Acetaminophen Flashcards
What is acetaminophen?
The inhibition an analgesic and antipyretic agent commonly used in many OTC medications
What are it’s effects believed to be related to?
The inhibition of prostaglandin synthetase, a mechanism shared by ASA and other related drugs
How does it produce an analgesic effect?
It is postulated that the analgesic effect is produced by elevation of the pain threshold
How does it produce an antipyretic effect?
It is produced through action on hypothalamic heat-regulating center
Acetaminophen is considered equipotent to _____ in its analgesic and antipyretic effects, but is unlikely to produce many of the side effects associated with ____
(same word)
ASA
Does acetaminophen have any anti-inflammatory effect?
No way jose
What is acetaminophen used for?
- MSK pain
- headache
- earache
- low back pain
- arthritis
- dysmenorrhea
- myalgias and neuralgias
- symptomatic reduction of fever
What types of medications are commonly found in composite acetaminophen preparations ?
- aspirin
- caffeine
- chlorpheniramine
- codeine
- destromethrophan
- diphenhydramine
- pseudoephedrine
What advantages do tablets offer the manufacturer ?
- economic
- stable
- convenient
What advantages do tablets offer the consumer?
- accuracy
- portability
- convenience
Describe:
Diluents
They are used to increase the mass of tablets in order to make the formulation a practical size for compression.
List some common diluents
- dicalcium phosphate
- calcium sulfate
- lactose
- cellulose
- mannitol
- sodium chloride
- starch and powdered sugar
Describe:
Binders
They are used to improve free-flowing qualities of the granules and to impart cohesiveness to the tablets so that the preparation remains intact with desired hardness and size after compression
List some commonly used binders
- starch
- gelatin
- sugars (sucrose, dextrose, molasses, etc.)
- natural and synthetic gums (acacia, sodium, alginate, etc)
Describe:
Lubricants
They prevent adhesion of tablet material to the surface of dies and punches, reduce inter particle friction, improve flowing rate of the tablet granules and facilitate ejection of the tablets from the die cavity
List some commonly used lubricants
- talc
- magnesium stearate
- stearic acid
- hydrogenated vegetable oils
- polyethylene glycol
Describe:
Disintegrants
They are able to absorb water rapidly and increase their size afterwards, so that tablets can break up or disintegrate after administration
List some commonly used disintegrants
- starches
- celluloses
- algins
- crosslinked polymers
Describe:
Glidants
substances that improve the flow characteristics of a powder mixture
Describe:
Colorants
substances that provide more appealing appearance to the preparation
Describe:
Flavoring agents
substances that add extra flavours to special tablets such as chewable tablets and effervescent tablets
______ ______ tablets use specific polymers or coating materials to achieve modified drug release properties
controlled release
What is the most widely used tableting procedure?
wet granulation
-bc it provides desirable physical characteristics to tablet granules to facilitate quality compression
What is included in a complete cycle of wet granulation?
- weighing
- mixing
- granulating
- wet screening
- drying
- dry screening
- lubricating
- compressing
For ____-____ Granulation, mixing, granulating and drying are processed in a single piece of equipment (fluid-bed granulator).
Fluid-Bed
What is Dry Granulation?
(also known as recompression or double compression) - eliminates the use of a granulation fluid, so that no moisture or high temperature is applied to sensitive active ingredients.
Dry granulation has been replaced by ?
Direct compression
What is Direct Compression?
involves mixing and compressing, which can shorten the processing time and reduce the production equipment and cost in tablet manufacture
Compresse tablets are characterized by a number of specifications: They include ?
-tablet size, shape, thickness, weight, hardness, drug content and uniformity, drug disintegration and dissolution
What is the purpose of quality control ?
Sufficient quality control testing is carried out by the manufacturers over the production process to assure tablet quality and batch-to-batch reproducibility.
Describe:
Tablet Hardness
The resistance of a tablet to chipping, abrasion and/or breakage under conditions of storage, transportation and handling before administration depends on its hardness.
How do you measure hardness?
Measurement of a tablet hardness is performed throughout the tableting process to determine the need for pressure adjustment on a tableting machine.
