Tablets Nsu.ppt

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Tablet Dosage

Forms

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Т

ABLETS

_ABLETS

 A tablet is a solid dosage form that is prepared by compressing or A tablet is a solid dosage form that is prepared by compressing or

molding of the drug into various sizes and shapes (round, oval or

square).

 Prepared with the aid of excipients.Prepared with the aid of excipients.

 Vary in size, shape, weight, hardness, thickness, disintegration and Vary in size, shape, weight, hardness, thickness, disintegration and

dissolution behavior.

 Most tablets are for oral administration but there are tablets for Most tablets are for oral administration but there are tablets for

other uses – sublingual, vaginal, buccal etc.

 Shape and dimension determined by the shape of punches and dies.Shape and dimension determined by the shape of punches and dies.

 Dissolution is the rate-limiting step in the delivery of drug from a Dissolution is the rate-limiting step in the delivery of drug from a

tablet to the systemic

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ADVANTAGES

 Production aspect:Production aspect:

 Large scale production at lowest costLarge scale production at lowest cost

 Easiest and cheapest to package and shipEasiest and cheapest to package and ship

 High stabilityHigh stability

 User aspect (doctor, pharmacist, patient):User aspect (doctor, pharmacist, patient):

 Easy to handlingEasy to handling

 Lightest and most compactLightest and most compact

 Greatest dose precision & least content variabilityGreatest dose precision & least content variability

 Sustained release product is possible by various techniques.Sustained release product is possible by various techniques.

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DISADVANTAGES

 Difficult to swallow in case of children and unconscious patients.Difficult to swallow in case of children and unconscious patients.  Some drugs resist compression into dense compacts.Some drugs resist compression into dense compacts.

 Drugs with poor wetting, slow dissolution, intermediate to large Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and

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 Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment

to oxygen or moisture may require encapsulation or entrapment

prior to compression or the tablets may require coating.

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ESSENTIAL PROPERTIES OF

TABLETS

 Accurate dosage of medicament, uniform in weight, appearance and diameter.Accurate dosage of medicament, uniform in weight, appearance and diameter.

 Elegant product identity which are free of defects like cracks, discoloration, and Elegant product identity which are free of defects like cracks, discoloration, and

contamination. contamination.

 Have the strength to withstand the rigors of mechanical shock encountered during Have the strength to withstand the rigors of mechanical shock encountered during

production, packaging, shipping and dispensing. production, packaging, shipping and dispensing.

 Release the medicinal agents in the body in a predictable and reproducible Release the medicinal agents in the body in a predictable and reproducible

manner. manner.

 Acceptable size and shapeAcceptable size and shape

 PPhysical stabilityhysical stability to maintain its physical attributes over time. to maintain its physical attributes over time.

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DISSOLUTION OF

DRUG FROM

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TYPES OF TABLETS



Route of administration:

 Oral tabletsOral tablets

 Sublingual or buccal tablets, e.g. Sublingual or buccal tablets, e.g. Vitamin C tablet Vitamin C tablet

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TYPES OF TABLETS

 Production process:Production process:

 Compressed tablets, Compressed tablets, e.g. Paracetamol tablet e.g. Paracetamol tablet

 Formed by compression and contain no special coating.Formed by compression and contain no special coating.

 Made from powdered, crystalline or granular materials ,alone or in Made from powdered, crystalline or granular materials ,alone or in

combination with binders , disintegrant , lubricants, diluents and

many cases, colorants.

 Multiple compressed tablets e.g. albuterol (calcium channel blocker)Multiple compressed tablets e.g. albuterol (calcium channel blocker)

 Tablets within a tablet: core and shellTablets within a tablet: core and shell

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TYPES OF TABLETS

 Sugar coated tablets, Sugar coated tablets, e.g. Multivitamin tablet e.g. Multivitamin tablet



Protect tablets from moisture



Mask odor and flavor



Elegance

 Film coated tablets, Film coated tablets, e.g. Metronidazole tablet e.g. Metronidazole tablet



Thin film coat

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TYPES OF TABLETS

 Enteric coated tablets, Enteric coated tablets, e.g. Naproxen tablet e.g. Naproxen tablet

 Thin layer or film Thin layer or film

 Water soluble materialWater soluble material

 Resist solution in gastric fluid but disintegrate in the intestine.Resist solution in gastric fluid but disintegrate in the intestine.

 Used for tablets containing drug substances which are inactivated Used for tablets containing drug substances which are inactivated

or destroyed in the stomach, for those which irritate the mucosa or

as a means of delayed release of the medication.

 Extended release tablets , e,g. Glipizide tabletExtended release tablets , e,g. Glipizide tablet

 Formulated to release the drug slowly over a prolonged period of Formulated to release the drug slowly over a prolonged period of

time

 Expressions such as Prolonged action, Repeat action, Sustained Expressions such as Prolonged action, Repeat action, Sustained

release .

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TYPES OF TABLETS

 Chewable tablets, Chewable tablets, e.g. Antacid tablet e.g. Antacid tablet



Rapid disintegration



Antacid, antiflatulent: rapid action



Children drugs

 Effervescent tablets, e.g. Dispirin tablet (Aspirin) Effervescent tablets, e.g. Dispirin tablet (Aspirin)



Contain mixtures of acids and sodium bicarbonate, which

release carbon dioxide when dissolved in water



Dissolve in the water before drinking.

 Hypodermic tablets , e.g. MorphineHypodermic tablets , e.g. Morphine



intended for use in making preparations for hypodermic

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INGREDIENTS USED IN TABLET

FORMULATIONS



Drugs/ API



Fillers, diluent, bulking agent

 To make a reasonably sized tabletTo make a reasonably sized tablet



Binders

 To bind powders together in the wet granulation To bind powders together in the wet granulation process.

process.

 To bind granule together during compression.To bind granule together during compression.



Disintegrants

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COMMON EXCIPIENTS



Lubricants

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

walls of the tablet and the walls of the die cavity.



Glidants

 To reduce friction between the particlesTo reduce friction between the particles

 To improve the flow properties of the granulations or To improve the flow properties of the granulations or powder.

powder.



Antiadherants

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

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COMMON EXCIPIENTS



Agents for Dissolution (enhancers and retardants)



Wetting agents



Antioxidants



Preservatives



Coloring agents

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DESIRED ATTRIBUTES OF

EXCIPIENTS

 Physiological inertness Physiological inertness

 Physical and chemical stability Physical and chemical stability  Compendial conformity Compendial conformity

 Commercial availability Commercial availability  Cost effectiveness Cost effectiveness

But there is always a compromise

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ATTRIBUTES AFFECTING

EXCIPIENT SELECTION



Solubility



pKa



Compatibility



Dose



Excipient Characteristics



Moisture Content and Uptake



Compressibility

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EXCIPIENT SELECTION

Depends on:



The Type of Tablets



Manufacturing Method

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REQUIREMENTS FOR

TABLETING



Fluidity



Compactibility



Lubricity



Excipients and the method of manufacture are chosen

to provide these characteristics.

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DILUENTS



Diluents are fillers used to make required bulk of the

tablet when the drug dosage itself is inadequate to

produce the bulk.



Secondary reason is to provide better tablet properties

such as improved cohesion, to permit use of direct

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DILUENTS

 Diluents should have following properties: Diluents should have following properties:

 They must be non toxic They must be non toxic

 They must be commercially available in acceptable grade They must be commercially available in acceptable grade  Their cost must be low Their cost must be low

 They must be physiologically inert They must be physiologically inert

 They must be physically & chemically stable by themselves & They must be physically & chemically stable by themselves &

with the drugs.

