Tabletting

● Single punch tablet press - only has 1 set of punches and 1 die cavity; small-scale
production
● Rotary tablet machines (high speed) - several sets of rotating punches;large-scale
manufacturing of tablets
● Induced die feeder - place the powders and/or granules so that it will be loaded to the
tablet press; facilitate the filling of die cavity
● Dedusting – removes traces of powder adhering to tablets after compression

Compendial Requirements for Tablets

● Weight and Weight Variation
○ Quantity of fill in the die of a tablet press
○ Die cavity - where the powders will be placed
○ USP Weight Variation test
● Content Uniformity
○ USP method - 10 tablets assayed individually (85% - 115%) - assay of API
that will be contained in the tablet
○ Ensure that has the same amounts of API
● Thickness
○ Determined amount of fill that enters the die, compaction characteristics of fill
materials and compression pressure
○ How hard the tablet will be pressed
○ Higher compression = decrease in the thickness; powders are not
compressible = increase in thickness
● Hardness
○ High pressure, high hardness
○ Hardness testers used to measure degree of force (Kgs, lbs, or N, arbitrary
units)
○ Tablets should be sufficiently hard to resist breakage during normal handling
but soft enough to disintegrate properly after administration; conventional
release tablets - 4 to 10kg or 4 to 8kg in some references
● Friability
○ Ability of tablets to crumble under determined stress factors (rolling in a drum
for specified time)
 ○ Measured as resistance to loss of weight
○ Maximum weight loss of 1% generally considered acceptable - USP

● Disintegration
○ Ability of tablets to disintegrate into smaller particles with increased surface
area for dissolution in body fluids
○ Measured in vitro using a Tablet Disintegration Testing Apparatus - 2 beakers
and a plunger which will submerge the tablets in water or other medium; not
checking if it will be dissolved but if it will be broken down into smaller particle
size when in contact with water or other liquid
● Dissolution
○ In vitro testing that provides reasonable prediction of or correlation with the
product’s in vivo bioavailability
○ Reasons for conducting dissolution tests
■ Guides formulation and product development toward product
optimization toward in vivo bioavailability
■ Component of overall quality assurance program in monitoring
manufacturing operations
■ Requirement for regulatory approval of products for marketing
● Apparatus 1 - basket
● Apparatus 2 - paddle
○ Usually for tablets and capsules
● Apparatus 3 - reciprocating cylinder
● Apparatus 4 - flow through cell (usually for poorly soluble API
and granules)
● Apparatus 5 - paddle over disk (transdermal DF)
● Apparatus 6 - rotating cylinder (transdermal)
● Apparatus 7 - reciprocating holder (transdermal and
non-disintegrating conventional release tablets)
● Moisture
● Impurities
● Packaging and storage

Factors affecting quality and performance of Solid Dosage Forms

● Changes in formulation
○ Use of starting raw materials – use materials of the same specifications as
standards set for components; there should be a level of quality
 ○ Use of different pharmaceutical excipients – magnesium vs calcium stearate
(can be chelated or can form complex)
○ Use of different quantities for same excipients in formulation – more
concentrated binder; would increase the disintegration
○ Addition of new excipients in formula – use of different coating formula
● Change in method of manufacture
○ Use of manufacturing equipment with different design
○ Change in steps or order in manufacturing process - order of addition
○ Different in-process controls – quality tests or assay methods
○ Different batch sizes
○ Different product reprocessing procedures - fine granules turned to good
granules
○ Different manufacturing site

Changes in Manufacturing
● Document
● Validate - check if constantly produces the desired results of the changes
● Register with regulatory body

Packaging and Storing Tablets

● store in tight containers in places of low humidity and protected from extremes in
temperature
● if prone to decomposition due to the presence of moisture, copackage with a
desiccant packet - to maintain a level of moisture since the desiccant packet will
maintain it
● if adversely affected by light, store in light-resistant containers (amber [colored
bottles])
● a coil or plug, usually cotton wool, may be added in the container to prevent abrasion
of tablets
○ Coil - prevents too much movement of the tablet inside the bottle

Important Considerations in Packaging

● Storage conditions
● Expiration date
● Dispense in similar type containers

DRUG RELEASE PATTERNS OF SOLID DF

● Immediate Release
○ Conventional release - it will be absorbed after a few hours without delay
○ Instantly Disintegrating
○ Buccal and Sublingual
○ Effervescent Tablets
● Modified-Release

Immediate Release Tablets

● Designed to release the drug without any rate-controlling features such as special
coatings and other formulation techniques
● Uncoated plain tablets; no release modifying excipients
Instantly Disintegrating or Dissolving Tablets
● Characterized by disintegrating or dissolving in the mouth within one minute
● Designed for children and elderly or any patient who has difficulty swallowing tablets
● Buccal and Sublingual - don't have to chew, just place it under the tongue or inside
the buccal pouch

Modified Release Dosage Forms

● Designed to release the drug in a predetermined manner
● Drug release features are based on time, course, and/or location that are designed to
accomplish therapeutic or convenience objectives

Delayed-Release Products
● Usually designed to pass through the stomach unaltered, later to release the
medication in the intestinal tract
● To protect a substance from destruction by gastric fluids or reduce stomach distress
caused by irritating drugs (enteric coating)
● To facilitate gastrointestinal transit for drugs that are better absorbed from the
intestines.
● Designed to release the drug at a time other than promptly after administration
● Delay may be time based or based on the influence of environmental conditions like
gastrointestinal pH

Delayed Release
● Targeted Release
○ Drug release is directed towards isolating or concentrating a drug in a body
region, tissue or site for absorption or for drug action
● Enteric Coated
○ Specifically coated to remain intact in the stomach and to yield their
ingredients in the intestines
○ Based on the level of pH
○ When unless acidic conditions (small intestine), it will be dissolved and
disintegrated
● Repeat Action
○ In 1 tablet it will have several release times

Extended Release Products

● Designed to release the medication in a controlled manner at a predetermined rate,
duration, and location to achieve and maintain optimum therapeutic blood levels of
drug
● Prolonging the effect or release of the product
● Allows a reduction in dosing frequency from that necessitated by a conventional
dosage form

Advantages of Extended Release Products

● Less fluctuations in drug levels
○ In extended release products - maintaining the conc of the drug in the body in
the therapeutic window
 ● Frequency reduction in dosing
● Enhanced convenience and compliance
○ Especially for people difficulty in remembering if they have already taken he
drug
● Reduction in adverse side effects
○ Maintaining tin a certain level of blood, it will not go above the minimum
● Reduction in overall healthcare costs
● Complex Formation

Extended Release Technology

● Rate of drug release modified by technologies based on:
○ Modifying drug dissolution by controlling access of biologic fluids to the drug
through the use of barrier coatings - the one employed in film coating,
preventing the dissolution of the core tablet through the use of coatings
○ Controlling drug diffusion rates from dosage forms - how the drug will be
diffusing outside into the absorption
○ Chemical reaction or interaction between the drug substance or its
pharmaceutical barrier and site specific biologic fluids - enteric coating - it will
not be dissolved in the stomach, just in the small intestines
● Coated Beads, Granules, and Microspheres
○ Solution of drug substance is placed on small inert nonpareil seeds or beads
made of sugar and starch or on microcrystalline cellulose spheres
■ Placing the API in an inert DF or bead - final product be a mixed of
uncoated granules or beads for immediate release and others will
have varying lipid materials to control release of rates
● Multitablet system
○ Small spheroid tablets of varying sizes having varying drug release
characteristics are placed in gelatin capsule shells to provide desired pattern
of drug release - clear hard capsule shells which has different color beads
○ Some uncoated for immediate release, others coated for extended drug
release
● Microencapsulated Drug
○ Drug in solid, liquid or even gaseous form is enclosed in microscopic particles
by formation of thin coatings of wall material around the substance
○ Wall material – gelatin, polyvinyl alcohol, ethylcellulose, polyvinyl chloride and
other synthetic polymers
● Embedding Drug in Slowly Eroding or Hydrophilic Matrix System
● Embedding Drug in Inert Plastic Matrix
● Ion Exchange Resins
● Osmotic Pump

USP Requirements of Extended or Modified Release

● Drug release
○ Based on drug dissolution from the dosage unit against elapsed time
● Uniformity of Dosage Units - coated granules or multitablet systems should have the
same release patterns
● In Vivo-In Vitro Correlations - important in drug dissolution
● Labeling