PharmaceuticaLFormulations

TABLETS AND CAPSULES

1 – EXCIPIENTS FOR TABLET PREPARATION

2-WET AND DRY GRANULATION

3- ROTARY PRESS (MULTISTATION )

4-DEFECTS OF TABLET COATING

5- CAPPING AND LAMIINATION

6- QUALITY CONTROL OF TABLETS.

Q5 , Give a detailed account of the different excipients and their functions used in the tablets?

the followingexcipient s are used in the manufac tu r e of conventional tablets : (1) diluents /fillers; (2) binders ; (3) disintegr a n t s ; (4) lubrican ts ; (5) glidants; and (6) miscellaneous .

Diluents/fillers

Diluents are employed in the formulation of tablet s (by all methods) to increase the mass of the tablet s that contain a low concen t r a t ion of therap e u t ic agent and thereby rende r the manufac tu r ing process more reliable and reproducible. Diluents must exhibit good compression prope r t i es and be inexpensive. Examples of diluents for tablet s are: (1) anhydrous lactose; (2) lactose monohydra t e ; (3) spray- dried lactose; (4) starch; (5) dibasic calcium phospha t e ; (6) microcrys t alline cellulose (MCC); and (7) mannitol. ANHYDROU S LACTOSEAnhydrous lactose is either pure anhydrous b lactose or a mixture ofanhydrous b lactose (70–80%) and 20–30% anhydrous a-lactose.

is commonly used as a diluent in wet granula t ion and dry granula t ion processe s . It is a crystalline mate r ial .Lactose monohydrateLactose monohydra t e is composed of the monohydra t e of a-lactose monohydra t e and, whilst crystalline in natur e . is available in a wide range of grades that offer differing physical proper t i es , e.g. par ticle size distribu tion/ densi ty (bulk and tapped).Spray-dried lactoseSpray- dried lactose is a mixture of crystalline a-lactose monohydra t e (80–90%) and 10–20% amorphous lactose. It is prepa r e d by spray- drying a suspension of a-lactose monohydra t e .StarchStarch is a polysaccha r ide composed of amylose and amylopec tin, which is used as a diluent (and also as a binder and disintegr a n t ) in tablet formulat ions.Dibasic calcium phosphateThis is a commonly used diluent in table t. It has excellent flow and compression proper t i es .Micr o c r y s t a l l i n e cel lul o s e .MCC is a crystalline powder that is prepar e d by the controlled acid hydrolysis of cellulose use as a diluent , MCC may also be used as a binder in wet granula tion (see below) and a disintegr a t ing agent .MannitolMannitol is a polyol that is commonly employed as a diluent in table ts , par ticula r ly chewable tablets , due to the inheren t sweetne ss and negative heat of solution.

BindersBinders are predominan t ly (but not exclusively) polymeric componen t s that are employed in the produc tion of table ts by the wet granula t ion method of

manufac tu r e . In this role, binders are either added as a solution or as a solid into the powder mix.Hydroxypropylcellulose 2–6% w/wHydroxypropylmethylcellulose 2–5% w/wDisintegrantsDisintegr an t s are employed in tablet formula tions to facilita te the breakdow n of the table t into granules upon entry into the stomach. If the formulat ed tablet is hydrophobic and/or it has been manufac tu r e d using a high compression force, the rate of wate r uptake into, and hence disintegr a t ion of, the tablet will be unaccep t a bly low. Disintegr an t s may increase the porosity and wettability of the compress e d tablet matrix. In so doing gast roin te s t inal fluids may readily penet r a t e the tablet matrix and thereby enable table t breakdow n to occur. In this approach it is necessa ry for the disinteg ra n t to be homogen eously dispersedthroughou t the tablet matrix (requiring concen t r a t ions between 5 and 20% w/w). Examples of disinteg ra n t s that opera t e in this fashion include:– starch– MCC– sodium starch glycolate .

Disintegr an t s may opera t e by swelling in the presence of aqueous fluids, thereby expediting tablet disintegr a t ion due to the increase in the internal pressur e within the tablet matrix.Examples : sodium starch glycolate ,p r e g e la t inised starch.Tablet disinteg ra t ion may also be media ted by the produc tion of gas wheneve r the tablet contac t s aqueous fluids. This is the mechanism of disintegr a t ion of effervescen t tablets .LubricantsDuring compres sion lubrican t s act at the interface between the face of the die and the surface of the tablet and act to reduce the friction at this interface during ejection of the tablet from the tablet press. Inadequa t e lubrica tion of this interface results in the produc tion of table ts with a pitted surface and is due to the inability of the tablet surface to detach from the surface of the tablet die.There are two main categories of lubrican t: (1) insoluble; and (2) soluble.Insolu b l e lubr ic a n t s are added to the final mixing stage prior to table t compression. high lubrican t concen t r a t ions resul t in reduced rates of disintegr a t ion and dissolution .Mag n e s i u m stear a t e : Magnesium stea r a t e is not a pure compound, beinga mixture of magnesium salts of a range of fatty acids, predomina n t ly (but not exclusively) stea ric and palmitic acid.Stear i c acid: stea r ic acid is a mixture of stearic ( _ 40% w/w) and palmitic acids.Glycer y l beh e n a t e : Glyceryl behena t e is a mixture of glyceryl fatty acid ester s .Glycer y l pal mi t o s t e a r a t e : Glyceryl palmitost ea r a t e is a mixture of mono- ,

