Tablet Formulation & Preparation Flashcards
What are tablets?
Compressed solid preparations with a single dose of one/more active medicaments
Properties of tablets
1) Exact dosage of active principles
2) Confer maximum stability as possible
3) Possess suitable mechanical properties
4) Only contain inert additives/excipients
5) Aesthetically pleasing
6) Suitable for its intended purpose
Advantages of tablets
1) Convenient
2) Deliver accurate dose
3) Small & compact
4) Stable product
5) Easy to handle & pack
6) Possible for high production throughout
Disadvantages of tablets
1) Poor compressibility (b/c of poor binding/high elastic component)
2) Poor wetting
3) Slow dissolution
4) Tablet would be too big if require high dose
5) Moisture-sensitive
6) Bitter taste/bad odour???
Preparation & formulation of effervescent tablets
Formulation: Alkali metal carbonates/bicarbonates & organic acids such as tartaric acid, citric acid
Preparation:
1) Wet fusion
- Citric acid moistened, added to sodium carbonate, granulated
2) Heat fusion
- Powders blended dry, w citric monohydrate used; apply heat - water of crystallization liberated, aids granulation
Major excipients (MUST-HAVES)
1) Diluent/fillers
Purpose: For low dose drugs
Impt: Inert. Low $, Compactability, Good flow
Eg. lactose, starch (corn starch), cellulose (microcrystalline cellulose)
2) Binder/adhesives Purpose: Strength Eg. MCC - High strength, low friability, self-lubricant Modified celluloses (Methylcellulose) Synthetic polymers Gums (Sodium alginate)
3) Disintegrant
Purpose: Improve bioavailability (Ensures tablet will break up)
Eg. MCC, Starch, Sodium starch glycolate, Modified cellulose gum, Crospovidone
4) Lubricants
Purpose: Improve tabletability
Functional classification of excipients
1) Affecting compaction
- Diluent/fillers
- Binder/adhesives
- Lubricants/glidants/ anti-adherants
2) Affecting bioavailability/stability/marketing considerations
- Lubricants
- Disintegrants
- Colouring/ flavouring/ fragrance
Functional classification of excipients
1) Affecting compaction
- Diluent/fillers
- Binder/adhesives
- Lubricants/glidants/ anti-adherants
2) Affecting bioavailability/stability/marketing considerations
- Lubricants
- Disintegrants
- Colouring/ flavouring/ fragrance
Mechanisms of disintegrant action
1) Swelling (eg. Starches)
- Expansion when wetted
2) Wicking (eg. MCC)
- Interparticular bonds broken
3) Strain recovery (Eg. Crospovidone)
4) Interruption of particle-particle bond
5) Heat of interaction
- Enthalpy change cause dosage form to break up
Types of colorant
1) Dyes
2) Lakes (or lake pigments containing soluble dyes)
- Often applied as film nowadays b/c coating is expensive
Types of “Lubricants” & their MOA
1) Glidants
- Improve flow by ball-bearing effect (Reduce friction between particles)
Eg. Silicates, Mg stearate, Starch, Talc
2) Lubricants
- Reduce friction btwn granulation & die wall during compaction
Eg. Fluid type: Mineral oil/paraffin
Solid type: Mg/Ca stearate, stearic acid, waxes (H2O-insoluble)
Carbowax (PEG), Na benzoate/acetate, leucine (H2O-soluble)
3) Anti-adherants
- Prevent sticking/adhesion of tablets/granules/powders to the faces of the punches
Eg. Silicates & derivatives, Starch, Talc, Mg/Ca/Zn stearate
Machines for Tablet Press
1) Single punch tablet machine
2) Rotary/multi-station tablet machine
- Tablets formed by compression using punches of granules feed into dies
Compaction forces
Stress: Amount of force applied to produce deformation
–> Deformation: Change in relative parts of the body, expressed as a strain which is a change in length per unit length
What are the events in die during plastic recovery?
1) Die filling
2) Pre-compression (Particle rearrangement)
3) Main compression (Fragmentation, plastic deformation, elastic deformation)
4) Ejection (Elastic recovery)
What is tabletability?
Capacity of a powdered material to be made into a tablet of specified strength under the effect of compression pressure
What is compressibility?
Ability to undergo vol reduction when subjected to applied pressure
What is compactability?
Ability of material to produce tablets with sufficient strength under effect of densification
Understanding the tableting process
Compaction pressure –Tabletability –> Tensile strength
Compaction pressure –Compressibility –> Solid fraction
Solid fraction –Compactability –> Tensile strength
Important to achieve better processing performance
Attributes of a good tablet
- Good mechanical properties: Hardness, friability
- Chemically stable
- Correct biopharmaceutical properties: Content, disintegration, dissolution
What does the mechanical strength of tablets depend on?
- Particle size, distribution, shape
- Granule porosity
- Moisture content
- Fragmentation & visco-elastic deformation
- Applied force (compaction load)
- Time of loading
- Time of unloading
- Elastic stress release upon ejection
Material requirements for tableting
1) Ideal brittle-plastic balance for good compressibility
2) Adequate granule porosity for compressibility
3) Sufficient moisture content for correct compressibility
4) Good powder flow for ideal tabletability
5) Correct level of lubrication for good compactability
Causes of capping (catastrophic event)
- Air entrapment
- Mechanism of vol reduction
- Compression speed
- Viscoelastic recovery
- Stress & density distribution
- Internal shear stress
Remedies to counter capping problem
- Lower compression force (to decrease elastic force in formulation) - Reduce compression speed - Decreasing ejection path in die - Tool design change - Extend dwell time
Balance between Plastic-Brittle material
Under compressive forces,
Plastic material –> Deform irreversibly
Brittle material –> Break down into small fragments
How to improve plasticity
Granulation
Why is powder flowability SO important?
- Ensure tablet weight uniformity
- Ensure tablets have consistent & reproducible properties
Why Continuous Manufacturing?
1) Reduce cost
2) Efficient & robust process development
3) Improve product quality
4) Flexibility in process
5) Reduce envt impact
