Transcript chewable tablets

MULTIVITAMIN
PRODUCTS
Department of Pharmaceutics
Hindu College of Pharmacy
MULTIVITAMIN
A multivitamin is a preparation intended to supplement a
human diet with vitamins, dietary minerals and other
nutritional elements.
A multivitamin/mineral supplement is defined as the
supplement containing 3 or more vitamins and minerals but
does not include herbs, hormones, or drugs with each
nutrient at a dose below the tolerable upper level
determined by the Food and Drug Board and the maximum
daily intake to not cause a risk for adverse health effects.
Such preparations are available in the form of tablets,
capsules,pastilles,powders,liquids and injectable
formulations.
The optimized formulations and manufacturing
process are required in order to ensure
acceptable appearance quality levels
The basic taste characteristics of various vitamins
follows
Vitamin A acetate, vitamin D 2 , and vitamin E –
“substantially tasteless”
Vitamin B1 – “yeasty” bitter
Vitamin B6 – taste less
Niacinamide- very bitter
Vitamin C –sour
Calcium pantothenate- bitter
CHEWABLETABLETS
Chewable tablets when chewed produce a pleasant tasting
residue in the mouth that when swallowed does not leave a
bitter or unpleasant after taste.
These tablets have been used in the tablet formulation for
children, especially multivitamin formulations and for the
administration of antacids and selected anti- biotics.
ADVANTAGES OF CHEWABLE TABLETS

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Patient convenience
use as a substitute for liquid dosage forms.
Improved patient acceptance
better bioavailability.
DISADVANTAGES OF CHEWABLE TABLETS
Bad tasting drugs should not be suitable,
 Drugs having high dosage levels should be
difficult to formulate.
Flow chart of various aspects to be considered in connection
with chewable tablets
TYPICAL PRODUCTS
Vitamins
Antacids
Analgesics
Cold Remedies
FORMULATION FACTORS
Amount of active substances as
a percent of total tablet weight
Flow
Lubrication
Disintegration
Compressibility
Compactability-Stability
Organoleptic considerations
DESIRED PRODUCT
ATTRIBUTES
Good taste and mouthfeel
Acceptable bioavailabilityand
bioactivity ",
Acceptable stability and quality
Economical formula and
process
FORMULATION TECHNIQUES Spray congealing and coating
Granulation and Coating
AND APPROACHES
Use of amino acid and protein
Microencapsulation
Solid dispersions
Ion exchange
hydrolysates
Inclusion complexes Molecular
complexes
EVALUATION
Taste panels
Blood levels (for adsorbed
drugs)
In vitro vs. in vivo correlation
for antacids
Stability (chemical, physival,
organoleptic)
Quality control and assurance
Formation of salts or derivatives
Excipients
Artificial sweeteners
Flavoring
Coloring
FORMULATIO
N FACTORS
TASTE AND FLOVOR:
• Salt and sour tastes are derived form substances capable of ionizing in
solution.
• The term flavor generally refers to a specific combined sensation of taste and
smell.
EX: sugars has a sweet taste but no flavor whereas honey has a sweet taste and
a characteristic smell – the combination of the two being known as honey
flavor
AROMA:
• Pleasant smells are generally referred as aromas
EX well formulated orange- flavored chewable tablets should
have a characteristic sweet and sour taste and aroma of fresh
orange.
MOUTH -FEEL
• The term mouth feel is related to the type of sensation or touch
that a tablet produces in the mouth upon chewing
AFTER –EFFECTS
 iron salts leave a rusty after taste
 saccharin in high amounts tends to leave a bitter after taste
 Another common after effect is a numbing sensation of a portion
of the whole surface of the tongue and mouth
PHYSICAL PROPORTIES
color,odor,taste,after taste , and mouth feel
Physical form: crystal , powders , amorphous solid, oily liquid etc
Melting or congealing temperature
Existing of polymers, Moisture content
Aqueous solubility.
Active drug stability on its own
Compressibility if applicable
CHEMICAL 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
Assessment of the Formulation Problems

The first step in the formulation of a chewable tablet is to obtain a
complete profile of the active drug.The drug profile should eliminate
potentially incompatible excipients, flavors, and the like at the outset,
leading to the use of excipients that would best compliment the drug
chemically, physically and organoleptically.
FORMULATION
TECHNIQUES
Formulation Techniques
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•
•
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Coating by Wet Granulation
Microencapsulation
Solid Dispersions
Adsorbate Formation Technique
– Solvent method
– Melting method
•
•
•
•
Ion Exchange
Spray congealing and spray coating
Formation of different salts or derivatives
Use of Amino acids and protein hydrolysates
COATING 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
(a) Top spray fluidized bed system. (b) Bottom spray fluidized system.
MICRO ENCAPSULATION
1.
Formation of three immiscible phases
i.e. liquid manufacturing vehicle phase , a core material drug
phase , and a coating material phase.
2.
Depositing the liquid polymer coating by sorption around the
core material under controlled physical mixing of the three
phases.
3.
Rigidizing the coating usually by thermal cross linking or
dissolution techniques to form a rigid microcapsule
• The resultant coated granules not only mask the taste of a drug but
also minimize any physical and chemical incompatibility between in
gradients
• The typical coating material include
carboxy methyl cellulose .
cellulose acetate phthalate
Ethyl cellulose.
Gelatin
Poly vinyl alcohol, gelatin –acacia, shellac .
SOLID DISPERSION
• Bad tasting drugs can be prevented from stimulating the taste buds by
adsorption on to substrates capable of keeping the drugs adsorbed while in
the mouth but releasing them eventually in the stomach or GIT
• Good example is the adsorption of dextrometharphan hydro bromide on to
magnesium trisilicate substrate
ADSORBATE FORMATION TECHNQUES
SOLVENT METHOD
 The formation of an adsorbate involves dissolving the
drug in a solvent ,mixing the solution with the
substrate and evaporating the solvent –leaving the
drug molecules adsorbed upon the substrate
MELTING METHOD
 Here the drug or drugs and a carrier are melted together by
heating, the melted mixture is then cooled and rapidly
solidified in an ice bath with vigorous stirring . The product is
then pulverized and sized.
 Heat liable drugs volatile drugs and drugs that decompose on
melting are obviously unsuitable
ION EXCHANGE
 It is the reversible interchange of ions between a solid and a
liquid phase in which there is no permanent change in the
structure of the solid . The solid is the ion exchange material
and the ion could be a drug
 When used as a drug carrier ion exchange materials provides a
mean for binding drugs on to an insoluble polymeric matrix and
can effectively mask the problems of taste and odor
SPRAY CONGELING AND SPRAY COATING
• Spray congealing involves cooling of melted substance in the form of fine
particles during their travel from a spray nozzle to the distant vicinity of a
spray chamber held at a temperature below their melting point.
• It must be noted that the weight of the active substance is
approximately one-third that of the spray-congealed preparation. For
small-dose entities, such as the vitamins, spray congealing is ideally
suited.
• The spray coating process involves the spraying of a
suspension of the drug particles in a solution of the
coating material through a atomizer in to a high –
velocity stream of warm air
• The coarse droplets delivered by the atomizer
consists of the drug particles enveloped by coating
solution , as the solvent evaporates the coating
materials encapsulates the drug particles
FORMTION OF THE DIFFERENT SALTS OR
DERIATIVES
It is an attempt made to modifies the chemical
composition of the drug include it self so as to render
it less soluble in saliva and there by less stimulating
for the taste buds or to obtain a taste less or less
bitter form
USE OF AMINO ACIDS AND PROTIEN HYDROLYSATES
• By combining amino acids their salts or a mixture of two it is
possible to substantially reduce the bitter taste of penicillin.
• Some of the preferred amino acids are sacrosin, alanine ,
taurine, glutamine acid and especially glycine.
EXCIPIENTS
NAME
SOURCE
PARTICLE
SIZE
LOD
BROWN
SUGAR
AMSTAR
92%ON 50
MESH
0.7%
MOLASSES
GRANULES
AMSTAR
100%ON 12
MESH
1%
50% ON 60
MESH
4%
COMPRASSI INGREDIENT 50% ON 60
BLE HONEY TECHNOLOGY MESH
4%
COMPRESSIBL INGREDIENT
E MOLASSES TECHNOLOGY
COMPRESSIBL AMSTAR
E SUGAR
75% ON 100
MESH
0.5%
DEXTRON/FR MENDELL
UCTOSE/MALT
OSE
3% ON 20
MESH
DEXTRONE
MENDELL
3% ON 20
MESH
9%
LACTOSE
SHEFFIELD
20 % ON 60
MESH
1%
7%
MANNITAL
_
75% ON 80
MESH
0.3%
SORBITAL
PFIZER
33%ON 60
MESH
1%
SWEETENERS
MATERIALS
RELATIVE SWEETNESS
ASPARTAME
CYCLAMATES
200
30 – 50
GLYCYRRHIZIN
SACCHARIN
DEXTRON(GLUCOSE)
50
450
0.7
FRUCTOSE(LEVULOSE)
LACTOSE
1.7
0.2
MALTOSE
MANNITOL
0.3
0.5-0.7
SORBOTAL
SUCROSE
O.5-0.6
1
FLAVORS
SWEET
VANILLA, STONE FRUITS,
GRAPE,BERRIES,MAPLE
SOUR
CITRUS,CHEERY,RASHBERRY,STRAW BEERY
SALTY
NUTTY,BUTTERY,SPICE,MELON
BITTER
LICORICE,ANISE,CHERRY,NUT,GRAPE FRUIT
ALKALINE
MINT , CHOCOLATE, CREAM
METALIC
GRAPE, LEMONE-,LIME
COLORANTS
Colorants are used in the manufacturing of the
chewable tablets for the following reason
1. To increase aesthetic appeal to the consumer
2. To aid in product identification and differentiation
3. To mask unappealing or non uniform color of raw
materials
4. To complement and match the flavor used in the
formulation
Two main forms of colorants are
1.DYES
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
chemical compounds that exhibit their coloring power when
dissolved in a solvent ,
cheaper and available in a wide range of shades with higher
coloring power than the natural pigments
2.LAKES
 Lakes have been defined by the FDA as the “aluminum salts of
fd&c water soluble dyes
 fd&c lakes are available in six basic colors one :yellow, one
:orange, two reds (a pink red and orange red) and two blues (a
green blue, and royal blue)
 concentration range of 0,1 to 0,3%
MANUFACTURING
PROCESS
Four important aspects of the chewable tablet manufacture are
the
1. Proper incorporation of the coloring agent
2. Assurance of necessary particle size distribution
3. Maintenance of correct moisture content
4. Achievement of the proper tablet hardness
•
If the granulation process involves wet granulation the extent of
wetting and the rate and extent of drying should be considered.
• Over wetting can expected to produce hard granules that may
have poor compression characteristics resulting in more softer
and friable tablets. So care must be taken
• The method and appropriate order for the addition of the flavor
and color must be determined if wet granulation is being used.
• Since most flavor substances are volatile they can not
be subjected to elevated temperatures for this reason
they can not be incorporated in wet granulation
• flavors can be added in the final blending operation of
the process
• The color if in the form of a lake would be incorporated
in the same step
• The concentration of these ingredients would not
exceed 0.1%
• An important consideration is the assurance of the
uniform blending
• During compression the granules fracture and release
fresh white material on to the surface resulting in
white spots on the colored back ground called
“speckling”.
CHEWABLE MULTI VITAMIN TABLETS
Vitamin A acetate
12.50 mg
Vitamin D1
4.50mg
VitaminD2
0.58mg
Vitamin E. 50 % SD
33.00mg
Ascorbic acid 90%
67.00mg
Folic acid
0.40mg
Vitamin B2
5.20mg
Vitamin B
6
6.00mg
Vitamin B 12
6.00
NIACINAMIDE
FERROUS FUMARATE
PHARMASWEET POWDER
60.00
18.00
8.70
NATURAL ORANGE
FLAVOR
EMDEX
10.90
COLOR ORANGE NO
S31282
MAGNESIUM STEARATE
938.52
q,s
8.70
• Mix vitamin D1 .D2 .folic acid and B12 with niacinamide
for 15 min
• To 1 add vitamin A,E , ascorbic acid ,B2,B6 ,ferrous
fumarate ,small portion of emdex, and mix thoroughly
for 15 min
• To 2 add remaining emdex ,flavor , and pharmasweet
and mix for 10 to 15 min
• Add color to 3 and blend thoroughly until it is evenly
distributed
• Add magnesium stearate to 3 ,blend 5 min and
compress
EVALUATION OF CHEWABLE TABLETS
 Organoleptic evaluation takes place at various stages in
the development of a chewable tablets
 For example evaluation of dextrometharphan,
ephidrine for their bitterness followed by the taste
comparison of these drugs after absorption onto a
polycarboxylic acid resin
CHEMICAL EVALUATION
ASSAY FOR DRUG CONTENT
A suitable analytical method (chromatographic ,
titrimetric, spectrophotometric, etc) is used to
determine the active content on a respective sample
(usually an aliquot of 20 randomly selected tablets
after pulverization)
The recovered amount of the active drug is then
expressed as percent of labeled drug content
DOSAGE UNIFORMITY
As is usually the case with chewable tablets where
provision is made for a large use of sweet excipients
,coating agents and for taste masking and mouth feel
.then individual assay of the given number of randomly
selected dosage unit is done to obtain drug content in
the various samples
PHYSICAL EVALUATION
• Tablet physical appearance : as one of the quality
control procedure tablets should be inspected for
smoothness, absence of cracks, chips and undesirable
characteristics
• If the tablets are colored this would include
examination for mottling and other evidence of non
uniform color distribution except where they are used
intentionally
HARDNESS
 The hardness test is performed to provide a measure of
tablet strength. Tablets should be hard enough to with
stand packing and shipping but not so hard to create
undue difficulty upon chewing
FRIABILITY
for chewable tablets friability value of up to 4%
are accepted
DISINTIGRATION
This test indicate the ability of the tablet to disintegrate
and still provide the benefit of the drug if it accidentally
swallowed
DISSOLUTION
Chewable tablets should be tested in two forms : intact
and partially crushed
STABLITY TESTING
• Stability testing of dosage forms or drug products is carried out
to evaluate time –dependent changes.
• Accelerated stability testing is used to predict quickly potential
changes that may occur in a product.
• There are three areas of major concern in the stability testing of
chewable tablets : organoleptic, chemical, physical the data
obtained from chemical evaluation of the tablets at elevated
tem and humidity ,stress condition are most useful
OTHER TESTS IN THE STABILITY PROGRAM
WOULD INCLUDE
• Active drug content determination.
• Changes in physical characterization of the tablet
• Change in the tablet hardness, friability ,dissolution rate and
extent of dissolution
• Moisture content of the tablets
• Stability of the coating systems
• Stability of the colorants
REFERENCES:
1. Pharmaceutical Dosage Forms: Volume 1 second edition,Revised and
Expanded Herbert A. Lieberman pg no 176 & 404 to 415
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