CHEWABLE TABLETS,formulation factors and various types of chewable tablets

chewable tablets,advantages formulation factors

1. CHEWABLE TABLETSCHEWABLE TABLETS

2. CHEWABLE TABLETSCHEWABLE TABLETS

Chewable tablets when chewed produce a Chewable tablets when chewed produce a
pleasant tasting residue in the mouth that when pleasant tasting residue in the mouth that when
swallowed does not leave a bitter or unpleasant swallowed does not leave a bitter or unpleasant
after taste, after taste,

These tablets have been used in the tablet These tablets have been used in the tablet
formulation for children , especially multivitamin formulation for children , especially multivitamin
formulations and for the administration of formulations and for the administration of
antacids and selected anti bioticsantacids and selected anti biotics

Chewable tablets prepared by compression Chewable tablets prepared by compression
usually contain manitol , sorbotal or sucrose as usually contain manitol , sorbotal or sucrose as
binders and filters and flavors to enhance their binders and filters and flavors to enhance their
appearance and taste.appearance and taste.

3. ADVANTAGES OF CHEWABLE TABLETSADVANTAGES OF CHEWABLE TABLETS
►Patient convenience through the elimination of Patient convenience through the elimination of
the need for water for swallowing the need for water for swallowing
►Possible use as a substitute for liquid dosage Possible use as a substitute for liquid dosage
forms where rapid onset of action is needed forms where rapid onset of action is needed
►Improved patient acceptance through pleasant Improved patient acceptance through pleasant
tastetaste
►Compared to solid dosage forms include better Compared to solid dosage forms include better
bioavailability through bypassing disintegrationbioavailability through bypassing disintegration

4. DISADVANTAGES OF CHEWABLE DISADVANTAGES OF CHEWABLE
TABLETSTABLETS
►Bad tasting drugs should not be suitable, Bad tasting drugs should not be suitable,
►Drugs having high dosage levels should Drugs having high dosage levels should
be difficult to formulate.be difficult to formulate.

6. FORMULATION FACTORSFORMULATION FACTORS
FlowFlow
lubricationlubrication
disintegrationdisintegration
compatibilitycompatibility
compressibilitycompressibility
Organoleptic considerationOrganoleptic consideration
Taste and flavorTaste and flavor
aromaaroma
mouth-feel mouth-feel
After effectsAfter effects

DESIRED PRODUCT
ATRIBUTES
Good Taste and mouth fell
Acceptable bioavailability
Acceptable stability
Economic formula and
process

7. FORMULATION FORMULATION
TECHNIQUESTECHNIQUES
COATING BY WET GRANULATIONCOATING BY WET GRANULATION
MICROENCAPSULATIONMICROENCAPSULATION
SOLID DISPERSIONSOLID DISPERSION
ION EXCHANGEION EXCHANGE
SPRAY CONGELLING AND SPRAY CONGELLING AND
COATING COATING
USE OF AMINO ACIDS AND USE OF AMINO ACIDS AND
PROTIEN HYDROLYSATESPROTIEN HYDROLYSATES
FORMATION OF SALTS OR FORMATION OF SALTS OR
DERIVATIVES DERIVATIVES
EVALUATION
Taste panels
Blood level (for
absorbed drug)
In vitro ,in vivo
correlation for
antacids
Stability (chemical,
physical, organoleptic)
Quality control and
assurance

8. TASTE AND FLOVORTASTE AND FLOVOR
►Salt and sour tastes are derived form Salt and sour tastes are derived form
substances capable of ionizing in solutionsubstances capable of ionizing in solution
►The term flavor generally refers to a specific The term flavor generally refers to a specific
combined sensation of taste and smellcombined sensation of taste and smell
EX EX sugars has a sweet taste but no flavor sugars has a sweet taste but no flavor
whereas honey has a sweet taste and a whereas honey has a sweet taste and a
characteristic smell – the combination of the characteristic smell – the combination of the
two being known as honey flavortwo being known as honey flavor

9. AROMAAROMA
►Pleasant smells are generally referred as Pleasant smells are generally referred as
aromasaromas
EXEX well formulated orange- flavored well formulated orange- flavored
chewable tablets should have a chewable tablets should have a
characteristic sweet and sour taste and characteristic sweet and sour taste and
aroma of fresh orangearoma of fresh orange

10. MOUTH -FEELMOUTH -FEEL
►The term mouth feel is related to the type The term mouth feel is related to the type
of sensation or touch that a tablet of sensation or touch that a tablet
produces in the mouth upon chewingproduces in the mouth upon chewing
►How ever for a formulation to be How ever for a formulation to be
successful the over all effect in the mouth successful the over all effect in the mouth
is important in general gritty or gummy is important in general gritty or gummy
texture are undesirabletexture are undesirable

11. AFTER -EFFECTSAFTER -EFFECTS
►The most common effect of the many The most common effect of the many
compounds is after taste.compounds is after taste.
EXEX iron salts leave a rusty after taste iron salts leave a rusty after taste
saccharin in high amounts tends to leave saccharin in high amounts tends to leave
a bitter after tastea bitter after taste

Another common after effect is a Another common after effect is a
numbing sensation of a portion of the numbing sensation of a portion of the
whole surface of the tongue and mouthwhole surface of the tongue and mouth

12. The first step in the formulation of a chewable The first step in the formulation of a chewable
tablet is to obtain a complete profile of the active tablet is to obtain a complete profile of the active
drugdrug
the drug profile should ideally contains the drug profile should ideally contains
information on the followinginformation on the following
PHYSICAL PROPORTIESPHYSICAL PROPORTIES
color. odor. Taste. After taste , and moth feelcolor. odor. Taste. After taste , and moth feel
Physical form: crystal , powders , amorphous Physical form: crystal , powders , amorphous
solid, oily liquid etcsolid, oily liquid etc
Melting or congealing temperatureMelting or congealing temperature
Existing of polymers, Moisture contentExisting of polymers, Moisture content
Aqueous solubility. Active drug stability on its ownAqueous solubility. Active drug stability on its own
Compressibility if applicableCompressibility if applicable

13. CHEMICAL PROPERTIESCHEMICAL PROPERTIES

Chemical structure and chemical class
Major reactions of this chemical class
Major incompatible compounds or class
of compounds
Drug dose and any limit on the final
dosage size

14. FORMULATION TECHNIQUESFORMULATION TECHNIQUES
COATING BY WET GRANULATIONCOATING BY WET GRANULATION
In this technique drug particles to be coated are
fluidized by means of suspension in a controlled
high –velocity warm air or stream directed through
a perforated plate into a coating chamber,
The drug particles undergoes cyclic flow past an
atomizing nozzle delivering coating agent in
solution or suspension
The sprayer may be mounted either to spray up
ward from the bottom or downward from the top

15. ►As the particles become coated they are As the particles become coated they are
removed from the spray field dried by removed from the spray field dried by
the warm air stream. And returned for re the warm air stream. And returned for re
coatingcoating
►This cycling continues until the desired This cycling continues until the desired
coating thickness has been achievedcoating thickness has been achieved
►In general this is the simplest approach In general this is the simplest approach
to taste maskingto taste masking

16. MICRO MICRO
ENCAPSULATIONENCAPSULATION
►Micro encapsulation is a method of Micro encapsulation is a method of
coating drug particles or liquid droplets coating drug particles or liquid droplets
with edible polymeric materials, there by with edible polymeric materials, there by
masking the taste and forming relatively masking the taste and forming relatively
free flowing microcapsules of 5 to 5000 free flowing microcapsules of 5 to 5000
μμm m sizesize
►Phase separation or coacervation Phase separation or coacervation
technique appears to be more relevant technique appears to be more relevant
and suitable for taste masking applicationand suitable for taste masking application
the process essentially consists of three the process essentially consists of three
stepstep

17. 1.1.Formation of three immiscible phasesFormation of three immiscible phases
i.e. liquid manufacturing vehicle phase , i.e. liquid manufacturing vehicle phase ,
a core material drug phase , and a a core material drug phase , and a
coating material phase.coating material phase.
2.2.Depositing the liquid polymer coating Depositing the liquid polymer coating
by sorption around the core material by sorption around the core material
under controlled physical mixing of the under controlled physical mixing of the
three phases.three phases.
3.3.Rigidizing the coating usually by Rigidizing the coating usually by
thermal cross linking or dissolution thermal cross linking or dissolution
techniques to form a rigid microcapsuletechniques to form a rigid microcapsule

18. ►The resultant coated granules not only The resultant coated granules not only
mask the taste of a drug but also minimize mask the taste of a drug but also minimize
any physical and chemical incompatibility any physical and chemical incompatibility
between in gradientsbetween in gradients
►The typical coating material include The typical coating material include
carboxy methyl cellulose .carboxy methyl cellulose .
cellulose acetate phthalate cellulose acetate phthalate
Ethyl cellulose. GelatinEthyl cellulose. Gelatin
Poly vinyl alcoholPoly vinyl alcohol
gelatin –acacia, shellac . gelatin –acacia, shellac .

19. SOLID DISPERSIONSOLID DISPERSION
►Bad tasting drugs can be prevented from Bad tasting drugs can be prevented from
stimulating the taste buds by adsorption stimulating the taste buds by adsorption
on to substrates capable of keeping the on to substrates capable of keeping the
drugs adsorbed while in the mouth but drugs adsorbed while in the mouth but
releasing them eventually in the stomach releasing them eventually in the stomach
or gitor git
►Good example is the adsorption of Good example is the adsorption of
dextrometharphan hydro bromide on to dextrometharphan hydro bromide on to
magnesium trisilicate substratemagnesium trisilicate substrate

20. ADSORBATE FORMATION TECHNQUESADSORBATE FORMATION TECHNQUES
SOLVENT METHODSOLVENT METHOD

The formation of an adsorbate involves The formation of an adsorbate involves
dissolving the drug in a solvent ,mixing dissolving the drug in a solvent ,mixing
the solution with the substrate and the solution with the substrate and
evaporating the solvent –leaving the drug evaporating the solvent –leaving the drug
molecules adsorbed upon the substratemolecules adsorbed upon the substrate

21. MELTING METHODMELTING METHOD

Here the drug or drugs and a carrier are Here the drug or drugs and a carrier are
melted together by heating, the melted melted together by heating, the melted
mixture is then cooled and rapidly mixture is then cooled and rapidly
solidified in an ice bath with vigorous solidified in an ice bath with vigorous
stirring . The product is then pulverized stirring . The product is then pulverized
and seized.and seized.

Heat liable drugs volatile drugs and drugs Heat liable drugs volatile drugs and drugs
that decompose on melting are obviously that decompose on melting are obviously
unsuitableunsuitable

22. ION EXCHANGEION EXCHANGE
It is the reversible interchange of ions It is the reversible interchange of ions
between a solid and a liquid phase in between a solid and a liquid phase in
which there is no permanent change in which there is no permanent change in
the structure of the solid . The solid is the the structure of the solid . The solid is the
ion exchange material and the ion could ion exchange material and the ion could
be a drugbe a drug

When used as a drug carrier ion When used as a drug carrier ion
exchange materials provides a mean for exchange materials provides a mean for
binding drugs on to an insoluble binding drugs on to an insoluble
polymeric matrix and can effectively polymeric matrix and can effectively
mask the problems of taste and odormask the problems of taste and odor

23. SPRAY CONGELING AND SPRAY COATINGSPRAY CONGELING AND SPRAY COATING
►The process of spray congealing involves The process of spray congealing involves
cooling of melted substance in the form of fine cooling of melted substance in the form of fine
particles during their travel from a spray nozzle particles during their travel from a spray nozzle
to the distant vicinity of a spray chamber held at to the distant vicinity of a spray chamber held at
a temperature below their melting point.a temperature below their melting point.
►For small dose entities such as vitamins spray For small dose entities such as vitamins spray
congealing is ideally suitablecongealing is ideally suitable
►The spray coating process involves the spraying The spray coating process involves the spraying
of a suspension of the drug particles in a of a suspension of the drug particles in a
solution of the coating material through a solution of the coating material through a
atomizer in to a high – velocity stream of warm atomizer in to a high – velocity stream of warm
airair

24. ►The coarse droplets delivered by the The coarse droplets delivered by the
atomizer consists of the drug particles atomizer consists of the drug particles
enveloped by coating solution , as the enveloped by coating solution , as the
solvent evaporates the coating materials solvent evaporates the coating materials
encapsulates the drug particlesencapsulates the drug particles

25. FORMTION OF THE DIFFERENT SALTS FORMTION OF THE DIFFERENT SALTS
OR DERIATIVESOR DERIATIVES
►It is an attempt made to modifies the It is an attempt made to modifies the
chemical composition of the drug include chemical composition of the drug include
it self so as to render it less soluble in it self so as to render it less soluble in
saliva and there by less stimulating for saliva and there by less stimulating for
the taste buds or to obtain a taste less or the taste buds or to obtain a taste less or
less bitter formless bitter form

26. USE OF AMINO ACIDS AND PROTIEN USE OF AMINO ACIDS AND PROTIEN
HYDROLYSATESHYDROLYSATES
►By combining amino acids their salts or a By combining amino acids their salts or a
mixture of two it is possible to mixture of two it is possible to
substantially reduce the bitter taste of substantially reduce the bitter taste of
penicillinpenicillin
►Some of the preferred amino acids are Some of the preferred amino acids are
sacrosin, alanine , taurine , glutamine sacrosin, alanine , taurine , glutamine
acid and especially glycineacid and especially glycine

27. EXCIPIENTSEXCIPIENTS
►Many of the excipients commonly used in Many of the excipients commonly used in
the tablet formation are applicable for the tablet formation are applicable for
use in chewable tablets due to their use in chewable tablets due to their
ability to provide the necessary ability to provide the necessary
properties of sweetness chewabilityproperties of sweetness chewability

28. NAMENAME SOURCESOURCE PARTICLE PARTICLE
SIZESIZE
LODLOD
BROWN BROWN
SUGARSUGAR
AMSTARAMSTAR 92%ON 50 92%ON 50
MESHMESH
0.7%0.7%
MOLASSES MOLASSES
GRANULES GRANULES
AMSTARAMSTAR 100%ON 12 100%ON 12
MESHMESH
1%1%
COMPRESSIBCOMPRESSIB
LE MOLASSESLE MOLASSES
INGREDIENT INGREDIENT
TECHNOLOGYTECHNOLOGY
50% ON 60 50% ON 60
MESH MESH
4%4%
COMPRASSCOMPRASS
IBLE IBLE
HONEYHONEY
INGREDIENT INGREDIENT
TECHNOLOGYTECHNOLOGY
50% ON 60 50% ON 60
MESH MESH
4%4%

29. COMPRESSIBCOMPRESSIB
LE SUGARLE SUGAR
AMSTAR AMSTAR 75% ON 100 75% ON 100
MESHMESH
0.5%0.5%
DEXTRON/DEXTRON/
FRUCTOSE/FRUCTOSE/
MALTOSEMALTOSE
MENDELLMENDELL 3% ON 20 3% ON 20
MESHMESH
7%7%
DEXTRONEDEXTRONE MENDELLMENDELL 3% ON 20 3% ON 20
MESHMESH
9%9%
LACTOSELACTOSE SHEFFIELDSHEFFIELD 20 % ON 60 20 % ON 60
MESHMESH
1 %1 %
MANNITALMANNITAL __ 75% ON 80 75% ON 80
MESHMESH
0.3%0.3%
SORBITALSORBITAL PFIZERPFIZER 33%ON 60 33%ON 60
MESHMESH
1 %1 %

30. SWEETENERSSWEETENERS
MATERIALSMATERIALS RELATIVE SWEETNESSRELATIVE SWEETNESS
ASPARTAMEASPARTAME 200200
CYCLAMATESCYCLAMATES 30 – 5030 – 50
GLYCYRRHIZINGLYCYRRHIZIN 5050
SACCHARINSACCHARIN 450450
DEXTRON(GLUCOSE)DEXTRON(GLUCOSE) 0.70.7
FRUCTOSE(LEVULOSE)FRUCTOSE(LEVULOSE) 1.71.7
LACTOSELACTOSE 0.20.2
MALTOSEMALTOSE 0.30.3
MANNITOLMANNITOL 0.5-0.70.5-0.7
SORBOTALSORBOTAL O.5-0.6O.5-0.6
SUCROSESUCROSE 11

31. FLAVORSFLAVORS
SWEET SWEET VANILLA, STONE FRUITS, VANILLA, STONE FRUITS,
GRAPE,BERRIES,MAPLEGRAPE,BERRIES,MAPLE
SOURSOUR CITRUS,CHEERY,RASHBERRY,STRAW BEERYCITRUS,CHEERY,RASHBERRY,STRAW BEERY
SALTYSALTY NUTTY,BUTTERY,SPICE,MELONNUTTY,BUTTERY,SPICE,MELON
BITTERBITTER LICORICE,ANISE,CHERRY,NUT,GRAPE FRUITLICORICE,ANISE,CHERRY,NUT,GRAPE FRUIT
ALKALINEALKALINE MINT , CHOCOLATE, CREAMMINT , CHOCOLATE, CREAM
METALIC METALIC GRAPE, LEMONE-,LIMEGRAPE, LEMONE-,LIME

32. COLORANTSCOLORANTS
Colorants are used in the manufacturing of the Colorants are used in the manufacturing of the
chewable tablets for the following reasonchewable tablets for the following reason
1.1.To increase aesthetic appeal to the consumer To increase aesthetic appeal to the consumer
2.2.To aid in product identification and To aid in product identification and
differentiationdifferentiation
3.3.To mask unappealing or non uniform color of To mask unappealing or non uniform color of
raw materialsraw materials
4.4.To complement and match the flavor used in To complement and match the flavor used in
the formulationthe formulation

33. ►Two main forms of colorants are used in Two main forms of colorants are used in
the manufacturing of chewable tablets the manufacturing of chewable tablets
depending on the process of depending on the process of
manufacturingmanufacturing
1.1.DYESDYES

dyes are chemical compounds that dyes are chemical compounds that
exhibit their coloring power when exhibit their coloring power when
dissolved in a solventdissolved in a solvent

dyes are synthetic ,usually cheaper and dyes are synthetic ,usually cheaper and
available in a wide range of shades with available in a wide range of shades with
higher coloring power than the natural higher coloring power than the natural
pigments pigments

34. LAKESLAKES
►Lakes have been defined by the FDA as the Lakes have been defined by the FDA as the
“aluminum salts of fd&c water soluble dyes“aluminum salts of fd&c water soluble dyes
►fd&c lakes are available in six basic colors fd&c lakes are available in six basic colors
one :yellow, one :orange, two reds (a pink red one :yellow, one :orange, two reds (a pink red
and orange red) and two blues (a green blue, and orange red) and two blues (a green blue,
and royal blue)and royal blue)
►Lakes are used in chewable tablets made by Lakes are used in chewable tablets made by
direct compression in a concentration range of direct compression in a concentration range of
0,1 to 0,3%0,1 to 0,3%

35. MANUFACTURINGMANUFACTURING
►Four important aspects of the chewable Four important aspects of the chewable
tablet manufacture are the tablet manufacture are the
1. 1. Proper incorporation of the coloring agent Proper incorporation of the coloring agent
2. 2. Assurance Assurance of necessary particle size of necessary particle size
distributiondistribution
3.3. Maintenance of correct moisture content Maintenance of correct moisture content
4.4. Achievement of the proper tablet Achievement of the proper tablet
hardnesshardness

36. ► if the granulation process involves wet if the granulation process involves wet
granulation the extent of wetting and the rate granulation the extent of wetting and the rate
and extent of drying must be defined and extent of drying must be defined
►Over wetting can expected to produce hard Over wetting can expected to produce hard
granules that may have poor compression granules that may have poor compression
characteristics resulting in more softer and characteristics resulting in more softer and
friable tabletsfriable tablets
►Due to the lesser degree of particle Due to the lesser degree of particle
deformation these tablets always have a gritty deformation these tablets always have a gritty
mouth feel when chewed. mouth feel when chewed.
►The method and appropriate order for the The method and appropriate order for the
addition of the flavor and color must be addition of the flavor and color must be
determined if wet granulation is being useddetermined if wet granulation is being used

37. ►Since most flavor substances are volatile they Since most flavor substances are volatile they
can not be subjected to elevated temperatures can not be subjected to elevated temperatures
for this reason they can not be incorporated in for this reason they can not be incorporated in
wet granulationwet granulation
► flavors can be added in the final blending flavors can be added in the final blending
operation of the process operation of the process
►The color if in the form of a lake would be The color if in the form of a lake would be
incorporated in the same stepincorporated in the same step
►The concentration of these ingredients would The concentration of these ingredients would
not exceed 0.1%not exceed 0.1%
►An important consideration is the assurance of An important consideration is the assurance of
the uniform blendingthe uniform blending
►During compression the granules fracture and During compression the granules fracture and
release fresh white material on to the surface release fresh white material on to the surface
resulting in white spots on the colored back resulting in white spots on the colored back
ground called “speckling”.ground called “speckling”.

38. ANTACIDSANTACIDS
►From a formulation prospective antacids From a formulation prospective antacids
present extreme difficulty due to the present extreme difficulty due to the
nature and quality of the active ingredientsnature and quality of the active ingredients
►they are generally metallic, they are generally metallic,
chalky ,astringent, and gritty thus chalky ,astringent, and gritty thus
providing a combination of bad taste and providing a combination of bad taste and
bad mouth –feel to be over comebad mouth –feel to be over come
► the usual high dose levels required results the usual high dose levels required results
in very large tabletin very large tablet
►Below antacids are used in combination of Below antacids are used in combination of
two or more to provide better therapeutic two or more to provide better therapeutic
actionaction

39. ALUMINIUM HYDROXIDEALUMINIUM HYDROXIDE 80 – 600mg80 – 600mg
CALCIUM CARBONATECALCIUM CARBONATE 194-850194-850
MAGNISIUM MAGNISIUM
HYDROXIDE/OXIDEHYDROXIDE/OXIDE
65-40065-400
MAGNISIUM TRISILICATEMAGNISIUM TRISILICATE 20-50020-500
ALUMINUM CARBONATEALUMINUM CARBONATE ------
DIHYDROXYALUMINUM DIHYDROXYALUMINUM
AMINOACETATEAMINOACETATE
------
DIHYDROXYALUMINUM DIHYDROXYALUMINUM
SODIUM CARBONATESODIUM CARBONATE
------
MAGNESIUM CARBONATEMAGNESIUM CARBONATE - ---- ---
MAGNESIUM GLUCONATEMAGNESIUM GLUCONATE --------
POTASSIUM BICARBONATEPOTASSIUM BICARBONATE --------
SODIUM BICARBONATESODIUM BICARBONATE --------

40. ► in addition to the antacid components in addition to the antacid components
other ingredients are often found in other ingredients are often found in
these products as adjunct activesthese products as adjunct actives
►These include simenthicone at a level of These include simenthicone at a level of
20 to 40 mg per tablet as an anti 20 to 40 mg per tablet as an anti
flatulent .peppermint oil approximately 3 flatulent .peppermint oil approximately 3
mg per tablet is some times used as mg per tablet is some times used as
carminative ,alginic acid 200 to 400 mg is carminative ,alginic acid 200 to 400 mg is
used by some companiesused by some companies

41. DEXTROSE ANTACIDDEXTROSE ANTACID
FMA- 11FMA- 11 400mg400mg
SYLOID 244SYLOID 244 5050
EMDEXEMDEX 11001100
PHARMASWEET PHARMASWEET
POWDERPOWDER
2020
MAGNESIUM STEARETEMAGNESIUM STEARETE 1616

42. ►mix the first two for 5 min and screen mix the first two for 5 min and screen
through 30 mesh and mix for 10 to 15 through 30 mesh and mix for 10 to 15
minmin
►Add emdex and pharmasweet to step 1 Add emdex and pharmasweet to step 1
and blend thoroughly for 10 to 15 minand blend thoroughly for 10 to 15 min
►Add magnesium stearate to step 2 blend Add magnesium stearate to step 2 blend
5 min and compress5 min and compress

43. COUGH AND ANALGESICSCOUGH AND ANALGESICS
The primary appeal of the products in this The primary appeal of the products in this
category is the pediatric market in to the teens, category is the pediatric market in to the teens,
generally the levels of the drug or one quarter or generally the levels of the drug or one quarter or
less of the adult dose, which would require the less of the adult dose, which would require the
use of a large number of tablets by an adult.use of a large number of tablets by an adult.
Drugs commonly encountered include aspirin, Drugs commonly encountered include aspirin,
acetaminophen, chlorpheniramin, acetaminophen, chlorpheniramin,
phenylpropanlamine, pseudo ephedrine, and phenylpropanlamine, pseudo ephedrine, and
dextrometharphanedextrometharphane
These may be used alone or in various These may be used alone or in various
combinations with appropriate attention to combinations with appropriate attention to
possible incompatibilities.possible incompatibilities.

44. 
The one common property all of these drugs The one common property all of these drugs
share is unpleasant taste . Aspirin is acidic and share is unpleasant taste . Aspirin is acidic and
astringent the others are all very bitterastringent the others are all very bitter

In compatible drugs that may be desired in the In compatible drugs that may be desired in the
combination such as aspirin and combination such as aspirin and
phenylpropanolamine require special treatment phenylpropanolamine require special treatment
as they would in a non chewable tabletas they would in a non chewable tablet

The drugs must kept separated this can be The drugs must kept separated this can be
accomplished by multilayer technology or accomplished by multilayer technology or
through coating both drugs prior to blendingthrough coating both drugs prior to blending

45. ACETAMINOPHEN TABLETACETAMINOPHEN TABLET
INGRADIENTSINGRADIENTS QANTITY PER TABLETQANTITY PER TABLET
MANNITOLMANNITOL 720.0mg720.0mg
SODIUM SACCHARINESODIUM SACCHARINE 6.0mg6.0mg
ACETAMINOPHENACETAMINOPHEN 120.0mg120.0mg
BINDER SOLUTIONBINDER SOLUTION 21.6mg21.6mg
PIPPERMINT OILPIPPERMINT OIL 0.5mg0.5mg
SYLOIDSYLOID 0.5mg0.5mg
BANANA, PERMASEAL F-BANANA, PERMASEAL F-
49324932
2.0mg2.0mg
ANISE. PERMASEAL F-2837ANISE. PERMASEAL F-2837 2.0mg2.0mg
SODIUM CHLORIDESODIUM CHLORIDE 6.0mg6.0mg
MAGNESIUM STEARATEMAGNESIUM STEARATE 27.5mg27.5mg

46. Screen the mannitol and sodium saccharine Screen the mannitol and sodium saccharine
through screen 40 mesh .through screen 40 mesh .
Blend thoroughly with acetaminophen ,using Blend thoroughly with acetaminophen ,using
180 ml of blinder solution per 100 tablets. 180 ml of blinder solution per 100 tablets.
granulate and dry overnight at 140 to 150 °fgranulate and dry overnight at 140 to 150 °f
Screen through a 12 mesh screen Screen through a 12 mesh screen
Adsorb the peppermint oil onto the syloid 244 Adsorb the peppermint oil onto the syloid 244
and mix with the flavors and sodium chloride and mix with the flavors and sodium chloride
Blend this flavor mixture and the dried Blend this flavor mixture and the dried
granulation, and the magnesium stearate.granulation, and the magnesium stearate.
Compress on ½ in flat –face bevel edge punches Compress on ½ in flat –face bevel edge punches
to a hardness of 12 to 15 kgto a hardness of 12 to 15 kg

47. VITAMINS/MINERALS/FOOD VITAMINS/MINERALS/FOOD
SUPPLIMENTSSUPPLIMENTS

It has long been common medical practice to It has long been common medical practice to
supplement the diet with vitamin –mineral supplement the diet with vitamin –mineral
products from infancy into elderliness. products from infancy into elderliness.
although such products may be presumed although such products may be presumed
unnecessary for those who consume an unnecessary for those who consume an
appropriate dietappropriate diet

Children's vitamin in recent years have Children's vitamin in recent years have
become extremely complex from a become extremely complex from a
manufacturing and tooling perspective manufacturing and tooling perspective

Marketing pressure have dictated the Marketing pressure have dictated the
adoption of extraordinarily detailed shapes adoption of extraordinarily detailed shapes
such as cartoon characters , animals etc.such as cartoon characters , animals etc.

48. 
Such tablets require punches and dies with Such tablets require punches and dies with
Numerous compound curves and punch faces Numerous compound curves and punch faces
with many detail marketing'swith many detail marketing's

These required optimized formulations and These required optimized formulations and
manufacturing process in order to ensure manufacturing process in order to ensure
acceptable appearance quality levelsacceptable appearance quality levels
the basic taste characteristics of various the basic taste characteristics of various
vitamins follows vitamins follows
Vitamin A acetate, vitamin D Vitamin A acetate, vitamin D
22 , and vitamin E – , and vitamin E –
“substantially tasteless”“substantially tasteless”
Vitamin BVitamin B
11 – “yeasty” bitter – “yeasty” bitter
Vitamin BVitamin B
66 – taste less – taste less

Niacinamide- very bitterNiacinamide- very bitter

49. 
Vitamin C –sourVitamin C –sour

Calcium pantothenate- bitterCalcium pantothenate- bitter

Biotin- tastelessBiotin- tasteless

Folic acid- nearly bitterFolic acid- nearly bitter

50. 
A multivitamin and mineral mixture will have A multivitamin and mineral mixture will have
a bitter plus sour plus salty plus metallic a bitter plus sour plus salty plus metallic
tastes.tastes.

The sourness can be depressed by adding a The sourness can be depressed by adding a
sweetness via the vehicle and additional sweetness via the vehicle and additional
sweetener sweetener

Reduction in the metallic taste of the ferrous Reduction in the metallic taste of the ferrous
fumarate has been accomplished by a fumarate has been accomplished by a
patented coating process in which the iron patented coating process in which the iron
salts is coated at least one of the following . A salts is coated at least one of the following . A
mono glycerate or a diglycerate of a mono glycerate or a diglycerate of a
saturated fatty acid using spray congealing saturated fatty acid using spray congealing
methodmethod

The most common single vitamin product is The most common single vitamin product is
vitamin C vitamin C

51. 
Since ascorbic acid is extremely sour tasting Since ascorbic acid is extremely sour tasting
additional steps are taken to improve the taste additional steps are taken to improve the taste

A combination of ascorbic acid and sodium A combination of ascorbic acid and sodium
ascorbate both of which are available in direct ascorbate both of which are available in direct
compressed form is less sour and therefore compressed form is less sour and therefore
easier to flavor easier to flavor

Another approach is coating the ascorbic acid Another approach is coating the ascorbic acid
with ethyl cellulose to reduce its solubility and with ethyl cellulose to reduce its solubility and
therefore its sournesstherefore its sourness

52. CHEWABLE MULTI VITAMIN TABLETSCHEWABLE MULTI VITAMIN TABLETS
Vitamin A acetateVitamin A acetate 12.50 mg12.50 mg
Vitamin DVitamin D
11 4.50mg4.50mg
VitaminDVitaminD
22 0.58mg0.58mg
Vitamin E. 50 % SDVitamin E. 50 % SD 33.00mg33.00mg
Ascorbic acid 90%Ascorbic acid 90% 67.00mg67.00mg
Folic acidFolic acid 0.40mg0.40mg
Vitamin BVitamin B
22 5.20mg5.20mg
Vitamin B Vitamin B
66 6.00mg6.00mg

53. VitaminVitamin B 12 B 12 6.006.00
NIACINAMIDENIACINAMIDE 60.0060.00
FERROUS FUMARATEFERROUS FUMARATE 18.0018.00
PHARMASWEET PHARMASWEET
POWDERPOWDER
8.708.70
NATURAL ORANGE NATURAL ORANGE
FLAVORFLAVOR
10.9010.90
EMDEXEMDEX 938.52938.52
COLOR ORANGE NO COLOR ORANGE NO
S31282S31282
q,sq,s
MAGNESIUM STEARATEMAGNESIUM STEARATE 8.708.70

54. ►Mix vitamin DMix vitamin D
1 1 .D.D
2 2 .folic acid and B.folic acid and B
1212 with with
niacinamide for 15 min niacinamide for 15 min
►To 1 add vitamin A,E , ascorbic To 1 add vitamin A,E , ascorbic
acid ,Bacid ,B
22,B,B
66 ,ferrous fumarate ,small portion of ,ferrous fumarate ,small portion of
emdex, and mix thoroughly for 15 minemdex, and mix thoroughly for 15 min
►To 2 add remaining emdex ,flavor , and To 2 add remaining emdex ,flavor , and
pharmasweet and mix for 10 to 15 minpharmasweet and mix for 10 to 15 min
►Add color to 3 and blend thoroughly until it is Add color to 3 and blend thoroughly until it is
evenly distributed evenly distributed
►Add magnesium stearate to 3 ,blend 5 min and Add magnesium stearate to 3 ,blend 5 min and
compresscompress

55. EVALUATION OF CHEWABLE TABLETSEVALUATION OF CHEWABLE TABLETS
►Organoleptic evaluation takes place at various Organoleptic evaluation takes place at various
stages in the development of a chewable tabletsstages in the development of a chewable tablets
►Stage 1,2,3 are generally carried out by the Stage 1,2,3 are generally carried out by the
formulating pharmacist either alone or in formulating pharmacist either alone or in
collaboration with a small taste panel with in a collaboration with a small taste panel with in a
development laboratory development laboratory
►For example evaluation of For example evaluation of
dextrometharphan.ephidrine for their bitter ness dextrometharphan.ephidrine for their bitter ness
followed by the taste comparison of these drugs followed by the taste comparison of these drugs
after absorption onto a polycarboxylic acid resinafter absorption onto a polycarboxylic acid resin
►The resin adsorbates are further coated with a 4:1 The resin adsorbates are further coated with a 4:1
ethyl cellulose –hydrohypropylmethylcellulose ethyl cellulose –hydrohypropylmethylcellulose
polymer at various concentrations of coating polymer at various concentrations of coating

56. ►Comparisons were made against pure Comparisons were made against pure
drug ,adsorbate drug ,and adsorbed drug with drug ,adsorbate drug ,and adsorbed drug with
variable coating percentages variable coating percentages
►For comparative quantitation caffeine solution For comparative quantitation caffeine solution
were chosen as the standard for bitterness were chosen as the standard for bitterness
intensity on a scale of 0 to 3,3 being strong intensity on a scale of 0 to 3,3 being strong
bitter ,2 moderate ,1 slight and 0 being no taste bitter ,2 moderate ,1 slight and 0 being no taste
,x being threshold,x being threshold

57. Form of dextrometharphan Degree of bitterness after time
hydro bromide 10sec 1min 2min 5min 10min 15min

Uncoated drug
powder
> 3>32.5 1.510.5
Uncoated adsorbate
powder
2 21.5 0.5X0
Uncoated adsorbate
In tablet
1.51.51.5 to21.51X
Powder adsorbate
Coated with 25.4%
polymer
0.5X to
0.5
X X 00
Adsorbate powder
Coated with 25.4%
polymer in tablet
X to
0.5
0.5X X X 0

58. ►The above table illustrates that although The above table illustrates that although
adsorption does reduces bitterness. It is adsorption does reduces bitterness. It is
necessary to reduce it further by polymeric necessary to reduce it further by polymeric
coatingcoating
►The uncoated adsorbate in the manitol -based The uncoated adsorbate in the manitol -based
tablet formulation is much more bitter than the tablet formulation is much more bitter than the
tablet made by with the coated adsorbatetablet made by with the coated adsorbate

59. CHEMICAL EVALUATIONCHEMICAL EVALUATION
►This aspect involves total drug assay and This aspect involves total drug assay and
content uniformity testing if applicablecontent uniformity testing if applicable
ASSAY FOR DRUG CONTENTASSAY FOR DRUG CONTENT
A suitable analytical method (chromatographic , A suitable analytical method (chromatographic ,
titrimetric, spectrophotometric, etc) is used to titrimetric, spectrophotometric, etc) is used to
determine the active content on a respective determine the active content on a respective
sample (usually an aliquot of 20 randomly sample (usually an aliquot of 20 randomly
selected tablets after pulverization)selected tablets after pulverization)
The recovered amount of the active drug is The recovered amount of the active drug is
then expressed as percent of labeled drug then expressed as percent of labeled drug
contentcontent

60. DOSAGE UNIFORMITYDOSAGE UNIFORMITY

This test is done to ensure that the batch of the This test is done to ensure that the batch of the
tablets is uniform as to the content of active tablets is uniform as to the content of active
ingredient per dosage unit within specified limitsingredient per dosage unit within specified limits

If the drug level in the dosage regimen is high. If the drug level in the dosage regimen is high.
then a weight variation test is sufficient to indicate then a weight variation test is sufficient to indicate
uniformity of drug content in the dosage unituniformity of drug content in the dosage unit

As is usually the case with chewable tablets where As is usually the case with chewable tablets where
provision is made for a large use of sweet provision is made for a large use of sweet
excipients ,coating agents and for taste masking excipients ,coating agents and for taste masking
and mouth feel .then individual assay of the give and mouth feel .then individual assay of the give
number of randomly selected dosage unit is done number of randomly selected dosage unit is done
to obtain drug content in the various samplesto obtain drug content in the various samples

61. ►The U.S pharmacopoeia (USP) gives in detail the The U.S pharmacopoeia (USP) gives in detail the
protocol and acceptance criteria for the protocol and acceptance criteria for the
determination of dosage uniformity for determination of dosage uniformity for
conventional tablets, which is also applicable to conventional tablets, which is also applicable to
chewable tabletschewable tablets
INVITRO AND IN VIVO EVALUATIONINVITRO AND IN VIVO EVALUATION

Since antacids represents a sizable proportion Since antacids represents a sizable proportion
of chewable tablets a description of their in of chewable tablets a description of their in
vitro and in vivo evaluation is considered vitro and in vivo evaluation is considered
importantimportant

Antacids are meant to exert their effect in the Antacids are meant to exert their effect in the
stomach and hence the gastric bioactivity is stomach and hence the gastric bioactivity is
prime concernprime concern

62. ►An antacid preparation should be evaluated for An antacid preparation should be evaluated for
its rate and extent of action and total acid-its rate and extent of action and total acid-
consuming capacity during in vitro and in vivo consuming capacity during in vitro and in vivo
testingtesting
►The tablets are comminuted to a particle size The tablets are comminuted to a particle size
between 20 and 100 mesh and an accurately between 20 and 100 mesh and an accurately
weighed amount equivalent to the minimum weighed amount equivalent to the minimum
labeled dosage is mixed with 40 ml of water labeled dosage is mixed with 40 ml of water
under standard conditions for 1 min under standard conditions for 1 min
►Then 10 ml of 0.5 N HCL is added to the slurry Then 10 ml of 0.5 N HCL is added to the slurry
and stirred under fixed conditions for 10 min .the and stirred under fixed conditions for 10 min .the
pp
HH
of the mixture is then read of the mixture is then read
►If the pIf the p
HH
is below 3.5 the product is not permitted is below 3.5 the product is not permitted
to be labeled as antacidto be labeled as antacid

63. ►While the determination of the acid – While the determination of the acid –
neutralization capacity is an important in vitro neutralization capacity is an important in vitro
parameterparameter
►The onset and duration of the neutralizing The onset and duration of the neutralizing
action are equally importantaction are equally important
►Using bachrach titration a fixed quantity of a Using bachrach titration a fixed quantity of a
tablet powder in a fixed volume water had an tablet powder in a fixed volume water had an
initial pinitial p
H H
of 8.66, which was initially lowered to of 8.66, which was initially lowered to
3.5 within 60 sec by the addition of 1.1 ml of 0.8 3.5 within 60 sec by the addition of 1.1 ml of 0.8
N HCL. To maintain the pN HCL. To maintain the p
HH
at 3.5 , 4.9 ml of the at 3.5 , 4.9 ml of the
acid was required. and the end point was acid was required. and the end point was
reached at 13.8 min reached at 13.8 min
►Further addition of the acid resulted in the Further addition of the acid resulted in the
lowering of the plowering of the p
HH
below 3.5 below 3.5

64. ►These data when compared to those for These data when compared to those for
suspension containing an equivalent suspension containing an equivalent
stoichiometric quantity of the active ingredient. stoichiometric quantity of the active ingredient.
indicated that the suspension required a large indicated that the suspension required a large
volume of the acid for initial on set .and that it volume of the acid for initial on set .and that it
took a long time for the acid to initially bring took a long time for the acid to initially bring
the ph 3.5 the ph 3.5
►Further more acid was needed to reach the Further more acid was needed to reach the
endpoint endpoint
►These all observations seemed to lead to the These all observations seemed to lead to the
conclusion that apparently the suspension was conclusion that apparently the suspension was
somewhat superior to the chewable tablet somewhat superior to the chewable tablet
containing the same active ingredientcontaining the same active ingredient

65. PHYSICAL EVALUATIONPHYSICAL EVALUATION
►The physical evaluation involves followingThe physical evaluation involves following
►Tablet physical appearance : as one of the Tablet physical appearance : as one of the
quality control procedure tablets should be quality control procedure tablets should be
inspected for smoothness, absence of cracks, inspected for smoothness, absence of cracks,
chips and undesirable characteristicschips and undesirable characteristics
►If the tablets are colored this would include If the tablets are colored this would include
examination for mottling and other evidence of examination for mottling and other evidence of
non uniform color distribution except where non uniform color distribution except where
they are used intentionallythey are used intentionally

66. HARDNESSHARDNESS

The hardness test is performed to provide a The hardness test is performed to provide a
measure of tablet strength. tablets should be measure of tablet strength. tablets should be
hard enough to with stand packing and hard enough to with stand packing and
shipping but not so hard to create undue shipping but not so hard to create undue
difficulty upon chewingdifficulty upon chewing

Tablet hardness is determined using equipment Tablet hardness is determined using equipment
from various suppliers that measure the force from various suppliers that measure the force
required to break up the tabletrequired to break up the tablet

67. FRIABILITYFRIABILITY

The friability test gives an indication of the The friability test gives an indication of the
tablets ability to resist chipping and abrasion on tablets ability to resist chipping and abrasion on
handling during packing and shippinghandling during packing and shipping

Usually for conventional tablets a friability value Usually for conventional tablets a friability value
of 1% or less is desired while for chewable of 1% or less is desired while for chewable
tablets friability value of up to 4% are acceptedtablets friability value of up to 4% are accepted

68. DISINTIGRATIONDISINTIGRATION

This test initially may not appear appropriate This test initially may not appear appropriate
for chewable tablets as these tablets are to be for chewable tablets as these tablets are to be
chewed before being swallowed ,however chewed before being swallowed ,however
patient especially patriotic and geriatric have patient especially patriotic and geriatric have
been kwon to swallow these chewable tablets been kwon to swallow these chewable tablets

This test would thus indicate the ability of the This test would thus indicate the ability of the
tablet to disintegrate and still provide the tablet to disintegrate and still provide the
benefit of the drug if it accidentally swallowed benefit of the drug if it accidentally swallowed

69. DISSOLUTIONDISSOLUTION
►The dissolution test measure the rate of The dissolution test measure the rate of
dissolution of the drug from the dosage form in dissolution of the drug from the dosage form in
vitrovitro
►It is usually expressed as extent of dissolution. It is usually expressed as extent of dissolution.
this test is necessary to help in the prediction of this test is necessary to help in the prediction of
the behavior of the drug in the dosage form the behavior of the drug in the dosage form
after ingestion and as a quickly control tool for after ingestion and as a quickly control tool for
checking batch – to batch uniformity checking batch – to batch uniformity
►Chewable tablets should be tested in two forms Chewable tablets should be tested in two forms
: intact and partially crushed: intact and partially crushed

70. STABLITY TESTINGSTABLITY TESTING
►Stability testing of dosage forms or drug Stability testing of dosage forms or drug
products is carried out to evaluate time –products is carried out to evaluate time –
dependent changesdependent changes
►Accelerated stability testing is used to predict Accelerated stability testing is used to predict
quickly potential changes that may occur in a quickly potential changes that may occur in a
productproduct
►There are three areas of major concern in the There are three areas of major concern in the
stability testing of chewable tablets : stability testing of chewable tablets :
organoleptic, chemical, physical. the data organoleptic, chemical, physical. the data
obtained from chemical evaluation of the obtained from chemical evaluation of the
tablets at elevated tem and humidity ,stress tablets at elevated tem and humidity ,stress
condition are most usefulcondition are most useful

71. ►The FDAs stability guidelines describe in The FDAs stability guidelines describe in
considerable details the appropriate condition considerable details the appropriate condition
for conducting stability studies in order to for conducting stability studies in order to
achieve the necessary goals and achievements achieve the necessary goals and achievements
►The stability testing of the chewable tablets The stability testing of the chewable tablets
include all the tests for conventional tablets include all the tests for conventional tablets
plus test unique to chewable tabletsplus test unique to chewable tablets

72. OTHER TESTS IN THE STABILITY OTHER TESTS IN THE STABILITY
PROGRAM WOULD INCLUDEPROGRAM WOULD INCLUDE
►Active drug content determination using a Active drug content determination using a
validated stability indicating assay methodvalidated stability indicating assay method
►Change , if any , in physical characterization of Change , if any , in physical characterization of
the tablet – mottling of colored tablets .color the tablet – mottling of colored tablets .color
migration, appearance of spotsmigration, appearance of spots
►Change in the tablet hardness, Change in the tablet hardness,
friability ,dissolution rate and extent of friability ,dissolution rate and extent of
dissolutiondissolution
►Moisture content of the tabletsMoisture content of the tablets
►Stability of the coating systemsStability of the coating systems
►Stability of the colorantsStability of the colorants