Tablet Technology Flashcards
What are the advantages of tablets?
Provide the greatest dose precision and the least content of variability
Least costly of all dosage forms.
Easiest and cheapest for product identification and to package and ship.
Easy to swallow
Potential for special release product such as enteric or delayed release
Best combination of properties in terms of chemical, mechanical and microbiological stability of all oral forms.
Better suited for large scale production
What is a tablet?
A unit form of solid medicament prepared by compression.
Most consist of mixtures of powders compacted in a die to produce a single rigid body
What are the disadvantages of tablets?
Some drugs resist compression into dense compacts due to their amorphous nature or low density
Drugs with poor wetting, slow dissolution properties may be difficult or impossible to formulate and manufacture as a tablet that will provide adequate or full drug bioavailability
Bitter tasting drugs, drugs with objectionable odour or drugs sensitive to oxygen or atmospheric moisture may require encapsulation or entrapment prior to compression or may require coating
What are the different classes of tablets?
Multiple compressed tablets
Standard compressed tablets
What are examples of multiple compressed tablets?
Layered tablets
Dry coated or compressed coated tablets
What are multiple compressed tablets?
Prepared by more than one compression cycle
What are layered tablets?
A type of multiple compressed tablet
Prepared by compressing additional tablet granulation over a previously compressed granulation to make tablets of 2 or 3 layers
What are dry coated or compressed coated tablets?
Tablets prepared by compressing a coat over a core
Why are multiple compressed tablets prepared?
To separate physically of chemically incompatible ingredients
To produce repeated action or prolonged action products
What are examples of different standard compressed tablets?
Prolonged action tablets including repeated action tablets, delayed action tablets, sustained release tablets,
Coated tablets including single coated tablets, film coated tablets, enteric coated tablets
Chewable tablets
Tablets used in the oral cavity
Tablets administered by other routes
Tablets designed to prepare solutions
What is a repeated action tablet?
Tablets which periodically release complete dose of drug in the GIT
What is a delayed release tablet?
Tablet which the release of drug is prevented for an interval of it mime or until certain physiological condition exists
What is a sustained release tablet?
…
What are sugar coated tablets?
Tablets covered by sugar coating
To produce elegant, glossy and easy to swallow dosage forms
To permit the separation of incompatible ingredients between coating and core
What is a Film coated tablet?
Tablet coated by a water soluble polymer such as hydroxypolymethylcellulose??? Or water insoluble polymers such as ethyl cellulose
What are enteric coated tablets?
Tablets covered by a thin layer of film of polymer that does not dissolve in the gastric fluid but dissolves in the intestinal fluid.
What are the reasons for enteric coating?
To reduce or eliminate irritation from some drugs e.g. Aspirin.
To protect the drug from the environmental condition of the stomach like low pH, enzymes, e.g. Erythromycin
The desire to release the drug undiluted and in the highest concentration possible within the intestine e.g. Intestinal antibacterial and antiseptic agent
What are chewable tablets?
Tablets which are intended to be chewed in the mouth prior to swallowing e.g. Aspirin chewable tablet for children.
Which type of drugs are not good candidates to formulate as chewable tablets?
Bitter or foul tasting drugs
Why are antacids formulated as a chewable tablet?
The dose of most antacids is large so a typical antacid tablet would be too large to be swallowed.
The activity of an antacid is related to particle size (small is better)
Chewable tablets may achieve better acid neutralising
What are the main types of tablets used in the oral cavity?
Buccal and sublingual tablets
Troches and lozenges
What are buccal and sublingual tablets?
Tablets held in the mouth where they release their drug contents for absorption directly through the oral mucosa of the mouth.
They are not designed to be swallowed as they contain drugs inactivated or not absorbed or destroyed in the stomach,
E.g. nitrate glycerine used for angina as a sublingual tablet.
Hormones are usually incorporated in buccal tablets.
What are the differences between buccal and sublingual tablets?
Buccal tablets are placed between the cheek and teeth or in the cheek pouch
They have a long disintegration time
Sublingual tablets are placed under the tongue.
They have a short disintegration time
What are the advantages of buccal/sublingual tablets?
Drug absorption by oral cavity avoids first pass metabolism
Gastric environment of stomach is avoided
More rapid onset of action than from tablets that are swallowed
What are troches and lozenges?
Tablets designed not to disintegrate in the mouth but to slowly dissolve over a period of time (30min or less)
They are used in the oral cavity to exert local effect in the mouth or throat.
They contain local anaesthetics, antiseptics, demulcents, astringents and anti-tussives
What are the types of tablets administered by other routes?
Implantation tablets
Vaginal tablets
What are implantation tablets?
Tablets designed for subcutaneous implantation in animal or man
Their purpose is to provide a prolonged drug effect ranging from one month to a year
What are vaginal tablets?
Tablets designed to undergo slow dissolution and release drug in the vaginal cavity e.g. Nystatin
What are examples of tablets designed to prepare solutions?
Effervescent tablets
Dispensing tablets
Hypodermic tablets
What are effervescent tablets?
Tablets containing the drug and an organic acid like citric or tartaric acid and sodium bicarbonate,
When dropped in a glass of water a chemical reaction is initiated between the acid and base to form a sodium salt of the acid to produce CO2 (disintegrant)
Why are effervescent tablets designed?
To improve the rate of disintegration of tablets
To improve the taste of the drug
What is the equation of an effervescent tablet in the presence of water?
Drug + citric/tartaric acid + NaHCO3 –> Na-citrate/tartarate + CO2 (disintegrant)
What are dispensing tablets?
Tablets intended to be added to a given volume of water by a pharmacist or the customer to produce a solution of a given concentration
What are the examples of materials commonly incorporated into dispensing tablets?
Mild silver proteinate,
bichlroide of mercury
Ammonium chloride
What are hypodermic tablets?
Composed of one or more drugs with other readily water soluble ingredients intended to add to sterile water or water for injection
What do conventional oral tablets for ingestion usually contain?
Some classes of essential and non essential components in addition to the drug
What are the main types of essential components?
Diluents or bulking agents Binders Disintegrants Lubricants Glidants Antiadhesvies
What are diluents?
Fillers designed to make up the required bulk of the tablet when the drug dosage itself is inadequate to produce this bulk
What are examples of diluents?
Lactose USP Spray dried lactose Starch Sucrose Hydrolysed starch (Emdex ) Dextrose Microcrystalline cellulose (avicel) Mannitol Sorbitol
What is important about mannitol as a diluent?
It is widely used in chewable tablets because of its negative heat of solution, pleasant feeling in mouth and its sweet taste.
It is not hygroscopic and can be used in multivitamin formulations
What is sorbitol?
An isomer of mannitol. It is also used in chewable tablets
How are diluents added to tablets?
They are added in the first step of tablet formulation by mixing with the active ingredient
What are binders?
Materials which bind powders together and make them cohesive
They are adhesive in the formulation
What are examples of powders?
Gums like acacia and tragacanth, Gelatin solution Starch paste Liquid glucose Modified natural polymer like alginate Cellulose derivatives like hydroxypropylmethylcellulose, Hydroxypropyl cellulose, ethyl cellulose Polyvinylpyrridone (PVP)
How are binders added to tablets?
There are two main ways depending on the method of tablet preparation.
A) for tablets prepared by direct compression, binders are added dry to the tablets to provide a cohesive compact.
B) for tablets prepared by wet granulation, binders can be added in dry, with a binding solvent to form a wet mass or they can be added with the binder already dissolved in the binding solvent to form a wet mass. This method is better as you result in better quality products due to binder being activated in the solvent
What are disintegrants?
Excipients added to the tablet formulation to facilitate the break up or disintegration of a tablet when it contacts water in the GIT
What are examples of disintegrants?
Starch Primogel Explotab Clays like bentonite, Veegum HV, Microcrystalline cellulose AC-Di-sol which is a modified cellulose derivative Sodiumcarboxymethylcellulose
How are disintegrants added to the tablet formulation ?
