Tablets

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Scope Introduction
Advantages and disadvantages of compressed tablets Types of tablets Tablet compression machine Tableting methods

Introduction
1843 a patent was granted to Thomas Brockedon (Englishman) for manufacturing pills and lozenges 1874 both rotary and eccentric presses 1885 glyceryl trinitrate

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

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

Absorpti on of drug form

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

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

Dissolution (enhancers and retardants) Wetting agents Antioxidants Preservatives Coloring agents Flavoring agents

Essential properties ofdosage of tablets Accurate

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

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

Sugar coated tablets Protect tablets from moisture Mask odor and flavor Elegance Film coated tablets Thin film coat Soluble or insoluble

Chewable tablets Rapid disintegrate Antacid, flatulance: rapid action Children drug Effervescent tablets Dissolve in the water before drink

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

Powder compressibility


The property of forming a stable, intact compact mass when pressure is applied

Tableting procedure
Filling Compression Ejection

Tablet Presses
Single Punch Rotary Press High Speed Rotary Press MultiMulti-layer Rotary Press

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

Single punch machine

The compression is applied by the upper punch Stamping press

Single Punch Machine (Tablets)

Upper and Lower Collar Collar locker

MultiMulti-station rotary presses that The head of the tablet machine

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 and lower turrets

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 weightweight-control cam (E), which reduces the fill in the dies to

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)

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

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 recam (C) and the cycle is repeated

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

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 lowsubstances such as waxes i.e. suppositories

Tableting methods
Dry methods
Direct compression Dry granulation

Wet methods
Wet granulation

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

Advantages
Economy
Machine: fewer manufacturing steps and pieces of equipment Labor: reduce labor costs Less process vallidation Lower consumption of power


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


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

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


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 batch-to-

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

Uniformity of particle size Greater stability of tablet on aging

Color Dissolution rate Fewer chemical stability problems would be encountered as


Concerns
Excipient available from only one supplier and often cost more than filler used in granulation Procedure conservation Machine investments Lack of material

Physical limitation of drug

No compressibility No flowability


Physical characteristics of materials (both drug and excipient)

Size and size distribution Moisture Shape and surface


Flowability Density


Lot to lot variability Dusting problem Coloring

Direct compression fillers

Common materials that have been modified in the chemical manufacturing process to improve fluidity and compressibility

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

Loss compressibility upon initial compaction Problem of browning due to contamination of 5hydroxyfurfural which was accelerated in the presence of basic amine drugs and catalyzed by tartrate, citrate and acetate


Fast-Flo lactose (early 1970s) Fast1970s) Spherical aggregates of microcrystals lactose monohydrate Held together by a higher concentration of glass (amorphous lactose) Much more compressible Highly fluid

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


Anhydrous lactose: free flowing crystalline lactose Produced by crystallization above 93C which produces 93C the beta form Pass through steam heated rollers Good flow property, contained high amount of fines, its fluidity is less than

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

Sucrose
Di-Pac: cocrystallization of Di97% 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) (>50%RH)

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%


Dilution potential 20-35% 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)


Nutab: 95.8% sucrose, 4% 95. 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

Dextrose
Emdex: spray crystallized 90-92% dextrose, 3-5% 90-92% maltose and the remainder higher glucose polysaccharides Available both anhydrous and a hydrate product Excellent compressibility Largest particle size, blending problem may

Sorbitol
Exists in a number of polymorphic crystalline forms and amorphous form Widely used in sugar-free sugarmints and as a vehicle in chewable tablets Cool taste and good mouth feel Forms a hard compact

Hygroscopic and will clump in the feed frame and stick to the surfaces of the die table when tableted at humidities > 50% 50% Lubricant requirements increase when the MC of the sorbitol drops below 0.5% or exceeds 2%

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

Maltodextrin
Maltrin Highly compressible Completely soluble Very low hygroscopic

Starch

Insoluble fillers

Starch 1500: intact starch 1500: grains and ruptured starch grains that have been partially hydrolyzed and subsequently aggromerated Extremely high MC (12-13%) (12-13%) Does not form hard compacts

Not generally used as fillerfillerbinder 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


Spray dried starch Era-Tab: spray-dried rice Eraspraystarch

Good fluidity  MC 10-13% 10-13%  Compressibility depend on moisture  Reworkability  Low bulk density


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

PH101 PH101 powder PH102 more agglomerated, PH102 larger particle size, slightly better fluidity but not significant decrease in compressibility Most compressible Highest dilution potential


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 >20%


Not used as the only filler because of its cost and density Usually used in the conc of 10-25% 10-25% as a filler-binderfiller-binderdisintegrant, rapid passage of water into the compact and the instantaneous rupture of hydrogen bonds


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 80%


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


Inorganic calcium salts

Dicalcium phosphate (Emcompress or DiTab) 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

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


References
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.

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