Tablet Formation Flashcards
4 methods of tablet manufacturing
Wet granulation
Dry granulation - slugging
Roller compaction - also dry
Direct compression
What is wet granulation
Mixing API with excipients and a wet binder to form granules which are then dried
What is wet granulation suitable for and what does it achieve
Drugs with poor solubility and flow properties
Enhances uniformity of drug distribution and improves compression characteristics
What is dry granulation
Compacts drugs and excipients under high presssure to form slugs which are milled into granules
What is dry granulation used for and what does it achieve
Used when a drug cannot withstand heat or moisture
Simpler and less expensive than wet but requires drugs and excipients with cohesive properties
What is roller compaction
A dry granulation technique where powder particles are made to adhere under high pressure between two counter-rotating rollers.
What is roller compaction used for
useful for moisture- sensitive drugs. It is efficient and eliminates the need for binders or liquids.
What is direct compression
The simplest method, where the drug and excipients are blended and compressed into tablets without prior granulation.
cost- effective and efficient but requires the drug and excipients to have excellent flow and compression characteristics.
Factors that determine the choice of manufacturing process
Compression Properties of the Therapeutic Agent
Particle size of therapeutic agent
Types of Excipients
Chemical Stability of the Therapeutic Agent
What is Compression Properties of the Therapeutic Agent
The ability of the drug to form a compact mass under pressure is crucial.
Drugs with good compressibility can be easily formulated using direct compression
drugs with poor compressibility, alternative methods such as wet granulation may be necessary
What is Particle size of therapeutic agent
The size of drug particles affects the dissolution rate, bioavailability, and homogeneity of the tablet. Smaller particles may enhance dissolution but can pose challenges in flowability and uniform mixing.
What is Types of Excipients
The compatibility of excipients with the drug and the desired release profile dictates the choice of excipients the manufacturing process.
For instance, moisture- sensitive drugs may benefit from dry granulation or direct compression to avoid exposure to water during wet granulation.
What is Chemical Stability of the Therapeutic Agent
The stability of a drug under various conditions influences the manufacturing process.
Processes that involve heat or moisture may not be suitable for thermolabile or hydrolytic drugs,
General steps in manufacturing of tablets
- Mixing of API with the excipients
- Granulation of the mixed powder
- Mixing of powder or granules with other excipients
- Compression of the powder / granule mixture into tablet
What part of the process is the drug added
Milling
What part of the process is the excipient added
Blending
What part of the process is the binder solution added
Wet granulation
What part of the process is the lubricant added
2nd blending after sieving
Types of excipient
Diluent/filler
Binder
Disintergrant
Lubricant
Glidant
Absorbent
Sweetening agent
Colouring agent
Surface active agent
Diluent/filler
Added in all manufacturing processes
Added to increases mass/bulk of tablet containing low conc of therapeutic agent
Eg. Anhydrous lactose - used in wet and dry
Eg. Spray dried lactose - used in direct compression
Eg. Starch - used as a liquid diluent
Eg. Mannitol - used in chewable tablets
Binders
Polymeric components
Mainly used in wet granulation
Can be added as solution or powder
Holds components together
Disintergrants
1st mechanism - Added to tablet formation to facilitate breakdown of tablet upon entry to stomach
Disintegration must occur within 15mins
Eg. Starch and MCC
2nd mechanism - Can also occur by swelling in presence of aqueous fluids, increasing the nternal pressure with the tablet
3rd mechanism - gas formation - effervescent tablets
Lubricants
During compression of tablets, lubricant act at the interface between the face of the die and the face of the tablet
Insoluble (added to final mix stage but prior to compression) and soluble
Glidants
Enhances the flow properties of the powders within the hopper into the tablet press
Essentially, reduces the friction between the powder/granulate and the surface of the hopper
Eg. Talc
Absorbents
These materials are used whenever it’s required to include a liquid or semisolid components. E.g. a drug or a flavour
Eg. MgO
Sweetening, colouring and surface-active agents
Sweetening agent – added to control the taste for bitter drugs and chewable
Colouring agent – added to improve the appearance of the tablet or to IDENTIFY the finished product.
Surface-active agents – added to enhance the wettability of hydrophobic tablets and aids the rate of disintegration.
Adv of wet granulation
Reduce segregation of formulation components
Good technique for manufacturing of tablet containing low concentration of drugs
Use conventional excipient and most manufacturing plants are built around wet granulation
Disadv wet granulation
Several processes are required
Solvent required in the process but may cause degradation
The drug may be solubilize in the granulation fluids
adv dry granulation
Conventional excipients are required
No heat or solvent is required
This method does not cause alteration in drug morphology
Disadv dry granulation
Require the use of special equipment of roller compaction
Segregation of the components may occur
There are issue regarding powder flow
Final tablet formed by dry granulation tend to be softer
Adv of direct compression
Few processing and manufacturing steps
No need for granulation fluids or solvents, ideal for therapeutic agents that are degradable in presence of solvent
Lubrication is performed in the same bowel as powder mixing, reduce transfer loss or contamination
Good for small dose tablets
DisAdv of direct compression
Specialist equipment is required
Segregation may occur but can be reduced by
using similar particle sizes
Issue with powder flow
Can not be used if colourant is required
Tablet compression process
Step 1: Filling of the die with the granules/powder
- feed by gravity
Step 2: Compression of the powder bed
- upper punch descent and stress applied
Step 3: Tablet ejection
- upper punch elevated, shoe of hopper moves across ad push away tablet
Types of tablet press
Type 1 : Single-punch presses
Type 2 : Rotary tablet presses
Technical problems during tabletting
Capping
Lamination
2 main formulations of tablet coating
Solutions nd emulsion
Solution
Coat in coating polymers, coating solvents nd other excipients
Increases conc of coating polymer, reducing coating time
May increase viscosity of coating matters making it harder to spray
Emulsion
More attractive process
Polymer dissolved in volatile organic phase
Spraying the coating emulsion followed by deposition, spreading and then evaporation of the volatile solvent. This encourages the formation of a coating film
Coating of tablet in practise
- Pan coater
- Air suspension coater
Factors affecting on fluidized air coating
- Evaporation rate of the solvent
- Fluidised air volume
- Specific humidity
- Coating spray rate and duration
