FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"PHARMACEUTICAL COMPOSITION COMPRISING CITICOLINE AND PIRACETAM"
2. APPLICANT:
(a) NAME: Lyka Labs Limited.
(b) NATIONALITY: Indian Company incorporated under the
Companies Act, 1956
(c) ADDRESS: 101, Shivshakti Industrial Estate, Andheri-Kurla Road,
Andheri (East), Mumbai - 400059, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be formed

TECHNICAL FIELD OF INVENTION:
The present invention relates to a pharmaceutical composition comprising a combination of nootorpic drugs, useful for the treatment of dementia which appears due to senility or Alzheimer's, disease and chronic cerebral vascular insufficiency. More particularly, the present invention relates to a fixed dose combination of Citicoline sodium equivalent to Citicoline and Piracetam in the form of tablet, liquid or combipack. The present invention further relates to a process for preparation thereof.
BACKGROUND OF THE INVENTION:
Citicoline is a naturally occurring substance found in most life forms. It is an intermediate metabolite in major pathway for the synthesis of Phosphatidylcholine. Phosphatidylcholine is a phospholipid that is a major component of cell membranes. Phosphatidylcholine is necessary for the structure and function of all cells and is crucial for sustaining life.
Citicoline is synthesized in cells by the reaction of the nucleotide cytidine triphosphate or CTP with phosphocholine. The enzyme catalyzing the reaction is called CTP: phosphocholine cytidyltransferase. This reaction is the rate-limiting step in the synthesis of phosphatidyl choline.
Phosphocholine is synthesized from choline, and for the synthesis of phosphatidylcholine. CITI-choline reacts with diacylglyceride, catalyzed by the enzyme Citicoline: 1. 2-diacyiglyceroi cholinephosphotransferase.
Citicoline has putative activity as a cognition enhancer and in cell-membrane repair.
Citicoline is an intermediate metabolite in the major pathway for the synthesis of the membrane phospholipids, phosphatidylcholine. Phosphatidylcholine is crucial for maintenance of cell-membrane fluidity and cellular integrity. CITI-choline, hypothetically, may aid in cell-membrane repair, particularly neuronal cell membrane that

have been damaged by trauma, ischemic events, toxins, infections and during the course of aging.
Citicoline is also a delivery form of choline and cytidine. Choline is a precursor of acetylcholine and betaine. Acetylcholine is a neurotransmitter whose deficiency in certain regions of the brain is believed to be an etiological factor in certain dementia syndromes, including Alzheimer's disease, Betaine is involved in the conversion of the amino acid homocysteine to the essential amino acid L-methionine. L-methionine is a protein amino acid. Cytidine, following conversion to cytidine triphosphate, participates In a few reactions, including the formation of citicoline and nucleic acids.
Citicoline is useful in the treatment of stroke and brain injury. It may be helpful in some with tardive dyskinesia, Parkinson's disease, Alzheimer's disease and other conditions characterized by impaired cognitive function, including memory loss. An indication may emerge for it to help visual acuity in those with amblyopia. Citicoline is more effective and have a number of advantages over other agents being developed for the reduction of infarct volume subsequent to an ischemic event. Being an endogenous compound, Citicoline is inherently safe. Citicoline has a very low toxicity and an extremely broad therapeutic index.
In numerous studies of Citicoline, favorable results have been obtained in cerebral ischemia and traumatic head injury. its efficacy in these studies has been attributed to its appare'nt ability to increase phosphatidylcholine synthesis in the brain. In animal studies, it has been shown to enhance cell-membrane formation and repair, to restore intracellular enzyme function, to limit nerve damage and decrease oedema.
The same mechanism, generally are said to account for favorable effects reported for it in the treatment of Parkinson's disease, Alzheimer's disease and a variety of cognitive disorders, including impaired memory associated with aging.
Citicoline is also known as cytidine diphosphate-choline (CDP-Choline) and cytidine 5'-diphosphocholine. Chemically, Citicoline is 5'-0-[hydroxy({hydroxyl [2(trimethyl

ammonio)ethoxy]phosphoryloxy)phosphoryl]cytidine. It has the following structural formula:

Piracetam is a derivative of gammaaminobutyric acid (GABA), an important neurotransmitter in the brain. It was one of the first nootropics to be marketed.
Although Piracetam is a derivative of GABA, its actions are unrelated to the properties of the neurotransmitter. The main action of Piracetam is action on membrane fluidity. Piracetam has been found to influence membrane fluidity, particularly when normal fluidity is compromised, as is often seen in aging. Piracetam was found to restore membrane fluidity in vitro studies when it was incubated with aged animal as well as human brains. Similar effects were observed in hippocampal membranes from patients with Alzheimer's disease.
Piracetam has also been shown to influence cholinergic, serotoninergic, noradrenergic and glutamatergic systems. The modulation of these systems by Piracetam does not result from direct receptor agonism or antagonism. Instead, Piracetam appears to increase the number of post synaptic receptors and/or restore the function of these receptors.
The effect of Piracetam on cholinergic and glutamatergic systems is likely to be particularly relevant to its clinical benefit in cognitive disorders; given the increasing evidence that dysfunction in these systems may be related to cognitive decline.
Preclinical studies also have shown that Piracetam has neuroprotective effects, effects on neuroplasticity and even anticonvulsant effects. Studies suggest that Piracetam may also exert beneficial effects on vascular system.

Piracetam is a cyclic derivative of GABA having chemical name 2-oxo-I-pyrroiidine acetamide; it shares the same 2-oxo-pyrrolidone base structure with 2-oxo-pyrrolidine carboxylic acid (pyroglutamate). It has the following structural formula:

An article titled, "Modulation of the effects on learning and memory of nootropic drugs and central stimulants when applied together" by Petkov VD, Konstantinova E, Petkov VV, Lazarova M, Petkova B. relates to the study of the effects on acquisition and retention of different combinations of the nootropic drugs such as meclofenoxate (Mf), citicholine (CCh). piracetam (Pc). the structural analogues of aniracetam p-P and p-F, standardized extract from ginseng roots (PG) and the psychostimulants caffeine (Caf) and amphetamine (Amph).
In view of the above prior arts, none of them specifically discloses Citicoline and Piracetam combination. Further, it can be envisaged that CDP-choline and Piracetam will have additive effects in enhancing brain metabolism and restoring membrane fluidity and neurotransmitter turnover. As the aging population grows, it becomes important to develop treatments to target the range of cognitive disorders in the elderly. A combination of Citicoline and Piracetam is useful in limiting age related cognitive deterioration or that related to Alzheimer's disease.
OBJECT OF THE INVENTION:
Thus, the main object of the current invention is to provide a fixed dose combination of a pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in the form of tablet, liquid or combipack, which is useful for the treatment of patients with dementia which appears due to senility or Alzheimer's disease and chronic cerebral vascular insufficiency.

SUMMARY OF THE INVENTION:
In accordance with the above objective, the present invention provides a fixed dose pharmaceutical composition comprising a combination of nootropic drugs such as Citicoline sodium equivalent to Citicoline and Piracetam, useful for the treatment of patients with dementia which appears due to senility or Alzheimer's disease and chrome cerebral vascular insufficiency. The invention further provides the process for preparation of said pharmaceutical composition in the form of tablet, liquid or combipack.
DETAILED DESCRIPTION OF THE INVENTION:
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
The present invention provides a fixed dose pharmaceutical composition comprising therapeutically effective amount of Citicoline sodium equivalent to Citicoline and Piracetam and the process for preparation thereof.
In one embodiment, the present invention provides a pharmaceutical composition comprising therapeutically effective amount of Citicoline sodium equivalent to Citicoline and Piracetam along with pharmaceutically acceptable excipients, for the treatment of patients with dementia which appears due to senility or Alzheimer's disease and chronic cerebral vascular insufficiency.
In a preferred embodiment, the present invention provides a pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline in an amount of 200 to 1000 mg and Piracetam in the range of 400 to 800 mg.
In accordance to the present invention, the said pharmaceutical composition is in the form of tablet, liquid and combipack.

