Tableting Flashcards
what are the advantages of tableting medications
Convenient and cheap Light and compact Dry so has longer shelf life Accurate dose Can give controlled release can mask taste
Disadvantages of tableting
Difficult to swallow
difficult dilute
difficult for liquid drugs
what id the usual size of tablets
50-500mg
List the general properties a good tablet need to have
Strong: withstand shock, manufacture, packing, shipping, dispensing and use
Must be bioavailable
reproducible and predictable
physically and chemically stable
consistent in weight, mass and content
elegant production quality to aid compliance
What are the types of tablets
Standard tablet Soluble/ dispersible Effervescent Chewable Buccal Sublingual Enteric coating controlled release
What steps are involved in tableting?
1> Mix powdered drugs with diluent
2>Add a suitable wetting agent and blend
3> Pass the moist mass through a suitable mesh screen to make particle size even
4> Dry granules
5> Blend other additives to the granules
6> compress the tablet
7> Add outer coating where necessary
List diluents used in tableting
- Lactose
- Microcrystalline cellulose
- Calcium phosphate
- Calcium sulfate
- Starch
- Dextrose
- Mannitol
- sorbitol
- Sucrose
- Xylitol
What is the purpose of adding a diluent?
This is to bulk up the tablets and make them a good size to tablet them well.
What is used to mix the drug and diluent together?
A cube shaped mixer is used. Rod called baffles ensure the mixing is thorough
Examples of binding agent added to the mixture?
Water Methylcellulose starch paste Gelatin Gum Acacia polyvinylpyrrolidone
What is the purpose of adding a wetting/binding agent?
To turn the powder into granules.
At what stage is the wetting agent added
Can be added along side wetting agent or the powder stage.
How is the wetting/binding agent mixed with the drug and why is it important?
A blender with S shaped blades that rotate.
This crushes granules to ensure that the is not dry powder inside.
What is the typical size of the mesh that the granules are pushed through?
2mm
Why are the granules pushed through a mesh?
This is to make the sizes uniform
How are the 2 ways granules dried
1: Tray dries- Granules spread evenly on a tray and placed in a oven
2: fluid bed dried: minute holes pass gas through the granules till they are suspended in the gas
Why are the granules dried
To make them the right temp to be compressed
What are the other additives added before compression.
Lubricant to stop stick to die well during compression.
Glidant: Allows granules to flow into the dies
Disintegrant: Rapid drug release
- Swelling
- plastic recovery
Types of lubricants added
Hydrophobic: Stearates
Hydrophilic: polyethylene glycols, sodium benzoate, sodium lauryl sulphate, isoleucine, glyceryl behenate, sodium stearyl fumarate
Steps to the compression stages are:
(i) Lower punch falls within the dye, leaving a cavity into which particulate matter can flow under gravity.
(ii) Upper punch descends and the punch tip enters the cavity, confining the particles, which aggregate to form a compact (the tablet)
(iii) The upper punch withdraws and simultaneously the lower punch raises until its tip becomes level with the top of the die. The tablet is thus rejected from the press.
Alternative method to compression when wetting agents can be used:
1>Drug, filler and lubricants are compressed into ‘slugs’ on a heavy duty press (with large flat faced punches)
2>Slugs broken down by milling and screening procedures into granules
Alternatively, the mass may be roller compacted (fed between rollers to form a compressed sheet prior to screening).
When is moist granulation unsuitable
When heat and moisture can be used.
Name some problems that can occur during compression.
Binding of tablet in the die cavity.
Picking and sticking of tablet surface. (picking: punch, sticking: die wall)
Capping and lamination of tablet.
Excess tablet weight variation.- particles getting stuck to punches and dies
Fissured and pitted tablet surface.
Soft Tablets/ hard tablets – rate of dissolution of tablets
Tablets that disintegrate very slowly.
Mottled tablets.
Benefits of tablet coating vs uncoated
> Protects the active ingredient- oxidation and hydrolysis. Light sensitive drugs as well
Organoleptic
Improves product quality
Aids identification (e.g. colour)
Protects tablet during packaging/storing
Prevents contamination and dust problems
Can control drug release
Addition mechanical strength- high speed packing machinery
Types of coating
Sugar coating
Film coating
press coating
How is a sugar coating applied?
tablet core sealed with a water insoluble base coat. (e.g. shellac).- cellulose acetate phthalate
Successive layers of filler (eg talc) are bound by sucrose/gum solution.: Bulking agent
Then smoothed by adding several applications of sucrose solution.- smooth surface which colourants may be added to
Finally, polished with a (Bees) wax solution.
Disadvantages of a sugar coating
Multistage (time consuming).
Difficult to automate.
Not able to use for controlled release.
Weight of coating leads to 30 – 50 % increase.
Indented logos not feasible as coating is thick
Advantage of sugar coating
Appearance – rounded, highly polished tablets produced.
How are film coatings applied
Sprayed by polymer solution such as HPMC. Include plasticizer which make coating more flexible
Colouring agents may be added
Solvent is normal organic but water is prevered when feasible
Advantages of film coating
Little increase in tablet size (2-3% by weight) Can be automated (e.g. Accela Cota) Single Stage Process Can be used for controlled release Indented logos can be used.
