301 Solid Dosage Forms Flashcards
What are the steps in making a tablet?
- Milling (making smaller/consistently sized particles) & mixing of ingredients
- Granulation to bind ingredients together
- Tableting - compression of ingredients
- Testing to ensure consistency within & between batches
Excipients (what goes into a tablet and why?)
‘Ingredients’ in tablet that are not API
Powder API formulated into tablet by granulation & then compression methods
Significantly influence stability & bioavailability of API in tablet
Types of excipients
Diluents/fillers
Binders
Disintegrants
Glidants
Lubricants
Coating materials
Colouring agents
Stabiliser
Sweeteners & flavouring agents
Other
What do tablets need to weight for patient use?
Minimum of 50mg
Very low dose drugs require diluent/filler/bulking agents to bring tablet weight up to 50mg
Soluble examples of diluents/fillers
Lactose, sucrose, dextrose & mannitol
Insoluble examples of diluents/fillers
Why can lactose not be used for drugs with amine groups?
- Dicalcium phosphate, starches, microcrystalline cellulose (MCC), sodium chloride
- Due to Maillard reaction -> mannitol used instead
What is maillard reaction?
Chemical between amino acids & reducing sugar to create melanoidins, compounds give browned food its flavour
When are binders/adhesives added in the tableting process?
Either dry or liquid to promote formulation of cohesive agglomerate (granule) or to promote cohesive compacts during direct compression
What do binders do in dry granulation?
Binders can be added to dry powder for preparing tablets by direct compression
What can binders do in wet granulation?
And what are examples of these binders?
As solution to mixed powders
Binders for wet are usually polymeric (example: starch, gelatin, PVP, alginic acid derivates, cellulose derivatives, glucose, sucrose)
What do disintegrants do in the tableting process?
- Facilitate breakup or disintegration when tablets come into contact with fluids in GI tract
- Increases effective SA & promotes rapid release & dissolution of drug
- Burst the tablet open and/or promote rapid water ingress into centre of tablet or capsule
Should occur in 15 minutes
Examples of disintegrants
Starch, cationic exchange resins, cross-linked PVP, celluloses, modified starches, alginic acid & alginates, magnesium aluminium silicate, cross-linked sodium carboxymethyl cellulose (CMC)
What is microcrystalline cellulose (MCC)?
Mild disintegrant which acts by capillary action through pores to allow water ingress
Disintegrant mechanisms
- Increase porosity and wettability of compressed tablets to enhance penetration & GI fluid uptake (starch & MCC)
- Swelling of disintegrant, increases internal pressure of tablet matrix leading to disintegration (sodium starch glycolate & croscarmellose)
Glidants
- Improve flow properties of granulations
- Act by reducing inter-particulate friction
- Hydrophobic so adversely affect disintegration, so amount in tablet should be carefully monitored
- Low levels used but have very low bulk density
Examples of glidants
Fumed/colloidal silica (silicon dioxide), starch, talc
Effervescent tablets - disintegrants
Alternative mechanism
Tablets contain acidic and CO2 generating component
Acidic: taratic or succinic acid
Basic: sodium carbonate or bicarbonate
API must be compatible with acidic & basic components & should be soluble and easily dispersible in water
What happens with disintegrants in effervescent tablets?
In water presence, additives react liberating CO2 which rapidly disintegrates tablets and produces effervescence
Flow properties of a tablet
Powders to move within hopper & into tablet die in tablet press
Packing of particles is also reproducible (property variation result in mass differences of powder filled into tablet)
No clumping of powders
Flow property assessment: angle of repose
Angle that powder makes with horizontal plane
Passed through funnel until angle of inclination of powder is too small to overcome cohesive forces between particles
Measure of cohesion within powder mass
Cohesive powder will form an irregular heap, non-cohesive will form a regular conical heap
Tangent of angle of repose
Referred to as measure of internal friction of powder bed
If measured angle exceeds 50 degrees, flow properties of powder are poor
25 degrees indicates powder that would be expected to exhibit suitable flow for manufacturing process
Functions of lubricants in tableting
Prevent adherence of tablet to die faces and punches
Reduce inter-particle friction and improve flow
Facilitate smooth ejection from die cavity
Reduce wear on dies and punches
Example of lubricant
Magnesium stearate
But is chemically incompatible with many drugs - talc or stearic acid are substituted
Amount of lubricant used may adversely affect disintegration and dissolution of tablets
Why are soluble lubricants used and why is it controversial?
Minimise adverse effects of insoluble lubricants on tablet disintegration & dissolution
Yet, soluble lubricants are not as effective as insoluble
What are coating materials?
Provide physical barrier coating on surface of compressed core tablets
Protect API from environment (humidity or acidic stomach) or to offer different release profiles
Examples of coating materials
Polymers like hydroxypropyl methyl cellulose (HPMC), ethyl cellulose (EC), poly(vinyl alcohol) (PVA)
Plasticisers like PEG
Opacifier like titanium dioxide
Colourants like iron oxide red and/or yellow
What do colouring agents do?
Improve the aesthetic appeal of final product
Colour added to binding solution or sprayed onto granules, dye mixed with dry powder blend before wet granulation
Colouring agents: key messages
Red, yellow, & orange drug formulations are perceived as stimulant & blue & green as tranquillising
Colour of drug influences effectiveness, but consistent trends not apparent
Examples: iron oxide red and/or yellow, FD&C Blue #6
What are stabilisers? And examples
Stabilise the API in the tablet from stresses such as oxidation
Antioxidants such as ascorbic acid, butylated hydroxy anisole (BHA), butylated hydroxy toluene (BHT) & α-tocopherol
What are sweeteners and flavouring agents used for?
Overcome drug taste and/or improve palatability for some types of tablets
Sweeteners but not sugars often used reduce the bulk volume
Available as oils or spry-dried beadlets to spray onto dry granules or incorporate in lubricant
Examples of sweeteners
Aspartame, saccharin sodium, sucralose, acesulfame potassium
Examples of flavourants
Proprietary flavours such as orange, pineapple
Other excipients: adsorbents
Capable of holding fluids in an apparently dry state
Oil-soluble drugs or fluid extracts are mixed with absorbents to develop a solid form for compression into tablets