Definition

 According to the BP:

 Dosage forms circular in shape with either flat or convex faces, prepared by
compressing the medicament or a mixture of medicaments with added
substances
 The most popular dosage form
 70% of all official pharmaceutical preparations produced
Outline
 History
 Tablets as dosage forms
 Advantages and disadvantages of compressed tablets
 Types of tablets
 Essential properties of tablets
Outline
 Tablet formulation
 Influence of tableting method on formulation
 Powder fluidity
 Powder compressibility
 The need for granulation prior to compression
 Dry granulation
 Wet granulation
 Tableting methods
 Hand method
 Direct method
 Indirect method
Outline
 Tablet excipients:
 Diluents
 Adsorbents
 Moistening agents
 Binding agents (adhesives)
 Glidants
 Lubricants
 Disintegrating agents
Outline
 Specific formulation requirements of other compressed dosage forms:
 Lozenges
 Effervescent tablets
 Chewable tablets
 Sublingual tablets
 Implants
 Multilayer tablets
 Sustained release tablets
Outline
 Sustained release tablets
 Advantages and disadvantages
 Types
 Formulation
 Methods of achieving sustained release
 Diffusion-controlled release
 Dissolution-controlled release
 Release controlled by ion exchange
 Release controlled by osmotic pressure
Outline
 Formulation factors affecting drug release drug from tablets:
 Effective surface area of the drug (particle size)
 Effect of binding agents
 Effect of disintegrants
 Effect of lubricants
 Effect of diluents
 Effect of granule size
Introduction
 Historical milestones:
 1843: a patent was granted to an English man (Thomas Brockedon) for a
machine to compress powder to form compacts
 1874: both rotary and eccentric presses were introduced
 1885: glyceryl trinitrate tablets listed in the BP
 1980: nearly 300 monographs for tablets
Advantages of tablets
 Production aspects:
 Large-scale production at the lowest cost
 Easiest and cheapest to package and ship
 High stability
 End user aspects (physician, pharmacist, patient):
 Easy to handle
 Light and most compact
 Greatest dose precision and least content variability
 Coating can mask unpleasant taste and improve patient acceptability
Disadvantages of tablets
 Poor compression:
 Some drugs resist compression into dense compacts
 Wetting and dissolution:
 Poorly wettable drugs, drugs with slow dissolution rates, intermediate to large
doses may be difficult or impossible to formulate and manufacture as a tablet
that provide adequate drug bioavailability
Disadvantages of tablets
 Poor organoleptic properties:
 Bitter tasting drugs, drugs with objectionable odors, or sensitive to oxygen or
moisture may require:
 Encapsulation or entrapment prior to compression
 Coating
 Special packaging
Types of tablets
 According to the route of administration:
 Oral tablets
 Sublingual or buccal tablets
 Vaginal tablets
 According to the production process:
 Compressed tablets
 Multiple compressed tablets
 Tablet within a tablet: core and shell
 Multilayer tablet
Types of tablets
 According to the type of coating:
 Sugar-coated tablets
 Protects tablets from moisture
 Masks odor and flavor
 Elegance
 Film-coated tablets
 Thin film coat
 Soluble or insoluble polymer film
Types of tablets
 According to the method of administration:
 Chewable tablets
 Rapid disintegration
 Antacid, flatulence: rapid action
 Pediatric use
 Effervescent tablets
 Dissolved in water before ingestion
Essential properties of tablets
 Accurate dose of drug, uniform in weight, appearance and diameter
 Have the strength to withstand the rigors of mechanical shocks
encountered in production, packaging, shipping and dispensing
 Release the medicinal agent(s) in a predictable and reproducible
manner
 Elegant product, acceptable size and shape
 Physically and chemically stable
Tableting procedure
 Filling
 Compression
 Ejection
Tableting
Tablet formulation
 Powders intended for compression into tablets must possess two essential
properties:
 Fluidity (good powder flow)
 Compressibility
Tablet formulation
 Fluidity (good powder flow)
 The powder material move efficiently from the hopper into the die
 To produce tablets of consistent weight
 Can be improved mechanically by the use of vibrators, or via the
incorporation of a glidant
Tablet formulation
 Compressibility:
 The property of forming a stable, intact compact mass when compression
(pressure) is applied
 Most of the times, there is a need for granulation prior to compression
Tablet formulation
 Ideal properties of granules:
 Have sufficient compressibility
 Uniform distribution of all components
 Good particle size distribution
 A nearly spherical shape as possible
 Robust enough to withstand handling, without breaking down
 Dust free
Tableting methods
 Dry methods:
 Direct compression
 Slugging
 Roller compaction
 Wet methods
 Wet granulation prior to compression
Direct compression
 More convenient than wet granulation because:
 Does not require the equipment and handling processes required in wet
granulation
 Less costly
 Can avoid aqueous hydrolysis of certain drugs
Direct compression
 In general, direct compression vehicles (diluents) should have the
following characteristics:
 Freely flowing
 Physiologically inert
 Tasteless
 White color
 Acceptable mouth feel
Direct compression
 Direct compression vehicles (contd):
 Improve the compressibility of poorly compressible drugs
 Inexpensive
 Promote rapid disintegration
 High capacity (the ability to produce tablets containing a high proportion of
non-compressible drugs)
DC diluents
 Diluents available for direct compression are classified according to
their disintegration and flow properties:
 Disintegranting agents with poor flow:
 Micro-crystalline cellulose
 Microfine cellulose
 Directly compressible starch
 Freely flowing/ do not disintegrate:
 Dibasic calcium phosphate
 Freely flowing powders which disintegrate by dissolution:
 Dextrose, spray-dried lactose, anhydrous lactose, spray-crystallized maltose, sucrose
DC diluents: examples
 Microcrystalline cellulose (MCC, Avicel®):
 Advantages:
 Probably the most important tablet diluent used in direct compression

