tablet coating and drug release Flashcards
whats a tablet coating?
a coating applied to the exterior of a tablet but its also used for multiparticulate system intended for midified release - you can get film coating sugar coatig and press coating
why do we use coatings?
to protect the drug from environment, mask flavours, easier to swallow, easy identification of colours and provide enteric or controlled release properties.
what does sugar coating involve?
sealing of the tablet to prevent entry of water
subcoating for rounded profile
sucrose syrup for smoothing
colourig
polishing with beeswax for high gloss finish
printing of logos
what does film coating involve?
deposition usually by spraying a thin film of polymer surrounding the tablet core. the coating liquid contains a polymer in a suitable liquid together with other ingredients like pigments and plasticisers. the solution is sprayed onto a rotating mixed tablet bed or fluid bed. drying conditions permit solvent removal to leave a thin deposition of coatig material around each tablet.
what are important process parameters of film coating?
inlet and bed temperatures, humidity, atomization air pressure, liquid spray rate, droplet size and drying time.
what are the differences between sugar coating and film coating?
sugar coating takes more time, cant add break lines to sugar coated tablets, sugar coating increases weight by 30-50%, produces a rounded tablet with high polish, sugar is a simple enteric coating wheras film can be used for controlled release.
what can go wrong with coatings?
coating may chip, cause roughness, cause sticking or have film cracking.
what could be the consequences if the coating chips etc.?
aesthetically unpleasing could reduce compliance, if its a functional coating like gastro resistant it will no longer be effective.
whats an enteric coating?
an enteric coating protects the tablet core from disintegration in the acid environment of the stomach.
why might an enteric coating be used?
- protect acid labile drugs
- facilitate absorption of a drug that preferntially absorbed further down gi tract
- taste masking
protect stomach from irritant effects of some drugs
what are the ideal ph sensitive polymers?
ideally we want polymers that are insoluble in an aqueous media at a low pH, but with increasing ph they experience an abupt well defined increase in solubility at a specific ph
what are some enteric coats used for direct film coating?
cellulose acetate pthalate and polyvinyl acetate pthalate.
how is an enteric coating added in sugar coating?
during sugar coating, a sealant coat is modified to comprise an enteric polymer - sufficient weight of the enteric polymer must be used to ensure an effect
how can we see the change in solubility for PVAP?
at ph1.1 just 1% will dissolve in an hour yet at ph7.5 this increase to 26%. this demonstrates the change in solubility due to ph changes. hence in the stomach the polymers will not dissolve hence trapping the api in the formulation, once the tablet is further down the gi tract the ph will increase and the enteric polymer will dissolve hence releasing the drug.
whats the activity of the polymers?
polymers have free carboxylic acid groups and are insoluble at low ph- they will then have a sharp increase in solubility at a specific ph.
whats a delayed release tablet?
the drug core is coated with a delayed release membrane, exposure to the ph of the small intestine will dissolve the coating thats resistant to low ph of the stomach the exposed drug core then disintegrates so the drug dissolves and is released.
what are multiparticulates?
multiparticulates provide oppurtunity for controlled release formulations, the drug does is divided into 1000s of spherical particles - these can then either be filled into a sachet, encapsulated or compressed into a tablet.
what are multiparticulates mainly used for?
controlled release medicines, gastro resistant medicine, extended release properties or for site specific drug delivery.
why is the performance of multiparticulates less dependedn on gastric emptying?
du to the small size they can pass through the pyloric sphincter and distribute along the gi tract. this overcoes the issues of a tablets irregular passage through the gi tractand irregular absorption due to variability in gi transit time. this may lead to increased bioavailability and reduced risk of systemic toxicity and local irritation.
how can drugs cause damage to the gi tract?
whole non disintegrating tablets can lodge within the gi tract and cause ulcerative damage to the gastric mucosa as the drug is leached from the tablet - this is not an issue with multiparticulates due to their small size.
whats another factor mking multiparticulates safer?
failure of an indiidual pellet and immediate release of all drug content at once poses little risk, however if a non disintegrating tablet fails consequences may be serious.
what are some disadvantages of multiparticulates?
control of membrane charactersistice using film coating may be difficult, multiparticulates are difficult to retain in the upper gi tract.
one type of multiparticulate is extruded/spheronised granulates, how are these produced?
in modifying granulating equipment in which the drug granulate is extruded through a mesh under pressure to form small particles for spheronization.
another type of multiparticulate are non pareils, what are these?
like hundreds and thousands, theyre a sucrose sphere coated with drug and an adhesive water soluble polymer. after formation and further immediate steps they are coated with an enterice controlled release layer.
what are some of the beneficial properties of multiparticulates?
exceellent stability, good flow properties, high bulk density, low hygroscopicity and easy to dose.
how can multiparticulates release drug through diffusion?
on contact with aqueous fluid in the gi tract, water enters the interior of the particle by diffusion. dissolution then occurs and the drug diffuses accross the controlled release coat.
how can multiparticulates release the drug through osmosis?
in allowing water to enter, osmotic pressure builds up within the pellet interior forcing the drug solution out/swelling.
how can multiparticulates release the drug through erosion?
some coatings are designed to gradually degrade over time hence releasing the drug contained in the pellet (degradation
what are MUPs?
multiple unit pellet systems are enteric coated particles compressed into a tablet - the polymer coat must therefore be more flexibledue to compression forces applied in the tabletting process.
whats the best suited enteric coating for mups?
methacrylic acid copolymers appear to be best suited for enterically coating the particles within mup tablets.
how do mups work?
in the same way as enteric coated graules in a capsule - tablet disintegration in the stomach allows the small enterically coated particles to pass through the pyloric sphincter.
how is gelatin derived?
gelatin is a protein substance derived from collagen in tendons etc. iti is produced by partial hydrolysis/boiling of connective tissues. type a is by acid hydrolysis while type b is by base hydrolysis.
what are the properties of gelatin?
gelatin forms strong transparent gels that are soluble in biological fluids at body temperature and in hot water.
what is dipping when referring yo gelatin?
stainless steel pins are dipped into a solution of gelatin at controlled temperatures, pins are then withdrwan roatated and dried.
whats a dosator?
a dosator is used to fill capsules with continous machines, they control fill weight by adjusting powder bed hight and dosator pin position.the dosator tube gets immersed into the powder bed dosator pin is then lowered to slightly compact the powder plug inside the tube, the dosator tube is shaken side to side to shear off confined dose from the powder reservoir. powder plug within the dosator tube can now be transferred to a capsule.
whats a vacuum drum used for?
for microdosing of cohesive powders with poor flow properties. a vacuum causes dosing chamber to fill then excessive powder is removed by a scraper blade.
what excipients are required in hard capsules?
diluents for low dose drugs, glidants and lubrica to reduce friction and improve flow.
how can granules or pellets be added to a hard capsule?
granules or pellets can be filled gravimetrically or via a metering system
what are some of the issues with hard shell capsules?
- gelatin crosllinking with polypeptide chains may make the capsule insoluble
- water loss causes brittle capsules to crumble
- water from the atmosphers can hydrate the capsule making it start to dissolve
- a poor seal at the cap body join can cause leaking
what are soft shell capsules?
a continuous gelatin shell surrounding a liquid or semi solid matrix material.
what compounds benefit from incorporation in a soft shell capsule?
compounds soluble in oil and hydrophilic liquids
soft gelatin capsules are fromed filled and sealed in one operation, what is this?
liquid gelatin is formed into two continous ribbons, ribbons are brought together between rotating dies, a metered volume of the formulation is injected between the ribbons, drying and packaging.
what are the advantages of soft capsules?
no need to compress drugs
no drug content uniformity issues
oily vehicle protects drugs sensitive to oxidation or hydrolysis
what are some of the limitations of soft capsules?
drugs/ecipients with high concentration of water cant be incorporated
surfactants affect the capsule seal
need to avoid ph below 2.5 and above 7.5
