I. Tablet Excipients
In addition, individual excipients can have different grades, types and sources depending on those different functional roles, for example, there are various grades of lactose commercially available that have different physical properties, e.g. flow characteristics & particle size distribution. This permits selection of what is considered the most suitable grade for a particular need, e.g. with tablet development:
- Wet Granulation: usually, finer grades of lactose are utilised as the binder is utilised more efficiently and this permits better mixing and granule quality.
- Direct Compression: in contrast here, spray dried lactose is used as it flows better and is more compressible.
II. In tablets, the key excipient types include:
- Diluents, e.g. lactose, microcrystalline cellulose
- Disintegrants, e.g. sodium starch glycolate, croscarmellose sodium
- Binders, e.g. PVP, HPMC
- Lubricants, e.g. magnesium stearate
- Glidants, e.g. colloidal SiO2
1. Tablet Diluents (Fillers)
Bulking agent
To make a tablet weight practical for the patient: minimum tablet weight is typically ~50mg. Actual API doses can be as low as ~20µg, e.g. for oral steroids.
Compression aid
Deforms and/or fragments readily to facilitate robust bonding in tablet compacts, e.g. microcrystalline cellulose.
Good bulk powder flow….diluents have a strong influence
Good flow of bulk powders is very important in designing a robust commercial tablet product. Lactose can exhibit poor flow characteristics, so is often combined with microcrystalline cellulose in wet granulation tablets, or is used as a better-flowing spray-dried version, particularly with direct compression formulations.
2. Tablet Disintegrants
As an aid to de-aggregation of compacted tablets. Disintegrants cause rapid break up (disintegration) of the tablet compact upon exposure to moisture.
Generally, disintegration is viewed as the first stage in the dissolution process, although dissolution does occur simultaneously with disintegration.
Mode of action:
In many cases water uptake alone will cause disintegration, by rupturing the intra-particle cohesive forces that hold the tablet together and resulting in subsequent disintegration.
If swelling occurs simultaneously with water uptake, the channels for penetration are widened by physical rupture and the penetration rate of water into the tablet increased.
3. Tablet Binders
Binders act as an adhesive to ‘bind together’ powders, granules and tablets to result in the necessary mechanical strength:
As a powder with other excipients in dry granulation (roller compaction, slugging) or as an extra-granular excipient in a wet granulation formulation.
As a powder with other excipients in wet granulation. When the granulating fluid is added, the binder may dissolve partially or completely to then exhibit adhesive binding properties.
Most commonly, the binder is added already dissolved in the granulating fluid to enable more rapid and, usually, more effective granulation.
Water is the most common granulating fluid, very occasionally in a co-solvent system with, e.g. ethanol.
Binders Examples:
- Dry binders: Microcrystalline cellulose, cross-linked PVP
- Solution binders: HPMC, PVP
- Soluble in water/ethanol mix: PVP
4. Tableting Lubricants
Lubricants prevent adherence of granule/powder to punch die/faces and promote smooth ejection from the die after compaction
- Magnesium stearate is by far the most extensively used tableting lubricant
- There are alternatives, e.g. stearic acid, sodium stearyl fumarate, sodium behenate
Lubricants tend to be hydrophobic, so their levels (typically 0.3 – 2%) need to be optimised:
- Under-lubricated blends tend to flow poorly and show compression sticking problems
- Over-lubricated blends can adversely affect tablet hardness and dissolution rate
Just to illustrate the need for effective lubrication (and powder flow); high speed tablet presses can operate at:
- 360,000 tablets/hour ≡ 6000 tablets/min
- 30 stations ≡ 200 tablets/min/station ≡ ca. 3 tablets/second/station
5. Tablet Glidants
Most commonly; colloidal silicon dioxide (traditionally, talc)
- Good bulk powder flowability is especially important during high speed processing
- Glidants improve flow by adhering to particles and so reducing inter-particulate friction
- Most common in dry powder formulations, e.g. direct compression tablets
- Can also be added to granules to improve flow prior to compression
- NB: can get undesirable “flooding” if flow is too good
- Very low levels required (ca. <0.2%)
- Control can be challenging with blends sensitive to levels
- Very low bulk density (0.03 – 0.04g/cm3)
- Difficult to work with (very voluminous) – not a standard excipient, only added if needed
- Issues with dust exposure
