Lecture 7: Tablets 1 Flashcards
Name the common types of tablet.
- Oral tablet
- Orally disintegrating tablet
- Chewable tablet
- Compressed lozenges
- Effervescent tablet
- Sublingual tablet
What are orally disintegrating tablets?
Tablets that dissolve rapidly in the mouth within seconds.
They produce a fine dispersion which is then swallowed by the patient.
Useful for people who have difficulty swallowing tablets.
What is the purpose of chewable tablets?
For people who have difficulty swallowing tablets
What is the purpose of compressed lozenges?
They allow for slow release of the medication into the mouth or throat
What are sublingual tablets used for?
For drugs readily absorbed by the oral mucosa
For drugs that get inactivated by enzyme action or acidity in the GI tract
What are the steps that allow for drug release from oral dosage forms?
- Wetting & disintegration/deagglomeration
- Dissolution
What are the main categories of excipients used in oral tablets?
- Diluent / filler
- Binder
- Disintegrant
- Glidant
- Lubricant
(Less important ones: Anticaking agent / Antioxidant / Coating agent / Colouring agent / Dissolution retardant /
Flavouring agent / Preservative / Solubilizing agent / Sweetening agent / Wetting agent)
What is the purpose of a diluent / filler?
To increase the tablet volume or weight
What are some properties that we desire from a diluent/filler?
- Good powder flow
- Good tablet compaction strength –> good tensile strength so they wont break easily
What are some common diluent/fillers used in tablets?
- Lactose
- Mannitol
- Microcrystalline cellulose
- Starch
- Talc
What is the purpose of a binder in tablets?
- Facilitates the adhesion of API and excipients during direct compression
- Facilitates the agglomeration of powder into granules during granulation
These help to improve the tensile strength of the tablets
What are some common binders used in tablets?
- Hydroxypropyl cellulose
- Hypromellose (HPMC)
- Lactose
- Povidone
- Starch
What is the purpose of a disintegrant in tablets?
To facilitate the uptake of water into the tablet, or allow the tablet to swell when it comes into contact with water.
This allows the tablet to expand, which breaks the bonds holding the tablet together.
What are common disintegrants used in tablets?
- Colloidal silicon dioxide
- Microcrystalline cellulose (MCC)
- Povidone
- Starch
- Sodium starch glycolate
- Starch
What are the mechanisms by which a disintegrant promotes disintegration of a tablet?
- Swelling
- Wicking
- Strain recovery
Explain the process of swelling for disintegrants.
There is a large increase in volume upon hydration, which forces the components apart
They remain as distinct entities after wetting
What are superdisintegrants? Give an example.
They have very strong swelling –> increase to 300x of its original volume
example: sodium starch glycolate
Explain the process of wicking for disintegrants.
Wicking happens to hydrophilic compounds because they attract water
The liquid is absorbed by capillary action.
Water reaches the disintegrants which swell. This causes the intermolecular forces to break.
Explain the process of strain recovery for disintegrants.
In the tablet, the disintegrant is deformed under compression. When it comes into contact with water, it regains its orginal shape, causing the tablet to disintegrate.
What is the purpose of a glidant in a tablet?
- It promotes powder flow
- Reduces caking and clumping, which can happen when powders are stored in bulk.
- Prevents the powder from sticking to surfaces during emptying of powder hoppers, processing and during compression, preventing blockages etc.
What are the mechanisms by which glidants promote powder flow and prevent sticking?
- They adsorb onto the surfaces of larger particles to help reduce particle-particle adhesive and cohesive forces
- They are dispersed between the larger particles and reduce the friction between them.
What are examples of glidants used in tablets?
- Colloidal silicon dioxide
- Talc
What is the purpose of lubricants in tablets?
They reduce frictional forces between formulation components and equipment surfaces like tablet punches and dies.
Why are lubricants added in very small quantites?
If you add too much it can reduce disintegration or dissolution because lubricants are hydrophobic and dont get wetted.
What is the mechanism by which lubricants reduce sticking of powder to equipment?
They adhere to the solid surfaces and reduce the particle particle or particle - equipment friction.
What are common lubricants used in tablets?
- Magnesium stearate
- Stearic acid
- Polyethylene glycol (PEG)
What is the excipient function of starch, and what is the concentration used?
Used as a diluent, binder - 5-15% w/w
or disintegrant - 3-15 % w/w
Why should starch be stored in a cool dry place?
Heated starch is physically unstable and gets attacked by microorganisms, forming derivates of starch, which have different physical properties than the original
What is the excipient function of microcrystalline cellulose, and what is the concentration used?
It is used as a binder/diluent - 20-90 %
or as a disintegrant - 5-15%
What is the excipient function of colloidal silica, and what is the concentration used?
glidant, 0.1-0.5%
What is the excipient function of magnesium stearate, and what is the concentration used?
lubricant, 0.25-5%
Why is the small particle size and large specific surface area of colloidal silica beneficial?
