Tablets 1 Flashcards
What is a tablet?
A tablet is a dose form of medication containing one or more drugs to which excipients may have been added and compressed as granules or powder to a definite shape
(70-80% of all medications taken are in tablet form)
What are the factors that make tablets a good dose form?
- Dosing accuracy
- Stability (drugs sold in a solid state are generally more chemically stable- may be coated to protect them from the environment and stomach acid)
- Patient acceptance (conveniently carried, odour or taste can be masked, attractive appearance)
- Diversity (most tablets intended to be swallowed but also sublingual, implant and chewable. Drug release may be immediate or sustained)
What are disadvantages to tablets?
- solid dose form may cause irritation to the GI mucosa
- may have bioavailability problems since dissolution must occur before drug is available for absorption
What attributes must a tablet have?
- able to withstand the rotors of mechanical tx during production, packaging, shipping, etc
- must be free of defects - cracks, ships, discolorations
- reasonable chemical and physical stability
- contain the proper amount of medication and release in a predictable and reproducible manner
What solubility and permeability properties does a class 1 drug have?
- class one drugs have few problems (is both soluble and permeable)
What solubility and permeability properties does a class 2 drug have?
- class two drugs - the rate limiting step for bioavailability is solubility/ dissolution
What are the solubility and permeability properties of class 3 drugs?
- class 3 drugs - the rate limiting step for bioavailability is crossing the biological membranes
What are the solubility and permeability properties of class 4 drugs?
- class 4 drugs present a problem- are not very efficient at crossing biological membranes or dissolving
What are the properties of granulation?
- materials intended for compression into a tablet must have 2 essential characteristics: fluidity and compressibility
Why is fluidity necessary?
- fluidity is necessary for the transport of the material through a hooper into a feeder frame or a die cavity
What is compressibility?
- the property of forming a stable compact when pressure is applied
Do powders flow freely?
- no, powders do not usually flow freely - the hopper may become plugged by bridging or may rat hole
What can poor flow properties lead to?
- poor flow properties can lead to variation in tablet weight, content and hardness
What attributes should good granulation have?
- good granulation should approach spherical shape (minimizes inter particle friction and static)
- should present a NARROW range of particle sizes (uniform full and bridging between particles when compressed)
- should have homogenous distribution of all materials (should have content uniformity)
- should have acceptable compression properties (tablet hard enough to remain intact yet able to disintegrate when taken)
What generally needs to be added to confer appropriate properties of granules?
- additives and excipients
What specifically does the additives or excipients aid in?
- aid in granule formation and flow, compression and disintegration and dissolution
What is a diluent (filler) used for with tablets?
- must be used to give the product adequate bulk- some potent drugs may have the dose in the microgram range
What excipients do diluents cover?
- lactose
- sucrose
- mannitol
- sorbitol
- calcium sulfate
- calcium phosphates
- starch
- microcrystalline cellulose
What are some of the properties of lactose?
- common diluent
- inexpensive, readily soluble and reasonably inert
- crystals tend to be plastic and deform under pressure - so good compressibility properties
- no hydroscopic
- prone to browning with some drugs and may lose compression characteristics with some drugs
What are some of the properties of sucrose?
- often used to impart hardness to tablets but used in small amounts since it is somewhat hydroscopic
- tablets containing sucrose tend to harden with time
- subject to browning with some drugs
What are some of the properties of mannitol?
- inert and non-hydroscopic
- used in chewable tablets because of mouth-feel properties (cool, smooth, slightly sweet)
What are some of the properties of calcium sulfate?
- low solubility and non-hydroscopic
- inexpensive and useful for acidic, neutral and basic drugs
- good adsorption of oils
- inert but combined with sugars it tends to harden over time
What are some of the properties of microcrystalline cellulose?
- insoluble, inert-free flowing filler which can also function as a binder and a disintegrant
- widely used in direct compression
- may be added dry to granules to improve binding, but is relatively expensive
What is the function of binders?
- hold together powders by adding cohesive forces to the diluent and are used as needed
- used with care since the tablet must disintegrate at some point
- usually sugars or polymers are added as solutions or slurries to powdered material
What are some examples of binders?
- starch
- pregelatinized starch
- gelatin
- polyvinylpyrolidone
- methylcellulose
- ethylcellulose
- polyvinyl alcohols
What are some of the properties of starch?
- most common binder
- neutral and non-reactive
- also functions as a disintegrating agent
- may give soft granules so additional excipients may be required
What are some of the properties of starch?
- stronger binder than starch
- use largely replaced by synthetic polymers
What are some of the properties of natural gums?
- acacia and tragacanth are still used but are widely being replaced by synthetic polymers
- bacterial contaminants are a problem
What are some of the properties of polyvinylpyrrolidone (PVP)?
- popular and a very useful binder
- slightly hydroscopic
- able to use alcoholic or hydro-alcoholic solvents
What are some of the properties of cellulose derivatives?
- good binding properties and are very versatile
- some are alcohol soluble
- most common are methylcelllose, carboxymethylcellulose, ethyl cellulose and hydroxypropylmethylcellulose
What is the function of a lubricant as an excipient?
- used to ease the ejection of the tablet from the die, to prevent sticking to the faces of the punches and to reduce wear on the tooling
- applied to coat granules therefore particle size of the lubricant is important since we want uniform coating
- may be water soluble or water insoluble depending on product requirements
- magnesium stearate is widely used
- slightly alkaline- can cause problems and tend to waterproof granules which may affect disintegration/dissolution properties of the tablet
What are some examples of the products used as lubricants?
- magnesium stearate
- calcium stearate
- zinc stearate
- sodium benzoate
- light mineral oil
- polyoxyethylene monostearate
- magnesium lauryl sulfate
- talc
- polyethylene glycol
- hydrogenated vegetable oils
- sodium lauryl sulfate
What are some examples of disintegrates? (see concentrations on slide 26)
- substance added to the granulation to cause the tablet to break apart in an aqueous environment
- reverses the effect of the binder and the compression force
- may be external or internal
(external when added to the formed granules, internal when it is a component of the granulation mixture) - function by swelling or reacting with water to cause disruptive forces
What are uses/properties of colorants? (see examples on side 29)
- usually added to tablet formulation to increase elegance or for identification
- pastel shades often used since these are least likely to slow mottling
- frequently used as lakes since these are less likely to bleed and have better uniformity
- some dyes are photosensitive and may discolor is not protected from the light
What is the most important step in tableting?
granulation
What are the different processes for producing granules?
- dry granulation
- wet granulation
- no granulation (direct compression)
What are the steps of wet granulation?
- milling of the drug and excipients
- mixing of the milled powders
- preparation of a binder
- preparation of wet mass
- screening of wet mass
- drying of granules
- screening dry granules
- mixing with lubricant
- tablet compression
What are the steps of dry granulation?
- milling of the drug and excipients
- mixing of milled powders
- compression into slugs
- screening of slugs
- mixing with lubricant
- tablet compression
What are the steps of direct compression?
- milling of drug and excipient
- mixing of milled powder
- tablet compression
