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 interAbsorption profiles of vitamins Overage recommended by FIP   

Limit prescribed

VITAMINVITAMIN-A  It undergo addition reactions with bisulphates and some solvents those have double bond in its molecule  Exists in cis-trans isomers cis When trans form changes to cis form can reduce 65-70% of potency Without showing 65any 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-pstabilizersdiphenylphenylene diamine,malt extract,tocopherol and 2-6-di-tertiary 2- dibutylbutyl-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 vitin 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 vitwith0.05% of methyl or ethyl gallate For combinations of A,E and C vitamins a mixture of NHGA and disodium EDTA may be better4


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 3.7At 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 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.


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.



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. 7Panthothenyl alcohol is more preferred in liquid preparations because of its comparative insensitivity to hydrolysis.


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.


Very stable, soluble in water Slightly soluble in alcohol It is neutral.


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, N-methyltryptophane, urethane, Gallic acidacid- 


Propylene glycol etc . Riboflavin phosphate is 100 times more soluble than riboflavin It is more sensitive to ultra-violet light. ultra-



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.



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.


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.


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



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.


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.


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. microThen 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 VIT A , D2, E Thiamine Hcl Pyridoxine Hcl Cyanocobalamine Niacinamide Biotin Folic acid Ascorbic acid Sodium ascorbate

TASTE SENSATION No taste Bitter & yeasty Slightly bitter & salty Tasteless Intensely bitter Tasteless Tasteless Sour Salty & soapy

Calcium pantothenate Bitter


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