Makes it a good glidant
It allows for enhanced adsorption on larger particles of powder mixture, improving flow.
Why is magnesium stearate used at a low concentration?
It is hydrophobic so can retard dissolution of a drug from tablet
What are the different classifications of tablet dosage forms?
- Immediate release
- Controlled release
- Delayed release
- Sustained release
Define modified release dosage.
The one for which the drug release characteristics of time, course and/or location are chosen to acomplish therapetuic or convenience objectives not offered by conventional dosage forms such as solutions, ointments, or promptly dissolving
dosage forms.
What are the different kinds of modified release dosage forms?
- Controlled release
- Delayed release
- Sustained release
What is controlled release?
It is a tru control of drug release rate
The drug plasma conc remians constant for an extended period of time
What is delayed release?
The release of a drug after a specified period of time
It has the same profile of an immediate release tablets, but with a delay
What is sustained release?
maintains drug release over a sustained period but not at a constant rate.
How to make a tablet delayed release?
Enteric coating (polymer)
Insoluble in ph 6 of below so no drug release in the stomach
Soluble in alkaline pH of the small intestine, where the drug is released
(delayed release tablets can also be time based)
List the purposes of an enteric coating.
- Protect acid labile drugs from the acidic gastric fluid
- Prevent gastric distress or nausea caused by some drugs like aspirin
- Deliver drugs that are best absorbed in the small intestine in its most concentrated form.
What are some polymers used in enteric coating?
- Cellulose acetate phthalate (CAP)
- Hydroxypropyl methyl cellulose phthlate (HPMCP)
- Polyvinyl acetate phthalate (PVAP)
What are the advantages of a controlled release tablet?
- Reduction in frequency of drug administration
- Improved patient compliance
- Reduction in drug level fluctuation in blood
- Reduction in drug toxicity (local/systemic)
- Product differentiation
- Patent extension
What are some problems associated with a controlled release tablet?
- Greater costs per unit dose compared to regular tablets
- It is dependent on how long the tablet stays in the GIT –> affected by GER
Are controlled release tablets influenced by pH and enzymes?
No
What is the ideal partition coefficient for a controlled release tablet?
High
Means lipophilic
So it can penetrate the membranes as its released
Should a controlled release drug have a short or long half life?
short
How do dissolution controlled formulations work?
- Reservoir system: API enclosed inside a polymeric membrane, which slowly dissolves and releases the API
- Matrix system: API is dispersed in a polymer matrix which dissolves and releases the API
For reservoir diffusion controlled formulatioons, how can we vary the rate of drug release?
By varying the thickness of the coating and its composition
For matrix diffusion controlled formulatioons, how can we vary the rate of drug release?
- The rate of drug release isw controlled by the rate of penetration of the dissolution fluid into the matrix
- Can change the porosity of the tablet by changing compression force, adhesion between adjacent particles & size + shapen of the particles
- Hydrophobic filters can be added to decrease the effective porpsity by limiting the number
of pores that can be penetrated by the eluting fluid
What are the different types (and sub categories) of controlled release formulations?
- Dissolution controlled formulation
a. matrix
b. reservoir - Diffusion controlled formulations
a. matrix
b. reservoir - Dissolution and diffusion controlled formulations
How do diffusion controlled systems work?
- Reservoir system: API enclosed inside a water insoluble polymer, the drug diffuses out of the polymer (equilibrium is reached)
- Matrix system: Drug dispersed in a water insoluble polymer matrix, and the drug diffuses through the matrix into the GI tract
In reservoir diffusion controlled formulation, is the drug merely encapsulated into the polymer?
No
In most cases the drug is also incorporated into the coating film
The drug at the coating film diffuses out faster, providing the initial dose
The drug in the reservoir provides the sustaining dose
In reservoir diffusion controlled formulation, what is the drug release dependent on?
It is dependent on the rate of diffusion
the release rate dM/dt is calculated by the equation
dM/dt = A x D x K x C change/ l
(no need to memorise the formula)
What are the different kinds of materials used in matrix diffusion controlled formulation and why?
- Rigid matrix: the polymers are insoluble plastics like PVP and fatty acids
- Swellable matrix/ glassy hydrogels: use hydrophilic gums like xanthum gum. (abit confused abt this)
How do Diffusion and Dissolution Controlled Release Formulations work? GIve an example
- The drug is enclosed in a polymer mixture of a soluble and insoluble polymer
- On contact with water the soluble polymer dissolves and creates pores
- The drug diffsues out of these pores into the GI tract
e.g. ethyl cellulose & methyl cellulose mixture: methyl cellulose dissolves in water &
creates pores in insoluble ethyl cellulose.
What are the advantages of chooosing tablets as the dosage form?
- Convenient and safe means of administering
- Accurate dosage
- Better chemical, physical and microbiological stability
- Can be mass-produced at a relatively low cost with robust quality control
