe compressed lozengers
- Slow drug release - No disintegrant
- Systemic and local drug delivery
- Filler and binder – water soluble and acceptable taste e.g. carbohydrates / sugars
- Colouring and flavouring
- High pressure – increased hardness and low porosity.
- e.g Strepsils, Nicotine
describe buccal/ sublingual
- Rapid systemic delivery avoiding first pass liver metabolism
- Subligual – under tongue / Buccal – side of cheek / between upper lip and gum.
- Small, porous, disintegrant (buccal).
- Slow release – polymers 1 – 2 hrs
- e.g. Nitroglycerin, Loratadine, Nicotine (Nicotinell), Nytroglycerin (Nitrostat).
- Tablets too soft?
- Tablets not disintegrating?
- Tablets breaking apart after manufacture?
- Active not being released from tablet during dissolution test?
- Powder will not flow correctly?
- binder or less distigrant
- add distigrant
- Add binder
- Distigrant
- glidant
- granulation
