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Quantity of ill in die of a tablet press determines the weight of the A volume of the dissolution medium is placed in the
tablet vessel and allowed to come to 37oC + 0.5oC
Stirrer rotated at the speed specified at stated interval
Content Uniformity samples of the medium are withdrawn for chemical
analysis of the proportion of drug dissolved
Amount of active ingredient in each dosage unit lies within: 85%
to 115% of the label claim is less than 6% standard deviation Successful in Vivo in Vitro Correlation (IVIVC)
Tablet Thickness Relates combination of drug’s solubility (high or low) and its
intestinal permeability (high or low)
Determined by the diameter of the die, amount of fill permitted to
enter the die, the compaction characteristics of the fill material, and Categories:
the force or pressure applied during compression
High solubility and high permeability: dissolution rate
Quality Standards and Compendial Requirements is slower than the rate of gastric emptying
Low solubility and high permeability: dissolution may
Tablet thickness be rate-limiting step for absorption
The greater the pressure, the harder the tablet High solubility and low permeability: permeability is
Hard enough to resist breaking (normal handling) and the rate-controlling step, and only a limited IVIVC may
yet soft enough to disintegrate (after swallowing) be possible
Minimum requirement for a satisfactory tablet: force of Low solubility and low permeability: significant
4 kg (hardness tester) problems are likely for oral drug delivery
Tablet hardness and friability
A tablet’s durability or tendency to crumble: the use of Method of Compressed Tablet Manufacture
a friabilator
Acceptable: maximum weight loss of not more than 1% Wet Granulation
of the weight of the tablets Widely employed method for production of compressed
Tablet disintegration tablets
The basket rack assembly is raised and lowered in the Advantages:
immersion fluid at 29-32 cycle per minute, the wire Traditional method for many drugs since it
screen always below the level of the fluid imparts compressibility
Tablet dissolution Useful for fluffy powder (don’t flow or mix
In vitro dissolution testing of solid dosage forms is well)
important: Thermolabile compounds
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Powders generating static change Conditions at which materials are applicable for dry
Wide range of available excipients granulation
Disadvantages:
Some drugs are moisture sensate Possesses free flowing and cohesive
(esterhydrolysis) or heat sensitive properties
Binder needed in the excipient mix Thus, be compressed directly in a tablet
Multiple steps, lots of equipment- time, machine without the need of granulation
space, money, personnel, material loss Direct compression tableting
Expertise required Compressed directly into a tablet machine without need
Steps: of granulation
Weighing and blending Granular chemicals possess free flowing and cohesive
o Diluents or filler, and properties (example: potassium chloride)
disintegrating agent are mixed by Free flowing property of a drug mixture is a
mechanical powder blender or requirement for the manufacture of tablets of these
mixer until uniform methods: wet granulation, dry granulation and direct
Preparing the damp mass compression
o A liquid blender is added to the
powder mixture to facilitate High Shear Granulation
adhesion of the powder particles
Screening the damp mass into pellets or Mixing and granulation
granules
o The wet mass is pressed through Combines the active powder with a binder solution using a high
a screen to prepare the granules speed mixing blade and chopper
Drying the granulation
o Granules may be dried in the
Capacity: from 36 to 1800L
thermostatically controlled ovens
that constantly record the time,
Precision Granulation
temperature, and humidity
Sizing the granulation by drying screening
o After drying, the granules are Granulate soluble and hygroscopic materials
passed through a screen of a Granulate fine particles
smaller mesh than that used to
prepare the original granulation Fluid Bed Processor
Adding lubrication and blending
o After dry screening, a dry For granulation, coating and pelletization, and solution layering
lubricant is dusted over the
spread-out granulation through a The GPS of Fluid Bed Process
mesh screen
Wet granulation pelletization Control real time process determination
Two all-in-one granulation methods
Fluid bed granulator performs the following Microwave Vacuum Process
steps: (continuous operation)
o Preblending the formulation Using microwave
powder Powder mix is mixed, wetted, agglomerated and dried
o Granulating the mixture by
spraying onto the fluidized Tablet Production Processing Problems Encountered
powder bed
o Drying the granulated product to Results from air entrapment and high speed production
the desired moisture content
Capping: partial or complete separation of the top or
Dry granulation bottom crowns of a tablet from the main body of the
tablet and unclean punches and imperfectly smooth or
Powder mixture is compacted in large pieces or by granulation with too much fine
slugging and broken down or sized into granules Splitting/laminations/horizontal striations: separation of
Either the active ingredient or the diluents must have the tablet into 2 or more distinct layers, aging tablets or
cohesive properties improper storage
Advantages: for materials degraded by moisture or
elevated temperature during drying Results from excessive moisture or substances with low melting
point temperatures in the formulation
Types of dry granulation
Picking: removal of tablet’s surface area
Slugging: after weighing or mixing the Sticking: adhesion of tablet material to a die wall
ingredients, the powder mixture is slugged,
or compressed into large flat tablets, or Results from use of a drug with a color from that of the tablet
pellets about 1 inch in diameter excipients or from a drug with a colored degradation products
Roller compaction: powder compactors
(instead of slugging) used to increase the
