DESC:BACKGROUND OF THE INVENTION
The invention relates to a process of preparing multivitamin pharmaceutical or nutritional supplement composition and method to reduce the degradation of multivitamin composition over time associated with tablets. The invention further relates to moisture stabilized, acid-stable, non-hygroscopic and odorless multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid and L Carnitine in pure base form.

It has long been established that a number of chemical compounds typically referred to as vitamins provide significant value to maintaining an individual in a healthy state and/or treating specific medical conditions even when supplied in relatively small amounts. The human body cannot synthesize most of the vitamins that are essential to maintaining the health of the human body. Thus, vitamins must be obtained from an external source. The two most common external sources are foods and nutritional supplements. As most people do not eat foods that consistently provide the necessary daily requirements of vitamins. Therefore nutritional supplementation has become a recognized method of meeting accepted medical and health standards.

Multivitamin preparations may be administered to treat specific medical conditions or as general nutritional supplements. As there are a number of vitamins needed and the daily amounts needed are relatively small, it is convenient to administer mixtures of vitamins in tablet or capsule form as a general supplement. Typical daily dosages of commercially available multivitamin supplements are one or two tablets or capsules per day. It is not unusual for such compositions to include two dozen or more nutrients in addition to the excipients needed to make the dosage form.

Multivitamin preparations are intended to be cosmetically elegant and odour-free as it provides long term nutritional benefits and no immediate relief from a symptom. Due to substandard appearance and bad odour the patient feel reluctant to take the formulation.
Most of the vitamins are acid, light, humidity and heat sensitive and oral preparations of the same requires protection from gastric pH especially to the highly acid labile candidates. An acid labile multivitamin formulation will cause the degradation of vitamins in the gastric fluid, thereby decreasing bioavailability and intended benefits.

Moreover the release of the vitamins in the small intestine and that to together at the same site will cause a better therapeutic action as some vitamins such as Mecobalamin requires presence of folic acid for its mechanism of action. For example Mecobalamin is involved with folic acid in haemopoeisis, conversion of folic acid to folinic acid requires vitamin C.

L Carnitine is an important amino acid naturally produced in the body and is involved in heart and blood vessel regulation and muscular and brain activity regulation.

L Carnitine pure base form is a preferred choice to be used in pharmaceutical formulations as the blood levels of the salts of L carnitine (Acetyl L carnitine and L Carnitine L Tartrate) are found to be low as they are quickly destroyed in blood due to hydrolysis.

L Carnitine pure base form is a highly hygroscopic compound which is difficult to formulate as tablets and the objective is generally attained by the use of L-Carnitine L Tartarate (less hygroscopic compared to L carnitine) for producing compositions for oral administration. Since the assay of L Carnitine in salt form is 68%, this results in increase in the tablet weight by 30-40% compromising on the appearance of the tablet.

There are several commercially available multivitamin(s) based products in the market including Conzo Forte®, Nunerve-LM®, Aksvit®, Ammtab®, Brexelant®, Oxitive®. Methylcobalamin (mecobalamin, MeCbl, or MeB12) is a cobalamin, a form of vitamin B12. Methylcobalamin is equivalent physiologically to vitamin B12, and can be used to prevent or treat pathology arising from a lack of vitamin B12 (vitamin B12 deficiency), such as pernicious anemia.

US Patent Number 5,994,324 discloses a water-soluble vitamin composition containing about 90 to 99.8% by weight of a water-soluble vitamin, a polymer binder and at least one additive.

US Patent Application Number 20120148717 discloses multivitamin composition delivered as a taste-neutral and clearly dissolving powder for addition to various beverages and food products during the manufacturing process.

US Patent Application Number 20130005679 discloses multivitamin compositions comprising vitamin B1, vitamin B2, vitamin B5, vitamin B6, vitamin B12, folic acid, magnesium glycinate, and selenium.

Despite of the various known formulations, it still remains challenging to develop a moisture stabilized, non-hygroscopic, acid-stable, heat stable, low-weight and cosmetically elegant odorless multivitamin formulation and further process to reduce the degradation of multivitamin composition over a period of time associated with tablets.

