Lecture 2- Excipients In Tableting

Question 1

Why tablets?

Answer 1

-convenient and safe way of drug administration
-higher chemical and physical stability
-accurate dosing
-convenient to handle
-low cost of manufacturing

Question 2

Types of tablets

Answer 2

-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

Question 3

Drug release profiles

Answer 3

Slide 6

Question 4

Why excipients?

Answer 4

-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

Question 5

Fillers/ diluents/ bulking agents

Answer 5

-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

Question 6

Fillers: lactose

Answer 6

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

Question 7

Fillers; Lactose: a-lactose monohydrate

Answer 7

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)

Question 8

Fillers: Anhydrous a-lactose

Answer 8

-used for direct compression with low moisture content
Advantages; good stability, not sensitive to temp changes
Disadvantages; poor flow properties and low compressibility

Question 9

Fillers: Modified lactose

Answer 9

1. Spray dried lactose
   -consists mainly of spherical particles containing micro crystals of a-lactose monohydrate with amorphous lactose
   -excellent flow properties
2. 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

Question 10

Fillers; sugars

Answer 10

-used in lozenges and chewable tabs due to their pleasant taste

Question 11

Fillers; celluloses + microcrystalline cellulose

Answer 11

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

Question 12

Fillers; inorganic salts; dicalcium phosphate dihydrate

Answer 12

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

Question 13

Binders

Answer 13

-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

Question 14

Why binder for granulation? - important factors

Answer 14

-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

Question 15

Why binder for granulation?

Question 16

Disintegrants

Answer 16

-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

Question 17

Tablet disintegration via capillary forces

Answer 17

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

Question 18

Tablet disintegration via swelling

Answer 18

-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

Question 19

Disintegration that swell

Answer 19

-sodium starch glycolate
-methyl cellulose
-carboxymethylcellulose
-powdered gums
-aligning acid and its sodium salt

Question 20

Tablet disintegration via gas release

Answer 20

-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

Question 21

Tablet disintegration via enzymatic lysis of binder

Answer 21

-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

Question 22

Superdisintegrants; substituted and crosslinked polymers

Answer 22

-effective at low concentration
-greater disintegrating efficiency
-more effective intragranularly

Disadvantage= hygroscopic= not used with moisture sensitive drugs

Question 23

Factors affecting disintegration

Answer 23

Effect of fillers, binders, lubricants and surfactants
Slide 40

Question 24

Lubricants

Answer 24

-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

Question 25

Mechanism of lubricant action

Answer 25

*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

Question 26

Important points for lubricants

Answer 26

-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

Question 27

Anti-adherents

Answer 27

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

Question 28

Glidants

Answer 28

-improve the flow properties of the powder mix or granules
-fine dry powders which are added to formulations in small quantities
Mechanisms- slide 49

Question 29

Absorbents

Answer 29

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

Question 30

Flavouring agents

Answer 30

-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

Question 31

Pharmaceutical colours

Answer 31

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