Via 3 different methods of addition:
1) the can be added to powder ingredients before wet granulation
2) they can be added to dry granules
3) they can be divide into 2 halves with 1half added to powder ingredients and the other half added to dry granules
What are lubricants?
Excipients which help the tablet to release from the die after compression
They reduce friction during tablet ejection between the will of the tablet and the wall of the die cavity
What are examples of lubricants?
Hydrocarbon oil (mineral oil)
Stearic acid and its salts like mg stearate, Ca stearate
Talc
High molecular weight polyethylatedglycans
Certain polymeric surfactants
What are glidants?
These are added to the tablet formulation to improve the flow properties of granules or powder
These reduce the friction between the particles to produce a uniform fill inside the die
What are examples of glidants?
Talc Corn starch Colloidal silica such as cab-o-sil Syloid Aerosil
What are anti adhesives?
Excipients added to the tablet formation to prevent sticking or adhesion of granules or powder to faces of the punches or the die to the die wall
What are examples of anti adhesives?
Talc,
Magnesium stearate
Starch
Colloidal silica
What are the main methods of tablet manufacturing?
Direct compression technique
Dry granulation technique (compression granulation technique)
Wet granulation technique
What is the direct compression technique?
Compressing the tablet from powdered materials without modifying the physical nature of the material itself.
Involves mixing, compression, to form the tablet.
What are the requirements for tablets undergoing the direct compression technique?
Materials must have good flow properties
And good compressibility
Why can’t most materials be compressed directly into a tablet?
Because they possess relatively weak intermolecular attraction forces
They may be coved with films of adsorbed gas which hinders compaction
How can we improve compression characteristics of a material?
By mixing the material with a directly compressible diluent or vehicle
What is a directly compressible diluent or vehicle?
This is an inert substance that may be compacted easily without difficulty and which may compress even when quantities of drugs are mixed with it.
What are the limitations with using directly compressible diluents?
Differences in particle size and bulk density between drug and diluent
Large dose drug may present problems with direct compression if it is not easily compressible by itself
Interaction between drug and direct compressible diluent e.g. Reaction between amine compounds and spray dried lactose shown by yellow discolouration
Static charges may build up which can occur during drug routine mixing, preventing a uniform distribution of drug in tablets
What is the dry granulation or compression granulation technique?
Compacting of a tablet component using tablet press or specially designed, machinery, followed by screening, prior to final compression into a tablet.
What are the processes involved in dry granulation technique?
Mixing of materials
Compaction into slugs
Screening into granules
Compression into tablets.
What are slugs?
Poorly formed tablet or compacted mass of powdered material
What machine is involved in the dry granulation technique?
Compression granulation is performed using a roller compactor (for large scale production)
Many aspirin and vitamin formulations are prepared for tableting by this compression granulation technique.
What is the process of the wet granulation technique?
Materials are mixed together and the binder is added.
This is kneaded into a wet mass.
Wet screening is conducted to select wet granules
These are dried to form dry granules
Dry granules are then screened for granules
The lubricants are added and then they are compressed into tablets
What are the two main types of tablet machines?
Hand tablet machine for small scale production
Rotary tablet machine for large scale production
What are tablet machines also known as ?
Presses
What are the basic components of tablet machines?
Hoppers Dies Punches Cam tracks Feeding mechanism
What are hoppers?
These are used for holding no feeding the granulation to be compressed
What are dies?
These define the size and shape of the tablet
What are punches?
The are used for compressing the granulation within the dies
What are cam tracks?
These are used for guiding the movement of the punches
What is the feeding mechanism?
This moves the granulation from the hopper into the dies
How are tablet presses also classified?
As hand tablet machines
multi stationary rotary presses
What are the tests of tablet quality control?
Uniformity of weight / weight variation tolerances test
Test of uniformity of drug content
Disintegration test
Dissolution test
Mechanical strength tests (friability and hardness tests)
How is the uniformity of content of active ingredient of a tablet tested?