SUMMARY OF THE INVENTION
The invention provides a stable pharmaceutical or nutraceutical composition of multivitamin comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the L-Carnitine is in pure base form.

In one general aspect of the invention, there is provided a stable pharmaceutical or nutraceutical composition of multivitamin comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutically acceptable excipients.

In another general aspect of the invention, there is provided a stable pharmaceutical or nutraceutical composition of multivitamin comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the L-Carnitine is in pure base form.

Conventionally, it has been believed that the water that contributes to degradation, is water in the environment nearby to the composition (e.g. environmental water) and/or water that is loosely associated with the surface or interfacial areas of the composition. For example, the commercially available nutritional supplementation product, One-A-Day® Active, includes a storage statement which reads, "If excess moisture enters the bottle, the iron may cause spotting on the tablet."

Accordingly as moisture promoted degradation reactions lead to a loss of potency and/or unappealing discoloration of multi-component pharmaceutical or nutritional multivitamins supplements, therefore a composition and /or methods are needed to reduce moisture promoted degradation in multi-component nutritional supplements.

In another general aspect of the invention, there is provided a stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutically acceptable excipients, wherein the composition is substantially free of mobile bound water.

In another general aspect of the invention, there is provided a stable pharmaceutical composition comprising multivitamins in the form of a tablet.

In another general aspect of the invention, there is provided a stable pharmaceutical composition comprising multivitamins in the form of a tablet is further seal coated under controlled environment conditions.

In another general aspect of the invention, the seal coated multivitamin tablets further enteric coated with hydroxypropylmethylcellulose phthalate and optimized concentrations of opacifiers and plastisizers.

In another general aspect of the invention, the tablets can be gloss coated with 0.2-0.3% gloss to have added cosmetic appearance.

In another general aspect, the oral pharmaceutical or nutraceutical composition may be in the form of tablets, powder, pellets, capsules, granules or pellets filled in capsule, tablet in capsule, multilayer tablet, bilayer tablet, trilayer tablet, or premixed powder filled in capsule. Preferred oral solid dosage form is tablet.

In another general aspect, the oral solid dosage form is further transformed into film coated solid dosage form by coating the cores with the coating suspension using a standard coating apparatus.

In another general aspect, the oral solid dosage form is further coated with one or more coating comprising pharmaceutically acceptable excipients.

In another general aspect, pharmaceutical acceptable excipients used in the present invention are selected from the group consisting of diluents, binders, fillers, disintegrants, glidants, lubricants, film coating agents, plasticizers, flavors and others.
In another general aspect, there is provided a stable oral pharmaceutical or nutraceutical composition of multivitamin comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the amount of binder in the composition ranges from 0.25% w/w to about 35% w/w of the composition, preferably from 0.45% w/w to about 15% w/w of the composition, more preferably from 0.75% w/w to about 5% w/w of the composition.

In another general aspect, there is provided a stable oral pharmaceutical or nutraceutical composition of multivitamin comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the amount of diluent in the composition ranges from 1.5% w/w to about 85.50% w/w of the composition, preferably from 2% w/w to about 40% w/w of the composition, more preferably from 5% w/w to about 15% w/w of the composition.

In another general aspect, there is provided a stable oral pharmaceutical or nutraceutical composition of multivitamin comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the amount of lubricant in the composition ranges from 0.25% w/w to about 15.75% w/w of the composition, preferably from 0.45% w/w to about 13.45% w/w of the composition, more preferably from 0.95% w/w to about 11.00% w/w of the composition.

In another general aspect of the invention, there is provided a process for preparing a stable multivitamin pharmaceutical composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and one or more pharmaceutically acceptable excipients.

In another general aspect of the invention, there is provided a process for preparing a stable multivitamin pharmaceutical composition comprising steps of:
a. mixing L-Carnitine, Aerosil and Corn starch together in a granulator to form a powder blend;
b. granulating the blended powder of step (a) with granulating agents and drying the granules in a rapid mixer granulator;
c. blending the lubrication premix in a blender;
d. mixing the dried granules of step (b) with the blend prepared in step (c) in a blender for predetermined time.
e. lubricating the blend obtained in step (c) with the lubricant in a blender for predetermined time and
f. compressing the lubricated blend of step (d) under controlled conditions using standard concave punch with beveled edges to form tablets.

In another general aspect, the pharmaceutical composition of the present invention can be produced by one of the methods of wet granulation, dry granulation, dry blending. In the pharmaceutical compositions of the present invention, the active agents can be formulated separately according to any production methods in the prior art; though, they can also be formulated together by using the same production method.

In the wet granulation process, the granulation liquid is a solvent such as IPA, methanol, isopropanol, acetone, water, ethanol, preferably IPA, and contains a binder such as povidone and ethyl cellulose. The solvent is a volatile component, which does not remain in the final product. The active ingredient and the other excipients with exception of the lubricant are premixed and granulated with the aqueous granulation liquid using a granulator. The wet granulation step is followed by an optional wet sieving step, drying and dry sieving of the granules.

The dried granules are sieved through an appropriate sieve. After addition of the other excipients with exception of the lubricant the mixture is blended in a suitable conventional blender followed by addition of the lubricant and final blending in the blender.

In another general aspect of the invention, there is provided a process for preparing a stable multivitamin pharmaceutical composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the L-Carnitine is in pure base form.

In another general aspect of the invention, the process for preparing a stable multivitamin pharmaceutical composition comprising steps of:
a. mixing L-Carnitine, Aerosil and Corn starch together in a granulator to form a powder blend;
b. granulating the blended powder of step (a) with granulating agents and drying the granules in a rapid mixer granulator;
c. blending the lubrication premix in a blender;
d. mixing the dried granules of step (b) with the blend prepared in step (c) in a blender for predetermined time.
e. lubricating the blend obtained in step (c) with the lubricant in a blender for predetermined time and
f. compressing the lubricated blend of step (d) under controlled conditions using standard concave punch with beveled edges to form tablets.

In another aspect, a stable multivitamin tablet pharmaceutical composition further seal coated under controlled environment conditions.

In another aspect, seal coated multivitamins tablets further enteric coated with HPMCP and optimized concentrations of opacifiers and plastisizers.

In another aspect, the tablets can be gloss coated with 0.2-0.3% gloss to have added cosmetic appearance.

DETAILED DESCRIPTION OF THE INVENTION

The term "multivitamin or "multivitamin supplements” may be interpreted to mean conventional commercial type vitamin supplements prepared from specific vitamin. Multivitamin includes compositions comprising, at least two vitamin.

As used herein, the term “nutraceutical” refers to a food substance or part of a food or multivitamin or multivitamin supplements. Nutraceutical can provide medical or health benefits, including the prevention, treatment or cure of a disorder.

The term "stable" means the quantitative composition does not significantly change over the time, during the entire shelf-life of the composition for at least 3 months, advantageously for at least 6 months, more advantageously for at least 12 months, even more advantageously for at least 36 months, under standard conditions of storage.

As used herein, the term "stability" may refer to chemical stability and/or physical stability. As used herein, the phrase "chemical stability" means the ability of a compound to maintain its chemical identity over time. Accordingly, stability implies the ability of a chemical species to resist oxidation or other degradation, for example. As used herein, the phrase "physical stability" means the ability of a composition to maintain consistent physical properties over time. The ability of a composition to maintain a consistent disintegration time over time is exemplary of physical stability.

The term "degradation" as used herein refers to change of a given chemical species to a different chemical species (e.g. chemical change). Chemical changes which produce spotting and/or decrease the potency of a component or compound or both are of particular interest in relation to this invention.

The term "potency" relates to the amount of efficacious component. Typically, as used herein, it refers to the efficacious amount of a given component at a given time in comparison to the efficacious amount of the same component at a second time. Typically, potency is expressed as a percentage. For example, a 20% reduction in potency of component A after three months means that the efficacious amount of component A present after a three month period is 80% of the original efficacious amount of component A.
The term "tablet" comprises tablets without a coating and tablets with one or more coatings. Furthermore the term “tablet” comprises tablets having one, two, three or even more layers and press-coated tablets, wherein each of the before mentioned types of tablets may be without or with one or more coatings.

Vitamins and related entities which may be included in multivitamin preparations include but are not limited to Vitamin C, Vitamin E, thiamin (Vitamin B1), riboflavin (Vitamin B2), niacin (Vitamin B3), pyridoxine (Vitamin B6), folic acid, cobalamins (Vitamin B12), Pantothenic acid (Vitamin B5), Biotin, Vitamin A (and Vitamin A precursors), Vitamin D, Vitamin K, other B complex vitamins, B complex related compounds such as Choline and Inositol, for example, and carotinoids such as lutein, lycopene, zeaxanthin, and astaxanthin.

In an embodiment, the stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients.

In another embodiment, the stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutically acceptable excipients, wherein the L-Carnitine is in pure base form.

In another embodiment, the multivitamin composition comprises Methylcobalamin in an amount of about 0.50 mg to 6.50mg, preferably in an amount of about 1 mg to 3 mg, more preferably in an amount of about 1.50 mg to 2.50mg.

In another embodiment, the multivitamin composition comprises Pyridoxine in an amount of about 1 mg to 8 mg, preferably in an amount of about 1 mg to 3 mg, more preferably in an amount of about 2.0 mg to 2.50mg.

In another embodiment, the multivitamin composition comprises Folic acid in an amount of about 0.5 mg to 9 mg, preferably in an amount of about 1 mg to 3 mg, more preferably in an amount of about 1.50 mg to 2.00 mg.

In another embodiment, the multivitamin composition comprises L-Carnitine in an amount of about 200 mg to 1200 mg, preferably in an amount of about 300 mg to 600 mg, more preferably in an amount of about 450 mg to 550 mg

In another embodiment, the Methylcobalamin is present in 0.21% w/w of the composition.

In another embodiment, the Pyridoxine is present in 0.29% w/w of the composition.

In another embodiment, the Folic acid is present in 0.21% w/w of the composition.

In another embodiment, the L-Carnitine is present as the pure base form in 71.43% w/w of the composition.

In another embodiment, the stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the composition is substantially free of mobile bound water.

In another embodiment, the tablets can be gloss coated with 0.2-0.3% gloss to have added cosmetic appearance.

In another embodiment, the stable oral pharmaceutical or nutraceutical composition of multivitamin composition comprising about 1.676 mg Methylcobalamin, about 2.01 mg Pyridoxine, about 1.66 mg Folic acid, about 501.50 mg L-Carnitine and pharmaceutical acceptable excipients, wherein the L-Carnitine is in pure base form

In another embodiment, the stable oral pharmaceutical or nutraceutical composition of multivitamin composition comprising about 1.50 mg Methylcobalamin, about 2.00 mg Pyridoxine, about 1.50 mg Folic acid, about 500.00 mg L-Carnitine and pharmaceutical acceptable excipients, wherein the L-Carnitine is in pure base form

In another embodiment, the stable oral pharmaceutical or nutraceutical composition of multivitamin composition comprising
a) about 1.50 mg Methylcobalamin,
b) about 2.00 mg Pyridoxine,
c) about 1.50 mg Folic acid,
d) about 500.00 mg L-Carnitine
e) about 100.00 mg Corn Starch
f) about 3.500 mg Aerosil
g) about 5mg povidone
h) about 5mg ethyl cellulose
i) about 3.500 mg magnesium stearate and
j) one or more pharmaceutical acceptable excipients, wherein the L-Carnitine is in pure base form

In another embodiment, the stable oral pharmaceutical or nutraceutical composition of multivitamin composition comprising
a) about 0.21% Methylcobalamin,
b) about 0.29% Pyridoxine,
c) about 0.21% Folic acid,
d) about 71.43% L-Carnitine
e) about 14.29% Corn Starch
f) about 0.50% Aerosil
g) about 0.71% povidone
h) about 0.71% ethyl cellulose
i) about 0.50% magnesium stearate and
j) one or more pharmaceutical acceptable excipients, wherein the L-Carnitine is in pure base form

In another embodiment, the stable oral pharmaceutical or nutraceutical composition is in the dosage form of a tablet.

