Solid Dosage FormsSolid Dosage Forms

SALMAN BIN ABDULAZIZ UNIVERSITY

COLLEGE OF PHARMACY

Dr. Mohammad Khalid Anwer

e-mail:- mkanwer2002@yahoo.co.in

TabletsTablets

Tablets defined as solid pharmaceutical dosage Tablets defined as solid pharmaceutical dosage

forms containing drug substances with or without forms containing drug substances with or without

suitable diluents and prepared by compression suitable diluents and prepared by compression

(large scale production) or molding methods (small (large scale production) or molding methods (small

scale operations).scale operations).

It is probable that at least 90% of all drugs used to It is probable that at least 90% of all drugs used to produce systemic effects are administered by the produce systemic effects are administered by the oral route.oral route.

Of drugs that are administered orally, solid oral Of drugs that are administered orally, solid oral dosage forms represent the preferred class of dosage forms represent the preferred class of product.product.

Tablets are theTablets are the

most commonlymost commonly

used solid dosageused solid dosage

forms. forms.

Advantages of solid dosage formsAdvantages of solid dosage forms

1)1) Accurate dosage. Accurate dosage.

2)2) Easy shipping and handling.Easy shipping and handling.

3)3) Less shelf space needed per dose than for Less shelf space needed per dose than for liquid.liquid.

4)4) No preservation requirements.No preservation requirements.

5)5) No taste masking problem.No taste masking problem.

6)6) Generally more stable than liquids, with Generally more stable than liquids, with longer expiration dates.longer expiration dates.

Advantages of TabletsAdvantages of Tablets Precision and low content variability of the unit Precision and low content variability of the unit

dose.dose.

Low manufacturing cost.Low manufacturing cost.

The lightest and most compact, thus easy to The lightest and most compact, thus easy to

package and ship.package and ship.

Simple to identify by employing an embossed or Simple to identify by employing an embossed or

monogrammed punch face.monogrammed punch face.

Easy to swallow.Easy to swallow.

Appropriate for special-release forms.Appropriate for special-release forms.

Best suited to large-scale production.Best suited to large-scale production.

Most stable of all oral dosage forms.Most stable of all oral dosage forms.

Essentially tamperproof.Essentially tamperproof.

In comparison to other oral dosage forms, tablets In comparison to other oral dosage forms, tablets provide advantages to:provide advantages to:

o The pharmacistThe pharmacistIn minimal storage space requirementsIn minimal storage space requirements

Ease of dispensingEase of dispensing

o The patientThe patientIn convenience of use, optimum portability, and lowest cost.In convenience of use, optimum portability, and lowest cost.

o The physicianThe physicianIn flexibility of dosage (with biIn flexibility of dosage (with bi sected tablets), and in sected tablets), and in accuracy and precision of dosage in general.accuracy and precision of dosage in general.

Disadvantages of TabletsDisadvantages of Tablets Some drugs resist compression into dense compacts, owing to Some drugs resist compression into dense compacts, owing to

their amorphous nature or flocculent, low-density character.their amorphous nature or flocculent, low-density character.

Some drugs (e.g., those with an objectionable taste or odor, Some drugs (e.g., those with an objectionable taste or odor,

those sensitive to oxygen or atmospheric moisture) require those sensitive to oxygen or atmospheric moisture) require

encapsulation or entrapment before compression. These encapsulation or entrapment before compression. These

drugs are more appropriate in capsule form.drugs are more appropriate in capsule form.

Some drugs with:Some drugs with: Poor wetting.Poor wetting. Slow dissolution properties.Slow dissolution properties. Intermediate to large doses. Intermediate to large doses.

Characteristics of ideal Characteristics of ideal tabletstablets

1)1) It should be an elegant product having It should be an elegant product having

its own identity and Free of defects its own identity and Free of defects

(e.g., chips, cracks, discoloration, (e.g., chips, cracks, discoloration,

contamination).contamination).

2)2) Strong enough to withstand the Strong enough to withstand the

mechanical stresses of production mechanical stresses of production

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

3)3) Chemically and physically stable over time.Chemically and physically stable over time.

4)4) Capable of releasing medicinal agents in a Capable of releasing medicinal agents in a

predictable and reproducible manner. predictable and reproducible manner.

Tablet Types and ClassesTablet Types and Classes

Tablets for oral ingestion

• Compressed tablets.• Multiple compressed

tablets - Layered tablets. - Compression-coated

tablets• Repeat-action tablets.• Delayed-action and

enteric-coated tablets.• Sugar and chocolate-

coated tablets.• Film-coated tablets.• Chewable tablets.

Tablets used in the oral Tablets used in the oral cavitycavity

• Buccal tablets.Buccal tablets.• Sublingual tablets.Sublingual tablets.• Lozenges, Troches and Lozenges, Troches and

dental cones. dental cones.

Tablets used to prepare Tablets used to prepare solutionssolutions• Effervescent tablets.Effervescent tablets.• Dispensing tablets.Dispensing tablets.• Hypodermic tablets.Hypodermic tablets.• Tablet triturates.Tablet triturates.

Tablets are classified according to their route of Tablets are classified according to their route of

administration, drug delivery system, and form and method administration, drug delivery system, and form and method

of manufacture.of manufacture.

Tablets for oral ingestionTablets for oral ingestion Tablets for oral ingestion are designed to Tablets for oral ingestion are designed to

be swallowed intact, with the exception of be swallowed intact, with the exception of

chewable tablets. chewable tablets.

(1) (1) Compressed TabletsCompressed Tablets (CT) (CT)

Compressed tablets are formed by Compressed tablets are formed by

compression and have no special coating.compression and have no special coating.

They are made from powdered, crystalline, They are made from powdered, crystalline,

or granular materials, alone or in or granular materials, alone or in

combination with excipients such as combination with excipients such as

binders, disintegrants, diluents, and binders, disintegrants, diluents, and

colorants.colorants.

After compression, some compressed After compression, some compressed

tablets may be coated with various tablets may be coated with various

materials.materials.

Most compressed tablets are employed for Most compressed tablets are employed for

the oral administration of drugs, but some the oral administration of drugs, but some

may be used for the sublingual, buccal, or may be used for the sublingual, buccal, or

vaginal administration of drugs. vaginal administration of drugs.

Generally each portion of fill is Generally each portion of fill is

colored differently to prepare colored differently to prepare

a multiple-colored as well as a a multiple-colored as well as a

multiple-layered tablet.multiple-layered tablet.

(2) Multiple Compressed Tablets (2) Multiple Compressed Tablets (MCT)(MCT)

Multiple compressed tablets are layered or Multiple compressed tablets are layered or

compression- coated.compression- coated.

(a) Layered tablets(a) Layered tablets are prepared by compressing are prepared by compressing

a tablet granulation over a previously a tablet granulation over a previously

compressed granulation to form a two- or three-compressed granulation to form a two- or three-

layered tablet, depending upon the number of layered tablet, depending upon the number of

separate fills.separate fills.

(b) Compression-coated, or dry-(b) Compression-coated, or dry-

coated, coated, tablets are prepared by feeding previously tablets are prepared by feeding previously

compressed tablets into a special tableting machine compressed tablets into a special tableting machine

to compress an outer shell around the tablets.to compress an outer shell around the tablets.

This process applies a thinner, more uniform coating This process applies a thinner, more uniform coating

than sugar-coating, and it can be used safely with than sugar-coating, and it can be used safely with

drugs that are sensitive to moisture.drugs that are sensitive to moisture.

This process can be used to:This process can be used to:

Separate incompatible materials.Separate incompatible materials.

Produce repeat action or prolonged-action products.Produce repeat action or prolonged-action products.

(3) Repeat-action tablets:(3) Repeat-action tablets:

Repeat-action tablets are Repeat-action tablets are

layered or compression-coated layered or compression-coated

tablets in which the outer layer tablets in which the outer layer

or shell rapidly disintegrates in or shell rapidly disintegrates in

the stomach. The components of the stomach. The components of

the inner layer or inner tablet the inner layer or inner tablet

are insoluble in gastric media, are insoluble in gastric media,

but soluble in intestinal media. but soluble in intestinal media.

Example., Dexchlor tabletsExample., Dexchlor tablets

(4) Delayed-action and Enteric-Coated (4) Delayed-action and Enteric-Coated

Tablets (ECT)Tablets (ECT)

These tablets delay the release of aThese tablets delay the release of a

drug from a dosage form. drug from a dosage form.

This delay is intended to:This delay is intended to:

Prevent destruction of the drug by gastric juices.Prevent destruction of the drug by gastric juices.

To prevent irritation of the stomach lining by the drug.To prevent irritation of the stomach lining by the drug.

To promote absorption, this is better in the intestine than To promote absorption, this is better in the intestine than

in the stomach.in the stomach.

Agents used to coat these tablets include fats, Agents used to coat these tablets include fats,

fatty acids, waxes, shellac, and cellulose acetate fatty acids, waxes, shellac, and cellulose acetate

phthalate.phthalate.

Enteric coated tablets Enteric coated tablets

are tablets with a are tablets with a

coating that resists coating that resists

dissolution or disruption dissolution or disruption

in the stomach but not in in the stomach but not in

the intestines, thereby the intestines, thereby

allowing for tablet allowing for tablet

transit through the transit through the

stomach in favor of stomach in favor of

tablet disintegration and tablet disintegration and

drug dissolution and drug dissolution and

absorption from the absorption from the

intestines.intestines.

e.g. Voltarene.g. Voltaren

(5) Sugar- and chocolate-Coated Tablets (5) Sugar- and chocolate-Coated Tablets

(SCT)(SCT)

The tablet that contains active ingredient(s) The tablet that contains active ingredient(s)

of unpleasant taste may be covered with of unpleasant taste may be covered with

sugar to make it more palatablesugar to make it more palatable..

This type of tablet should be administered in This type of tablet should be administered in

whole formwhole form..

Example: Vitaferro, QuinineExample: Vitaferro, Quinine..

(6) Film-Coated Tablets (FCT)(6) Film-Coated Tablets (FCT)

The tablet is coated with a membrane of The tablet is coated with a membrane of

polymeric substances that improves polymeric substances that improves

physicochemical stability of the drug and delays physicochemical stability of the drug and delays

the rate of drug absorptionthe rate of drug absorption..

e.g. Augmentine.g. Augmentin

((77 ) )Chewable tabletsChewable tabletsThe tablets are placed in the mouth, chewed The tablets are placed in the mouth, chewed and swallowedand swallowed . .

e.g. Talcid, Aspirin Directe.g. Talcid, Aspirin Direct

Tablets used in the oral cavityTablets used in the oral cavityTablets used in the oral cavity are allowed to Tablets used in the oral cavity are allowed to

dissolve in the mouth.dissolve in the mouth.

(1) Sublingual tablets(1) Sublingual tablets

The tablet is placed under the tongueThe tablet is placed under the tongue

Sublingual tablets are absorbed quickly into the Sublingual tablets are absorbed quickly into the bloodstreambloodstream

e.g. Nitroglycerin, Uprimae.g. Nitroglycerin, Uprima

(2) Buccal and sublingual tablets(2) Buccal and sublingual tablets Buccal tablets are placed in the pouch between Buccal tablets are placed in the pouch between the cheek and gumthe cheek and gum

They are usually small, flat and oval in shapeThey are usually small, flat and oval in shape

e.g. Progesterone taqblete.g. Progesterone taqblet

(2) Troches, lozenges(2) Troches, lozengesTroches (lozenges or pastilles)Troches (lozenges or pastilles)

The tablets contain a drug substance in flavored baseThe tablets contain a drug substance in flavored base..

Lozenges are allowed to dissolve in the mouth. They are commonly used for cold and sore Lozenges are allowed to dissolve in the mouth. They are commonly used for cold and sore

throatthroat..

e.g. Chlorhexidinee.g. Chlorhexidine

Tablets used to prepare Tablets used to prepare solutionssolutions

Tablets used to prepare solutions are dissolved Tablets used to prepare solutions are dissolved

in water before administration.in water before administration.

(1) Effervescent tablets(1) Effervescent tablets

Effervescent tablets are prepared by Effervescent tablets are prepared by

compressing granular effervescent compressing granular effervescent

salts or other materials (e.g., citric acid, salts or other materials (e.g., citric acid,

tartaric acid, sodium bicarbonate) that release tartaric acid, sodium bicarbonate) that release

carbon dioxide gas when they come into carbon dioxide gas when they come into

contact with water to musk undesirable taste or contact with water to musk undesirable taste or

to encourage rapid dissolution and absorption. to encourage rapid dissolution and absorption.

Tablet Ingredients (Formulation)

• In addition to the active or therapeutic ingredient (s), tablets contain a number of inert materials. (additives or excipients) that have special functions.

• Tablet excipients must meet certain criteria in the formulation:

1) Their cost must be low.

2) Nontoxic

3) Be commercially available

4) Be physiologically inert.

5) Must not be contraindicated by themselves (e.g., sucrose).

6) Physically and chemically stable by themselves and in combination with the drug(s) and other tablet components.

7) Free of any unacceptable microbiologic "load."

8) Be color-compatible (not produce any off-color appearance).

9) If the drug product is classified as a food, (certain vitamin products), the diluent and other excipients must be approved direct food additives.

10) Have no deleterious effect on the bioavailability of the drug(s) in the product.

(1) Diluents• Diluents are fillers designed to make up

the required bulk of the tablet when the drug dosage amount is inadequate.

• Diluents may improve cohesion, permit direct compression, or promote flow.

• Common diluents include: kaolin, lactose, mannitol, starch, microcrystalline cellulose, powdered sugar, and calcium phosphate.

• Selection of the diluent is based on:

the experience of the manufacturer

the cost of the diluent

its compatibility with the other ingredients.

• For example, calcium salts cannot be used as fillers for tetracycline products because calcium interferes with the absorption of tetracycline from the gastrointestinal tract.

• The dose of some drugs is sufficiently high that no filler is required (e.g., aspirin and certain antibiotics).

LactoseLactose is the most widely used diluent in tablet is the most widely used diluent in tablet

formulation.formulation.

but Lactosebut Lactose may discolor in the presence may discolor in the presence

of amine drug bases or salts of alkaline of amine drug bases or salts of alkaline

compounds.compounds.

Spray-dried lactoseSpray-dried lactose is one of several diluents now is one of several diluents now

available for direct compression. available for direct compression. Microcrystalline cellulose, (Avicel), is a direct compression material.

Two tablet grades exist:•PH 101 (powder).•PH 102 (granules).

(2) Binders and adhesives

Binders and adhesives are added in either dry or liquid form to promote granulation or to promote cohesive compacts during direct compression.

Common binding agents include: 10%-20% aqueous preparation of corn starch; 25%-50% solution of glucose; molasses; Various natural gums )e.g., acacia(; )usually contaminated with

bacteria( Cellulose derivatives )e.g., methylcellulose,

carboxymethylcellulose, microcrystalline cellulose(; Gelatins; and povidone.

(3) Disintegrants

Disintegrants are added to tablet formulations to facilitate disintegration when the tablet contacts water in the gastrointestinal tract.

Disintegrants function by drawing water into the tablet, swelling, and causing the tablet to burst.

Tablet disintegration may be critical to the subsequent dissolution of the drug and to satisfactory drug bioavailability.

Common disintegrants include: Corn starch and potato starch;Corn starch and potato starch; Starch derivatives (sodium starch glycolate);Starch derivatives (sodium starch glycolate); Cellulose derivatives (sodium carboxymethylCellulose derivatives (sodium carboxymethyl

cellulose);cellulose); Clays (e.g., Veegum, bentonite);Clays (e.g., Veegum, bentonite);

A portion of disintegrantA portion of disintegrant can be added, with the can be added, with the

lubricant, to the prepared granulation of the drug. lubricant, to the prepared granulation of the drug.

This approach causes double disintegration of the This approach causes double disintegration of the

tablet.tablet.

o The tablet break into small pieces, or chunks. The tablet break into small pieces, or chunks.

o The pieces of tablet break into fine particles. The pieces of tablet break into fine particles.

)a( Lubricants reduce the friction that occurs between

the walls of the tablet and the walls of the

die cavity when the tablet is ejected.

Ex.: Talc, magnesium stearate, and

calcium stearate.

)b( Antiadherents reduce sticking, or adhesion, of the

tablet granulation or powder to the faces

of the punches or the die walls.

)c( Glidants promote the flow of the tablet granulation

or powder by reducing friction among

particles.

(4) Lubricants, anti-adherents, and glidants

(5) Colors and dyes

Colors and dyes provide product identification, and produce a more aesthetically appealing product.

The availability of natural vegetable colors is limited, and these colors are often unstable.

Two forms of color have typically been used in tablet preparation )FD&C and D&C dyes( which are applied as solutions.

Lakes are dyes that have been absorbed on a hydrous oxide. and used as dry powders.

(6) Flavoring agents

Flavoring agents are usually limited to chewable tablets or tablets that are intended to dissolve in the mouth.

Water-soluble flavors usually have poor stability.

For this reason, flavor oils or dry powders are used.

Usually, the maximum amount of oil that can be added to a granulation without affecting its tablet characteristics is 0.5%-0.75%.

(7) Artificial sweeteners

Artificial sweeteners, like flavors, are typically used only with chewable tablets or tablets that are intended to dissolve in the mouth.

Some sweetness may come from the diluent )e.g., mannitol, lactose(.

Other agents )e.g., saccharin, aspartame(

Saccharin has an unpleasant aftertaste.

(8) Adsorbents

Adsorbents )e.g., magnesium oxide,

magnesium carbonate, bentonite, silicon

dioxide( hold quantities of fluid in an

apparently dry state.

Methods of Tablet Methods of Tablet PreparationPreparation

The three basic methods for the The three basic methods for the preparation of compressed tablets are:preparation of compressed tablets are:

1)1) Wet granulation method.Wet granulation method.

2)2) Dry granulation method.Dry granulation method.

3)3) Direct compression.Direct compression.

The Wet Granulation The Wet Granulation MethodMethod

This method has more This method has more operational manipulations, operational manipulations, and is more time-consuming and is more time-consuming than the other methods.than the other methods.

The wet granulation method is The wet granulation method is not suitable for drugs which not suitable for drugs which are thermolabile or are thermolabile or hydrolyzable by the presence hydrolyzable by the presence of water in the liquid binder.of water in the liquid binder.

General steps involved in a wet General steps involved in a wet

granulation process are: granulation process are:

1)1)The powdered ingredients are weighed The powdered ingredients are weighed

and mixed intimately by geometric and mixed intimately by geometric

dilution. dilution.

2)2)The granulating solution or binder is The granulating solution or binder is

prepared. prepared.

3)3)The powders and the granulating The powders and the granulating

solution are kneaded (pressed) to solution are kneaded (pressed) to

proper consistency. proper consistency.

4)4)The wet mass is forced through a The wet mass is forced through a

screen or wet granulator. screen or wet granulator.