 Exhibits the highest capacity and compressibility

 A good disintegrant

 Disadvantages:
 High initial moisture content

 Hygroscopic (this property may allow its use as a moisture scavenger)

 Relatively poor flow

DC diluents
 Dibasic calcium phosphate:
 Water-insoluble direct compression diluent
 Advantages:
 Cheap
 Good fluidity
 Disadvantages:
 Poor disintegration properties (requires a strong disintegrant such as sodium starch
glycollate and cationic exchange resins)
 Slightly alkaline
DC diluents
 Dibasic calcium phosphate:
 Disadvantages (Cont):
 Unsuitable for alkaline sensitive drugs such as ascorbic acid and thiamine HCl
 May alter the absorption of certain drugs (e.g., tetracycline derivatives)
Tablet formulation
 Ingredients used in tablet formulations
 Drugs
 Fillers, diluent, bulking agent (to make a reasonably sized tablet)
Tablet formulation
Lactose
 Three forms:
 α-lactose.H2O (lactose monohydrate)
 Spray-dried lactose
 Anhydrous lactose
Lactose monohydrate
 Characteristics:
 Not directly compressible and therefore suitable for use in wet granulation
 Has poor flow properties
 Water soluble
 Produces a hard tablet and the hardness increases on storage
 Inexpensive
Lactose monohydrate
 Characteristics (contd):
 Contains approximately 5% moisture and hence is a potential source of
instability especially with moisture sensitive drugs
 Usually unreactive, except for discoloration (browning) when formulated
with amines and alkaline materials (Maillard reaction)
Lactose monohydrate

Maillard reaction
Spray dried lactose
 Characteristics:
 Directly compressible diluent
 Exhibits free flowing characteristics
 Requires high compression pressures in order to produce hard tablets
 Its compressibility is adversely affected if dried to a level below 3% moisture
Spray dried lactose
 Characteristics:
 More prone to darkening in the presence of excess moisture, amines due to
the presence of a furaldehyde:

 Usually, neutral or acid lubricant should be used when spray dried lactose is
employed
 Expensive compared to anhydrous and lactose monohydrate
Anhydrous lactose
 Characteristics:
 Directly compressible diluent
 Does not exhibit free flowing property
 Can pick up moisture at elevated humidity causing to possible changes in
tablet dimensions
 Does not undergo Maillard reaction to the extent shown by spray dried
lactose, although this may occur in some cases to a slight degree
 Inexpensive
Sucrose
 Characteristics:
 Water soluble
 Possesses good binding properties
 Slightly hygroscopic
 Inexpensive
 Produces gritty mouth feel (not free from grittiness)
 Calorigenic and cariogenic
Mannitol
 Characteristics:
 An optical isomer of sorbitol (sugar alcohol)
 Exhibits poor flow properties
 Water soluble
 Requires high lubricant content
 Probably the most expensive sugar used as a tablet diluent
Mannitol
 Widely used in chewable tablets because of its:
 Negative heat of solution
 Slow solubility
 Mild cooling sensation in mouth
 Free from grittiness
 Possesses low caloric value and noncariogenic
Sorbitol
 Characteristics:
 Often combined with mannitol formulations in order to reduce diluent cost
 Highly compressible
 Water soluble
 Has a good mouth feel and a sweet cooling taste
 Free from grittiness
 Has low caloric value and is noncariogenic
Sugar diluents
 Poorly absorbed sugar alcohols such as sorbitol and mannitol can decrease
intestinal transit time
 Absorption may be altered for drugs that are preferentially absorbed from
this region
Adsorbants
 These additives are included in a formulations that are capable of holding
fluids
 Some commonly employed adsorbents:
 Fumed silica
 MCC
 MgCO3
 Bentonite and kaolin
Granulation fluids
 Moistening or granulating fluids:
 Water
 Isopropanol
 Ethanol
Binders
 Adhesives
 Used to bind powder particles together in wet granulation
 Binds granules together during compression
 Added to ensure that granules and tablets can be formed with the
required mechanical strength
Binders
 Can be used in dry form which will be mixed with ingredients before wet
or dry granulation
 Or can be used as a solution which is used in wet granulation
 Examples:
 Gelatin, ployvinyl pyrrolidone (PVP), cellulose derivatives such as
methylcellulsoe, CMC and corn starch
Glidants
 Reduce friction between particles
 Added to improve the flow properties of powders and granules
Lubricants
 Also called anti-adherents
 Used to reduce the friction during tablet ejection between the tablet and
the walls of the die cavity
 Prevent the cohesiveness between the powder and the wall of the machine
Lubricants
Disintegrants
 These are added to tablet formulations to facilitate tablet
disintegration upon tablet contact with water followed by breakup of
the tablet
 They appear to function by drawing water into the tablet, swelling
and causing the tablet to burst apart
 Example:
 Cornstarch and potato starch, starch derivatives such as sodium starch
glycollate, cellulose derivatives such as sodium carboxymethylcellulose,
carbone dioxide
Other additives
 Antioxidants
 Flavoring agents
 Preservatives
 Coloring agents:
 Help the manufacturer to control the product during its preparation as well
as serves as a means of identification to the user
Lozenges
 Solid preparations containing one or more drugs, flavored in sweetened
base
 They are intended to dissolve slowly in the mouth to produce:
 Localized effects: often contains an antiseptic agent and a demulcent (a
substance that soothes inflamed mucous membranes)
 Systemic effect (contain vitamins)
Lozenges
 Prepared by molding or compression
 Manufacturing involves the compression of the formulation between flat-
faced punches to allow greater compression
 Do not contain disintegrants
Effervescent tablets
 Are intended to be dissolved in water before ingestion
 Effervescence is the evolution of gas bubbles from a liquid, as the result of
a chemical reaction between NaHCO3 and citric and tartaric acids
Effervescent tablets
 Two methods are used to produce effervescent tablets:
 Wet fusion technique
 Heat fusion technique
 A water soluble lubricant is normally used to prevent an insoluble
‘scum’ forming on the surface of water (change)
 Saccharin is used as a sweetener instead of sucrose because sucrose
is too hygroscopic and adds bulk to the tablets
Chewable tablets
 Advantages compared to liquid dosage forms:
 Better palatability
 Higher stability
 More accurate dosing
 Better portability
 Easier administration
 Better effectiveness
 Better safety
Chewable tablets
 Disintegrate smoothly and rapidly when chewed or allowed to dissolve in
the mouth
 Formulated with mannitol
 Used mainly for pediatric multivitamin tablets, antacids, and anti-
flatulents
 Contain high amount of disintegrant and low amount of binder (low
hardness)
Sublingual tablets
 Intended to be placed under the tongue to produce immediate systemic
effect
 Avoids first-pass metabolism
 Usually small and flat, compressed lightly to keep them soft
 Should dissolve quickly allowing the active ingredient to be absorbed
quickly
 Designed to dissolve in small quantity of saliva
Sublingual tablets
 After the tablet is placed in the mouth below the tongue, the patient
should avoid:
 Eating, drinking, smoking and possibly talking in order to keep the tablet in
place
 Swallowing of saliva should also be avoided since the saliva may contain
dissolved drug
Sublingual tablets
 Bland excipients are used to avoid salivary stimulation
 Due to inconvenience in administration, this dosage form is prepared only
for those drugs for which the only satisfactory non-parenteral method is
this route
 Examples:
 Glyceryl trinitrate (vasodilator)
 Isoprinosine sulfate (bronchodilator)
Buccal tablets
 This type of tablets should be kept for 30-60 minutes in oral cavity
 Care should be taken to ensure that all the ingredients are finely divided
to avoid gritty or irritating sensation
 Designed not to disintegrate
 They are flat elliptical or capsule shaped tablets as it can be easily held
between gum and cheek
Buccal tablets
 This tablet is most often used for hormone replacement therapy
 Antifungal drugs are preferred to be administered by this route. e.g.,
miconazole – under preclinical trial – still not in market
Implants
 Inserted into subcutaneous tissue by surgical procedures
 Slowly absorbed over a period of months or longer (a year)
 A special injector with a hollow needle and plunger is used to
administer the rod shaped tablet. For other shapes, surgical insertion
is required
 Implants can be pellet, cylindrical or rosette (like a rose) -shaped
with a diameter not larger than 8 mm
Implants

Pellets
Implants
Implants
 Sterile formulation without excipients and made hard with large particle
size to achieve gradual drug release
 These tablets are produced by:
 A sterile single punch
 Hand operated machine in which the die cavity is filled with hand since the
material does not normally flow well
Multilayer tablets
 Prepared by compressing the fill material more than once:
 The initial compression of a portion of fill material in a die followed by
additional fill material and compression to form two or more layered tablets
depending upon number of separate fills
 Each layer contains different medicinal agent(s) separated from one another
to minimize physical and chemical incompatibilities
 Example: phenylephedrine HCl and ascorbic acid in a mixture with
paracetamol
Multilayer tablets
Sustained release tablets
 They provide immediate release of a portion of the drug that promptly
produces the desired therapeutic effect, followed by gradual release of
additional amounts of drug to maintain its therapeutic effect over a
predetermined period
Sustained release tablets
Sustained release tablets
 Advantages of SR tablets:
 Improve patient compliance, since usually only one tablet has to be taken
daily
 Maintain therapeutic activity during the night
 Time saving for nurses who use SR tablets in hospital is achieved
 Provide further advantage with psychiatric patients who forget to take their
medications
 Cost saving due to better disease management
 SR are the right choice for faithful patients or Muslims who must take their
medication during the month of Ramadan
Sustained release tablets
 Disadvantages of SR tablets:
 Only drugs that have the appropriate physicochemical characteristics are
candidates for sustained release formulations
 Possible toxicity due to overdose, if SR are improperly formulated (dose
dumping)
 Difficulty swallowing due to the large size
SR tablets
 Methods of achieving sustained-release:
 Diffusion-controlled
 Dissolution-controlled
 Ion exchange
 Osmotic pressure
Diffusion-controlled
 Diffusion is a driving force where the movement of drug molecules
occurs from high concentration in the tablet to lower concentration
in gastro intestinal fluids
 Diffusion depends on:
 Surface area exposed to gastric fluid
 Diffusion pathway
 Drug concentration gradient
 Diffusion coefficient of the system
 Divided into:
 Matrix (or monolithic) systems
 Reservoir systems
Matrix technology
 Matrix tablets
 Drug is dispersed as solid particles within a porous matrix:
 The GI fluids penetrate the matrix
 Drug diffuses out of the matrix and is absorbed
 The initial dose is normally placed in the tablet coat
 Release is described using Higuchi-type equation
Matrix

A sustained-release matrix tablet Rate-controlling step: diffusion

prepared using a hydrophilic polymer of dissolved drug in matrix
Reservoir devices
 Drug release from reservoir device is governed by Fick’s law of diffusion
 Common methods used to develop these systems include:
 Microencapsulation of drug particles and press coating of tablets containing
drug cores
Dissolution-controlled systems
 Dissolution of the drug is the rate limiting step
 Methods of achieving prolonged drug dissolution:
 Drugs with poor dissolution rates are inherently prolonged
 Prolongation of dissolution of water-soluble drugs can be achieved by:
 Removing the disintegrant

