Tablets Flashcards
What is the most popular dosage form and why?
- Tablets are the most popular dosage forms
- Oral route is convenient and a safe way of drug administration
- Better physical and chemical stability than liquid dosage forms
- Accurate dosing of the drug (fixed dose per tablet)
- Convenient to handle and use (patient’s preference)
- Production procedures can be quality-controlled
- Mass production, low cost(manufacturer’s consideration)
Tablets are mainly used for which drug delivery
Systemic drug delivery
Before being absorbed what must happen to the drug
Drug must dissolve first before being absorbed – Need to break down to small pieces (disintegration)
– Need to dissolve (dissolution)
– Formulation strongly influences these processes
Administration of tablets
– swallowing whole
– after being chewed
– retaining in the mouth (can avoid the acidic environment of the stomach
– Buccal - designed to release the drug slowly
– Sublingual - designed for fast action
– dissolve or disperse first in water before administration
Disadvantages of tablets as a dosage form
– Poor bioavailability of poorly water-soluble drugs or poorly
absorbable drugs
– Difficult to swallow for some patients, e.g. children.
– Irritation to the G.I tract (some drugs)
Good tablets – some general attributes
- Correct dose
- Elegant; weight and size are consistent
- Drug should be released in a controlled and reproducible way
- Biocompatible – not toxic excipients, contaminants, microorganisms
- Sufficient mechanical strength to survive transport and handling
- Physically, chemically and biologically stable
- Acceptable by the patient for the intended use (e.g. excipients for chewable tablets? Need to consider taste?)
- Properly packed
How are tablets normally formed?
Normally tablets are formed by forcing particles into close proximity to each other by powder compaction, so that the particles cohere into a POROUS solid of defined shape
Powder compression
reduction of volume of a powder due to the application of a force
Powder compaction
the formation of a porous specimen of defined geometry by powder compression (remains in a certain shape)
Three stages in tablet formation
– The filling stage–powder fills the die by gravity or centrifugal force
– The compression stage–the upper punch lowers into the die and the powder is compressed; then upper punch moves up
– The ejection stage–lower punch moves up to reject the tablet
Single punch tablet press
- One die and one pair of punches
- The hopper shoe moves to and from the die by translational or rotational movement
- Tablet weight (amount of material filled into the die) is controlled by the position of the lower punch
- Lower punch remains stationary during compaction
- About 200 tablets per minute
Rotary tablet presses
- Many dies on the die table and many pairs of punches
- Die table and punches rotate together,
- The same punches always works with the same die
- 10000 tablets per min can be achieved. Suitable for mass production
Instrumentation of tablet press – in research & development
• Forces during compression are recorded – Forces from the upper and lower punches – Forces transmitted to the die
• Displacement (position of punches) is recorded
• Used in research. Normally instrumented single-punch hydraulic presses (also called compaction simulator) are used in this case
– Useful to investigate the relation between applied force and the properties of tablets produced
– To describe and analyse compression properties of powders by recording punch forces and punch displacement
Instrumentation of tablet press - in production
• Normally only forces are recorded on production machines.
– Variation in force is an indication of variation of tablet weight.
- Each time the punch goes down, force can be recorded
Reasons for granulation for tableting
– To improve flowability of the powder
– To improve mixing homogeneity and reduce segregation
– To improve the compactability of the powder (e.g. by adding a binder)
– To improve the density of the powder
– To ensure a homogeneous colour of the tablets
– To improve dissolution of poorly soluble drugs by dispersing fine powders of the drug in hydrophilic diluent
Tableting via wet granulation
Dry powder (Disintegrants can also be included in this stage) -> Wet mixing granulation -> Dry granules -> Dry granules of controlled particle sizes -> Tableting
Disadvantages of tablet production via wet granulation
• Production time is long
• Consumes energy in the drying process in wet granulation
• Stability problems
– Some drugs are not stable in wet conditions
– Some drugs are not stable when heated in the drying process
• High cost
Tablet production by direct compaction - Advantages
– Simplified production procedure. There are only two steps in
operation : powder mixing and tableting
– Reduced production time
– Reduced consumption of energy
– Low cost due to the reduction in production time and energy
– Less stability issue (no solvent and heat involved)
– Potential faster dissolution due to quick disintegration into primary particles
Tablet production by direct compaction - Disadvantages
– Need special grades of excipients (tend to be more expensive! - designed for direct compaction)
– Higher risk of powder segregation
– Powders of high drug content is difficult to form into tablets, if the drug has poor compactability
Direct compaction has been used mainly for two types of drugs
– Drugs that have good flowability (e.g. powders with large size)
– Potent drugs that are of low content (e.g. a few mg) in the tablet. In this case, the powder properties are mainly controlled by the excipients.
Type of tablet excipients
• Diluent (filler, or bulking agent) • Disintegrant • Binding agent (binder) • Glidant (improves the flow of powders) • Lubricant (reduces the friction between powder and die • Other – Anti-adherent – Sorbent – Taste adjusting agent
Tablet excipients – diluent
• Low dose drugs need diluent (filler) so that tablets of certain weight (normally > 50 mg) can be produced
Desired feature of an ideal diluent
– Biocompatible (non-toxic, non irritant etc) – Chemically inert
– Non-hygroscopic
– Low cost
– Good compressibility and compactibility – Acceptable taste
– Low cost
• All these requirements cannot be met by a single excipient. There are many different excipients to choose from
Tablet excipients – diluent examples
- Lactose
- Cellulose powders
- Microcrystalline cellulose (one of the cellulose group)
- Dextrose, glucose
- Sucrose
- Mannitol
- Inorganic salts, e.g. calcium carbonates and calcium phosphates
Tablet excipients – diluent (Lactose)
– The most common filler in tablets
– Dissolves readily in water
– Pleasant taste
– Available as anhydrous and crystalline
– Anhydrous lactose dissolves faster than crystalline
– Anhydrous lactose possesses excellent compaction properties, so used for direct compression
– Disadvantage:
• intolerant to some people
• Anhydrous lactose may spontaneously convert to the more stable crystalline form, in suitable conditions, e.g. high temp and humidity.
Tablet excipients – diluent (Cellulose powders)
– Biocompatible – Inert – Good disintegrating property – Good compatibility (can be used as dry binders) – Disadvantage: hygroscopic
Tablet excipients – diluent (Microcrystalline cellulose)
– Are prepared by hydrolysis of cellulose followed by spray drying
– Particles formed are aggregates of smaller cellulose fibres
– The particles have crystalline and amorphous regions
– The crystallinity may vary depending on the source of the cellulose and preparation procedure
– The crystallinity will affect the properties of the particles, inc hygroscopicity and powder compactability
Tablet excipients – diluent (Dextrose, glucose)
Often used in chewable tablets
