tablet coating and drug release

Question 1

whats a tablet coating?

Answer 1

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

Question 2

why do we use coatings?

Answer 2

to protect the drug from environment, mask flavours, easier to swallow, easy identification of colours and provide enteric or controlled release properties.

Question 3

what does sugar coating involve?

Answer 3

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

Question 4

what does film coating involve?

Answer 4

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.

Question 5

what are important process parameters of film coating?

Answer 5

inlet and bed temperatures, humidity, atomization air pressure, liquid spray rate, droplet size and drying time.

Question 6

what are the differences between sugar coating and film coating?

Answer 6

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.

Question 7

what can go wrong with coatings?

Answer 7

coating may chip, cause roughness, cause sticking or have film cracking.

Question 8

what could be the consequences if the coating chips etc.?

Answer 8

aesthetically unpleasing could reduce compliance, if its a functional coating like gastro resistant it will no longer be effective.

Question 9

whats an enteric coating?

Answer 9

an enteric coating protects the tablet core from disintegration in the acid environment of the stomach.

Question 10

why might an enteric coating be used?

Answer 10

• 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

Question 11

what are the ideal ph sensitive polymers?

Answer 11

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

Question 12

what are some enteric coats used for direct film coating?

Answer 12

cellulose acetate pthalate and polyvinyl acetate pthalate.

Question 13

how is an enteric coating added in sugar coating?

Answer 13

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

Question 14

how can we see the change in solubility for PVAP?

Answer 14

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.

Question 15

whats the activity of the polymers?

Answer 15

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.

Question 16

whats a delayed release tablet?

Answer 16

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.

Question 17

what are multiparticulates?

Answer 17

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.

Question 18

what are multiparticulates mainly used for?

Answer 18

controlled release medicines, gastro resistant medicine, extended release properties or for site specific drug delivery.

Question 19

why is the performance of multiparticulates less dependedn on gastric emptying?

Answer 19

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.

Question 20

how can drugs cause damage to the gi tract?

Answer 20

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.

Question 21

whats another factor mking multiparticulates safer?

Answer 21

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.

Question 22

what are some disadvantages of multiparticulates?

Answer 22

control of membrane charactersistice using film coating may be difficult, multiparticulates are difficult to retain in the upper gi tract.

Question 23

one type of multiparticulate is extruded/spheronised granulates, how are these produced?

Answer 23

in modifying granulating equipment in which the drug granulate is extruded through a mesh under pressure to form small particles for spheronization.

Question 24

another type of multiparticulate are non pareils, what are these?

Answer 24

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.

Question 25

what are some of the beneficial properties of multiparticulates?

Answer 25

exceellent stability, good flow properties, high bulk density, low hygroscopicity and easy to dose.

Question 26

how can multiparticulates release drug through diffusion?

Answer 26

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.

Question 27

how can multiparticulates release the drug through osmosis?

Answer 27

in allowing water to enter, osmotic pressure builds up within the pellet interior forcing the drug solution out/swelling.

Question 28

how can multiparticulates release the drug through erosion?

Answer 28

some coatings are designed to gradually degrade over time hence releasing the drug contained in the pellet (degradation

Question 29

what are MUPs?

Answer 29

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.

Question 30

whats the best suited enteric coating for mups?

Answer 30

methacrylic acid copolymers appear to be best suited for enterically coating the particles within mup tablets.

Question 31

how do mups work?

Answer 31

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.

Question 32

how is gelatin derived?

Answer 32

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.

Question 33

what are the properties of gelatin?

Answer 33

gelatin forms strong transparent gels that are soluble in biological fluids at body temperature and in hot water.

Question 34

what is dipping when referring yo gelatin?

Answer 34

stainless steel pins are dipped into a solution of gelatin at controlled temperatures, pins are then withdrwan roatated and dried.

Question 35

whats a dosator?

Answer 35

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.

Question 36

whats a vacuum drum used for?

Answer 36

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.

Question 37

what excipients are required in hard capsules?

Answer 37

diluents for low dose drugs, glidants and lubrica to reduce friction and improve flow.

Question 38

how can granules or pellets be added to a hard capsule?

Answer 38

granules or pellets can be filled gravimetrically or via a metering system

Question 39

what are some of the issues with hard shell capsules?

Answer 39

• 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

Question 40

what are soft shell capsules?

Answer 40

a continuous gelatin shell surrounding a liquid or semi solid matrix material.

Question 41

what compounds benefit from incorporation in a soft shell capsule?

Answer 41

compounds soluble in oil and hydrophilic liquids

Question 42

soft gelatin capsules are fromed filled and sealed in one operation, what is this?

Answer 42

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.

Question 43

what are the advantages of soft capsules?

Answer 43

no need to compress drugs
no drug content uniformity issues
oily vehicle protects drugs sensitive to oxidation or hydrolysis

Question 44

what are some of the limitations of soft capsules?

Answer 44

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