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TYPES OF DILUENTS

Soluble

 LactoseLactose

 SucroseSucrose

 DextroseDextrose

 MannitolMannitol

 SorbitolSorbitol

Insoluble

 Microcrystalline Microcrystalline Cellulose

Cellulose

 Calcium Sulfate, Calcium Sulfate, dihydrate

dihydrate

 Calcium Phosphate, Calcium Phosphate, dibasic

dibasic

 Calcium Phosphate, Calcium Phosphate, Tribasic

Tribasic

 Calcium CarbonateCalcium Carbonate  StarchStarch

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COMMONLY USED TABLET

DILUENTS



Lactose (anhydrous and spray dried lactose )



Directly compressed starch



Hydrolyzed starch



Microcrystalline cellulose



Dibasic calcium phosphate dihydrate



Calcium sulphate dihydrate



Mannitol



Sorbitol



Sucrose

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BINDERS AND ADHESIVES



These materials are added either dry or in wet form to

form granules or to form cohesive compacts for direct

compression of tablets.



A binder should have following properties:

 High water dispersibility and solubilityHigh water dispersibility and solubility  Low viscosity Low viscosity

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TYPES OF BINDERS

 Natural PolymersNatural Polymers

 StarchStarch

 Pregelatinized starchPregelatinized starch  GelatinGelatin

 AcaciaAcacia

 TragacanthTragacanth  AlginicacidAlginicacid

 Sodium AlginateSodium Alginate

 SugarsSugars

 GlucoseGlucose  SucroseSucrose  SorbitolSorbitol

 Synthetic PolymersSynthetic Polymers

 PVPPVP

 Methyl CelluloseMethyl Cellulose  HPMCHPMC

 Sodium CMCSodium CMC  Ethyl CelluloseEthyl Cellulose

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COMMONLY USED BINDERS

 Examples: Examples:

- Acacia, tragacanth- Solution of 10-25% Conc. Acacia, tragacanth- Solution of 10-25% Conc.

- Cellulose derivatives- Methyl cellulose, HPC, HPMCCellulose derivatives- Methyl cellulose, HPC, HPMC - Gelatin- 10-20% solution Gelatin- 10-20% solution

- Glucose- 50% solution Glucose- 50% solution

- Polyvinylpyrrolidone (PVP)- 2% conc.Polyvinylpyrrolidone (PVP)- 2% conc.

-- Starch paste-10-20% solutionStarch paste-10-20% solution

-- Sodium alginateSodium alginate

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DISINTEGRANTS



Added to a tablet formulation to facilitate its breaking

or disintegration when it has contact with water in the

GIT.



Promote moisture penetration which results in

dispersion and aids in exposing primary drug particles.



Disintegrants are hygroscopic

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DISINTEGRANTS



Example:

•

Starch- 5-20% of tablet weight.

•

Starch derivative – Primogel and Explotab (1-8%)

•

Clays- Veegum HV, bentonite 10% level in colored

tablet only Cellulose

•

Cellulose derivatives- Ac- Di-Sol (sodium carboxy

methyl cellulose)

•

Alginate

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SUPERDISINTEGRANTS

 Swells up to ten fold within 30 seconds when contact water. Swells up to ten fold within 30 seconds when contact water.  Example:Example:

 Crosscarmellose- cross-linked cellulose, Crosscarmellose- cross-linked cellulose,

 Crosspovidone- cross-linked povidone (polymer), Crosspovidone- cross-linked povidone (polymer),  Sodium starch glycolate- cross-linked starch. Sodium starch glycolate- cross-linked starch.

 These cross-linked products swell upto 10 fold with in 30 These cross-linked products swell upto 10 fold with in 30 seconds when in contact with water.

seconds when in contact with water.

 A portion of disintegrant is added before granulation and a A portion of disintegrant is added before granulation and a portion before compression, which serve as glidant or lubricant.

portion before compression, which serve as glidant or lubricant.

 Evaluation of carbon dioxide in effervescent tablets is also one Evaluation of carbon dioxide in effervescent tablets is also one way of disintegration

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LUBRICANT

 Lubricants are intended to prevent adhesion of the tablet materials Lubricants are intended to prevent adhesion of the tablet materials

to the surface of dies and punches

to the surface of dies and punches during compression and ejection.during compression and ejection.



 Reduce friction by forming a film of low shear strength between the Reduce friction by forming a film of low shear strength between the

tablet mass and the confining die wall.

 Sometimes lubricants are combined, e.g., magnesium stearate and Sometimes lubricants are combined, e.g., magnesium stearate and

silica to achieve optimum effect.



