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Tablets. Assoc. Prof. Dr. Jomjai Peerapattana Faculty of Pharmaceutical Sciences Khon Kaen University. Scope. Introduction Advantages and disadvantages of compressed tablets Types of tablets Tablet compression machine Tableting methods Direct compression. Introduction.

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tablets

Tablets

Assoc. Prof. Dr. Jomjai Peerapattana

Faculty of Pharmaceutical Sciences

Khon Kaen University

scope
Scope
  • Introduction
  • Advantages and disadvantages of compressed tablets
  • Types of tablets
  • Tablet compression machine
  • Tableting methods
    • Direct compression
introduction
Introduction
  • 1843 a patent was granted to Thomas Brockedon (Englishman) for manufacturing pills and lozenges
  • 1874 both rotary and eccentric presses
  • 1885 glyceryl trinitrate tablets was in the BP
  • No other tablet monograph appeared until 1945
  • 1980 nearly 300 monographs for tablets
advantages
Advantages
  • Production aspect
    • Large scale production at lowest cost
    • Easiest and cheapest to package and ship
    • High stability
  • User aspect (doctor, pharmacist, patient)
    • Easy to handling
    • Lightest and most compact
    • Greatest dose precision & least content variability
    • Coating can mark unpleasant tastes & improve pt. acceptability
disadvantages
Disadvantages
  • Some drugs resist compression into dense compacts
  • Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability
  • Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating
ingredients used in tablet formulations
Ingredients used in tablet formulations
  • Drugs
  • Fillers, diluent, bulking agent
    • To make a reasonably sized tablet
  • Binders
    • To bind powders together in the wet granulation process
    • To bind granule together during compression
  • Disintegrants
    • To promote breakup of the tablets
    • To promote rapid release of the drug
slide8
Lubricants

To reduce the friction during tablet ejection between the walls of the tablet and the walls of the die cavity

Glidants

Reducing friction between the particles

To improve the flow properties of the granulations

Antiadherants

To prevent adherence of the granules to the punch faces and dies

slide9
Dissolution (enhancers and retardants)
  • Wetting agents
  • Antioxidants
  • Preservatives
  • Coloring agents
  • Flavoring agents
essential properties of tablets
Essential properties of tablets
  • Accurate dosage of medicament, uniform in weight, appearance and diameter
  • Have the strength to withstand the rigors of mechanical shocks encountered in its production, packaging, shipping and dispensing
  • Release the medicinal agents in the body in a predictable and reproducible manner
  • Elegant product, acceptable size and shape
  • Chemical and physical stabilities
types of tablets
Types of tablets
  • Route of administration
    • Oral tablets
    • Sublingual or buccal tablets
    • Vaginal tablets
  • Production process
    • Compressed tablets
    • Multiple compressed tablets
      • Tablet within a tablets: core and shell
      • Multilayer tablet
slide12
Sugar coated tablets
    • Protect tablets from moisture
    • Mask odor and flavor
    • Elegance
  • Film coated tablets
    • Thin film coat
    • Soluble or insoluble polymer film
slide13
Chewable tablets
    • Rapid disintegrate
    • Antacid, flatulance: rapid action
    • Children drug
  • Effervescent tablets
    • Dissolve in the water before drink
tablet production
Tablet production
  • Powders intended for compression into tablets must possess two essential properties
    • Powder fluidity
      • The material can be transported through the hopper into the die
      • To produce tablets of a consistent weight
      • Powder flow can be improved mechanically by the use of vibrators, incorporate the glidant
slide15
Powder compressibility
    • The property of forming a stable, intact compact mass when pressure is applied
tableting procedure
Tableting procedure
  • Filling
  • Compression
  • Ejection
tablet compression machines
Tablet compression machines
  • Hopper for holding and feeding granulation to be compressed
  • Dies that define the size and shape of the tablet
  • Punches for compressing the granulation within the dies
  • Cam tracks for guiding the movement of the punches
  • Feeding mechanisms for moving granulation from the hopper into the dies
single punch machine
Single punch machine
  • The compression is applied by the upper punch
  • Stamping press
slide19

Single Punch Machine (Tablets)

Upper andLower Collar

Collar locker

multi station rotary presses
Multi-station rotary presses
  • The head of the tablet machine that holds the upper punches, dies and lower punches in place rotates
  • As the head rotates, the punches are guided up and down by fixed cam tracks, which control the sequence of filling, compression and ejection.
  • The portions of the head that hold the upper and lower punches are called the upper an lower turrets
slide23
The portion holding the dies is called the die table
  • The pull down cam (C) guides the lower punches to the bottom, allowing the dies to overfill
  • The punches then pass over a weight-control cam (E), which reduces the fill in the dies to the desired amount
slide24
A swipe off blade (D) at the end of the feed frame removes the excess granulation and directs it around the turret and back into the front of the feed frame
  • The lower punches travel over the lower compression roll (F) while simultaneously the upper punches ride beneath the upper compression roll (G)
slide25
The upper punches enter a fixed distance into the dies, while the lower punches are raised to squeeze and compact the granulation within the dies
  • After the moment of compression, the upper punches are withdrawn as they follow the upper punch raising cam (H)
  • The lower punches ride up the cam (I) which brings the tablets flush with or slightly above the surface of the dies
slide26
The tablets strike a sweep off blade affixed to the front of the feed frame (A) and slide down a chute into a receptacle
  • At the same time, the lower punches re-enter the pull down cam (C) and the cycle is repeated
slide29
Although tablet compressing machinery has undergone numerous mechanical modifications over the years, the compaction of materials between a pair of moving punches within a stationary die has remained unchanged
  • The principle modification from earlier equipment has been an increase in production rate which is regulated by
    • Number of tooling sets
    • Number of compression stations
    • Rotational speed of the press
slide30
Special adaptations of tablet machines allow for the compression of layered tablets and coated tablets
  • A device that chills the compression components to allow for the compression of low-melting point substances such as waxes i.e. suppositories
tableting methods
Tableting methods
  • Dry methods
    • Direct compression
    • Dry granulation
  • Wet methods
    • Wet granulation
direct compression
Direct compression
  • Tablets are compressed directly from powder blends of the active ingredient and suitable excipients
  • No pretreatment of the powder blends by wet or dry granulation procedures is necessary
slide33
Advantages
    • Economy
      • Machine: fewer manufacturing steps and pieces of equipment
      • Labor: reduce labor costs
      • Less process vallidation
      • Lower consumption of power
slide34
Elimination of granulation process
    • Heat (wet granulation)
    • Moisture (wet granulation)
    • High pressure (dry granulation)

Processing without the need for moisture and heat which is inherent in most wet granulation procedures

slide35
Avoidance of high compaction pressures involves in producing tablets by slugging or roll compaction
  • Elimination of variabilities in wet granulation processing
    • Binders (temp, viscous, age)
      • Viscosity of the granulating solution (depend on its temp),
      • How long it has been prepared,
slide36
Rate of binder addition and kneading can affect the properties of the granules formed
  • The granulating solution, the type and length of mixing and the method and rate of wet and dry screening can change the density and particle size of the granules, which can have a major effect on fill weight and compaction qualities
slide37
Type and rate of drying
    • can lead not only to critical changes in equilibrium MC but also to unblending as soluble active ingredients migrate to the surfaces of the drying granules

More unit processes are incorporated in production, the chances of batch-to-batch variation are compounded

slide38
Prime particle dissociation
    • Each primary drug particle is liberated from the tablet mass and is available for dissolution
    • Disintegrate rapidly to the primary particle state
slide39
Uniformity of particle size
  • Greater stability of tablet on aging
    • Color
    • Dissolution rate

Fewer chemical stability problems would be encountered as compared to those made by the wet granulation process

slide40
Concerns
    • Excipient available from only one supplier and often cost more than filler used in granulation
    • Procedure conservation
    • Machine investments
    • Lack of material knowledge
slide41
Physical limitation of drug
    • No compressibility
    • No flowability
  • Physical characteristics of materials (both drug and excipient)
    • Size and size distribution
    • Moisture
    • Shape and surface
slide42
Flowability
    • Density
  • Lot to lot variability
  • Dusting problem
  • Coloring
direct compression fillers
Direct compression fillers
  • Common materials that have been modified in the chemical manufacturing process to improve fluidity and compressibility
soluble fillers
Soluble fillers
  • Lactose
    • Spray dried lactose
      • Lactose is placed in aqueous solution, removed impurities and spray dried
      • Mixture of large alpha monohydrate crystals and spherical aggregates of smaller crystals
      • Good flowability but less compressibility
      • Poor dilution potential
slide45
Loss compressibility upon initial compaction
  • Problem of browning due to contamination of 5-hydroxyfurfural which was accelerated in the presence of basic amine drugs and catalyzed by tartrate, citrate and acetate ions
slide46
Fast-Flo lactose (early 1970s)
    • Spherical aggregates of microcrystals lactose monohydrate
    • Held together by a higher concentration of glass (amorphous lactose)
    • Much more compressible
    • Highly fluid
    • Non hygroscopic
slide47
Tablets are three to four times harder than regular spray dried
  • Tabletose: aggromerate form of lactose
    • More compressible than spray dried but less compressible than Fast Flo lactose
slide48
Anhydrous lactose: free flowing crystalline lactose
    • Produced by crystallization above 93C which produces the beta form
    • Pass through steam heated rollers
    • Good flow property, contained high amount of fines, its fluidity is less than optimal
    • Can be reworked
slide49
At high RH anhydrous lactose will pick up moisture forming the hydrated compound  increase in the size of tablets if the excipient makes up a large portion of the total tablet weight
  • Excellent dissolution property
slide50
Sucrose
    • Di-Pac: cocrystallization of 97% sucrose and 3% modified dextrin
      • Small sucrose crystals glued together by dextrin
      • Good flow properties and needs a glidant only when atmospheric moisture levels are high (>50%RH)
      • Excellent color stability on aging
slide51
Concentration of moisture is extremely critical in terms of product compressibility
  • compressibility increases rapidly in a moisture range of 0.3-0.4%, plateaus at a level of 0.4-0.5% and rises again rapidly up to 0.8% when the product begins to cake and lose fluidity
slide52
Dilution potential 20-35%
  • Tablets tend to harden slightly during the first hours after compression or when aged at high humidities and then dried (this is typical of most direct compression sucroses or dextroses)
slide53
Nutab: 95.8% sucrose, 4% convert sugar (equimolecular mixture of levulose and dextrose) and 0.1 to 0.2% each of cornstarch and magnesium strarate
    • Large particle size distribution and good fluidity
    • Poor color stability
slide54
Dextrose
    • Emdex: spray crystallized
      • 90-92% dextrose, 3-5% maltose and the remainder higher glucose polysaccharides
      • Available both anhydrous and a hydrate product
      • Excellent compressibility
      • Largest particle size, blending problem may occur
slide55
Sorbitol
    • Exists in a number of polymorphic crystalline forms and amorphous form
    • Widely used in sugar-free mints and as a vehicle in chewable tablets
    • Cool taste and good mouth feel
    • Forms a hard compact
slide56
Hygroscopic and will clump in the feed frame and stick to the surfaces of the die table when tableted at humidities > 50%
  • Lubricant requirements increase when the MC of the sorbitol drops below 0.5% or exceeds 2%
slide57
Mannitol
    • Exists in a number of polymorphic forms
    • Not make as hard a tablet as sorbitol
    • Less sensitive to humidity
    • Widely used where rapid and complete solubility is required
    • Use as a filler in chewable tablets
    • Cool mouth feel but expensive
slide58
Maltodextrin
    • Maltrin
      • Highly compressible
      • Completely soluble
      • Very low hygroscopic
insoluble fillers
Insoluble fillers
  • Starch
    • Starch 1500: intact starch grains and ruptured starch grains that have been partially hydrolyzed and subsequently aggromerated
      • Extremely high MC (12-13%)
      • Does not form hard compacts
      • Dilution potential is minimal
slide60
Not generally used as filler-binder but as filler disintegrant
  • Retains the disintegrant properties of starch without increasing the fluidity and compressibility of the total formulation
  • Deforms elastically when a compression force is applied, it imparts little strength to compacts
  • Lubricants tend to dramatically soften tablets containing high concentrations of Starch 1500
slide61
Spray dried starch
    • Era-Tab: spray-dried rice starch
      • Good fluidity
      • MC 10-13%
      • Compressibility depend on moisture
      • Reworkability
      • Low bulk density
slide62
Celulose
    • Microcrystalline cellulose (Avicel)
      • The most important tablet excipient developed in modern times
      • Derived from a special grade of purified alpha wood cellulose by severe acid hydrolysis to remove the amorphous cellulose portions, yielding particles consisting of bundles of needlelike microcrystals
slide63
PH101 powder
  • PH102 more agglomerated, larger particle size, slightly better fluidity but not significant decrease in compressibility
  • Most compressible
  • Highest dilution potential
slide64
A strong compact is formed due to the extremely large number of clean surfaces brought in contact during the plastic deformation and the strength of the hydrogen bonds formed
  • Extremely low coefficient of friction, no lubricant requirement
  • When >20% of drugs or other excipients are added, lubrication is necessary
slide65
Not used as the only filler because of its cost and density
  • Usually used in the conc of 10-25% as a filler-binder-disintegrant, rapid passage of water into the compact and the instantaneous rupture of hydrogen bonds
slide66
Fluidity is poor because of its relatively small particle size, small amount of glidant are recommended in the formulations containing high conc of MCC
  • Tablets are soften on exposure to high humidities
  • This softening is reversible when tablets are removed from the humid environment
  • >80% MCC may slow the dissolution rates of AI having low water solubility
slide67
Small particles get physically trapped between the deformed MCC particles, which delays wetting and dissolution
  • This phenomenon can be overcome by adding portions of water soluble excipient
slide68
Inorganic calcium salts
    • Dicalcium phosphate (Emcompress or DiTab)
      • Free flowing aggregates of small microcrystals that shatter upon compaction
      • Inexpensive and possesses a high degree of physical and chemical stability
      • Nonhygroscopic at a RH of up to 80%
      • Good fluidity
slide69
Slightly alkaline with a pH of 7.0 to 7.3
    • Precludes its use with AI that are sensitive to even minimal amounts of alkalinity
  • Tricalcium phosphate (TriTab) is less compressible and less soluble, higher ratio of calcium ions
references
References
  • ยาเม็ด (ม.มหิดล)
  • Pharmaceutics. The science of dosage forms design. (M.E. Aulton)
  • The theory and practice of industrial pharmacy.
  • Pharmaceutical dosage forms : Tablets. Volume 2.
  • Pharmaceutical dosage forms and drug delivery systems.