1. TABLET COMPOSITION:
The present invention describes a pharmaceutical composition comprising a combination of Citicoline sodium equivalent to Citicoline and Piracetam in a solid dosage form, preferably a tablet and the process for preparation thereof.
Accordingly in a preferred embodiment the present invention describes a pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a solid dosage form preferably a tablet, along with the pharmaceutically acceptable excipients selected from the group comprising diluents, binders, wetting agents, disintegrant and lubricants.
According to the another embodiment, the pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline in the range of 200 to 1000 mg and Piracetam in the range of 400 to 800 mg in a tablet form is prepared by wet granulation method where both Citicoline and Piracetam are mixed with other suitable diluents and disintegrants; followed by granulation with appropriate binding agent, dried, lubricated and compressed into tablets and coated with coating material having pharmaceutically acceptable excipients.
According to the present invention, the tablets of Citicoline sodium equivalent to Citicoline and Piracetam can be prepared having various amounts of active ingredient such as Citicoline+Piracetam (500 mg-400 mg), Citicoline+Piracetam (200 mg+400 mg), Citicoline+Piracetam (500 mg+800 mg)
According to the present invention, depending upon the strength of the dosage form the recommended dose of Citicoline sodium equivalent to Citicoline and Piracetam tablet is one to two tablets daily.
According to the present invention, the pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a tablet form is prepared using diluents selected from microcrystalline cellulose, lactose, maize starch, dibasic

calcium phosphate, and can be used individually or in combination to give desired product parameters.
According to the present invention, the pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a tablet form is prepared using binders such as purified water along with maize starch, Hydroxy propyl methyl cellulose. povidone K-30 or purified water alone or isopropyl alcohol alone or mixture of purified water and isopropyl alcohol may be used in optimum concentrations.
According to the present invention, the pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a tablet form is prepared using wetting agents such as Polyethylene glycol (PEG) 6000.
According to the present invention, the pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a tablet form is prepared using disintegrants such as croscarmellose Sodium, crosslinked Povidone. Sodium starch glycolate, maize starch, pregelatinized starch alone or in combination may be used.
According to the present invention, the pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a tablet form is prepared using lubricants such as magnesium stearate. colloidal silicon dioxide, talc alone or in combination may be used.
According to the present invention, the tablets are film coated using coating polymer along with plasticizer, opacifier, colouring pigment and suitable solvents.
In a most preferred embodiment, the process for manufacturing the pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a tablet form is as follows:
1. Weighing and sifting Citicoline sodium equivalent to Citicoline, Piracetam. microcrystalline cellulose, maize starch and croscarmellose Sodium through 40 # sieve:

2. sifting polyethylene glycol 6000 through 80 # sieve;
3. mixing the sifted ingredients of step 1 and step 2 for sufficient time to get uniform blend;
4. preparing starch paste using maize starch and purified water; or mixture of purified water and isopropyl alcohol in the ratio of 1:1 is used as binding solution;
5. granulating the blend of step 3 with starch paste or purified water and isopropyl alcohol mixture of step 4 to obtain wet mass of suitable consistency;
6. passing the wet mass through 12 # sieve;
7. drying the granules in tray dryer at 55°C - 60°C for sufficient time:
8. passing dried granules through 18 # sieve to obtain a particular size:
9. weighing and sifting colloidal silicon dioxide, croscarmellose Sodium and maize starch through 40 # sieve;
10. mixing dried granules of step 8 and sifted lubricants of step 9 for sufficient time to get uniform blend;
11. weighing and sifting magnesium stearate through 40 #sieve and mixing with blend of step 10 for sufficient time to get uniform blend;
12. compressing the lubricated granules into tablet;
13. preparing film coating solution by using ready to use coating material or In-House prepared coating material with either aqueous or non-aqueous solvents; and
The process for preparation of film coated tablets further comprises film coating using Non-aqueous or Aqueous or In-house prepared Non-aqueous coating solutions as mentioned below, wherein said coating process further comprises:
a) Coating the compressed tablets obtained in step 12 with a non-aqueous coating solution, prepared by Opadry ready mix coating powder manufactured by colorcon mix with Isopropyl alcohol and Methylene chloride

Non-aqueous coating comprises:
i. Opadry 6%
ii. Isopropyl alcohol 40%
iii. Methylene Chloride 52%
b) Coating the compressed tablets obtained in step 12 with an aqueous coating solution
prepared by Opadry ready mix coating powder manufactured by colorcon, mix with
distilled water.
Aqueous coating comprises:
i. Opadry 8%
ii. Distilled water 92%
c) Coating the compressed tablets obtained in step 12 with in-house prepared non
aqueous coating solution prepared by dispersing Hypromellose (E5),
Diethylphthalate. Polyethylene Glycol 4000, Titanium dioxide, Talc and color,
Quinoline yellow lake in Isopropyl alcohol & Methylene Chloride mixture and
homogenised in colloidal mill.
In-house prepared Non-aqueous coating solution comprises:
i. Hypromelllose (E5) 3%
ii. Diethylphalate 0.45%
iii. Polyethylene Glycol 4000 0.45%
iv. Titanium dioxide 1.1%
v. Talc 0.7%
vi. Color: Quinoline yellow lake 0.1%
vii. Isopropyl alcohol 40%
viii. Methylene chloride 54.2%
14. film coat the tablets using coating solution of step 13 till a weight gain of 2-3% over core weight is obtained.

2. LIQUID COMPOSITION:
Further, the present invention describes a pharmaceutical composition comprising a combination of Citicoline sodium equivalent to Citicoline and Piracetam in a liquid form and the process for preparation thereof.
Accordingly in an embodiment the present invention describes a sugar free liquid pharmaceutical composition comprising therapeutically effective amount of Citicoline sodium equivalent to Citicoline and Piracetam along with pharmaceutically acceptable excipients selected from sugar alcohol, co-solvents, sweetener, flavours, colours. preservatives and the process for preparation thereof.
In a most preferred embodiment, the process for manufacturing the pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a liquid form is as follows:
1. Using purified water having pH between 4.5 to 7.0 for the batch.
2. taking glycerin, sorbitol solution and filtering it through 120 mesh Nylon cloth into a clean main s.s. vessel and stirring with the stirrer;
3. taking purified water in a separate s.s. vessel, adding and dissolving Citicoline sodium under stirring, transferring the solution to main s.s. vessel of step 2 with continuous stirring and again rinsing the same s.s. vessel with purified water twice and transferring the rinsing to main vessel of step 2 under stirring.
4. taking purified water in a separate s.s vessel, adding and dissolving Piracetam under stirring, transferring the solution to main s.s. vessel of step 2 with continuous stirring and rinsing the same s.s vessel with purified water twice and transferring the rinsing to main vessel of step 2 under stirring;
5. dissolving methyl paraben and propyl paraben in propylene glycol by heating in a separate s.s. vessel, transferring the solution to main s.s. vessel of step 2 under stirring and rinse the same s.s vessel with hot propylene glycol and transferring the rinsing to main vessel of step 2 under stirring;
6. dissolving saccharine Sodium, disodium edetate in purified water, transferring the solution to main s.s. vessel of step 2 under stirring and rinsing the same s.s. vessel

with purified water and transferring the rinsing to main vessel of step 2 under stirring;
7. dissolving colour Sunset yellow in Purified water, transferring the solution to main s.s. vessel of step 2 under stirring and rinse the same s.s. vessel with purified water twice and transferring the rinsing to main vessel of step 2 under stirring.
8. mixing properly flavor with propylene glycol or with purified water or with suitable excipients in a separate s.s. vessel, adding the said solution to main s.s. vessel of step 2 under stirring and rinsing the same vessel with propylene glycol and transferring the said rinsing to the main vessel of step 2 under stirring; and
9. checking pH of bulk solution (pH: 5.0-7.0) and making up the volume with purified water, stirring the said solution for 30 minutes, filtering through 120 mesh Nylon cloth and checking pH and clarity of final solution (Final pH: 5.0 -7.0).
3. COMBIPACK COMBINATION:
The present invention describes a pharmaceutical composition comprising individual unit dosage forms of Citicoiine sodium equivalent to Citicoline and Piracetam provided in a combipack. Accordingly, each combipack contains one tablet of Citicoline sodium equivalent to Citicoline (500 mg) and one tablet of Piracetam (400 mg).
Process for preparation of Citicoiine tablets 500 mg of Combipack:
1. Weighing and sifting Citicoline sodium equivalent to Citicoline, microcrystalline cellulose, maize starch and croscarmellose Sodium through 40 # sieve;
2. mixing the sifted ingredients of step 1 in a poly bag for sufficient time to get uniform blend;
3. preparing starch paste using maize starch and purified water;
4. granulating the blend of step 1 with starch paste of step 3 to obtain wet mass of suitable consistency;
5. passing the wet mass through 12 # sieve and drying the granules in tray dryer at temperature of 60°C;

6. sizing the dried granules by sifting it through 18 # sieve on the sifter;
7. sifting colloidal silicon dioxide, croscarmellose Sodium and maize starch through 40 # mesh sieve;
8. mixing the dried granules of step 6 and sifted lubricants of step 7 in poly bag for sufficient time to get uniform blend;
9. sifting magnesium stearate through 40 # sieve, and mixing the same with granules of step 8 for sufficient time to get uniform blend;
10. compressing the lubricated granules in to tablet;
11. preparing film coating solution by using ready to use coating material or In-house prepared coating material with either aqueous or non aqueous solvents; and
12. film coating the tablets using coating solution of step II till a weight gain of 2-3% over core weight is obtained.
Process for preparation of Piracetam tablets 400 mg of Combipack:
1. Passing Piracetam, and microcrystalline cellulose (Avicel PH-102) through 40 # mesh sieve;
2. passing of polyethylene glycol 6000 through 80 # mesh sieve;
3. mixing the sifted ingredients of Step 1 and Step 2 for 5 minutes for obtaining a uniform blend;
4. passing of colloidal silicon dioxide and magnesium stearate through 40 # sieve and mixing with the blend of step 3 for sufficient time;
5. compressing the lubricated blend of step 4 into tablet;
6. preparing film coating solution by using ready to use coating material with either aqueous or non-aqueous solvents; and
7. film coating the tablets using coating solution of step 6 till a weight gain of 2-3% over core weight is obtained.
The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.

EXAMPLE:
1. For Tablets
Label Claim: Citicoline and Piracetam tablet (500 + 400) mg Each film-coated tablet contains:
Citicoline sodium equivalent to Citicoline .500 mg
Piracetam IP 400 mg
Excipients , q.s.
Colour: Red oxide of Iron

S.NO. INGREDIENTS QTV/T ABLET RANGE
I. Citicoline sodium equivalent to Citicoline 500.00 mg —
2. Piracetam 400.00 mg —
3. Microcrystalline Cellulose (Avicel PH 102) 215.75 mg 175.0 to 240.0 mg
4. Maize Starch 50.00 mg 40.0 to 50.0 mg
5. Poly ethylene glycol 6000 15.00mg 10.0 to 20.0 mg
6. Croscarmellose Sodium 40.00 mg 25.0 to 50.0 mg
7. Colloidal silicon dioxide 8.00 mg 5.0 to 10.0 mg
8. Magnesium stearate 10.00 mg 5.0 to 15.0 mg
9. Purified water q.s. q.s.
10. Isopropyl Alcohol q.s. q.s.
2. For Tablets
Label Claim: Citicoline and Piracetam tablet (500 + 800) mg
Each film-coated tablet contains:
Citicoline sodium equivalent to Citicoline 500 mg
Piracetam IP 800 mg
Excipients q.$.
Colour: Yellow oxide of Iron

S.NO. INGREDIENTS QTY/TABLET RANGE
I. Citicoline sodium equivalent to Citicoline 500.00 mg —

2. Piracetam 800.00 mg —
3. Microcrystalline Cellulose (Avicel PH 102) 50.00 mg 40.0 to 60.0 mg
4. Maize Starch 60.00 mg 50.0 to 70.0 mg
5. Poly ethylene glycol 6000 15.00mg 10.0 to 20.0 mg
PVP K-30 8.0mg 5.0 to ll.Omg
6. Croscarmellose Sodium 40.00 mg 25.0 to 50.0 mg
7. Colloidal silicon dioxide 8.00 mg 5.0 to l0.0mg
8. Magnesium stearate 10.00 mg 5.0 to 15.0 mg
9. Purified water q.s. q.s.
10. Isopropyl Alcohol q.s. q.s.
3. For Tablets
Label Claim: Citicoline and Piracetam tablet (200 + 400) mg
Each film-coated tablet contains:
Citicoline sodium equivalent to Citicoiine 200 mg
Piracetam IP 400 mg
Excipients q.s.
Colour: Red oxide of Iron

S.NO. INGREDIENTS QTY/TABLET RANGE
I. Citicoline sodium equivalent to Citicoiine 200.00 mg —
2. Piracetam 400.00 mg —
3. Microcrystalline Cellulose (Avicel PH 102) 92.0 mg 75.0 to 105.0 mg
5. Poly ethylene glycol 6000 l0.00mg 5.0 to 15.0 mg
6. Croscarmellose Sodium 15.00 mg 10.0 to 20.0 mg
7. Colloidal silicon dioxide 5.00 mg 3.0 to 7.0 mg
8. Magnesium stearate 7.00 mg 5.0 to l0.0mg
9. Purified water q.s. q.s.
10. Isopropyl Alcohol q.s. q.s.

4. For Liquids
Label Claim: Citicoline and Piracetam syrup (500 + 400) mg
Each 5 ml contains:
Citicoline sodium equivalent to Citicoline ...500 mg
Piracetam IP 400 mg
Base q.s.
Colour: Sunset yellow supra

S.NO. INGREDIENTS QTY/ LITER RANGE
1. Citicoline sodium equivalent to Citicoline 100.00 g —
2. Piracetam 80.00 g —
3. Glycerin 156.75 g 100.0 to 200.0 g
4. Propylene Glycol 15.54 g 10.0 to 20.0 g
5. Sorbitol Solution (70%w/v) 536.43 g 500.0 g to 600.0 g
6. DiSodium Edetate 0.05 g 0.04 to 0.06 g
7. Sodium Saccharin 0.04 g 0.02 to 0.06 g
8. Methyl Paraben 0.072 g 0.05 to 0.10 g
9. Propyl Paraben 0.0073 g 0.005 to 0.010 g
10. Colour: Sunset yellow supra 0.006 g 0.005 to 0.010 g
11. Flavour 7.50 ml 5.0 to 12.0 g
12. Demineralized Water (Purified water) q.s. to 1 liter q.s. to 1 liter
3. For Combipack
Each Combi-kit contains:
a) One Citicoline Tablet 500 mg Each film coated tablet contains: Citicoline sodium equivalent to Citicoline 500 mg
Excipients q.s.
Colour: Titanium dioxide IP

b) One Piracetam Tablet 400 mg Each film coated tablet contains:
Piracetam IP 400 mg
Excipients q.s.
Colour: Sunset yellow lake
a) For Citicoline tablets 500 mg of Combipack

S.NO. INGREDIENTS QTY./ TABLET RANGE
1. Citicoline sodium equivalent to Citicoline 500.00 mg —
2, Microcrystalline Cellulose 195.65 mg ] 75.0 g to 250.0 g
3. Maize Starch 92.00 mg 75.0 g to 120.0 g
4. Croscormellose Sodium 32.00 mg 25.0 g to 45.0 g
5. Colloidal Silicon dioxide 8.00 mg 5.0 g to 10.0 g
6. Magnesium Stearate 14.00 mg 8.0 g to 18.0g
b) For Piracetam tablets 400 mg

