Pradip ppt

Compaction and

Compression

PRESENTED BYPRADIPKUMAR.L.GHORI

DEPT. OF PHARMACEUTICSM.M.C.P

A. Transitional repacking or particle rearrangement.

B. Deformation.C. Fragmentation and deformation.D. Bonding.E. Deformation of solid body.F. Decompression.G. Ejection.H. Descriptions of process.

Granules to be placed in the hopper of the tablet press.

Formulation and processing are designed to ensure that at a fast production rate the weight variation of the final tablet is minimal.

The particle size distribution of granulation and the shape of the granules determine the initial packing as the granules is delivered in to the die cavity.

In the initial event the punch and particle movement occur at low pressure.

The granule flow with respect to each other, with the finer particle entering the void between the larger particle, and the bulk density of the granulation is increased.

Spherical particle undergo less particle rearrangement then irregular particle as the spherical particle tend to assume a close packing rearrangement initially.

To achieve a fast flow rate required for high-speed presses the granulation is generally processed to produce spherical or oval particles.

Thus, particle rearrangement and the energy expended in rearrangement are minor consideration in the total process of compression

When the stress is applied to a material, deformation (change of forms) occurs.

If the deformation disappears completely (return to the original shape) upon release of stress , it is an Elastic deformation.

A deformation that dose not completely recover after release of the stress is known as a Plastic deformation.

The force required to initiate plastic deformation is known as the yield stress.

When the particles of a granulation are so closely packed that no further filing of the void can occur, a further increases of compressional force cause deformation at he point of contact.

Both plastic and elastic deformation may occur although one type predominates for a given material.

Deformation increase the area of true contact and the formation of potential bonding areas.

At higher pressure, fracture occur when the stresses within the particles become great enough to propagate cracks.

fragmentation further densification, with the infiltration of the smaller fragment in to the void space

Fragmentation increase the number of particle and form new, clean surface that are potential bonding area.

The relative amount of deformationproduce by such force is a dimensionlessquality called strain. e.g. if the solid road compressed by force acting each end to cause reduction in

length of H from an unload length D0

H0 then the compressive stress Z given D

by the equation H H0

Z= H / Ho The ratio of force F necessary to produce this strain to the area A over which it act is called the stress σ = F / A

The specific surface of the starch and sulfathiazole granulation was 0.18 m2/g; the tablet compressed at a pressure of 1600kg/cm2 had a specific surface of 0.9m2/g

specific 1.0 surface 0.8 m2/g 0.6 0.4 0.2 2000 4000 pressure , kg/cm2

Several mechanism of bonding in the compression process have been conceived, but they have not been useful in in the prediction of the compressional properties of material.

Three theory are 1 . Mechanical theory 2 . The intermolecular theory. 3 . The liquid surface film theory.

Mechanical theory:-This theory proposes that under pressure the

individual particle undergo elastic, plastic or brittle deformation and that the edges of the particle intermesh, forming a mechanical bond.

If only the mechanical bond exists, the total energy of compression is equal to the sum of the energy of deformation, heat and energy adsorb for each constituent.

Mechanical inter locking is not a major mechanism of bonding in pharmaceutical tablets.

The inter molecular theory:-

The molecule (or ions) at the surface of the solid have unsatisfied intermolecular force, which interacts with other particles in true contact.

According to the intermolecular forces theory, under pressure the molecules at the point of true contact between new, clean surface of the granules are close enough so that van der Waals forces interact to consolidate the particle.

A microcrystalline cellulose tablet has been described as a cellulose fibril in which the crystals are compressed close enough together so that hydrogen bonding between them occurs.

It appear that very little deformation or fusion occur in the compression of microcrystalline cellulose.

Aspirin crystals under go slight deformation and fragmentation at low pressure, it appear that hydrogen bonding has strongly bonded the tablet, because the granules retain their integrity with further increase in pressure .

The liquid surface film theory:-The liquid surface film theory attributes bonding to

the presence of a thin liquid film, at the surface of the particle induced by the energy of compression.

During the compression an applied force is exerted on the granules; however, locally the force applied to a small area of true contact so that a very high pressure exists at the true contact surface.

The local effect of the high pressure on the melting point and solubility of a material is essential to bonding.

The relation of pressure and melting point (clapeyron)

dT T(V1-Vs) T-temperature dP H

Where, dT/dP is the change in melting point with the pressure V1 and Vs are the molar volume of liquid melt and the solid, respectively.

By analogous reasoning , the pressure distribution in compression is such that the solubility is increased with increasing pressure.

With an increase in solubility at the point of true contact, solution usually occur in the film of adsorb moisture on the surface of the granule.

When the applied pressure is released and the solubility decrease, the solute dissolve in the adsorbed water crystallizes in small crystals between the particles.

the strength of the bridge depend on the amount of material deposited and rate of crystallization.

At higher rates of crystallization, a finer crystalline structure and a greater strength are obtained.

The poor compressibility of most water insoluble material and the relative ease of compression of water soluble materials suggest that pressure induced solubility is important in tableting.

The moisture may be present as that retain from the granulating solution after drying or that adsorb from the atmosphere.

Granulation that are absolutely dry have poor compressional characteristics.

Deformation of solid body:-As the applied pressure is further increased,

the bonded solid is consolidated towards a limiting density by plastic or elastic deformation of the tablet within the die .

1.6 1.5 density 1.4 g/cm3 1.3 1.2 1.1 1000 2000 3ooo 4ooo 5000 Pressure , kg/cm2

sulfathiazole

Decompression:-After the compression and consolidation of the

powder in the die, the formed compact must be capable of

withstanding the stresses encountered during decompression and tablet ejection.

The rate at which the force is removed (dependent on the compression roller diameter and the machine speed) can have a significant effect on tablet quality.

The same deformation characteristics that come into play during compression, play a role during decompression.

After application of the maximum compression force, the tablet undergoes elastic recovery.

While the tablet is constrained in the die, elastic recovery occurs only in the axial direction. If the rate and degree of elastic recovery are high, the tablet may cap or laminate in the die due to rapid expansion in the radial direction only.

Tablets that do not cap or laminate are able to relieve the developed stresses by plastic deformation.

Since plastic deformation is time-dependent, stress relaxation is also time-dependent.

Formulations which contain significant concentrations of microcrystalline cellulose typically form good compacts due to its plastic deformation properties.

However, if the machine speed and the rate of tablet compression are significantly increased, these formulations exhibit capping and lamination tendencies.

The rate of decompression can also have an effect on the ability of the compacts to consolidate (form bonds).

Based on the liquid-surface film theory, the rate of crystallization or solidification should have an effect on the strength of the bonded surfaces. The rate of crystallization is affected by the pressure (and the rate at which the pressure is removed).

High decompression rates should result in high rates of crystallization Typically, slower crystallization rates result in stronger crystals.

Therefore, if bonding occurs by these mechanisms, lower machine speeds should result in stronger tablets.

The rate of stress relieve is slow for acetaminophen so cracking occurs while the tablet is within the die. with microcrystalline cellulose the rare of stress relieve is rapid, and intact tablets result.

As the lower punch rises and pushes the tablet upward there is a continued residual die wall pressure and considerable energy may be expanded due to the die wall friction.

As the tablet removed from the die, the lateral pressure is relieved, and the tablet undergoes elastic recovery with an increase (2 to 10%) in the volume of that portion of the tablet removed from the die.

During ejection that portion of the tablet within the die is under strain, and if this strain exceeds the sheer strength of tablet, the tablet break as elastic recovery.

The process of compression has been described in term of the relative volume (ratio of volume of the compressed mass to the volume of mass at zero void ) and applied 1000 H

pressure. G applied 100 pressure F kg/cm2 10 E A 1.5 2.0 2.5 3.0

relative volume

AE – the decrease in relative volume during transitional repacking.

With further increase in pressure EF – temporary support between the particle.FG – fragmentation and/or plastic deformation .Some higher pressureGH – bonding and consolidation of the solid

occur to some limiting value.For compression process, HECKEL proposed

equation V kP + V0 V – V1 V0 – V1V = volume at pressure PV0 = original volume of powder including voidsV1 = volume of solid k = constant

Heckel relationship in term of relative density(P rel) log 1 KP + A 1 – P rel 2.303 calcium

phosphateP = applied pressure 100

starch(4.5%)A = constantK = heckel constant, related to the reciprocal of the 1 10mean yield pressure. 1 – P rel minimum pressure required to cause deformation. 1 2000 4000 6000

applied pressure, kg/cm2

A large value of the heckel constant indicate the onset of plastic deformation at relatively low pressure.

A heckel plot permits an interpretation of the mechanism of bonding.

For dibasic calcium phosphate dihydrate, which undergoes fragmentation during compression, the heckel plot is nonlinear and has small value for its slope (a small heckel constant).

As dibasic calcium phosphate dihydrate fragments, the tablet strength is essentially independent of particle size.

For sodium chloride a heckel plot is linear indicating that sodium chloride undergoes plastic deformation during compression. no fragmentation occur.

At least two major component to the frictional force can be distinguished

Interparticulate friction :- This arises at particle /particle contacts and can be expressed in term of a coefficient of interparticulate friction μ 1. it is more significant at low applied loads.

Material that reduce this effect are referred to as glidants.

Ex:- colloidal silica, talc, corn starch

Die-wall friction :-this result from material being pressed against the die wall and moved down it ; it is expressed as μw, the coefficient of die wall friction.

This effect become dominant at high applied forces when particle rearrangement has ceased and is particularly important in tabletting operations.

Most tablets contain a small amount of an additive design to reduce die wall friction; such additives are called lubricants.

Ex:-magnesium stearate, talc, PEG, waxes, stearic acid

FA

FL

FR FD

HOHD

Force distribution

Diagram of a cross section of a typical simple punch and die assembly

This investigation carried on single station press.Force being applied to the top of a cylindric

power mass and the following basic relationships apply.

FA=FL+FD

Where, FA =is the force applied to upper punchFL =is that proportion of it transmitted to the

lower punchFD =is a reaction at the die wall due to friction at

this surfaceBecause of this difference between the force

applied at the upper punch and that affecting material closed to the lower punch, a mean compaction force, FM where, FA+FL

2FM

A recent report confirm that FM offer a practical friction-independent measure of compaction load, which is generally more relevant then FA.

In single station presses, where the applied force transmission decay exponentially, a more appropriate geometric mean force FG, might be

0.5 FG=(FA . FL) Use of this force parameters are probably more

appropriate then use of FA when determining relationships between compressional force and such tablet properties as tablet strength.

As the compressional force increased and any repacking of the tabletting mass is completed, the material may be regarded to some extent as a single solid body.

Then as with all other solid, compressive force applied in one direction (e.g. vertical) result in decrease in H in the height, i.e. a compressive stress.

In the case of an unconfined solid body, this would be accompanied solid body, this would be accompanied by an expansion in the horizontal direction of D

The ratio of these two dimensional changes is known as poisson ratio of the material, defined as:

DPoisson ratio = HThe poisson ratio is a characteristic constant for

each solid and may influence the tabletting process in following way.

Under the condition illustrated in figure , the material in not free to expand in horizontal plane because it is confined in the die.

Consequently, a radial die wall force FR develops perpendicular to the die wall surface, material with larger poisson ratios giving rise to higher value of FR.

Classic friction theory can then be applied to deduce that the axial frictional force FD is related to FR by the expression:

FD = mw.FR

Where mw is the coefficient of die wall friction.

Note that FR is reduced when material of small poisson ratio are used, and that in such cases, axial force transmission is optimum.

Most pharmaceutical tablet formulation require the addition of a lubricant to reduce friction at the die wall .

Die wall lubricant function by interposing a film of low shear strength at the interface between the tabletting mass and the die wall.

Preferably, there is some chemical bonding between this boundary lubricant and the surface of the die wall as well as the edge of the tablet.

The best lubricant are those with low shear strength but strong cohesive tendencies in direction at right angles to the plane of shear.

Radial die wall forces and die wall friction also effect the ease with which the compressed tablet can be removed from the die.

