MULTIVITAMINS

Most popular dosage form

Liquid products for oral use, compressed
tablets and capsules
In developing the formula of any
multivitamin we should want to follow….
 The limits prescribed under drugs and
cosmetics act and rules
 Stabilities of individual vitamin compounds
and inter-vitamin incompatibilities
 Absorption profiles of vitamins
 Overage recommended by FIP
Limit prescribed
STABILITIES

VITAMIN-A
 It undergo addition reactions with
bisulphates and some solvents those have
double bond in its molecule
 Exists in cis-trans isomers

 When trans form changes to cis form can

reduce 65-70% of potency Without showing
any change in chemical assay
 Oxidation is the most important reason
 Air, peroxides and the presence of
catalysts etc…..
 Trace metal like Cu and Fe promote
oxidative degradation
 Antioxidant agents like
nordihydroguaiaretic acid (NHGA) and
ascorbyl palmitate will prevent
oxidations
 Vitamin A stabilizers- N-N-diphenyl-p-
phenylene diamine,malt
extract,tocopherol and 2-6-di-tertiary
butyl-4-methyl phenol…
 Readily degraded in aqueous media
than oily vehicles.
 Vit A alcohol has been reported to be
more stable than palmitate in aqueous
dispersions containing polysorbate 80
 Vit A is thermostable.
 Uv radiations inactivate it.
 Most stable at pH 6.
 Decomposed in the presence of vit-B
in most vehicles
 The best vehicle for combinations of
vit A,B1andC is
SYRUP:GLYCERIN:WATER
In 2:2:1 proportions
 Mixture of nordihydroguaiaretic acid
and ascorbyl palmitate will be ideal
antioxidant.
 In oily solutions vit-A can be stabilized
with0.05% of methyl or ethyl gallate
 For combinations of A,E and C
vitamins a mixture of NHGA and
disodium EDTA may be better4
VITAMIN –B1

 Sensitive to heat and oxidation in

solution
 In solid form, however, it is neither
thermostable nor liable oxidation. it is
stable to light.
 Optimum pH is 3.7-4
 At pH 2,100%stability for 6 months at
37Oc has been reported.
 Vit B1 is reported to interact with
panthothenic acid, cynocobalamine
and riboflavin
 In capsules and tablets calcium
panthothenate should be used.
 In solutions panthothenyl alcohol fares
better
 Ferric chloride helps to overcome its
incompatibility with vit B12 ratio which
should not exceed 120:1.
 Riboflavin has been reported to
interact with thiamine in aqueous
solutions producing precipitates
 Riboflavin has been reported to
interact with thiamine in aqueous
solutions producing precipitates of
thiochrome or chloroflavin in traces.
 This difficult can be entirely eliminated
by incorporation of ascorbic acid.
FOLIC ACID

 Folic acid dissolves in acids and

alkalies.
 Insoluble in water and alcohol.
 Inactivated by heat and light.
 It is also sensitive to oxidation and
reduction.
 It gets decomposed in the presence of
acids and alkalis.
 Folic stabilized in pH 6.5.
 Inclusion of anti oxidants and storage
in the absence of light and air.
NICOTINIC ACID

 Appreciably soluble in water and

alcohol.
 It is stable to oxidation and heat and
its solutions can be autoclaved without
loss of activity.
 1% solution has a pH of about 3.
PANTHOTHENIC ACID
 It is a yellow viscous oil and is used only in
the form of its calcium salts.
 It is thermostable and destroyed by alkalies.
 Calcium salt is very stable and the stabilizing
effect on calcium panthothenate at pH 7-9.
 Panthothenyl alcohol is more preferred in
liquid preparations because of its
comparative insensitivity to hydrolysis.
BIOTIN
 Biotin is slightly soluble in water and alcohol
 Readily soluble in alkalies.
 Stable in oxygen and heat in the pure
crystalline form as well as in the form of
neutral or slightly acidic solution.
 Solutions remain reasonably stable, upto pH
9.
 Oxidizing agents decompose it.
IONOSITOL

 Very stable, soluble in water

 Slightly soluble in alcohol
 It is neutral.
RIBOFLAVIN

 Crystalline riboflavin is stable under normal

conditions of storage
 Its solutions are subject to influence of light
and alkaline substances.
 The degradation can be considerably
reduced by buffering water.
 Its solubility can be increased by solubilizing
agents such as N-methyl- acetamide,
tryptophane, urethane, Gallic acid-
 Propylene glycol etc….
 Riboflavin phosphate is 100 times
more soluble than riboflavin
 It is more sensitive to ultra-violet light.
PYRIDOXINE
HYDROCHLORIDE
 Soluble in about 5 parts of water and
1% aqueous solution has a pH of 3.
 Solutions are stable to heat.
 Stability decreases with rise in pH.
 In solid state the vitamin is quite
stable to oxygen although light
destroys it at a slow rate.
VITAMIN –B12
 Cynocobalamine is soluble in 80 parts of
water but is freely soluble in alcohol.
 Aqueous solutions are neutral.
 Stability is maximum b/w pH4 and 7 at
room temperature.
 Its crystals are hygroscopic and absorb
about 12% water on exposure to air
 sensitive to light and reducing substances.
 Vitamin C causes rapid decomposition
in solution.
 70% sorbitol as such or in combination
with glycerol are suitable vehicles for
vitamin B12 and vitamin C
combinations.
VITAMIN C
 Strong monobasic acid.
 Powerful reducing agent in neutral and
acidic solutions.
 Degraded mainly due to oxidation.
 First oxidation product is dehydroascorbic
acid which can be reversed back to
ascorbic acid on reaction with hydrogen
sulfide or hydrogen iodide.
 Further oxidation converts vitamin C into
oxalic acid and this reaction is not
reversible.
 Aqueous solution of ascorbic acid are
rapidly decomposed by atmospheric
oxygen particularly at high temperatures.
 Light, alkalies, trace metals hasten the
decomposition.
 Reducing agents like potassium iodide,
however, retard the degradation.
 In the solid state vit. C is
comparatively more stable.
 Vitamin C has been reported to be
more stable in syrup and polyhydroxy
vehicles.
VITAMIN-D
 It occurs in several forms like D2
(calciferol), D3 and D4.
 It is an oil soluble vitamin and is relatively
stable to heat and oxidation.
 Prolonged exposure to light , however,
reduces its potency
 Calciferol is liable to oxidation.
 Vitamin D3 is also oxidised and inactivated
in moist air
VITAMIN-E
 It occurs in the form of 3 homologues
namely alpha, beta and gamma tocopherols,
 Alpha tocopherols are most active.
 It is practically insoluble in water. but it is
soluble in fats.
 It undergoes slow oxidation in the air.
 The acetate of alpha tocopherol is stable to
light and oxidation.
VITAMIN-K

 Stable to oxidation and moisture but

it is photosensitive.
 It is unaffected by dilute acids but is
susceptible to alkalies.
 Vitamin K oxide is more stable to light.
MULTIVITAMIN
FORMULATIONS
 Stabilities of multivitamins is very big
problem.
 Certain degree of pH one vit is stable
and deteriorate the other .. Same way
for vehicle…..
 One formulation for multivitamins in
water,glycerin and propylene glycol in
the ratio of 20:40:40
 Another series in 20% water and 80%
propylene glycol.
 Some of these formulations had EDTA
to mop up trace metals and some
included antioxidants
 All the formulations were analyzed for
vitamin contents at the start and after
storage at 47oc for 1 month.
 From the observations some
generalizations were made,
 Thiamine and pyridoxine are more
stable in formulations containing
minimal amount of water.
 Riboflavin stability varied from 65 to
92% in all formulations
 Formulations containing either
sequestering agents or anti oxidants
increased stabilities of vit C and vit A.
 General conclusion - FORMULATION
CONTAINING SMALL AMOUNT OF
WATER WERE STABLE.
 The liquid products were based on a
number of vehicles such as sorbitol
46%w/v,glycerin24%,propylene glycol
24%v/v and sorbitol25%w/v,
glycerin10%v/v,propylene
glycol50%v/v and sorbitol 18.75%w/v.
 The pH in all cases was adjusted at
3.5,4 and 4.5 and chelating agents
and antioxidants were presents in
each formulations
 Stored in amber coloured bottles at
37Oc for30.60and 90 days.

 Number of Additives should be there

in all multivitamin products
 The additives besides the ones needed
for a particular dosage form may be
listed as:.
 Vehicles such as water, alcohol,
propylene glycol, glycerin, sorbitol
liquid(70%), liquid glucose etc…
 Antioxidants such as sodium
metabisulphite,thiourea,BHA,BHT,prop
ylgallate.
 Sequestering agents such as EDTA
and its salts.
 Synergists like citric acid, tartaric acid,
phosphoric acid.
 Viscosity builders such as acacia,
Tragacanth, gelatin, methyl cellulose, CMC
etc..
 Preservatives such as parabens, benzoates,
sorbates etc
 Excipients such as sorbitol, mannitol,
sucrose, dextrose etc..
 Typical formula
elixer
 Chewable tablet
Preparation of tablets
 For preparing the tablets the ingredients can
be mixed in a powder blender except
vitamins A and D.
 Then slugs can be made with flat faced
punches and ground to give granules of 15
mesh.
 To these granules vitamin A and D can be
added as micro-capsules.
 Then granules can be compressed.
Patient acceptability

 Any product depends on its

organoleptic properties, particularly
flavor and taste.

 As far as vitamins concerned the

following are the taste are listed in
the literature
 VITAMINS TASTE SENSATION
VIT A , D2, E No taste
Thiamine Hcl Bitter & yeasty
Pyridoxine Hcl Slightly bitter & salty
Cyanocobalamine Tasteless
Niacinamide Intensely bitter
Calcium pantothenate Bitter
Biotin Tasteless
Folic acid Tasteless
Ascorbic acid Sour
Sodium ascorbate Salty & soapy
REFRENCES

 A textbook of pharmaceutical
formulations by B.M MITHAL…. Page
no.325-332.