 Because lubricants are hydrophobic, if used tooBecause lubricants are hydrophobic, if used too

 much, they can interfere with bonding, soften tablets, and decrease much, they can interfere with bonding, soften tablets, and decrease

hardness.

 Hence, lubricants are often added in the last step of manufacturing Hence, lubricants are often added in the last step of manufacturing

process.

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LUBRICANT



Example:

 Stearic acid, Stearic acid,

 Stearic acid salt - Magnesium stearate, Stearic acid salt - Magnesium stearate, Calcium StearateCalcium Stearate  Talc, Talc,

 PEG (Polyethylene glycols), PEG (Polyethylene glycols),  Surfactants Surfactants

 Glyceryl Behenate ,Glyceryl Behenate ,  Mineral OilMineral Oil

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GLIDANTS

 Glidants are intended to promote flow of granules or powder Glidants are intended to promote flow of granules or powder material by reducing the friction between the particles.

material by reducing the friction between the particles.

 It is used to improve the flow of granules/powder from the hopper It is used to improve the flow of granules/powder from the hopper to the die cavity to ensure uniform fill for each tablet.

to the die cavity to ensure uniform fill for each tablet.

 Glidants enhance the flow property of direct compression Glidants enhance the flow property of direct compression mixtures.

mixtures.

 Best used at optimum concentration such that the amount is just Best used at optimum concentration such that the amount is just enough to coat bulk powder particles.

enough to coat bulk powder particles.

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GLIDANTS



Example

 Corn Starch – 5-10% conc., Corn Starch – 5-10% conc.,

 Talc-5% conc., Talc-5% conc.,

 Silica derivative - Silica derivative - Calcium Silicate, Magnesium SilicateCalcium Silicate, Magnesium Silicate

 Silicon DioxideSilicon Dioxide

 Colloidal silicas such as Cab-O-Sil, Syloid, Aerosil in 0.25-Colloidal silicas such as Cab-O-Sil, Syloid, Aerosil in 0.25-3% conc.

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ANTIADHERANTS

 Antiadherents or anti-sticking agents prevent adhesion of Antiadherents or anti-sticking agents prevent adhesion of

the tablet surface to the die walls and the punches the tablet surface to the die walls and the punches

 Protect tablets from the picking or sticking .Protect tablets from the picking or sticking .

 Example:Example:

 TalcTalc

 CornstarchCornstarch  Collidal silicaCollidal silica  DL-LeucineDL-Leucine

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COLORING AGENT

 The use of colors and dyes in a tablet has three purposes: The use of colors and dyes in a tablet has three purposes:

 Masking of off color drugs Masking of off color drugs

 Product Identification Product Identification

 Production of more elegant product Production of more elegant product

 All coloring agents must be approved and certified by FDA. Two forms of All coloring agents must be approved and certified by FDA. Two forms of

colors are used in tablet preparation – FD &C and D & C dyes. These dyes are colors are used in tablet preparation – FD &C and D & C dyes. These dyes are applied as solution in the granulating agent or Lake form of these dyes. Lakes applied as solution in the granulating agent or Lake form of these dyes. Lakes are dyes absorbed on hydrous oxide and employed as dry powder coloring.

are dyes absorbed on hydrous oxide and employed as dry powder coloring.

 Example: Example:

FD & C yellow 6-sunset yellow FD & C yellow 6-sunset yellow FD & C yellow 5- Tartrazine FD & C yellow 5- Tartrazine FD & C blue 2 - Indigo carmine FD & C blue 2 - Indigo carmine D & C red 3- Erythrosine.

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FLAVORING AND SWEETENING

AGENTS

Flavoring agents: For chewable tablet

Sweetening agents: For chewable tablets

Examples:

• Sugar, Sugar, • mannitol.mannitol.

 Saccharine (artificial): 500 time’s sweeter than sucrose Saccharine (artificial): 500 time’s sweeter than sucrose

Disadvantage:

Disadvantage: Bitter aftertaste and carcinogenic Bitter aftertaste and carcinogenic  Aspartame (artificial) Aspartame (artificial)

Disadvantage: