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Name:
Pharmaceutical Dosage
Chapter 8: Tablets
Tablets
y Solid dosage forms prepared by compression with the aid of
suitable pharmaceutical excipients
y Vary in: size, shape, weight, hardness, thickness, disintegration
and dissolution characteristics and in other aspects, depending on
their intended use and method of manufacture
y For oral administration of drugs, others sublingually, buccally or
vaginally, with features mist applicable to the routes of
administration
y Some are scored allow to be easily broken into two or more parts
Characteristics of Ideal Tablets
y Free of defects: chips, cracks, discoloration and contamination
y Strength to withstand mechanical stresses of production
y Stable
y Release medicinal agents in a predictable and reproducible manner
Types of Tablets
y Compressed tablets (CT)
No special coating manufactured with tablet machine
with great pressure or compacting the powdered or
granulated tableting material
Contain pharmaceutical adjuncts: diluents or filters,
binders or adhesives, disintegrants, antidiarrheals, etc
y Multiple compressed tablets (MCT)
Prepared by: subjecting the fill material to more than a
single compression
Result: multiple layer or a tablet within a tablet, inner
tablet (core) and outer portion (shell)
y Sugarcoated tablets (SCT)
Compressed tablets with colored or uncoloured sugar
layer:
o Protects the enclosed drug from the
environment
o Provides a barrier to objectionable taste of
odor
o Enhances the appearance
o Permits imprinting of identifying
manufacturers information
Disadvantages:
o Time and expertise needed in the coating
process
o Increased shipping cost: 50% larger and
heavier than uncoated
y Film-coated tablets (FCT)
Are compressed tablets coated with a thin layer of
polymer (cellulose acetate phthalate) capable of
forming a skin like film
Advantage: more durable, less bulky and less time
consuming to apply than sugar-coating
y Gelatin-coated tablets (GCT)
Innovation product: gelcap, a capsule shaped
compressed tablet
Allows the coated product to be about 1/3 smaller than
a capsule filled with an equivalent amount of powder
More case in swallowing and more tamper evident
y Enteric-coated tablets (ECT)
Have delayed release features
Pass unchanged through the stomach to the intestines
(tablet disintegrate and allow drug dissolution and
absorption and/ or effect)
Needed when drug substance:
Destroyed by gastric acid
Irritating to the gastric mucosa
By-pass the stomach enhances the drug
absorption in the intestines
y Tablets used in the oral cavity:
Buccal and sublingual tablets
Flat oval tablets to be dissolved in the buccal
pouch (buccal tablet) or beneath the tongue
(sublingual tablet)
For oral absorption of drugs destroyed by
gastric acid or poorly absorbed in the GIT
Lozenges or troches
Disc-shaped solid forms in a hard candy or
sugar base
Dissolved slowly for localized effect or
systemic effect
y Chewable tablets
Pleasant tasting have smooth, rapid disintegration
(chewed or allowed to dissolve in the mouth)
Have a creamy base, specially flavoured and colored
mannitol
Prepared by compression or wet granulation
Xylitol: may be used in the preparation of sugar-0free
chewable tablets
y Effervescent tablets
Prepared by compressing granular effervescent salts
that release gas when in contact with water
y Molded tablet triturate (MIT)
May be prepared by molding rather than by
compression
Resultant tablets are very soft and soluble and are
designed for rapid dissolution
The mold is made of hard rubber, hard plastic or metal
Has 2 parts: the upper part (die) and the mower part
(flat punches)
Base is a mixture of finely powdered lactose with or
without portion of powdered sucrose
y Compressed tablet triturate (CTT)
Small, usually cylindrical, molded or compressed
tablets (limited pressure) containing small amounts of
usually potent drugs
Sucrose and lactose are used for diluents
Declined its use
y Hypodermic tablets (H.T.)