5)5) The granules are dried in an oven The granules are dried in an oven

or a fluidized bed dryer. or a fluidized bed dryer.

6)6) The dried granules are screened The dried granules are screened

to a suitable size for to a suitable size for

compression. compression.

7)7) A lubricant and a disintegrating A lubricant and a disintegrating

agent are mixed with the agent are mixed with the

granulation. granulation.

8)8) The granulation is compressed The granulation is compressed

into the finished tablet. into the finished tablet.

Wet Granulation Manufacturing Steps

The Dry Granulation The Dry Granulation MethodMethod

The granulation is formed by compacting large masses of The granulation is formed by compacting large masses of

the mixture and subsequently crushing and sizing these the mixture and subsequently crushing and sizing these

pieces into smaller granules.pieces into smaller granules.

By this method, either the By this method, either the

active ingredient or the diluent must have cohesive active ingredient or the diluent must have cohesive

properties in order for the large masses to be formedproperties in order for the large masses to be formed

This method is especially applicable to materials that This method is especially applicable to materials that

cannot be prepared by the wet granulation method due cannot be prepared by the wet granulation method due

to their degradation by moisture or to the elevated to their degradation by moisture or to the elevated

temperatures required for drying.temperatures required for drying.

Direct CompressionDirect Compression

In the direct compression of tablets, the In the direct compression of tablets, the

tableting excipients used must be materials with tableting excipients used must be materials with

properties of fluidity and compressibility. properties of fluidity and compressibility.

Some granular chemicals like potassium chloride Some granular chemicals like potassium chloride

and methenamine possess free flowing as well as and methenamine possess free flowing as well as

cohesive properties that enable them to be cohesive properties that enable them to be

compressed directly in a tablet machine without compressed directly in a tablet machine without

need of either wet or dry granulation. need of either wet or dry granulation.

Tableting excipients having the desired Tableting excipients having the desired

characteristics are used include:characteristics are used include:

Fillers:Fillers: lactose, microcrystalline cellulose, and lactose, microcrystalline cellulose, and

dicalcium phosphate; dicalcium phosphate;

Disintegrating agentsDisintegrating agents:: starch, sodium starch, sodium

carboxymethyl cellulose carboxymethyl cellulose

Lubricants-Lubricants-magnesium magnesium stearate and talc; stearate and talc;

Glidants:Glidants: silicon dioxide.silicon dioxide.

Tablet Compression Tablet Compression MachinesMachines

► The basic units in tablet The basic units in tablet

compression machine are two steel compression machine are two steel

punches within a steel die cavity.punches within a steel die cavity.

► The tablet is formed by the The tablet is formed by the

pressure exerted on the granulation pressure exerted on the granulation

by the punches within the die by the punches within the die

cavity, cavity,

► The tablet takes the size and shape The tablet takes the size and shape

of the punches and dies used.of the punches and dies used.

► The use of the tablet sometimes determines its shape; The use of the tablet sometimes determines its shape;

Effervescent tablets are usually large, round and flat,Effervescent tablets are usually large, round and flat,

Vitamin tablets are prepared in capsule-shaped Vitamin tablets are prepared in capsule-shaped

forms. forms.

► Tablets prepared using deep-cup punches appear to be Tablets prepared using deep-cup punches appear to be

round and when coated take the appearance of pills.round and when coated take the appearance of pills.

► Veterinary tablets often have a bolus shape and are Veterinary tablets often have a bolus shape and are

much larger than those used in medical practice. much larger than those used in medical practice.

((11 ) )Single Punch MachineSingle Punch Machine► The simplest tableting The simplest tableting

machines machines

► The majority are power driven, The majority are power driven, and several are hand-operated and several are hand-operated models.models.

► Compression is accomplished Compression is accomplished on a single-punch machine. on a single-punch machine.

The feed shoe filled with the The feed shoe filled with the granulation is positioned over granulation is positioned over the die cavity which then fills.the die cavity which then fills.

Upper punch lowers to compress Upper punch lowers to compress

the granulation within the die the granulation within the die

cavity.cavity.

The upper punch retracts and the The upper punch retracts and the

low punch rises to eject the low punch rises to eject the

tablet.tablet.

As the weight of the tablet is determined by As the weight of the tablet is determined by

the volume of the die cavity; the lower punch the volume of the die cavity; the lower punch

is adjustable to increase or decrease the is adjustable to increase or decrease the

volume of granulation, thus increasing or volume of granulation, thus increasing or

decreasing the weight of the tablet.decreasing the weight of the tablet.

((22 ) )Rotatory Tablet MachineRotatory Tablet Machine::► Rotary machines are used for Rotary machines are used for

increased production.increased production.

► A head carrying a number of sets of A head carrying a number of sets of

punches and dies revolves punches and dies revolves

continuously while the tablet continuously while the tablet

granulation runs from the hopper, granulation runs from the hopper,

through a feed frame and into the through a feed frame and into the

dies placed in a large, steel plate dies placed in a large, steel plate

revolving under it.revolving under it.

► This method promotes a uniform fill This method promotes a uniform fill

of the die and therefore an accurate of the die and therefore an accurate

weight for the tablet.weight for the tablet.

► Compression takes place as the upper Compression takes place as the upper

and lower punches pass between a and lower punches pass between a

pair of rollers.pair of rollers.

Processing ProblemsProcessing Problems

CappingCapping is the partial or is the partial or complete separation of complete separation of the top or bottom crown the top or bottom crown from the main body of from the main body of the tablet. the tablet.

Lamination Lamination is separation is separation of a tablet into two or of a tablet into two or more distinct layers. more distinct layers.

Capping and LaminationCapping and Lamination

Capping (top) and lamination (right)

Capping and lamination may occur hours or Capping and lamination may occur hours or

even days later.even days later. These problems are usually caused by These problems are usually caused by

entrapment of air among the particles or entrapment of air among the particles or

granules and do not escape until the granules and do not escape until the

compression pressure is released.compression pressure is released. Rapid decompression results in tablets Rapid decompression results in tablets

fracture.fracture. Often, deep concave punches produce tablets Often, deep concave punches produce tablets

that cap.that cap. A granulation that is too dry tends to cap or A granulation that is too dry tends to cap or

laminate for lack of cohesion.laminate for lack of cohesion.

Tablet lamination or capping problems Tablet lamination or capping problems

can be eliminated by:can be eliminated by:

1.1.Precompression.Precompression.

2.2.Slowing the tabletting rate.Slowing the tabletting rate.

3.3.Reducing the final compression pressure.Reducing the final compression pressure.

4.Addition of a hygroscopic substance4.Addition of a hygroscopic substance

5.Use Flat punches5.Use Flat punches

6. Use force feeder 6. Use force feeder

PickingPicking is removal of the surface material of is removal of the surface material of

a tablet by a punch.a tablet by a punch.

StickingSticking is adhesion of tablet material to a is adhesion of tablet material to a

die wall.die wall.

These problems are caused by excessive These problems are caused by excessive

moisture in the formulation. moisture in the formulation.

Low-melting-point substances, either active Low-melting-point substances, either active

ingredients or additives such as stearic acid ingredients or additives such as stearic acid

and polyethylene glycol, may soften from the and polyethylene glycol, may soften from the

heat of compression to cause sticking. heat of compression to cause sticking.

Picking and StickingPicking and Sticking

Picking and StickingPicking and Sticking can be eliminated by:can be eliminated by:

1)1) The tablet can be reformulated to a larger size.The tablet can be reformulated to a larger size.

2)2) Plating of the punch faces with chromium is a Plating of the punch faces with chromium is a

method for producing a smooth, non-adherent method for producing a smooth, non-adherent

face.face.

3)3) Dilution of the active ingredient with higher- Dilution of the active ingredient with higher-

melting-point materials melting-point materials

4)4) Drying of the granulesDrying of the granules

Mottling Mottling is unequal color distribution, with light is unequal color distribution, with light

or dark areas standing on a uniform surface.or dark areas standing on a uniform surface.

This problem occurs when a drug has a different This problem occurs when a drug has a different

color than the tablet excipients or when a drug color than the tablet excipients or when a drug

has colored degradation products.has colored degradation products.

MottlingMottling

Mottling can be eliminated by:Mottling can be eliminated by: The formulator may change the solvent system, The formulator may change the solvent system,

change the binder system, reduce the drying change the binder system, reduce the drying

temperature, or grind to a smaller particle size. temperature, or grind to a smaller particle size.

The weight of a tablet is determined by the amount The weight of a tablet is determined by the amount

of granulation in the die prior to compression. of granulation in the die prior to compression.

Therefore, anything that can alter the die-filling Therefore, anything that can alter the die-filling

process can alter tablet weight and weight process can alter tablet weight and weight

variation.variation.

Granule Size and Size Distribution Before Granule Size and Size Distribution Before

Compression.Compression.

Poor Flow.Poor Flow.

Weight VariationWeight Variation

Depending on the geometry of the hopper, two Depending on the geometry of the hopper, two

causes for poor flow: "arching" or "bridging," causes for poor flow: "arching" or "bridging,"

and "rat-holing." phenomena may arise.and "rat-holing." phenomena may arise.

BridgingBridging rat-holingrat-holing

Weight variation due to poor flowability Weight variation due to poor flowability

can be eliminated by:can be eliminated by:

The addition of a glidant such as talcum or The addition of a glidant such as talcum or

colloidal silica, or an increase in the amount colloidal silica, or an increase in the amount

already present, may be helpful.already present, may be helpful.

When poor hopper flow occurs, it may be When poor hopper flow occurs, it may be

controllable with vibrators attached to the controllable with vibrators attached to the

hopper sides to induce the granulation flow.hopper sides to induce the granulation flow.

Hardness variation is a problem that has the Hardness variation is a problem that has the

same causes as weight variation.same causes as weight variation.

Hardness depends on the weight of material and Hardness depends on the weight of material and

the space between the upper and lower punches the space between the upper and lower punches

at the moment of compression.at the moment of compression.

If the volume of material or the distance If the volume of material or the distance

between punches varies, hardness is between punches varies, hardness is

unacceptable.unacceptable.

Hardness VariationHardness Variation

Tablet CoatingTablets are coated for a number of reasons including:

1.1. To mask the taste, color, or To mask the taste, color, or

odor of the drug.odor of the drug.

2.2. To control drug release.To control drug release.

3.3. To protect the drug from the To protect the drug from the

acid environment of the acid environment of the

stomach.stomach.

4.4. To protect the medicinal agent To protect the medicinal agent

against destructive exposure to against destructive exposure to

air and/or humidity.air and/or humidity.

5.5. To improve appearance.To improve appearance.

Sugar Coating TabletsSugar Coating Tablets

The sugarcoating of tablets may be The sugarcoating of tablets may be

divided into the following steps:divided into the following steps:

1.1. Waterproofing and sealingWaterproofing and sealing

)if needed(.)if needed(.

1.1. Subcoating.Subcoating.

2.2. Smoothing and final rounding.Smoothing and final rounding.

3.3. Finishing and coloring Finishing and coloring

)if desired(.)if desired(.

5.5. Polishing.Polishing.

Waterproofing and sealing coatsWaterproofing and sealing coatsSealing tablet core- application of a water impermeableSealing tablet core- application of a water impermeable

polymer such as polymer such as Shellac, cellulose acetate phthalate andShellac, cellulose acetate phthalate and

polyvinyl acetate phthalatepolyvinyl acetate phthalate, which protects the core from, which protects the core from

moisture, increasing its shelf lifemoisture, increasing its shelf life..

Sub coatingSub coating by adding bulking agents such as calcium carbonate orby adding bulking agents such as calcium carbonate or

talc in combination with talc in combination with sucrose solutionsucrose solution..

Smoothing and final roundingSmoothing and final rounding Remove rough layers formed in step 2 with theRemove rough layers formed in step 2 with the

application of sucrose syrupapplication of sucrose syrup..

PolishingPolishing effectively polished to give characteristiceffectively polished to give characteristic

shine, commonly using beeswax, carnauba waxshine, commonly using beeswax, carnauba wax..

Film-Coating TabletsFilm-Coating Tablets The film-coating process, which places a thin, The film-coating process, which places a thin,

skin tight coating of a plastic-like material over skin tight coating of a plastic-like material over

the compressed tablet, was developed to the compressed tablet, was developed to

produce coated tablets having essentially the produce coated tablets having essentially the

same shape, and size as the originally same shape, and size as the originally

compressed tablet.compressed tablet.

Advantages of Film coating :Advantages of Film coating :

1.1. Minimal weight increase )typically 2 to 3% of table core Minimal weight increase )typically 2 to 3% of table core

weight( weight(

2.2. Significant reduction in processing times. Significant reduction in processing times.

3.3. Increased process efficiency and output. Increased process efficiency and output.

4.4. Increased flexibility in formulations. Increased flexibility in formulations.

5.5. Improved resistance to chipping of the coating. Improved resistance to chipping of the coating.

Film-coating solutions may be Film-coating solutions may be non-aqueousnon-aqueous or or

aqueousaqueous..

The non-aqueous solutionsThe non-aqueous solutions generally contain the generally contain the

following types of materials to provide the desired following types of materials to provide the desired

coating to the tablets:coating to the tablets:

1.1. Film formerFilm former capable of producing smooth, thin films capable of producing smooth, thin films

reproducible under conventional coating conditions reproducible under conventional coating conditions

and applicable to a variety of tablet shapes.and applicable to a variety of tablet shapes.

Example: Example: cellulose acetate phthalatecellulose acetate phthalate..

2.2. An alloying substanceAn alloying substance providing water solubility or providing water solubility or

permeability to the film to ensure penetration by body permeability to the film to ensure penetration by body

fluids and therapeutic availability of the drug.fluids and therapeutic availability of the drug.

Example: Example: polyethylene glycol.polyethylene glycol.

3.3. A plasticizerA plasticizer to produce flexibility and elasticity of the to produce flexibility and elasticity of the

coating and thus provide durability.coating and thus provide durability.

Example: Example: castor oil.castor oil.

4.4. A surfactantA surfactant to enhance spreadability of the film to enhance spreadability of the film

during application.during application.

Example: Example: polyoxyethylene sorbitan derivativespolyoxyethylene sorbitan derivatives..