di- and triglycerides of fatty acids containing between 16 and 18 carbon atoms.Soluble lubricantsSoluble lubrican ts are principally employed to overcome the possible delete r ious effects of their insoluble counte rp a r t s on the time required for tablet disinteg ra t ion and hence drug dissolution.The use of soluble lubrican t s does overcome these issues.Polye t h y l e n e glyco l (PEG)Polyoxy e t h y l e n e st ear a t e sGlidantsGlidants act to enhance the flow proper t i es of the powders within the hopper and into the tablet die in the tablet press. The reduced friction between the powders /g r a n u les and the surfaces of the hopper and dies has been sugges t e d to be due to the ability of the par ticles of the glidants to locate within the spaces between the particles/g ra n ule s . To achieve this effect it is therefore necess a ry for the glidant par ticles to be firstly small and, secondly, to be arrang ed at the surface of the par ticles/g ra n ule s . Glidants are typically hydrophobic and therefore care should betaken to ensure that the concen t r a t ion of glidants used in the formula tion does not (in a similar fashion to lubrican ts) adverse ly affect tablet disintegr a t ion and drug dissolution. Examples of glidants used in tablet manufac tu r e include: (1) talc; and (2) colloidal silicon dioxide.TalcChemically talc is hydrat ed magnesium silicate (typicallyMg6(SiO2)4(OH)4) and is a crystalline mate rial of small par ticlesize.Colloidal silicon dioxide.Colloidal silicon dioxide is commonly used in tablet formula tions as a glidant(0.1–0.5% w/w) due to a combina tion of its hydrophobic proper t i es and low (colloidal) particle size (typically _ 15 nm).Miscellaneous excipients used in the formulation ofTabletsAdsorbents:Adsorben ts are used wheneve r it is required to include a liquid or semisolid componen t , e.g. a drug or a flavour, within the table t formulation. As the produc tion of table ts require s solid compone n t s , the liquid/semisolid constituen t is adsorbed on to a solid componen t which, in many cases, may be one of the othercomponen t s in the tablet formula tion (e.g. diluent) during mixing. If this approach is not possible, an adsorbe n t is specifically included in the formulat ion. Examples of these include: (1) magnesium oxide/carbon a t e ; and (2) kaolin/ben toni te .Magnesium oxide/carbonate: Magnesium oxide is a solid adsorben t that is commercially available in two forms termed light (less dense, 5 grams,occupying circa 40–50 ml) and heavy (more dense, occupying 10–20 ml). Both salts are employed as adsorben t s in tablets . In addition,

magnesium oxide may also be used as a glidant .Kaolin/bentonite: These are natur al mate rials that are composed of hydra te aluminium silicate . These excipient s are employed as adsorben t s .Sweetening agents/flavoursSweete ning agents and flavours (in accordanc e with other dosage forms) are employed to control the taste and hence the acceptabili ty of tablet s .ColoursColoured tablet s are generally formulate d either to improve the appea r a nc eor to identify the finished produc t uniquely.Surface-active agentsSurface- active agents may be incorpora t e d into tablets to improve the wetting proper t ie s of hydrophobic tablet s and hence increase the rate of tablet disinteg ra t ion . In addition, surface- active agents may increas e the aqueous solubility of poorly soluble drugs in the gast roin t e s t inal trac t and, as a resul t, the rate of dissolution of the active agent will increase .Eg : sodiu m lauryl sulp ha t e .Flavoring AgentsIn addition to the swee tnes s that may be afforded by the diluents of the chewable tablet (e.g., mannitol or lactose) artificialsweetening agents may be included. Formerly, the cyclamate s , either alone or in combina tion with saccha rin, were used widely.

Q4 Classify granulation techniques. Describe the wet granulation method along with equipment used in each step Tablets are commonly manufac tu r e d by one of the following manufac tu r ing processe s :

■ wet granul a t i o n■ dry gran ula t i o n (slug g i n g or rollercomp a c t i o n )■ direc t compr e s s i o n .

Stage 1: mixing of the therapeutic agent with the powdered excipients (excluding the lubricant)This step involves the introduc tion of the powdere d excipients and drug (excluding the lubrican t) into a powder mixer. The mixing speed and time must be sufficient to ensure that a homogeneo us mixture is produced, i.e. inwhich theconcen t r a t ion of each componen t in each region of the mixer/sam ple is identical. The efficiency of mixing is enhanc edby the use of powders that have similar average particle size/dis t r ibu t ion, although this is often not the case in manymixing opera t ions . Generally the shear rate required to mix pharm ac e u t ica l powders is low. Examples of mixers that are used within the indust ry include: