Lecture 2- Excipients In Tableting Flashcards
Why tablets?
-convenient and safe
-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- easier to handle tabs
-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
-amorphous part is responsible for better compressibility - 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
E.g. glucose, sucrose, sorbitol + d-mannitol
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 depending on the relative position of the cellulose chains within the solid
-excellent binding properties
-acts as disintegration agent
Fillers; inorganic salts; dicalcium phosphate dihydrate
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
Dicalcium phosphate;
*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= binder is mixed dry, then partly/ fully dissolved when liquid is added
*solution= binder is already dissolved in liquid
*dry binder - mixed dry with other ingredients before making tablets
Why binder for granulation? - important factors
Hydroxy propyl cellulose- good binder- reduces possibility of tablet capping
-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
Binders/ adhesives
Both solutions + dry binders= included in formulations when at low concentrations 2-10%
Conc of binder used + its method = significantly affect the granulation size
Disintegrants
-added to ensure that the tablet will break up into small fragments when in contact with liquid 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 drug particles easier to wet by water- helping it soak= dissolves better
Conc= 5-20%
Disintegration time depends on the step (intragranular or extragranular) that the excipient has been added
Tablet disintegration via swelling
-almost all disintegrants swell
-extent and rate of swelling is important
- some disintegrants can become sticky/jelly-like = makes tab harder to break apart.
- important to use the right amount
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- disintegrants need strict contol of temp + humidity during tab making
- avoid problems= usually added just before compressing the tablet
Tablet disintegration via enzymatic lysis of binder
-adding small amounts of enzymes= help tablets break apart faster
-enzymes present in the body break down binders in tablet
Superdisintegrants; substituted and crosslinked polymers
-effective at low concentration
-greater disintegrating efficiency
-more effective intragranularly
Disadvantage= hygroscopic= not used with moisture sensitive drugs
E.g. crosscarmellose, crosspovidone
Factors affecting disintegration
Fillers;
Soluble fillers= slow disintegration by making the fluid thicker
Insoluble fillers- rapid disintegration
Binders;
Stronger/higher binder amounts- slower disintegration
Lubricants;
Hydrophobic; lubricants stop water from soaking in = slowing disintegration
Worse= if no disintegration is present
Surfactants;
Help water soak in and reduce drugs water resistance
Faster disintegration if right amount is used
Lubricants
-work by creating a layer between the tablet and die wall- help it eject smoothly
-added last after granulation - to avoid overmixing
-efficiency depends on surface area of the lubricant
-avoid= mixing disintegration and lubricant at the same time
Better= add disintegrant first then lubricant