Used by physicians for extemporaneous preparation of
parenteral solutions rendered sterile
Dissolved in suitable vehicle sterility attained, and the
injection performed
Easily carried in the physicians medicine bag and
injections prepared to meet the needs of the individual
patients
Advent of prefabricated injectable products and
disposable syringes, declined its use
y Dispensing tablets (D.T.)
Compounding tablets
Used by the pharmacist to compound prescription and
not dispensed to patients
Contains large amount of potent substances enabling
the pharmacist to obtain pre-measured amounts
For compounding multiple dosage units
y Immediate-release tablets (I.R.)
Disintegrate and release their medication with
No special rate-controlling features, such as special
coating and other techniques
y Instant disintegrating or dissolving tablets
Disintegrate or dissolve in the mouth within 10 seconds
to 1 minute
Method of instant-release or disintegrating tablets
Lyophilized foam (lyophilization techniques)
o Prepared by foaming a mixture of gelatin,
sugar, drug and other components and
pouring the foam into a mold
o Zydis: 1
st
entry into the RTD field
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o Disadvantage: taste masking can be a
problem since the drug is incorporated
during the formation of the tablet
Soft direct compression
o Using standard tableting technology will
enhance fluid uptake and tablet
disintegration and dissolution
o Example product: Dimetapp: ND orally
disintegrating tablet
Use of water-soluble excipients
o Designed to wick water into the
tablet for rapid disintegration
Large scale lyophilizers
o Water is removed from temperature
sensitive or unstable product solutions
and transformed to stable dry products
with its original properties
y Extended-release tablets (E.R.) or controlled release (C.R.) tablets
Are designed to release their medication in a
predetermined manner over an extended period
y Vaginal tablets or inserts
Uncoated bullet-shaped or ovoid tablets inserted into
the vagina for local effect
Contain antibacterials (against Hemophilia vaginitis)
and antifungals (against Candida albicans)
Compressed Tablets
y Physical features of compresses tablets are well known: oblong,
round or unique in shape, thick or thin; large or small in diameter;
flat or convex; unscored or scored in halves, thirds or quadrant
y The less concave the punch the more flat the resulting tablets
y Punches with raised impressions will have recessed impressions on
the tablets
y Tablet diameters and shapes are determined by the die and punches
used in compression
Tablet Weight and USP Weight Variation Test
y Quantity of ill in die of a tablet press determines the weight of the
tablet
Content Uniformity
y Amount of active ingredient in each dosage unit lies within: 85%
to 115% of the label claim is less than 6% standard deviation
Tablet Thickness
y Determined by the diameter of the die, amount of fill permitted to
enter the die, the compaction characteristics of the fill material, and
the force or pressure applied during compression
Quality Standards and Compendial Requirements
y Tablet thickness
The greater the pressure, the harder the tablet
Hard enough to resist breaking (normal handling) and
yet soft enough to disintegrate (after swallowing)
Minimum requirement for a satisfactory tablet: force of
4 kg (hardness tester)
y Tablet hardness and friability
A tablets durability or tendency to crumble: the use of
a friabilator
Acceptable: maximum weight loss of not more than 1%
of the weight of the tablets
y Tablet disintegration
The basket rack assembly is raised and lowered in the
immersion fluid at 29-32 cycle per minute, the wire
screen always below the level of the fluid
y Tablet dissolution
In vitro dissolution testing of solid dosage forms is
important:
Guides formulation and product
development toward product optimization
Manufacturing monitored: a component of
the overall quality assurance program
Ensures bioequivalence from batch to batch
A requirement for regulatory approval of
marketing for products registered with the
FDA and regulatory agencies of other
countries
Factors Affecting Tablet Disintegration and Dissolution
y Particle size of the drug substance
y Solubility and hygroscopicity of the formulation
y Type and concentration of the disintegrant, binder and lubricant
y Manufacturing, particularly the compactness of the granulation and
compression force used in tableting
Apparatus Assembly Used for Drug Release and Dissolution Testing
y USP apparatus 1 and 2 consists of the following:
Variable: speed stirrer motor
Cylindrical stainless steel basket on a stirrer shaft (USP
Apparatus 1) or a paddle as a stirring element (USP
Apparatus 2)
1L vessel of glass or other inert transparent material
fitted with a cover having a center port for the shaft of
the stirrer and 3 additional ports, two for removal of
samples and one for the thermometer
Water bath
Pooled dissolution testing
y The tablet must meet the stated monograph requirement for rate of
dissolution
y Steps:
A volume of the dissolution medium is placed in the
vessel and allowed to come to 37
o
C + 0.5
o
C
Stirrer rotated at the speed specified at stated interval
samples of the medium are withdrawn for chemical
analysis of the proportion of drug dissolved
Successful in Vivo in Vitro Correlation (IVIVC)
y Relates combination of drugs solubility (high or low) and its
intestinal permeability (high or low)
y Categories:
High solubility and high permeability: dissolution rate
is slower than the rate of gastric emptying
Low solubility and high permeability: dissolution may
be rate-limiting step for absorption
High solubility and low permeability: permeability is
the rate-controlling step, and only a limited IVIVC may
be possible
Low solubility and low permeability: significant
problems are likely for oral drug delivery
Method of Compressed Tablet Manufacture
y Wet Granulation
Widely employed method for production of compressed
tablets
Advantages:
Traditional method for many drugs since it
imparts compressibility
Useful for fluffy powder (dont flow or mix
well)
Thermolabile compounds
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Powders generating static change
Wide range of available excipients
Disadvantages:
Some drugs are moisture sensate
(esterhydrolysis) or heat sensitive
Binder needed in the excipient mix
Multiple steps, lots of equipment- time,
space, money, personnel, material loss
Expertise required
Steps:
Weighing and blending
o Diluents or filler, and
disintegrating agent are mixed by
mechanical powder blender or
mixer until uniform
Preparing the damp mass
o A liquid blender is added to the
powder mixture to facilitate
adhesion of the powder particles
Screening the damp mass into pellets or
granules
o The wet mass is pressed through
a screen to prepare the granules
Drying the granulation
o Granules may be dried in the
thermostatically controlled ovens
that constantly record the time,
temperature, and humidity
Sizing the granulation by drying screening
o After drying, the granules are
passed through a screen of a
smaller mesh than that used to
prepare the original granulation
Adding lubrication and blending
o After dry screening, a dry
lubricant is dusted over the
spread-out granulation through a
mesh screen
Wet granulation pelletization
Two all-in-one granulation methods
Fluid bed granulator performs the following
steps: (continuous operation)
o Preblending the formulation
powder
o Granulating the mixture by
spraying onto the fluidized
powder bed
o Drying the granulated product to
the desired moisture content
y Dry granulation
Powder mixture is compacted in large pieces or
slugging and broken down or sized into granules
Either the active ingredient or the diluents must have
cohesive properties
Advantages: for materials degraded by moisture or
elevated temperature during drying
Types of dry granulation
Slugging: after weighing or mixing the
ingredients, the powder mixture is slugged,
or compressed into large flat tablets, or
pellets about 1 inch in diameter
Roller compaction: powder compactors
(instead of slugging) used to increase the
density of the powder by pressing it between
roller at 1 ton to 6 tons of pressure
Property of granulation important in making tablets
Provides the powders free flowing
Increases material density (use of roller
compaction) improving powder
compressibility
Conditions at which materials are applicable for dry
granulation
Possesses free flowing and cohesive
properties
Thus, be compressed directly in a tablet
machine without the need of granulation
y Direct compression tableting
Compressed directly into a tablet machine without need
of granulation
Granular chemicals possess free flowing and cohesive
properties (example: potassium chloride)
Free flowing property of a drug mixture is a
requirement for the manufacture of tablets of these
methods: wet granulation, dry granulation and direct
compression
High Shear Granulation
y Mixing and granulation
y Combines the active powder with a binder solution using a high
speed mixing blade and chopper
y Capacity: from 36 to 1800L
Precision Granulation
y Granulate soluble and hygroscopic materials
y Granulate fine particles
Fluid Bed Processor
y For granulation, coating and pelletization, and solution layering
The GPS of Fluid Bed Process
y Control real time process determination
Microwave Vacuum Process
y Using microwave
y Powder mix is mixed, wetted, agglomerated and dried
Tablet Production Processing Problems Encountered
y Results from air entrapment and high speed production
Capping: partial or complete separation of the top or
bottom crowns of a tablet from the main body of the
tablet and unclean punches and imperfectly smooth or
by granulation with too much fine
Splitting/laminations/horizontal striations: separation of
the tablet into 2 or more distinct layers, aging tablets or
improper storage
y Results from excessive moisture or substances with low melting
point temperatures in the formulation
Picking: removal of tablets surface area
Sticking: adhesion of tablet material to a die wall
y Results from use of a drug with a color from that of the tablet
excipients or from a drug with a colored degradation products
y Mottling: unequal distribution on a tab with light or dark areas,
standing out on an otherwise uniform surface
y Tablet dedusting: removes traces of loose powder adhering to
tablets following compression, the tablets are conveyed directly
from the tableting machine to a deduster
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Manesty Tablet Deduster
Reasons for Tablet Coating
y Protect medicinal agent against destructive exposure to air and/or
humidity
y Mask the taste of the drug
y Provide special characteristics of drug release
y Provide aesthetics or distinction to the product
Tablet Coatings
y Sugarcoating tablets
y Divided into following steps:
Waterproofing and sealing: containing components
that may be adversely affected by moisture
Subcoating: 3 to 5 subcoat of a sugar-based syrup are
applied
Smoothing and final rounding: 5 to 10 additional
coating of a thick syrup and applied to complete the
rounding and smooth the coating
Finishing and coloring: performed in a clean pan free
from previous coating materials
Polishing
Coated tablets may be polished in several
ways
Special drum-shaped pans or ordinary
coating pans lined with canvass as or other
cloth impregnated with carnauba wax or
beeswax
Three ways of Imprinting Logos or ID on Tablets
y Debossed: imprinted with a mark below the surface
y Embossed: imprinted with a mark raised above the surface
y Engraved: imprinted with a code that is cut into the surface during
production
Film-Coating Tablets
y Places: a thin, skintight coating of a plastic-like material over the
compressed tablet
y Developed to produce coated tablets having essentially the same
weight, shape, and size as the originally compressed tablet
y More resistant to destruction by abrasion than are sugarcoated
tablets
Types of Materials Found in Nonaqueous Film-Coating Solutions
y Film former
Capable of producing smooth, thin films reproducible
under convention coating conditions and applicable to a
variety of tablet shape
Example: cellulose acetate phthalate
y Alloying substance
Water solubility or permeability to the film to ensure
penetration by body fluids and therapeutic availability
of the drug
Example: PEG (polyethylene glycol)
y Plasticizer
To produce flexibility and elasticity of the coating and
thus provide durability
Example: castor oil
y Surfactant
To enhance spreadability of the film during application
Example: polyoxyethylene sorbitan derivatives
y Opaque and colorant
To make the appearance of the coated tablets handsome
and distinctive
Example:
Opaquant: titanium dioxide
Colorant: FD&C and D&C dyes
y Sweeteners, flavors, and aromas
To enhance the acceptability of the tablet to the patient
Examples
Sweeteners: saccharin
Flavors and aromas: vanillin
y Glossant
To provide luster to the tablet without a separate
polishing operation
Example: beeswax
y Volatile solvent
To spread of the other components over the tablets
while allowing rapid evaporation to permit an effective
yet speedy operation
Example: alcohol mixed with acetone
Enteric Coating
y Pass through the stomach intact to disintegrate and release their
drug content for a absorption along the intestine
y Applied to either whole compressed tablets or to drug particles or
granules used in the fabrication of tablets or capsules
y Coating applied in multiply portions to build a thick coating or as a
thin film coat
y Designed to dissolve at pH 4.8 and greater
y Materials used: pharmaceutical shellac
hydroxypropylmethylcellulose phthalate, polyvinyl acetate
phthalate, diethyl phthalate, and cellulose acetate phthalate
y Important factor to consider for enteric coated tablets: transmit
time required for passage to the intestines and pH
Fluid Bed or Air Suspension Coating
y Spray coating of powders, granules, beads, pellets or tablets held in
suspension by a column of air
y Fluid bed equipment is multifunctional and may also be used in
preparing tablet granulation
Flo-Coater
y Systems to provide the fastest possible spray rates and the most
efficient drying results
y Providing benefits for both top spray granulation and fluid bed
drying processes
Wurster Process
y Named after its developer
y The items to be coated are fed into a vertical cylinder and are
supported by a column of air that enters from the bottom of the
cylinder.
