Lecture 2- Excipients In Tableting Flashcards
Why tablets?
-convenient and safe way of drug administration
-higher chemical and physical stability
-accurate dosing
-convenient to handle
-low cost of manufacturing
Types of tablets
-disintegrating (swallow)
-chew
-sublingual
-buccal= bypasses GI tract so gets to the system faster
-lozenge
-effervescent= no need for the disintegration process so quick action
Drug release profiles
Slide 6
Why excipients?
-to ensure that the tableting operation runs satisfactorily and a good quality is produced
Examples;
-fillers, disintegrates, binders anti-frictional agents, dissolution modifiers, absorbents, flavouring, colouring and wetting agents, antioxidants and preservatives
Fillers/ diluents/ bulking agents
-added to increase the bulk volume of the powder + size of the tab- makes it easier to swallow
-fillers necessary when dosage is very small
Ideal properties of a filler= chemically inert, biocompatible, low cost, acceptable taste and good technical, properties
Fillers: lactose
Exists in two isomeric forms:
*a-lactose; either monohydrate or anhydrous
*B-lactose; anhydrous
-can be in both crystalline and amorphous (more soluble and less stable) form
-crystalline= formed by precipitation
-lactose of various particle sizes is obtained depending on the milling procedure
Fillers; Lactose: a-lactose monohydrate
Lactose solution —> spray drying
Advantages:
-amorphous lactose dissolves more rapidly compared to crystalline
-better compressibility and good flow properties
Disadvantages:
-hygroscopic and physically unstable (high temp and humidity)
Fillers: Anhydrous a-lactose
-used for direct compression with low moisture content
Advantages; good stability, not sensitive to temp changes
Disadvantages; poor flow properties and low compressibility
Fillers: Modified lactose
- Spray dried lactose
-consists mainly of spherical particles containing micro crystals of a-lactose monohydrate with amorphous lactose
-excellent flow properties - Agglomerated lactose
-binding property can be improved by conversion into granulated form
-produced in fluid-bed granulatior-drier
-good flow properties
-binding properties better than a-lactose but not as good as those of spray dried lactose
Fillers; sugars
-used in lozenges and chewable tabs due to their pleasant taste
Fillers; celluloses + microcrystalline cellulose
Cellulose:
-not compatible with many drugs but it is hygroscopic so it should not be combined with drugs prone to hydrolysis
Advantages;
-biocompatible, chemically inert and good tablet-forming and disintegrating properties
^used as dry binder and disintegrant
Microcrystalline cellulose:
-particles have both crystalline and amorphous regions
-excellent binding properties
-acts as disintegration agent
Fillers; inorganic salts; dicalcium phosphate dihydrate
Advantages:
-good flow properties
-low-cost insoluble diluent
-poor compression characteristics
Disadvantages:
-hydrophillic- easily wet by water
-slightly alkaline- not compatible with pH sensitive drugs
*highly compressible and promotes rapid dissolution
Binders
-added in the drug filler mixture to increase the mechanical strength between the granules/tablets formed
Can be added to a powder in the following:
*dry powder before wet agglomeration
*solution used as agglomeration liquid
*dry powder - mixed with other ingredients before compaction
Why binder for granulation? - important factors
-compatibility with the other tablet components
-sufficient cohesion to the powders to allow for normal processing
-allows the tablet to disintegrate
-allows the tablet to dissolve upon ingestion
Why binder for granulation?
Disintegrants
-added to ensure that the tablet will break up into small fragments when in contact with liquid so to promote rapid drug dissolution
Mechanisms of disintegration:
-uptake of water induces capillary forces
-swelling
-release of gas to disrupt the tab
-enzymatic lysis of the binder
Tablet disintegration via capillary forces
Crucial factor= water uptake
Depends on= pore structure of the tablet and inherent hydrophobicity of tablet
Disintegrants in this group must:
-maintain a porous structure in the compressed tablet
-show a low interfacial tension towards aqueous fluids
*starch and surface active agents induce capillary forces
*surface active agents= make the drug particles more hydrophillic and promotes the wetting of the solid and the penetration of the liquid into pores of the tablet
Tablet disintegration via swelling
-almost all disintegrants swell
-extent and rate of swelling is important
*many disintegrants produce a sticky/gelatinous mass that resists the breakup of the tablet- making it important to optimize the concentration present within the granulation
Disintegration that swell
-sodium starch glycolate
-methyl cellulose
-carboxymethylcellulose
-powdered gums
-aligning acid and its sodium salt
Tablet disintegration via gas release
-used when rapid disintegration or a readily soluble formulation is required
*mixtures of citric acid + tartaric acid with carbonates/bicarbonates are used
Disadvantage- strict control over environmental conditions during the manufacture of tablets made with these materials = disintegrants are often incorporated immediately prior to compression
Tablet disintegration via enzymatic lysis of binder
-small quantities of appropriate enzyme may help to produce rapid disintegration
-enzymes present in the body act as disintegrants which destroy the binding action of binder and helps in disintegration
Superdisintegrants; substituted and crosslinked polymers
-effective at low concentration
-greater disintegrating efficiency
-more effective intragranularly
Disadvantage= hygroscopic= not used with moisture sensitive drugs
Factors affecting disintegration
Effect of fillers, binders, lubricants and surfactants
Slide 40
Lubricants
-act by interposing an intermediate layer between the tablet constituents and the die wall
-act at the tooling/material interface= incorporated in the final mixing step after all granulation is complete to avoid overmixing
-efficiency depends on surface area of the lubricant
-large SA= significant decrease in both ejection forces and tablet hardness
Mechanism of lubricant action
*fluid lubrication=
-layer of fluid is located between and separates the moving surfaces of the solids from each other reducing friction
*boundary lubrication=
-sliding surfaces are separated by a very thin film of lubricant
Important points for lubricants
-its added dry when the other components are in homogenous state
-mixed for only 2-5min
-over mixing = reduction of dissolution rate
-should not be added to wet granulations
-water soluble lubricants can be added as alcoholic solutions
-most effective true lubricants are hydrophobic, if high amounts are added = disintegration time and dissolution are reduced
-can interfere with bonding and soften the tabs
Anti-adherents
Aim= to reduce adhesion between the powder and the punch faces
-prevention of powder sticking to the punches, also known as sticking
-picking can be shown in powders which contains excess moisture
Glidants
-improve the flow properties of the powder mix or granules
-fine dry powders which are added to formulations in small quantities
Mechanisms- slide 49
Absorbents
Aim= to absorb quantities of fluids in a dry state
Used if:
-if oils/oil-drug solutions are included in the table. Magnesium oxide and magnesium carbonate are used as sorbets
-if hygroscopic ingredient is contained in the formulation
Flavouring agents
-to give a pleasant taste or mask unpleasant one
-latter can be achieved by coating the tab/drug particles
-they are thermolabile so they are added after granulation
-usually volatile oils that are dissolved in alcoholic solutions + sprayed on the dried granules or have been adsorbed onto another excipient
Pharmaceutical colours
Aim= to enhance aesthetic appearance, identification and patient compliance
-available as either soluble dyes/insoluble pigments
-colourants do not contribute to bioavailability, therapeutic activity or product stability
