Solid Dosage Forms - Excipients

Why are drugs not administered as pure substances? -No control of absorption -Taste -Size/does too small What is the role of sodium bicarbonate in Increase the rate of tablet disintegration effervescent tablets? and dissolution What is an excipient? All other components of a formulation other than an API What is a bulking agent? Makes the tablet bulkier and easier to compress Why is lactose commonly used as a diluent/bulking agent? -Pleasant taste -Rapidly dissolves -Cost-effective Why is dicalcium phosphate commonly used as a diluent/bulking agent? -Insoluble in water -Good compressibility -Inert -Cost-effective Why are starches commonly used as a diluent/bulking agent? -Very hygroscopic -Inert and highly compressible -Cost-effective What is hygroscopicity? Ability to absorb water Why is microcrystalline cellulose (MCC) commonly used as a diluent/bulking agent? -Excellent compressibility -Inert -Cost-effective -Lubrication properties How is microcrystalline cellulose made? Partial hydrolysis of cellulose What are two commonly used lubricants for punch/pressing devices? -Talc -Magnesium stearate What is the most commonly used lubricant for the die of a tablet formulation device? Stearic acid The piece of metal that decides the shape of the tablet 1/8 What is the die in terms of tablet formation? Do die or punch lubricants come into contact with the tablet/drug? Die lubricants as punch lubricants are purely for the machinary What is the role of a flow agent? Improve flow properties of flow agents How do flow agents work? Reduce Inter-particulate friction What is the most commonly used flow agent (glidant)? Fumed silica What is the role of a disintergrant? Promote break up of tablets What are the four most common mechanism of disintegrant action? -Swelling -Capillary action (porosity) -Deformation -Gas production What is the most common disintegrant? Starch What can be used instead of starch as a 'super' disintegrant? Modified starch What is the issue of modified starch? More hygroscopic What is the role of binding agents? Bind powders together in the wet granulation phase or granules in direct compression What is the most important and common binding agent? PVP (polyvinylpyrrolidone) Why is PVP so important? Soluble in water and alcohol so releases drug rapidly What is the role of adsorbents in solid dosage forms? -Hold fluid in an apparent drug state -Control moisture -The most common is fumed silica (fluid agent) -Can also be mixed with liquid flavourings 2/8 What are the main advantages of tablets? -Accurate dosage -Convineince -Mass production -More stable than liquids What are the disadvantages of tablets? -Swallowing -Poor wetting and low solubility drugs -Bitter taste -O2 and H2O sensitive What are the 8 stages of making a tablet? 1)weighing 2)dry mixing 3)granulation 4)tableting 5)QC check (quality check) 6)Coating 7)Dissolution 8)QA check (quality assurance) 1)Particles must be free-flowing What are the three vital properties of 2)Particles when subjected to force cotablets for them to be made into tablets? here adequately 3)Adhesion must be avoided What are the three stages of compression of a powder bed (tablet)? 1)Rearrangement 2)Deformation 3)Bonding What is the premise of stage one tablet compression - rearrangement? Tablets undergo densification to minimise space between particles -When particles can not get any more dense What is the premise of stage two tablets -Permanent changes of the shape of macompression - deformation? terial occur -Physicochemical properties of powders affect the type of deformation 1)Elastic (goes back to normal after force What are the three main types of defor- is removed) mation? 2)Plastic (Stays squashed once force is removed) 3/8 3)Brittle (Crack breaks into smaller fragments) What is the premise of stage three tablet Interparticle bonding occurs resulting in formation - bonding? the production of a tablet What are 7 common components of a direct compression tablet? -Active drug -Dilutent -Lubricant -Disintegrant -Gilidant (flow agent) -Flavouring/colour -Particle binder What is granulation? Process by which powder particles adhere to form large entities called granules -Produces uniform particles Why does the industry prefer compres- -Which have good flow properties and sion of granules? are resistant to agglomeration and segregation What is wet granulation? Use of a liquid binder (granulating solvents) to form granules What are the most common granulating solvents? Water, ethanol and isoprpanol What is dry granulation (slugging)? -Formation of granules without the use of a liquid binder and instead just compression -After which they are ground into uniform sizes What is the benefits of dry granulation over wet granulation? -Economical -Less equipment needed -Can cope with a wider range of materials -No addition of moisture or heat What are the three main types of coating? -Film -Sugar -Press 4/8 What are the 3 main reasons for coating tablets? 1)Protection 2)Taste 3)Easier to swallow What are the main problems with tablet coating? -Chipping -Roughness -Sticking -Cracking / peeling What is the role of enteric coating? Protects core from disintegration in an acidic environment (stomach) 1)Prevention of acid attack on a drug that is unstable at low pH What are the 3 main reasons for the use 2)Protect stomach from irritant effect of of enteric coating? some drugs 3)Facilitate absorption in intestine What are the different types of enteric polymers for direct-film coating? -Cellulose acetate phthalate (CAP) -Polyvinyl acetate phthalate (PVAP) How many times the weight is needed for a enteric polymer coating compared to a simple film coating? 2 -3 Is enteric coating possible using sugar or film coating? Both What is the role of multi-particulate coatings? Used in modified release tablets What are the advantages of multi-particulates? -More consistenet GI trasnit -Less likely to suffer dose dumping -Difficult to retain in the upper GI tract What are the disadvantages of multi-par-Control of membrane characteristics ticulates? can be difficult What are the 3 main ways in which drugs are released from multi-particulates? 1)Diffusion 2)Osmosis 3)Erosion Why do most enteric tablets say do not This would break the coat and cause the chew on them? tablet to dissolve in the gastric fluid What is a multi-unit pellet system? 5/8 Enteric coated particles compressed into a tablet Why must the polymer coat be flexible in Due to compression forces being applied multiple-unit pellet systems? after the coat has been applied What is the mian source of gelatin? -Collagen in tendons and ligaments -Usually from cows or pigs How is gelatin produced? Partial hydrolysis What are the two types of hydrolysis for the extraction of gelatin? Acid and Basic What is dipping? Steel pins dipped into solution of gelatin to form capsule shell -Hard gelatin capsules have a body and What is the difference in filling between a cap that fit one inside the other -Soft gelatin capsules are manufactured hard and soft capsules? and filled in one operation What is a Dosator? Device used for precise filling of dose into capsules -Crosslinking (gelating crosslinking with polypeptide chains) What are the four main issues with hard -Embrittlement (brittle capsules) shell capsules? -Sticking/solvation (capsule absorbs water and starts to dissolve) -Leaking (poor seal) What are Vegetarian capsules formed from? HPMC, starch, pullulan or PVA What are the main advantages of soft gelatin capsules? -No need to compress drugs -No uniformity issues as the drug is dissolved -Oil vehicle increases stability -Oily vehicle increases bioavailability -Drugs containing high concentrations of What are the main disadvantages of soft water can not be incorporated gelatin capsules? -Surfactants affect capsule seal -Can't be too acidic or basic 6/8 What is the name for urethral suppositories? Bougie What is the pH of rectal fluid? 7-8 How are suppositories formed? DIssolving drug in a base What are the two most common bases to dissolve suppository APIs in? -Oil of theobroma (cocoa butter) -Glycogelatin How does particle size affect suppository Smaller the particle, faster the dissoludissolution? tion rate (noyes-witney) What is vital for bases used in suppositories? Must melt or dissolve in the rectum What is the issue with cocoa butter as a base? Expensive and not suitable for high-speed mass production What sort of base is cocoa butter? Fatty base What key physiological property does cocoa butter possess that alters its ability to melt in the rectum? -Polymorphism -Different polymorphs have different melting points What is a glycogelatin suppository? Glycerol + Water + Gelatin What are glycogelatin suppositories exclusively used for? Laxative or vaginal therapy What is an example of a vegetable based, base used in suppositories? Hydrogenated vegetable bases What is PEG? Polyethylene glycol, common suppository base What are the advantages of PEGs? -Melting point can be altered -Released of drug is not purely dependant on melting point -Physical stability on storage is improved -Chemically more reactive than fats (may be incompatible with some drugs) -Care required in processing What are the disadvantages of PEGs? -Release rate is inversely proportional to MW of PEG used -More irritating 7/8 Why should cocoa butter and glycogelatin suppositories be kept in the fridge? Low melting point What is a displacement value (DV)? Number of parts of drug that displace a number of parts of base 8/8