The force necessary to eject a finished tablet follows a distinctive pattern of three stage.

The first stage involves the distinctive peak force required to initiate ejection, by braking of tablet/die wall adhesions.

A smaller force usually follows, namely that required to push the tablet up the die wall.

The final stage is marked by declining force of ejection as the tablet emerges from the die.

Variation on this pattern are sometimes found, especially when lubrication is inadequate and/or “slip-stick” condition occur between the tablet and the die wall, owing to continuing formation and breakage of tablet die wall adhesion.

A direct connection is to be expected between die wall frictional forces and the force required to eject the tablet from the die, FE.

For e.g. well lubricated systems have been shown to lead to smaller FE values.

Monitoring of that proportion of the applied pressure transmitted radially to the die wall has been reported by several groups of workers.

For many pharmaceutical materials, such investigation lead to characteristic hysteresis curves , which have been termed compaction profiles.

The radial die wall forces arises as a result of tabletting mass attempting to expand in the horizontal plane in response to the vertical compression.

The ratio of this two dimensional changes, the Poisson ratio, is an important material dependent property affecting the compressional process.

When the elastic limit of the material is high, elastic deformation may make major contribution, and on removal of the applied load, the extent of the elastic relaxation depend upon the value of the materials modulus of elasticity (young’s modulus).

If this value is low, there is considerable recovery, and unless a strong structure has been formed, there is the danger of structural failure.

If the modulus of elasticity is high, there is small dimensional change on decompression and less risk of failure.

C

D radial pressure E B c’ A O axial pressure

compress

ion

decompression

The area of the hysteresis loop (OABC’) indicate the extent of departure from ideal elastic behavior, science for perfectly elastic body, line BC’ would coincide with AB.

In many tabletting operation the applied force exceed the elastic limit (point B), and brittle fracture and/or plastic deformation is then a major mechanism.

For example, if the material readily undergoes plastic deformation with a constant yield stress as the material is sheared, then the region B to C should obey the equation.

PR = PA – 2SWhere S is the yield stress of the material

The slope of this plot is unity, so that mark deviation from this value may indicate a more complex behavior.

Deviation could also be due to the fact that the material is still significantly porous.

For e.g. since point C represent the situation at the maximum compressional force level, the region CD is therefore the initial relaxation response as the applied lode is removed.

In practice, many compaction profiles exhibit a marked change in the slope of this line during decompression, and a second yield point D has been reported.

Perhaps the residual redial pressure (intercept EO), when all the compressional force has been removed, is more significant, since this pressure is an indication of the force being transmitted by the die wall to the tablet.

As such, it provide a measure of possible ejection force level and likely lubricant requirements, it suggests a strong tablet capable of at least withstanding such a compressive pressure.

A low value of residual redial pressure, or more significantly, a sharp change in slop (DE) is sometime indicative of at least incipient failure of the tablet structure.

In practical term this may mean introducing a plastically deforming component (e.g.pvp as binder).

Tablet machines, roller compactors, and similar types of equipment required a high input of mechanical work.

The work involve in various phase of tablets operation includes,

That necessary to overcome friction between particles,

That necessary to overcome friction between the particles and machine parts,

That required to induce elastic and/or plastic deformation of the materials,

That required to cause brittle fracture within the materials, and

That associated with the mechanical operation of various machine parts.

Nelson and associate, who compared the energy expenditure in lubricated and unlubricated sulfathiazole granules.

Lubrication reduce energy expenditure by 70%, chiefly because of a lessening of the major component, namely energy utilized during ejection of the finished tablet.

Lubricant has no apparent effect on the actual amount of energy required to compress the material.

Compression Energy expended(joules)

process Unlubricated Lubricated

Compression 6.28 6.28

Overcoming die wall friction 3.35 --

Upper punch withdrawal 5.02 --

Tablet ejection 21.35 2.09

Total 36.00 8.37

By assuming that only energy expended in the process of forming the tablet cause a temperature rise, Higuchi estimated the temperature rise to be approximately 5 c.

For a single punch machine operating at 100 tablets per min, and approximately 43 kcal/hr were required for unlubricated granules.

Wurster and creekmore by use of an internal temperature probe found a 2 to 5 c rise in the temperature of tablet compressed from microcrystal cellulose, calcium carbonate, starch and sulfathiazole

The temperature of compressed tablet is affected by the pressure and speed of tablet machine.

In non instrumented single punch tablet machine set at minimum pressure, the compression of 0.7 g of sodium chloride caused a temperature increase of 1.5 c ; when the machine was set near maximum pressure , the temp. increase was 11.1 c .

When the machine was operating at 26 and 140 rpm the increase in temp. was 2.7 and 7.1 respectively.

When the machine was operating at 26 and 140 rpm to compress 0.5 g of calcium carbonate, the increase in temp. was 16.3 and 22.2 c respectively.

Higuchi and train were the first pharmaceutical scientists to study the effect of compression on tablet characteristics.

The relationship between applied pressure and weight, thickness, density, and the force of ejection are relatively independent of the material being compressed

1. Density and porosity2. Hardness and tensile strength3. Specific surface4. Disintegration 5. Dissolution

1.5 1.4 Density g/cm 3 1.3 sulphathiazole

tablet 1.2

1.1 500 1000 2000 4000 logarithm applied pressure,

kg/cm 2

30 Lactose porosity 20 % lactose-

aspirin 10 aspirin 500 1000 2000 4000 applied pressure, kg/cm 2

The effect of applied pressure on the porosity of various tablet with 10% of starch. Porosity and density inversely proportional to each other.

30

Lactose hardness 20 lactose-

aspirin s.c unit 10 aspirin 500 1000 2000 4000 applied pressure, kg/cm 2

80 radial tensile 60 strength kg/cm 2 40 20

axial

200 4000 6000 8000 applied pressure,

kg/cm 2The effect of applied pressure on tensile strengths of

tablet of dibasic calcium phosphate granulated with 1.2% starch.

Specific surface is the surface area of 1 g of material. 0.8 fragmentation

specific 0.6 surface lactose-

aspirin m 2/g 0.4 lactose 0.2

aspirin

10% starch 2000 4000 6000 8000 applied pressure, kg/cm 2

100 lactose 60 disintegration 40 aspirin time, sec 10 lactose-

aspirin 6 4 1000 3000 5000 applied pressure, kg/cm 2

600 400 1% corn starch 5% 200 disintegration 10% time, sec 100 60 40 15% 20 10 1000 3000 5000 applied pressure, kg/cm

2

sulfadiazine

Shah and parrot :-dissolution rate is independent of applied pressures from 53 to 2170 kg/cm2 for non-disintegrating spheres of aspirin, benzoic acid, salicylic acid, equimolar mixture of aspirin and salicylic acid, aspirin caffeine.

Mitchell and savill:- dissolution rate of aspirin to be independent of pressure over range 2000 to 13000 kg/cm2 and particle size of granules.

Kanke and sekiguchi :- dissolution rate of benzoic acid is independent of particle size and applied pressure.

For conventional tablet it is dependent on,

Pressure range.Dissolution medium.Properties of medical component.Properties of excipients.

If fragmentation of granule occur during compression, the dissolution is faster as applied pressure is increased, and the fragmentation increased the specific surface.

If the bonding of particle is the predominant phenomena in compression, the increase in applied pressure causes a decrease in dissolution.

Four most common dissolution – pressure relation are:

1.The dissolution is more rapid as the applied pressure is increased.

2.The dissolution is slowed as the applied pressure is increased.

3.The dissolution is faster, to a maximum, as the applied pressure is increase, and further increase in applied pressure slow dissolution.

4.The dissolution is slowed to a minimum, as the applied pressure is increase, and further increase in applied pressure speed dissolution.

Effect of compressional force on dissolution of sulfadimide tablet with various granulating agent.

t 50% (min) Pressure starch methyl cellulose gelatin (MN/m2) paste solution solution200 54.0 0.5 10.0400 42.0 0.8 4.5600 35.0 1.1 3.0800 10.0 1.2 4.61000 7.0 1.4 4.92000 3.3 1.8 6.5

1. Particle size2. Moisture content3. Lubricants4. Applied pressure

A decrease in particle size resulted in the increase in the tablet strength

Very large particle often exists as agglomerates of small crystal on compression such as agglomerates , being more friable than the crystal, breakdown in smaller units the strength of the tablets prepared from such aggregates is higher.

With very fine particle , such as those produced by a fluid energy mill , the powder are very cohesive even in the uncompressed state. On compaction strong compact of tablet can be formed .

At a given pressure the use of a very small particle increases the chances of grapping & the volume of air entrapped also increases.

general equation formed for the effect of particle size is :

Here,

K= constant a= material constant lies between (0.2

to 0.47) Fc= hardness of the impact d= diameter of the granule

In the preparation of the pharmaceutical tablet , it is generally accept that a small proportion of the moisture is present and in some cases this is required to form a coherent tablets.

Wet granulation of the powder material with hydrophilic adhesive was shown to yield tablet whose mechanical strength is dependant on the optimum content above or below with the tablets strength was reduced

With the optimum moisture content there is :Die wall lubricationInter-particulate lubricationHydro-dynamic resistance to consolidationExpression of intestinal liquid to the die wall

Lubricating agent assist particle movement and consolidation of the tablet by reducing die wall friction.

But during compression the lubricant is spread over the surface of the particles and therefore reduce the strength of the bond between the particles.

By proper selection of the lubricating agent and adding adequate quantity of granules leads to the increase in the strength of the tablet.

At higher forces due to fragmentation new surfaces are formed causing an increase in surface area, hence more area is available for bond formation, hence more will be the hardness of the compact

Fc = Fc0 Vr-m

Where, Fc0 = strength of the tablet when Vr =1 (i.e. completely consolidated) m = is a constant for particular system (here Vr is the relative volume defined as Vr = 1/1-εWhere ε is the porosity of the compact

And, shotton and Ganderton gave a general equation for the effect of applied pressure on the strength of the compact.

Log P = nFe + CWhere,P= applied pressureFe= strength of the compactC= constant

In addition to good adsorption, the ideal drug for sublingual use should be small in dose, usually not more then 10 to 15 mg.

. The ideal compound should not have any undesirable taste, since bitter or bad tasting compound will stimulate saliva flow.

It will be absorbed by the highly vascular mucosal lining of the mouth.

Objective:-1. Take drug for absorption directly through

the mucosa2. Drugs administered to produce systemic

effect fast 3. To overcome first pass metabolism.

Two type:-1.Molded sublingual tablet

2. Compressed sublingual tablets

Sublingual tablets are intended to be placed beneath to the tongue and held there until absorption taking place.

They must dissolve or disintegrate quickly, allowing the medicament to be rapidly absorbed, there fore, sublingual tablet are frequently formulated as molded tablets.

IngredientsIngredients Quantity par tablets Quantity par tablets

1. Codeine phosphate (powder)1. Codeine phosphate (powder) 30.0mg30.0mg

2. Lactose2. Lactose 17.5 mg17.5 mg

3. Sucrose( powder) `3. Sucrose( powder) ` 1.5 mg1.5 mg

Alcohol-water (60:40)Alcohol-water (60:40)Q.s.Q.s.

Formulation :-Molded sublingual tablets are usually formulated with

soluble ingredients only, So They contain lactose, dextrose, sucrose, mannitol or other rapidly soluble material or the mixtures of these ingredients

To insure rapid solubility of the soluble tablets, the excipients put through a fine screen or 120 mesh blotting cloth.

Excipient: Mainly beta-lactose is used as diluents. Antioxidant-sodium sulfite, sodium tri sulfate and

buffer added to improve physical and chemical stability of the product.

Formula for codeine phosphate tablet (30 mg).

Compressed sub lingual tablet have been prepared which disintegrate quickly and allow the active ingredient to dissolve rapidly.

To allow the active ingredient to dissolve rapidly in saliva and to be available for absorption without requiring the complete solution of all the ingredient of the formula . Compared to molded tablets, compressed tablets have less weight variation and better content uniformity.

Ingredients Quantity par tablets

1. Nitro glycerin 3.0 mg

2. Mannitol 2.0 mg

3. Microcrystalline cellulose 29.0 mg

4. Flavor Q.s.

5.sweetener Q.s.

6.coloring agent Q.s.

The purpose of buccal tablets is the same as that of sublingual tablets, i.e. Absorption of the drug through the lining of the mouth .

Buccal tablets are most often used when replacement hormonal therapy is the goal.

Flat, elliptical or capsule shaped tablets are usually selected for buccal tablets, since they can be most easily held between the gum and cheeks.

Formula for methyl testosterone buccal tablets (10 mg):-

Ingredients Quantity par tablets

1. Methyl testosterone

10 mg

2. Lactose 86mg

3. Acacia 87mg

4.talc 10 mg

5.magnessiunm state

6 mg

6.water Q.s.

Chewable tablet mean chewing in the mouth prior to the swallowing and are not intended to be swallowed intact .

Chewable dosage form, such as soft pill, tablets, gums, and new chewy squares .

The main purpose of this formulation is to, more easy administration of medicament to the infant, children’s and old people where they face problem of swallowing.

Advantage:- Large tablet is difficult to swallow the particle size is reduced in the mouth it also increases the dissolution rate Better bioavailability through bypassing disintegrationPatient convenience patient acceptance through pleasant taste and having better stability

Disadvantage:-Not suitable for the drugs those are bitter in taste & which irritate the mucosa of the mouth

Formulation:-In these formulations, importance is given to

Amount of active substanceFlow propertiesCompatibility-stabilityOrganoleptic propertiesCompressibilityDisintegrationLubrication

Here, desired product attribute: good taste and mouth feel Acceptable bioavailability and bioactivityAcceptable stability and qualityEconomic formula and progress

Direct compression vehicles:- Sucrose, dextrose, fructose, sorbitol, mannitol

Lubricant: magnesium, calcium salt of stearic acid Sweeteners: Sucrose, saccharine, and mannitol Flavoring agent :-

For antacids: - chocolate, mint, orange, vanilla, butterscotch

For cough/cold: - black current, spice vanilla, wild cheery, clove, and menthol and eucalyptus

For vitamins: - fresh pineapple, grape, raspberry, almond, blueberry, strawberry

There are three types of chewable tablets:1. Multivitamin chewable tablets2. Antacids chewable tablets3. Analgesic chewable tablets

Lozenges are the flavored medicated dosage forms intended to the sucked and held in the mouth.

. They may contain Vitamins, Antibiotic, Antiseptics, Local Anesthetics, Aromatic, Anti Histamines, Decongestants, and Corticosteroids, Astringent, Analgesics, And Demulcents or combination of these ingredients.

There are 2 types of lozenges1. Hard candy lozenges2. Compressed tablets lozenges

It is a mixture of sugar and other carbohydrates that are kept in amorphous or glossy condition. These are solid syrup of sugar having moisture content from 0.5-1.5%

Raw material used:Sugar, Corn syrup, Invert sugar, Reducing

sugar, Flavor, Medicament:

Ingredient % used Quantity

1. Liquid sugar 67%w/w 88.90lb

2. Corn syrup 80.5% w/w 49.70lb

3. Ground candy salvage

3.00lb

4.chlorpheniramine maleate

72.75gm

5. Wild cherry flavor

72.75gm

6. Benzyl alcohol 72.75gm

7. Citric acid red ( fine granules)

3.00gm

8. Red color cubes 10.00gm

With the desired area of activity on the mucous membrane of the mouth and pharynx, are usually large diameter tablets (5/8-3/4 in.) Compressed in a weight range of 1.5 to 4.0 gm and formulated with a goal of slow, uniform and smooth disintegration or erosion over an extended time period (5 to 10 min)

Raw material :- Tablet base, binder, flavor, colors, lubricants, and medicaments

Ingredients Quantity

1. Dextromethorphen10% adsorb rate

4.0 %

2. Benzocaine 2.0%

1. Confectioners sugar 6(3% corn starch)

53.0%

2. Polyethylene glycol6000(powdered)

15.0 %