 Incorporation of the drug with a water-insoluble carrier

 Encapsulating the drug with a slowly soluble coating materials of varying thickness
Ion exchange
 Ion exchangers are water insoluble resins containing salt forming
anionic or cationic groups
 Procedure:
 Drug solution is mixed with resin and dried to form beads which are tableted
 Drug release depends upon high concentration of charged ions in GIT where
the drug molecules are exchanged and diffuse out of the resin into the
surrounding fluid
Osmotic-controlled
 More suitable for hydrophilic drugs
 Drug may be osmotically active, or combined with an osmotically active
salt (e.g., NaCl)
Osmotic-controlled
 Principle:
 The tablet is coated with a semipermeable membrane (e.g., cellulose acetate)
with a hole on one end of tablet made by a laser beam
 Gastric fluid penetrates through the membrane, solubilizes the drug and
increase the internal pressure which pumps the drug solution out of the
aperture and releases the drug in gastric environment
Osmotic-controlled

Pattern of drug release from osmotic

tablet
Osmotic-controlled
 OROS (Osmotic-controlled Release Oral delivery System)
 Absorption is less affected by factors such as pH, food intake, GI motility,
and differing intestinal environments
Osmotic-controlled
Osmotic-controlled
Osmotic-controlled
 List of OROS medications
 Acutrim (phenylpropanolamine)  Exalgo/Jurnista (hydromorphone)
 Adalat OROS (nifedipine)  Glucotrol XL (glipizide)
 Alpress LP (prazosin)  Invega (paliperidone)
 Cardura XL (doxazosin)  Minipress XL (prazosin)
 Concerta (methylphenidate)  Procardia XL (nifedipine)
 Covera HS (verapamil)  Sudafed 24 (pseudoephedrine)
 Ditropan XL/Lyrinel XL (oxybutynin)  Tegretol XR (carbamazepine)
 Dynacirc CR (isradipine)  Volmax (salbutamol)
Formulation factors affecting release
 Formulation factors affecting the release of a drug from tablets:
 The effective surface area: controlled by particle size
Formulation factors
 The effective surface area
Formulation factors
Formulation factors
 Effect of binding agents (type and quantity):
 As binding capacity of the binder increases, disintegration time of tablet
increases
 The concentration of the binder can also affect the disintegration time of
tablet
Formulation factors
Formulation factors
 Effect of lubricants
Formulation factors
 Effect of surfactants
 Sodium lauryl sulfate increases water penetration in tablets
 Surfactants are recommended to decrease the hydrophobicity of drugs
because the more hydrophobic the tablet is the greater the disintegration
time
 The disintegration time of granules of water-soluble drugs did not seem to be
greatly improved by the addition of nonionic surfactant during granulation
 But the desired effect of a surfactant appeared when granules were made of
slightly soluble drugs
Formulation factors
 Effect of diluents
 Effect of granule size
 In general, granule size is not a critical factor
Tablet testing
 Uniformity of weight
 Also important for divisible tablets
 Content uniformity of active ingredient
 Disintegration time
 Conventional tablets (IR) within 30 min
 Coated tablets within 2 hr
 Sublingual tablets within 3 min
 Dissolution
Dissolution tester
Tablet testing
 Mechanical strength:
 Assess the effect of formulation and production variables on the resistance of
a tablet to fracturing and attrition during formulation work, process design,
and scaling up
 Control the quality of tablet during production (in process and batch control)
 Characterize the fundamental mechanical properties of materials used in
tablet formulation
Mechanical strength: methods
 Attrition resistance (friability test):
 Tablets are subjected to a tumbling motion during coating, packaging, and
transport
 These stresses are not severe enough to break the tablet, but may abrade
small particles from tablet surface
 The test:
 Tablets are subjected to uniform tumbling motion for specified time and
weight loss is measured
 “Roche” Friabilator is most frequently used for this purpose
Friability testing

Roche Friabilator
Mechanical strength: methods
 Fracture resistance (hardness):
 The test measures crushing strength property defined as compression force
isapplied to the tablet diametrically until fracturing it
 Conducted using hardness tester