S.No. INGREDIENTS QTY / TABLET RANGE
1. Piracetam 400.00 mg
2. Microcrystalline cellulose (Avicel pH 102) 94.00 mg 75.0 g to 125.0 g
3. Polyethyleneglycol 6000 l0.00mg 7.5 gto 12.5 g
4. Colloidal silicon dioxide 5.00 mg 3.0 g to 7.0 g
5. Magnesium Stearate 3.00 mg 2.0 gto 5.0 g
Overages of Citicoline and Piracetam can be added for the long term stability purpose.
STABILITY DATA:
Stability study of the products is carried out as per ICH guideline for 6 months at accelerated condition of 40°c / 75% RH and real time condition of 30°c / 65%RH. Product is stable.

We Claim,
1. A pharmaceutical composition comprising a combination of therapeutically effective amount of Citicoline sodium equivalent to Citicoline and Piracetam along with pharmaceutically acceptable excipients, useful for the treatment of dementia which appears due to senility or Alzheimer's disease and chronic cerebral vascular insufficiency.
2. The pharmaceutical composition as claimed in claim J, wherein the Citicoline sodium equivalent to Citicoline is present in an amount of 200 mg to 1000 mg.
3. The pharmaceutical composition as claimed in claim 1, wherein the Piracetam is present in an amount of 400 mg to 800 mg.
4. The pharmaceutical composition as claimed in claim 1, wherein the composition is in the form of tablet, liquid or combipack.
5. The pharmaceutical composition as claimed in claim 1 and 4, wherein the pharmaceutically acceptable excipients for tablets are selected from the group comprising diluents, binders, wetting agents, disintegrant and lubricants.
6. The pharmaceutical composition as claimed in claim 1 and 4, wherein the pharmaceutically acceptable excipients for sugar free liquid composition are selected from sugar alcohol, co-solvents, sweetener, flavours, colours and preservatives.
7. The pharmaceutical composition as claimed in claim 1 and 4, wherein the process for manufacturing of pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a tablet form comprises of following steps:
1) Weighing and sifting Citicoline sodium equivalent to Citicoline, Piracetam, microcrystalline cellulose, maize starch and croscarmellose Sodium through 40 # sieve;

2) sifting polyethylene glycol 6000 through 80 # sieve;
3) mixing the sifted ingredients of step 1 and step 2 for sufficient time to get uniform blend;
4) preparing starch paste using maize starch and purified water; or mixture of purified water and isopropyl alcohol in the ratio of i: 1 is used as binding solution:
5) granulating the blend of step 3 with starch paste or purified water and isopropyl alcohol mixture of step 4 to obtain wet mass of suitable consistency;
6) passing the wet mass through 12 # sieve;
7) drying the granules in tray dryer at 55°C - 60°C for sufficient time;
8) passing dried granules through 18 # sieve to obtain a particular size;
9) weighing and sifting colloidal silicon dioxide, croscarmellose Sodium and
maize starch through 40 # sieve;
10) mixing dried granules of step 8 and sifted lubricants of step 9 for sufficient time to get uniform blend;
11) weighing and sifting magnesium stearate through 40 # sieve and mixing with blend of.step 10 for sufficient time to get uniform blend;
12) compressing the lubricated granules in to tablet;
13) preparing film coating solution by using ready to use coating material or In-house prepared coating material with either aqueous or non-aqueous solvents; and
14) film coat the tablets using coating solution of step 13 till a weight gain of 2-3% over core weight is obtained.
8. The pharmaceutical composition as claimed in claim 1 and 4, wherein the process for manufacturing of pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in a liquid form comprises of following steps: f) using purified water having pH between 4.5 to 7.0 for the batch;
2) taking glycerin, sorbitol solution and filtering it through 120 mesh Nylon cloth into a clean main s.s. vessel and stirring with the stirrer;
3) taking purified water in a separate s.s. vessel, adding and dissolving Citicoline sodium under stirring, transferring the solution to main s.s. vessel of step 2 with continuous stirring and again rinsing the same s.s. vessel with purified water twice and transferring the rinsing to main vessel of step 2 under stirring;

4) taking purified water in a separate s.s vessel, adding and dissolving Piracetam under stirring, transferring the solution to main s.s. vessel of step 2 with -continuous stirring and rinsing the same s.s vessel with purified water twice and transferring the rinsing to main vessel of step 2 under stirring;
5) dissolving methyl paraben and propyl paraben in propylene glycol by heating in a separate s.s. vessel, transferring the solution to main s.s. vessel of step 2 under stirring and rinse the same s.s vessel with hot propylene glycol and transferring the rinsing to main vessel of step 2 under stirring;
6) dissolving saccharine Sodium, diSodium edetate in purified water, transferring the solution to main s.s. vessel of step 2 under stirring and rinsing the same s.s. vessel with purified water and transferring the rinsing to main vessel of step 2 under stirring;
7) dissolving colour Sunset yellow in Purified water, transferring the solution to main s.s. vessel of step 2 under stirring and rinse the same s.s. vessel with purified water twice and transferring the rinsing to main vessel of step 2 under stirring.
8) mixing properly flavor with propylene glycol or with purified water or with suitable excipients in a separate s.s. vessel, adding the said solution to main s.s. vessel of step 2 under stirring and rinsing the same vessel with propylene glycol and transferring the said rinsing to the main vessel of step 2 under stirring; and
9) checking pH of bulk solution (pH: 5.0-7.0) and making up the volume with purified water, stirring the said solution for 30 minutes, filtering through 120 mesh Nylon cloth and checking pH and clarity of final solution (Final pH: 5.0 -7.0).

9. A pharmaceutical composition as claimed in claim 1 and 4. wherein the combipack comprises unit dosage form of Citicoline sodium equivalent to Citicoline and Piracetam,
10. A pharmaceutical composition as claimed in claim 1,4 and 9, wherein the process for manufacturing of pharmaceutical composition comprising Citicoline sodium equivalent to Citicoline and Piracetam in the form of Combipack comprises following steps:

Process for preparation of Citicoline tablets 500 mg of Combipack:
1. Weighing and sifting Citicoline sodium equivalent to Citicoline, microcrystalline cellulose, maize starch and croscarmellose Sodium through 40 # sieve;
2. mixing the sifted ingredients of step 1 in a poly bag for sufficient time to get uniform blend;
3. preparing starch paste using maize starch and purified water;
4. granulating the blend of step 1 with starch paste of step 3 to obtain wet mass of suitable consistency;
5. passing the wet mass through 12 # sieve and drying the granules in tray dryer at temperature of 60°C;
6. sizing the dried granules by sifting it through 18 # sieve on the sifter;
7. sifting colloidal silicon dioxide, croscarmellose Sodium and maize starch through 40 # mesh sieve;
8. mixing the dried granules of step 6 and sifted lubricants of step 7 in poly bag for sufficient time to get uniform blend;
9. sifting magnesium stearate through 40 # sieve, and mixing the same with granules of step 8 for sufficient time to get uniform blend;
10. compressing the lubricated granules in to tablet;
11. preparing film coating solution by using ready to use coating material or In-house prepared coating material with either aqueous or non-aqueous solvents; and
12. film coating the tablets using coating solution of step 11 till a weight gain of 2-3% over core weight is obtained.
Process for preparation of Piracetam tablets 400 mg of Combipack:
1. Passing Piracetam, and microcrystalline cellulose (Avicel PH-102) through 40 # mesh sieve;
2. passing of polyethylene glycol 6000 through 80 # mesh sieve;
3. mixing the sifted ingredients of Step 1 and Step 2 for 5 minutes for obtaining a uniform blend;
4. passing of colloidal silicon dioxide and magnesium stearate through 40 # sieve and mixing with the blend of step 3 for sufficient time;
5. compressing the lubricated blend of step 4 into tablet:

6. preparing film coating solution by using ready to use coating material with either aqueous or non-aqueous solvents; and
7. film coating the tablets using coating solution of step 6 till a weight gain of 2-3% over core weight is obtained.