Via the uniformity of weight or weight variation tolerances test
And test if uniformity of drug content
How is the uniformity of weight or weight variation tolerances test conducted?
Collect a sample of tablets, usually 20 from a batch.
Determine their individual weights.
Calculate the average weight
The batch complies with the BP standards if the individual weight do not deviate from the mean more than is permitted, in terms of %
What are the weight tolerances for tablets if the average weight is 80mg or less?
10% deviation
What are the weight tolerances for tablets if the average weight is between 80mg and 250mg?
7.5%
What are the weight variation tolerances for tablet if the average tablet weight is 250mg or more?
5%
How is the test of uniformity of drug content carried out?
Collect a sample of tablets, usually 10,
Determine the amount of drug in each tablet.
The average drug content is calculated and the content of the individual tablets should fall within specified limits in terms of % deviation within the mean
What is the disintegration test?
Test is carried out by agitating a given number of tablets in an aqueous medium at a defined temperature & the time to reach the end point of the test is recorded
The batch complies with the test if the time to each this endpoint is below a given limit
What is the endpoint for disintegration tests?
This is the point in which all visible parts of the tablets have been eliminated from a set of tubes in which the tablets hVe been held during agitation
What is used to conduct the disintegration test?
Disintegration apparatus (A?)
Why are dissolution tests carried out?
To evaluate the potential effect of formulation and process variables on the bioavailability of a drug
To ensure that preparations comply with product specifications
To indicate the performance of the preparation under in vivo conditions
What factors affect the dissolution process?
Factors affecting the solubility of the substance (composition and temperature of dissolution medium)
The concentration of the dissolved substance.
The flow conditions of the fluid in dissolution chamber.
Normally the concentration of the drug substance in the bulk of the dissolution medium does not exceed more than 10% i.e. Sink conditions.
What re the two types of dissolution test apparatus that are officially recognised?
Apparatus I: rotating basket method
Apparatus II: paddle method
Both apparatus use the same type of vessel which is filled with the dissolution medium of controlled temperature and volume
What are the differences between the rotating basket method and paddle method?
In the rotating basket method the tablets are placed in a small basket formed from a screen which is then immersed in dissolution medium and rotated at a given speed.
In the paddle method, the tablet is placed in the vessel and the dissolution medium is agitated by a rotating paddle.
Why are mechanical strength tests carried out?
To assess the importance of formulation and production variables for the resistance of a tablet towards fracturing and attribution during formulation work, process design and upscale.
To control the quality of tablets during production (in process and batch control)
To characterise the fundamental mechanical properties of materials used in tablet formulation
What are the most commonly used methods for strength testing?
Attrition resistance method (friability test )
Fracture resistance method (tensile strength test)
How is the attrition test conducted?
This involves the rotation of tablets in a cylinder followed by the determination of weight loss after a given number of rotations.
This is conducted with a friabilator
A selected sample size of tablets are dusted, weighed, and then placed in the drum and rotated for 25 rpm for 4 minutes (i.e. 100 revolutions) tablets are taken out, redusted and reweighed. The % loss in weight is calculated.
If the loss in weight is >1%, the test is repeat twice and the mean of the 3 tests is calculated.
A maximum loss of 1% of the mass of tablets is considered to be acceptable for most products
How is the sample size for the attrition resistance method test chosen?
If the tablet weighs up to 650mg, a sample size of 20 is selected.
If the tablet weighs more than 650mg, a sample size of 10 is selected.
How is the % loss in weight calculated in a friability/attrition resistance test?
% loss in weight = (W0-W1)/W0 x 100
How is the fracture resistance or tensile strength test conducted?
This involves the application of a load on the tablet and the determination of the force needed to fracture or break the tablet along its diameter.
This is often conducted using a Monsanto hardness tester
What is the crushing strength of the tablet or the hardness of the tablet?
The force needed to fracture the tablet on its diameter
How is the tensile strength calculated?
Tensile strength (σt) = 2F/πDt Where F = force needed to fracture the tablet D = diameter of tablet t = thickness of the tablet