Types of Fluid Bed System
y Top sprays
Provides greater capacity up to 1500kg than the other
air suspension coating method
For taste masking, enteric release, and barrier films on
particles or tablets
Most effective when coatings are applied from aqueous
solutions, latexes, or hot melts
y Tangential spray technique
Used in rotary fluid bed coater
Used for layering coating and for sustained-release and
enteric coated
y Bottom Spray
For sustained-release and enteric-release products
Employed using a modified apparatus used for bed
coaters
Pharmaceutical Spray Dryers (PSD)
y Dries solutions, suspensions, and emulsions into powders
Compression Coating
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y Anhydrous operation safely employed in the coating of tablets
containing a drug that is labile to moisture
y Preparation of multiple compressed tablets having inner core and
outer shell of drug material, core tablets may be sugarcoated by
compression
Impact of Manufacturing Changes on solid Dosage Forms
y Changes in formulation arising from use of:
Starting raw materials including both the active
ingredient and pharmaceutical excipients that have
different chemical or physical characteristics than the
standard set of the original components
Different pharmaceutical excipients
Different quantities of the same excipients in a
formulation
Addition of a new excipient to a formulation
y Changes in the method of manufacture
Use of processing or manufacturing equipment of a
different design
Change in the steps or order in the process or method of
manufacture
Different in process controls, quality test, assay
methods
Production of different batch size
Employment of different product reprocessing
procedures
Employment of a different manufacturing site
Other Solid Dosage Forms for Oral Administration
y 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
y 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
y Pills
Small, round solid dosage forms containing a medicinal
agent and intended to be administered orally
Examples of Types of Tablets
Compressed: Actifed, Thyroid, Synthroid
Film coated: Erythrocin filmtab, Tagamet, Elavil
Enteric coated: various brands of ASA, Slow-Fe, Entabs, Entrophen,
AltiErythromycin, Sugar Coated Advil, M&Ms, Smarties, Chlortripolon,
Repetabs, Dimetapp, Extentabs, Dixarit; small, blue, sugar coated tablets
containing 0.025mg Clonidine, Cytoxan (cyclophosphamide), Ex-Lax
Chewable: Flintstones Multivitamins, Tums, Vitamin C Chewable Tablets,
Dilantin, Infatebs and Amoxil, Chewable Tablets Pepcid, Complete Chewable
Tablet
Effervescent: Alka-Seltzer, Gramcal, Redoxon, K-lyte, Novartis Phosphate

Precautions in Packaging and Storing Volatile Drugs
y Containing nitroglycerin: drug migrate between tablets in the
container, resulting in a lack of uniformity among tablets
y Packaging materials (cotton and rayon) and glycerine tablets:
absorb varying amounts of nitroglycerin, thus reducing potency of
tablets
y Nitroglycerine tablets (according to USP): preserved in tight
containers (glass) at controlled room temperature and dispensed in
original unopened container with the warning label to avoid loss
of potency and closed tightly after use