Disadvantages of film coating:
Environmental – extraction of organics into atmosphere.
Safety – explosion / fire / & toxic hazards (expensive to deal with)
Solvent residues must be investigated.
Press coating
Based on compaction of coating around pre-formed core.
Mainly used to separate incompatible materials (one in layer, one in core).
Requires relatively complex, specialist equipment. Little used today as it is relatively expensive
Types of functional coating:
Enteric coating
Controlled release
Uses of enteric coating
Insoluble at low pH so not attacked in the stomach.
harp increase in solubility at higher pH e.g. 5.2 for cellulose acetate phthalate coating
What are enteric coating made from?
Cellulose acetate phthalate
Polyvinyl acetate phthalate and acrylic derivatives.
Benefit of enteric coating
Stops the potential damaging of the stomach lining
what are controlled release polymers made of?
polymers with restricted water solubility or permeability.
Mechanism of controlled release coating
> Diffusion control. Rate of release controlled by rate of diffusion of drug through the coating
Erosion. Coatings designed to ‘erode’ gradually.
Osmosis. Osmotic pressure used to control release of drug.
What are capsules
They are drugs enclosed in a water soluble shell made of gelatin
Why is gelatin used
Non toxic
Soluble at body temperature
Has good film forming properties
Changes from a gel to sol at temperatures just above room temperature.
What is gelatin prepared from
hydrolysis of collagen.
- Gelatin A is formed by acid hydrolysis of collagen.
- Gelatin B is formed by basic hydrolysis.
What are Hard capsules
Comprises a two piece shell (body and cap) which lock together.
Drug must not react with gelatin (no aldehydes or water)
What are the different capsule sizes
0= 0.67 1= 0.48 2= 0.37 3= 0.28 4= 0.20
Types of hard capsule fillers
Powders, granules, pellets, tablets, paste, thixotropic, thermosofterning material
Low viscosity, non aqueous liquids have been used as fills, but the cap and body have then to be sealed to prevent leakage.
what are the properties of the hard capsule powders fillers
Must be of a certain volume to allow an accurate fill (may need a diluent).
Must flow (not as critical as for tableting).
Must not adhere to filling equipment.
Must allow drug release
How are the hard capsules shells made
dipping rows of steel pins into a heated solution containing around 30% gelatin and the required colouring agent and then removing the pins and allowing the gelatin film to set and dry.
What are the steps to filling the capsules
The two halves of the capsule are separated.
An exact dose is placed into the smaller half (the body)
The cap is then locked onto the smaller half (the capsule is designed so that the cap and body lock together and do not easily pull apart).
The filled capsule is removed from the machine.
What are the uses of soft capsules
Consists of a solid flexible shell
surrounding a liquid or semi-solid fill.
Permit liquids to be presented as solid dosage forms.
Low inter-capsule variation.
Drug is protected from water and oxygen.
Shell comprises gelatin, plasticiser (usually glycerol, sorbital or propylene glycol), water, preservatives, dyes.
What are the sizes of soft capsule and what are they filled with
Normally filled with 0.1 to 0.8 mL of non-aqueous liquid
Liquid can be hydrophilic (e.g. polyols, surfactants) or lipophilic (i.e. mineral or natural oils e.g. cod liver oil).
Hydrophilic oils can allow rapid attainment of therapeutic drug levels (e.g. with temazepam).
What are the problems with soft gels
- Migration of fill material through the capsule shell (sweating)
- Migration of shell contents the other way, possibly causing instability
- Both soft and hard capsules are unstable for drugs that are unstable in the presence of moisture. Moisture in atmosphere may cause shell to soften and break. Dry conditions may cause cracking.
What factor determine whether to make capsules or tablets
Company policy Market Research Competitor products Production Preferences Equipment available Production Costs Required unit dose Dissolution Rate Compression characteristics Particle size Stability
Lozenges
- Normally intended to stay in mouth 10-15 minutes
- Often release an antibacterial or anaesthetic (local effect)
- Contain no disintegrant.
-Diluent selected to ensure smooth texture and pleasant taste.
>Sugars (e.g. sucrose/glucose) often used
Chewable Tablets
- Designed to be broken down rapidly in the buccal cavity by action of teeth.
- Mannitol often used for a cooling taste.
- Flavouring agent is also frequently used.
- No disintegrant.
- No need for all ingredients to be water soluble
Dispersible tablets
Must disintegrate rapidly in cold water to produce a\ suspension for ingestion.
Disintegrant effective in water is paramount.
Effervescent tablets
- Effervesence gives rapid disintegration
- Wet granulation cannot be used.
- Sucrose is hygroscopic therefore often used as sweetener and to increase stability.
- ‘Standard’ lubricants cannot normally be used. Magnesium stearate slows access of water and leaves a scum on surface of water. Sodium lauryl sulphate often used.
Sublingual and buccal tablets
- Adsorbed through mucosa and passed to jugular vein; hence bypassing GI tract and liver.
- Tablets should not disintegrate.
- Rapid dissolution is required.
- Avoid unpleasant tastes.