5.5. OpaquantsOpaquants and and colorantscolorants to make the appearance of to make the appearance of

the coated tablets handsome and distinctive.the coated tablets handsome and distinctive.

Examples: Opaquant, Examples: Opaquant, titanium dioxidetitanium dioxide..

colorant, colorant, F.D.&C. or D.&C. dyesF.D.&C. or D.&C. dyes..

6.6. SweetenersSweeteners, , flavorsflavors, , and and aromasaromas to enhance the to enhance the acceptability of the tablet to the patient.acceptability of the tablet to the patient.

Examples: Examples: sweeteners, saccharin; flavors and sweeteners, saccharin; flavors and aromas, vanillin.aromas, vanillin.

7.7. A glossantA glossant to provide luster to the tablets without a to provide luster to the tablets without a separate polishing operation.separate polishing operation.

Example: Example: beeswax.beeswax.

8.8. A volatile solventA volatile solvent to allow the spread of the other to allow the spread of the other components over the tablets while allowing rapid components over the tablets while allowing rapid evaporation to permit an effective, speedy operation.evaporation to permit an effective, speedy operation.

Example: Example: alcohol acetone mixture.alcohol acetone mixture.

Tablets are film coated by the application or spraying of Tablets are film coated by the application or spraying of

the film-coating solution upon the tablets in ordinary the film-coating solution upon the tablets in ordinary

coating pans.coating pans.

The volatility of the solvent enables the film to adhere The volatility of the solvent enables the film to adhere

quickly to the surface of the tablets.quickly to the surface of the tablets.

A typical aqueousA typical aqueous

film-coating formulation contains the following:film-coating formulation contains the following:

1)1) Film-forming polymer Film-forming polymer )7-18%(. )7-18%(. Examples: Examples: hydroxypropyl methylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose.hydroxypropyl cellulose.

2)2) Plasticizer Plasticizer (0.5-2.0%). (0.5-2.0%).Examples: Examples: glycerin, propylene glycol, polyethylene glycerin, propylene glycol, polyethylene glycol.glycol.

3)3) ColorantColorant and and opacifieropacifier (2.5-8%). (2.5-8%).Examples: Examples: FD&C or D&C Lakes and iron oxide FD&C or D&C Lakes and iron oxide pigments.pigments.

4)4) Vehicle Vehicle ))waterwater, to make 100%(., to make 100%(.

Problems attendants to aqueous film-coating, Problems attendants to aqueous film-coating,

The appearance of small amounts The appearance of small amounts ((pickingpicking) )

or larger amounts or larger amounts ((peelinpeelingg) )

of film fragments flakingof film fragments flaking

from the tablet surface.from the tablet surface.

Roughness of the tablet surface due to failure of Roughness of the tablet surface due to failure of

spray droplets to coalesce )spray droplets to coalesce )orange peel effectorange peel effect(.(.

An uneven distribution of color on the tablet surface An uneven distribution of color on the tablet surface

))mottlingmottling(.(.

Filling-in of the score-line or indented logo on theFilling-in of the score-line or indented logo on the

tablet by the film )tablet by the film )bridgingbridging(.(.

Enteric CoatingEnteric Coating The design of an enteric coating The design of an enteric coating

may be based upon the transit may be based upon the transit

time required for the passage of time required for the passage of

the dosage form the stomach into the dosage form the stomach into

the intestines. the intestines.

This may be accomplished This may be accomplished

through coatings of sufficient through coatings of sufficient

thickness to resist dissolution in thickness to resist dissolution in

the stomachthe stomach

An enteric coating is based upon the pH of the An enteric coating is based upon the pH of the

environment, being designed to resist dissolution in environment, being designed to resist dissolution in

the highly acid environment of the stomach but the highly acid environment of the stomach but

dissolve in the less acid environment of the intestine.dissolve in the less acid environment of the intestine.

Some enteric coatings are designed to dissolve at pH Some enteric coatings are designed to dissolve at pH

4.8 and greater.4.8 and greater.

Enteric coating materials may be applied to either whole Enteric coating materials may be applied to either whole compressed tablets or to drug particles or granules used compressed tablets or to drug particles or granules used in the fabrication of tablets or capsules.in the fabrication of tablets or capsules.

The coatings may be applied in multiple portions to build The coatings may be applied in multiple portions to build a thick coating or they may be applied as a thin film coat.a thick coating or they may be applied as a thin film coat.

The coating systems may be aqueous-based or organic-The coating systems may be aqueous-based or organic-solvent-based so long as the coating material resists solvent-based so long as the coating material resists breakdown in the gastric fluid.breakdown in the gastric fluid.

Materials used in enteric coatings are shellac, Materials used in enteric coatings are shellac, hydroxypropyl methylcellulose phthalate, polyvinyl hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, and cellulose acetate phthalate and acetate phthalate, and cellulose acetate phthalate and poly-acrylics as Eudragit-Lpoly-acrylics as Eudragit-L100100..

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