Mottling: unequal distribution on a tab with light or dark areas,
density of the powder by pressing it between
standing out on an otherwise uniform surface
roller at 1 ton to 6 tons of pressure
Property of granulation important in making tablets
Provides the powders free flowing Tablet dedusting: removes traces of loose powder adhering to
Increases material density (use of roller tablets following compression, the tablets are conveyed directly
compaction) improving powder from the tableting machine to a deduster
compressibility
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Manesty Tablet Deduster To enhance the acceptability of the tablet to the patient
Examples
Reasons for Tablet Coating Sweeteners: saccharin
Flavors and aromas: vanillin
Protect medicinal agent against destructive exposure to air and/or Glossant
humidity To provide luster to the tablet without a separate
Mask the taste of the drug polishing operation
Provide special characteristics of drug release Example: beeswax
Provide aesthetics or distinction to the product Volatile solvent
To spread of the other components over the tablets
Tablet Coatings while allowing rapid evaporation to permit an effective
yet speedy operation
Example: alcohol mixed with acetone
Sugarcoating tablets
Divided into following steps:
Enteric Coating
Waterproofing and sealing: containing components
that may be adversely affected by moisture
Subcoating: 3 to 5 subcoat of a sugar-based syrup are Pass through the stomach intact to disintegrate and release their
applied drug content for a absorption along the intestine
Smoothing and final rounding: 5 to 10 additional Applied to either whole compressed tablets or to drug particles or
coating of a thick syrup and applied to complete the granules used in the fabrication of tablets or capsules
rounding and smooth the coating Coating applied in multiply portions to build a thick coating or as a
Finishing and coloring: performed in a clean pan free thin film coat
from previous coating materials Designed to dissolve at pH 4.8 and greater
Polishing Materials used: pharmaceutical shellac
Coated tablets may be polished in several hydroxypropylmethylcellulose phthalate, polyvinyl acetate
ways phthalate, diethyl phthalate, and cellulose acetate phthalate
Special drum-shaped pans or ordinary Important factor to consider for enteric coated tablets: transmit
coating pans lined with canvass as or other time required for passage to the intestines and pH
cloth impregnated with carnauba wax or
beeswax Fluid Bed or Air Suspension Coating
Three ways of Imprinting Logos or ID on Tablets Spray coating of powders, granules, beads, pellets or tablets held in
suspension by a column of air
Debossed: imprinted with a mark below the surface Fluid bed equipment is multifunctional and may also be used in
Embossed: imprinted with a mark raised above the surface preparing tablet granulation
Engraved: imprinted with a code that is cut into the surface during
production Flo-Coater
Film-Coating Tablets Systems to provide the fastest possible spray rates and the most
efficient drying results
Places: a thin, skintight coating of a plastic-like material over the Providing benefits for both top spray granulation and fluid bed
compressed tablet drying processes
Developed to produce coated tablets having essentially the same
weight, shape, and size as the originally compressed tablet Wurster Process
More resistant to destruction by abrasion than are sugarcoated
tablets Named after its developer
The items to be coated are fed into a vertical cylinder and are
Types of Materials Found in Nonaqueous Film-Coating Solutions supported by a column of air that enters from the bottom of the
cylinder.
Film former
Capable of producing smooth, thin films reproducible Types of Fluid Bed System
under convention coating conditions and applicable to a
variety of tablet shape Top sprays
Example: cellulose acetate phthalate Provides greater capacity up to 1500kg than the other
Alloying substance air suspension coating method
Water solubility or permeability to the film to ensure For taste masking, enteric release, and barrier films on
penetration by body fluids and therapeutic availability particles or tablets
of the drug Most effective when coatings are applied from aqueous
Example: PEG (polyethylene glycol) solutions, latexes, or hot melts
Plasticizer Tangential spray technique
To produce flexibility and elasticity of the coating and Used in rotary fluid bed coater
thus provide durability Used for layering coating and for sustained-release and
Example: castor oil enteric coated
Surfactant Bottom Spray
To enhance spreadability of the film during application For sustained-release and enteric-release products
Example: polyoxyethylene sorbitan derivatives Employed using a modified apparatus used for bed
Opaque and colorant coaters
To make the appearance of the coated tablets handsome
and distinctive Pharmaceutical Spray Dryers (PSD)
Example:
Opaquant: titanium dioxide Dries solutions, suspensions, and emulsions into powders
Colorant: FD&C and D&C dyes
Sweeteners, flavors, and aromas Compression Coating
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Anhydrous operation safely employed in the coating of tablets original unopened container with the warning label “to avoid loss
containing a drug that is labile to moisture of potency and closed tightly after use
Preparation of multiple compressed tablets having inner core and
outer shell of drug material, core tablets may be sugarcoated by
compression
Lozenges
Can be made by compression or molding
Compressed lozenges are made using a tablet machine
and large, flat punches
Have a special place in the delivery of medication
Lollipop
Fentanyl actiq: a raspberry lollipop that differs from the
fentanyl oralet
Sugar-based lozenge on a tstick and contain fentanyl
citrate
Provide almost immediate relief as the drug starts being
absorbed in the mouth and starts to work within
minutes
Effect lasts for only about 15 minutes
Pills
Small, round solid dosage forms containing a medicinal
agent and intended to be administered orally