In another embodiment, the multivitamin tablet comprising
a) about 0.21% Methylcobalamin,
b) about 0.29% Pyridoxine,
c) about 0.21% Folic acid,
d) about 71.43% L-Carnitine
e) about 21% Corn Starch
f) about 0.80% Aerosil
g) about 0.71% povidone
h) about 0.71% ethyl cellulose
i) about 0.50% magnesium stearate and
j) one or more other pharmaceutical acceptable excipients, wherein the L-Carnitine is in pure base form

In another embodiment, the stable oral pharmaceutical or nutraceutical composition is substantially free of mobile bound water.

In another embodiment, the multivitamin tablet comprising
a) about 0.21% Methylcobalamin,
b) about 0.29% Pyridoxine,
c) about 0.21% Folic acid,
d) about 71.43% L-Carnitine
e) about 21% Corn Starch
f) about 0.80% Aerosil
g) about 0.71% povidone
h) about 0.71% ethyl cellulose
i) about 0.50% magnesium stearate and
j) one or more other pharmaceutical acceptable excipients, wherein the composition is substantially free of mobile bound water

In another embodiment, the stable oral pharmaceutical or nutraceutical composition further coated with one or more coating comprising pharmaceutically acceptable excipients.

In another embodiment, the ratio of the methylcobalamin to L-Carnitine is in the range from about 1:500 to about 500:1 by weight.

In another embodiment, the ratio of the pyridoxine to L-Carnitine is in the range from about 1:400 to about 400:1 by weight.

In another embodiment, the ratio of the folic acid to L-Carnitine is in the range from about 1:350 to about 350:1 by weight.

In another embodiment, the process for preparing a stable oral multivitamin pharmaceutical composition comprising steps of:
a. L-Carnitine, Aerosil and Corn starch are sieved through 60 mesh and mixed together in a granulator under controlled conditions (RH <40%) to form a powder blend;
b. granulating the blended powder of step (a) with separately prepared solution of PVP K90 and Ethyl cellulose (10 cps) in IPA and drying the granules in a rapid mixer granulator for 20 mins
c. lubrication premix containing other vitamins, corn starch, croscarmellose sodium and aerosil (except magnesium stearate) are blended together in a double cone blender for 30 minutes
d. mixing the dried granules of step (b) with the blend prepared in step (c) in a double cone blender for 10 minutes
e. lubricating the blend obtained in step (c) with the lubricant in a blender for 5 minutes
f. compressing the lubricated blend of step (d) under controlled conditions using 18*8 mm caplet standard concave punch with beveled edges

In another embodiment, the stable multivitamin tablet pharmaceutical composition further seal coated under controlled environment conditions.

In another embodiment, the seal coated multivitamins tablets further enteric coated with HPMCP and optimized concentrations of opacifiers and plastisizers.

In another embodiment, the tablets can be gloss coated with 0.2-0.3% gloss to have added cosmetic appearance.

In another embodiment, the process for the preparation of a stable oral pharmaceutical composition according to the invention comprising one or more granulation processes wherein the one or two active pharmaceutical ingredients are granulated together with one or more excipients.

In another embodiment, the granulation step is carried out in a rapid mixer granulator, fluidized bed processor or one-pot granulation. Preferred method is rapid mixer granulator.

In another embodiment, the pharmaceutically acceptable solvents used for granulation process may be selected from aqueous or non-aqueous solvents. The solvents comprise, but not limited to, water, isopropyl alcohol, acetone, ethanol, methylene chloride or combination thereof.

In further embodiment, the process of preparing a stable pharmaceutical or nutraceutical multivitamin composition comprising a) about 0.21% Methylcobalamin, b) about 0.29% Pyridoxine, c) about 0.21% Folic acid, d) about 71.43% L-Carnitine e) about 21% Corn Starch f) about 0.80% Aerosil g) about 0.71% povidone h) about 0.71% ethyl cellulose and i) about 0.50% magnesium stearate wherein the composition is prepared by steps of:
a. L-Carnitine, Aerosil and Corn starch are sieved through 60 mesh and mixed together in a granulator under controlled conditions (RH <40%) to form a powder blend;
b. granulating the blended powder of step (a) with separately prepared solution of PVP K90 and Ethyl cellulose (10 cps) in IPA and drying the granules in a rapid mixer granulator for 20 mins
c. lubrication premix containing other vitamins, corn starch, croscarmellose sodium and aerosil (except magnesium stearate) are blended together in a double cone blender for 30 minutes
d. mixing the dried granules of step (b) with the blend prepared in step (c) in a double cone blender for 10 minutes
e. lubricating the blend obtained in step (c) with the lubricant in a blender for 5 minutes
f. compressing the lubricated blend of step (d) under controlled conditions using 18*8 mm caplet standard concave punch with beveled edges

In further embodiment, the stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the composition at least 90% of the potency of the vitamins when stored at temperature 40°C and 75% relative humidity for a period of at least 3 months.

In an another embodiment, the stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the composition comprises less than 1% w/w of total impurity.

In an another embodiment, the stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the composition comprises less than 0.5% w/w of total impurity.

In an another embodiment, the stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the composition comprises less than 0.1% w/w of total unknown impurity.

In an another embodiment, the stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients, wherein the composition comprises less than 0.05% w/w of total unknown impurity.

The invention further includes methods of improving health in a mammal comprising administering a multivitamin composition to the mammal, wherein the composition comprises Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients. The term "improving health" refers herein to an increase in the mammal's sleep cycle length, an increase in the mammal's energy, a decrease in the mammal's need or use of an antidepressant, a decrease in the mammal's need or use of an antianxiety medication, normalization of the mammal's menstrual cycle, and/or an improvement of the mammal's hormonally based symptoms. Normalizing a mammal's menstrual cycle refers to returning a mammal's menstrual cycle to an approximately 28 day cycle. In some embodiments, normalizing a mammal's menstrual cycle further includes regular, monthly ovulation.

The invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

EXAMPLES
Example 1: Multivitamin Composition.
Table 1
Sr. No. Ingredients Unit Qty. (mg)
Dry Mixing
1 L-Carnitine 500.00
2 Corn Starch 50.00-150.00
3 Aerosil 1.500-5.500
Binding Solution
4 PVPK-90 2.5-7.5
5 Ethyl Cellulose(10cps) 2.5-7.5
6 IPA
Lubrication
7 Methylcobalamin 1.50
8 Pyridoxine 2.00
9 Folic acid 1.50
10 Corn Starch 35.00-60.75
11 Cell-o-sol 15.45-45.60
12 Aerosil 1.00-3.00
13 Magnesium stearate 1.50-5.56
Total 700.00
Seal Coating
14 HPMC,EC Plastisizer mix 20-40
15 IPA q.s.
16 MDC q.s.
Film Coating
17 HPMCP, Plastisizer mix 20-40
18 IPA q.s.
19 MDC q.s.
Glow Coating
20 Instaglow IG-001 White 1.5-5.6
21 IPA q.s.
22 MDC q.s.

Procedure:
a. L-Carnitine, Aerosil and Corn starch were sieved through 60 mesh and mixed together in a granulator under controlled conditions
b. Further the blended powder was granulated with a separately prepared solution of PVP K90 and Ethyl cellulose in IPA. The granules were dried in a rapid mixer granulator for 20 mins
c. A lubrication premix containing other vitamins, corn starch, croscarmellose sodium and aerosil (except magnesium stearate) were blended together in a double cone blender for 30 minutes
d. The dried granules of step b were then lubricated with blend prepared in step c and blended in a double cone blender for 10 minutes
e. Magnesium stearate was added to the above mix and blended for 5 minutes
f. The tablets of weight 700 mg were compressed under controlled conditions using 18*8 mm caplet standard concave punch with beveled edges
g. The tablets were further seal coated with optimized HPMC, EC and Tio2 mix with IPA and MDC as a solvent mix under controlled environment conditions with minimal exposure of the tablets to moisture
h. Further the seal coated tablets were enteric coated with HPMCP and optimized concentrations of opacifiers and plastisizers to obtain final multivitamin tablets with stable attributes.
i. The tablets can be gloss coated with 0.2-0.3% gloss to have added cosmetic appearance.

Example 2: Multivitamin Composition.
Table 2
Sr. No. Ingredients Unit Qty. (mg)
Dry Mixing
1 L-Carnitine 501.50
2 Corn Starch 100.00
3 Aerosil 3.500
Binding Solution
4 PVPK-90 5.00
5 Ethyl Cellulose(10cps) 5.00
6 IPA
Lubrication
7 Methylcobalamin 1.676
8 Pyridoxine 2.01
9 Folic acid 1.66
10 Corn Starch 47.00
11 Cell-o-sol 29.00
12 Aerosil 2.000
13 Magnesium stearate 3.50
Total 700.00
Seal Coating
14 HPMC,EC Plastisizer mix 28
15 IPA q.s.
16 MDC q.s.
Film Coating
17 HPMCP, Plastisizer mix 28
18 IPA q.s.
19 MDC q.s.
Glow Coating
20 Instaglow IG-001 White 4
21 IPA q.s.
22 MDC q.s.

Procedure: Same as described in example 1 of this invention.
,CLAIMS:1. A process of preparing a stable pharmaceutical or nutraceutical multivitamin composition comprising steps of:
a. L-Carnitine, Aerosil and Corn starch are sieved through 60 mesh and mixed together in a granulator under controlled conditions (RH <40%) to form a powder blend;
b. granulating the blended powder of step (a) with separately prepared solution of PVP K90 and Ethyl cellulose (10 cps) in IPA and drying the granules in a rapid mixer granulator for 20 mins;
c. lubrication premix containing other vitamins, corn starch, croscarmellose sodium and aerosil (except magnesium stearate) are blended together in a double cone blender for 30 minutes;
d. mixing the dried granules of step (b) with the blend prepared in step (c) in a double cone blender for 10 minutes;
e. lubricating the blend obtained in step (c) with the lubricant in a blender for 5 minutes; and
f. compressing the lubricated blend of step (d) under controlled conditions using 18*8 mm caplet standard concave punch with beveled edges.

2. The process according to claim 1, wherein the stable pharmaceutical or nutraceutical multivitamin composition comprising Methylcobalamin, Pyridoxine, Folic acid, L-Carnitine and pharmaceutical acceptable excipients

3. The process according to claim 1, wherein the L-Carnitine is in pure base form

4. The process according to claim 1, wherein the composition is in the form of a tablet.

5. A process of preparing a stable pharmaceutical or nutraceutical multivitamin composition comprising a) about 0.21% Methylcobalamin, b) about 0.29% Pyridoxine, c) about 0.21% Folic acid, d) about 71.43% L-Carnitine e) about 21% Corn Starch f) about 0.80% Aerosil g) about 0.71% povidone h) about 0.71% ethyl cellulose and i) about 0.50% magnesium stearate wherein the composition is prepared by steps of:
a. L-Carnitine, Aerosil and Corn starch are sieved through 60 mesh and mixed together in a granulator under controlled conditions (RH <40%) to form a powder blend;
b. granulating the blended powder of step (a) with separately prepared solution of PVP K90 and Ethyl cellulose (10 cps) in IPA and drying the granules in a rapid mixer granulator for 20 mins;
c. lubrication premix containing other vitamins, corn starch, croscarmellose sodium and aerosil (except magnesium stearate) are blended together in a double cone blender for 30 minutes;
d. mixing the dried granules of step (b) with the blend prepared in step (c) in a double cone blender for 10 minutes;
e. lubricating the blend obtained in step (c) with the lubricant in a blender for 5 minutes; and
f. compressing the lubricated blend of step (d) under controlled conditions using 18*8 mm caplet standard concave punch with beveled edges.

6. The process according to claim 5, wherein the composition is in the form of a tablet.


7. The process according to claim 5, wherein the L-Carnitine is in pure base form.