If a tablet is too hard .. ?
it may not meet the disintegration and/or dissolution requirements
If a tablet is too soft .. ?
it will not withstand handling conditions during subsequent processing such as coating, packaging and shipping
Describe:
Tablet Friability
Friability evaluates the ability of a tablet to withstand abrasion during packaging, handling and shipping.
How is tablet friability tested?
After a given number of rotations and free falls in a friability apparatus, tablets are weighed and the weight loss will indicate the ability of the preparation to withstand this type of wear.
How is friability testing different from hardness testing ?
friability test is normally conducted using finished tablet products
Describe:
Content Uniformity
In order to ensure that every tablet within a batch of product contains the correct drug amount with little variation, content uniformity is tested for some tablet preparations, partially those containing small amounts of active ingredients or have small tablet weight (less than 50 mg).
What is key to achieving desirable content uniformity ?
Appropriate dilution and mixing of the active ingredient with other additives
Describe:
Tablet Disintegration
The disintegration test tells how fast a tablet breaks into small particles once in contact with a medium.
To be _______, a drug substance must be in solution first
absorbed
Why is the disintegration test useful?
Useful for manufacturers as a quality assurance tool to measure batch-to-batch production reproducibility.
What types of dosage forms is the disintegration test applied to?
conventional oral dosage forms such as compressed tablets, film-coated tablets, enteric-coated tablets, buccal/SL tablets and soft/hard gelatin capsules.
Since drug absorption and bioavailability directly depend on drug substance in _______ state, drug dissolution from a solid dosage form is more important than disintegration in reflecting satisfactory preparation properties.
dissolved
Similar to the disintegration test, the _____ test is a type of in vitro study that measures the amount of time required for a given percentage of drug substance in a tablet to go into solution under specific conditions.
dissolution
Dissolution testing is one step forward to disintegration testing … why ?
because it determines the physiological availability of an active ingredient instead of the breakage of a solid preparation
Why was Avicel (microcrystalline cellulose) added?
diluent or disintegrant ?
Why was Explotab (sodium starch glycolate) added?
binder or diluent or disintegrant ?
Why was magnesium stearate added?
lubricant
Why was talc added?
lubricant
Why was granulating solution added?
to granulate the tablets ?
Why did we make for 160 tabs instead of 150 ?
to compensate for mass loss during wet granulation processing
The average hardness should be between ______
10-15 kg
How did we test the friability of the tablets?
- Weight tablet first
- Spin in friability apparatus at 25+/- rpm for 4 minutes (100 rotations)
- Weigh tablet after
Weight loss should be less than 0.8%
What are the parameters for testing weight uniformity ?
To pass this test, no more than one tablet should differ from the average weight by more than 5% and no tablet should differ by more than 10%.
How did we test tablet content ?
-Take 10 tablets
-Weight the tablets using analytical balance and calculate average tablet weight
-Grind tablets into powder
-Weight out a portion equivalent to 50 mg of acetaminophen
(avg tablet weight = 0.3947 g)
0.3947 g = 325 mg acetaminophen
x g = 50 mg acetaminophen
x = 0.0607 g
- put this amount into 200 mL volumetric flask
- fill with water, mix
- transfer 1 mL of filtrate into 25 mL volumetric flask
- fill with water to 25 mL mark
-measure and record UV absorbance of the solution at 249 nm, using distilled water as the blank
Criteria for passing tablet content test?
The tablets should contain not less than 90% and not more than 110% of the labelled amount of acetaminophen.
Describe the dissolution test
- Weighed 2 tablets
- Placed them into separate dissolution vessels and started counting dissolution time
- Withdraw 3 mL of dissolution medium at 15 and 30 mins using a disposable syringe
- Pass sample through Nalgene filter membrane and collection the filtrate into a small test tube
- Replenish with 3 mL of fresh dissolution medium into the dissolution vessel after each sampling
- Pipette 1 mL into 25 mL volumetric flask and dilute
- Measure absorbance at 249 nm using distilled water as the blank control
**Calculate amount of acetaminophen dissolved using standard curve provided.
FIGURE OUT HOW TO DO IT
How does a tablet pass the dissolution test?
Not less than 80% of the labelled amount of acetaminophen is dissolved in 30 minutes.
