FORM2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"A STABLE SOLID ORAL FREE FLOWABLE ESSENTIAL PHOSPHOLIPID FORMULATION"
2. APPLICANT(S):
(a) NAME: NEON LABORATORIES LIMITED
(b) NATIONALITY: Indian Company incorporated under Companies
Act, 1956
(c) ADDRESS: 140, Damji Shamji Industrial Complex, Mahakali Caves Road,
Andheri (East), Mumbai - 400093, Maharashtra, India
3.PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner
in which it is to be performed.

FIELD OF INVENTION
The present invention relates to a stabte, cost effective and time saving manufacturing process of free flowable, nonsticky granules of essential phospholipid which is strongly lipid in nature and has very poor compressibility characteristics hence difficult to formulate solid oral dosage like tablet with optimum bioavailability and desirable properties.
BACKGROUND AND PRIOR ART
Essential (Phosphatidylcholine or PPC, with or without synergistic vitamins) is a preparation of essential phospholipids. Essentiale normalizes the metabolism of lipids and proteins, improves the detoxification function of the liver, restores the cellular structure of the liver and retards the production of conjunctive tissue. Essentiale medications are indicated for the treatment of fatty degeneration of the liver, hepatitis (including toxic hepatitis, liver damage caused by medicines or alcohol abuse), cirrhosis of the liver, disturbances in liver function associated with different illnesses.
Essentiale forte belongs to a group of medicines called hepatoprotectors. The active ingredient of Essentiale represents phosphatidylcholine obtained from soybeans containing 93% (3-sn-phosphatidyl) choline (EPL essential phospholipids). The medication provides the affected liver with essential phospholipids which are very close in structure and functions with endogenous phospholipids. Essential phospholipids are the main elements in the structure of membranes of liver cells.
The prominent pharmaceutical companies which are involving in the manufacturing of essential phospholipid are Sanofi-Aventis; Gerot Pharrnazeuttka , Nattermann , Cassella-Med; Nicholas Piramal; Abbott etc. These drugs are available in the market under the tradename ESSENTIALE, ESSENTIALE FORTE N, ESSENTIALE N, ESSENTIALE FORTE thereof.
One of the leading Pharma Company is Lipoid which is the world's leading cGMP manufacturer of purified lecithin's and phospholipids for pharmaceutical use. Lipoid produces natural purified lecithins and phospholipids derived from soy and egg.

WO2000/045770 describes compositions primarily comprised of phospholipids, commercially known as lecithin, wherein the phospholipids form a solid mass - a liquid crystal phospholipids (LCP) without the use of emulsifiers or other ingredients which are typically used as carriers for phospholipids. The invention also describes the methods for making the phospholipids compositions. The invention further relates to a physical form of a phospholipids and its use as a topical cosmetic skin bar, as a nutrient supplement or as a pharmaceutical dosage form if taken orally. Regardless of the exact shape of the new phospholipids composition, it comprises an amount of phospholipids equal to at least about 20 % by weight of the total product. The new composition of the phospholipids appears as a solid which is produced by subjecting granular or powdered phospholipids to high levels of pressure which result in the formation of the solid phospholipids composition.
United States Patent 5,169,645 describes directly compressible, wax-containing granules having improved flow properties are obtained when waxes are admixed in the melt with certain flow improving additives, followed by cooling and granulation of the admixture. In certain embodiments of the invention, only the wax itself melts in the melt combination of the wax(es) and additives(s), and in other cases both the wax(es) and the addiiives(s) will both melt. In either case, the melt combination of the wax(es) with the additive(s) yields, upon cooling and granulation, a wax-containing particulate drug diluent having improved and unexpected flow properties.
US patent 4590062 describes the selection of: a hydrophobic carbohydrate polymer, e.g. ethyl cellulose; and, generally at least one digestive-difficulty soluble component, i.e. a wax, e.g. carnauba wax, fatty acid material or neutral lipid provides upon dry direct compression a controlled and continuous release matrix for tablets or implants of biologically active agents. Preferred for producing dry direct compressed products is the combination of: a hydrophobic cellulose derivative; a wax, and, a fatty acid material and/or a neutral lipid since it provides upon dry direct compression a controlled and continuous release tablet or implant of improved structurally integrity against externally imposed forces.

U.S. Pat. No. 4,882,167 describes a controlled and continuous release matrix for tablets or implants of biologically active agents. The matrix comprises a hydrophobic carbohydrate polymer such as ethyl cellulose, and optionally at least one digestive-difficulty soluble component such as wax, fatty acid material or a neutral lipid.
Several commercials products of essential phospholipids are available in the market. Different manufacturing methods are adopted to enhance the performance of these products. The available products in the market are in the form of injectable (Intravenous) and oral formulations like capsules.
The existing oral dosage form is available as capsule with semisolid mass content of EPL. Semisolid mass is difficult to fill in to capsule and it is quite costly as it requires specially designed machine for capsule filling with appropriate dosing. Due to stickiness of lipids, it is difficult to prepare a free flowable granule which is suitable for compression in tablet press.
The another disadvantage with lipid inheres in their flow properties., Although melted waxes have satisfactory flow properties under some circumstances, most waxes tend to clump, not flow, and as such are generally inappropriate for use in tableting presses and similar production machinery even when attempts are made to grate or divide them. Therefore, preparation of tablet dosage forms is a difficult task. Accordingly, only capsules dosage forms are available in the market with semisolid content of EPL and tablet dosage forms are not available in the market.
Therefore, there remains a need in the art to provide essential phospholipids in the form of free flowing granules that can be used to prepare variety of solid dosage forms like, tablets, sachet, dry syrup and the like. Accordingly, it is an object of the present invention to provide essential phospholipids in the form of non-sticky and free flowing granules to compress to form tablet that can be used to achieve desired therapeutic benefits.
SUMMARY OF THE INVENTION
In accordance with the above object, the present invention provides lipidic active

ingredients, such as essential phospholipid in highly stabilized solid oral composition form, derived from soya lecithin containing 94% of phosphotidylcholine.
In one aspect, the present invention provides solid oral form of essentia] phospholipid material useful for tablet manufacturing.
In another aspect, the present invention provides nonsticky and free flowing granules which can be easily compressed and hence reduces the cost and time consumption.
A further aspect of the present invention is to provide good storage stability of the formulations proposed in the instant invention. It's mandatory that Capsules should be stored at temperature not more than 20°C and Vials should be stored at 2° - 8°C.but in the case of tablet it can be easily stored at normal condition( room temperature).
A further aspect of the present invention is to provide free flowing non-sticky granules having sufficient compressibility to form suitable tablet dosage form because essential phospholipids are strongly lipoid in nature and has very poor compressibility characteristies.
A further aspect of the present invention is to provide High dose of EPL about 300mg.
Another aspect of the invention relates to a method for treating or preventing diseases in a subject comprising administering a therapeutically effective amount of the pharmaceutical formulation of the invention to a subject in need thereof.
The preparation of essential phospholipid according to the present invention is 100% natural and hence free of side-effects. The composition of the present invention comprises solid mass of non-sticky, free flowable essential phospholipid granules as compared to available marketed products which contain semisolid mass of essential phospholipid in a capsule form.
A further aspect of the present invention is to provide accelerated disintegration by combining two disintegrants together in the instant formulations. The tablets of

crospovidone exhibit significantly higher hardness and acts by wicking action and the croscarmellose sodium which acts mainly by swelling action. Therefore, the above combination of the disintegrants complements each other, thereby accelerating the disintegration process when used together. The water uptake by the tablet is facilitated by the wicking action of crospovidone, while the tablet disintegration is facilitated by the swelling force exhibited by croscarmellose sodium.
DETAILED DESCRIPTION
The technical Subject of the present invention is to provide a useful composition of essential phospholipid which is made from free flowable powdered or granular phospholipids. Surprisingly, when subjected to pressure, the powdered or granular phospholipids are compressed into tablet which is essentially a change of state in solid oral form of the essential phospholipid without stickiness to a previously unknown form that has novel and useful properties.
The powdered or granular essential phospholipid or enriched essential phospholipid components of the present invention are used to prepare a solid oral composition, preferably in tablet form. The solid essential phospholipid composition is made by placing a desirable amount of the essential phospholipids in a tablet press followed by compression.
The composition of the invention comprises of active ingredient which typically is essential phospholipid substance with the pharmaceutically acceptable excipients such as Adsorbent, Binder, Solubilizer, Solvent, Disintegrant, Diluent and Lubricant thereof.
The protective barrier (membrane) around every cell in human body is made from phospholipids. Many of the structures inside each cell are also made from phospholipids. The body can synthesize some phospholipid compounds but others must be supplied by the diet. Phospholipids that can only be obtained through dietary intake are called "essential phospholipids." The term essential phospholipid means phospholipid derived from soya lecithin containing (3-sn-phosphatidylchoiin).

The present invention is directed to a composition comprised of an amount of essential phospholipid preferably 30%, by weight of the total composition and can contain an amount of phosphatidylcholine equal to as much as 94% by weight of the total composition.
In another embodiment, the present invention discloses Povidone K-30 used as an appropriate binder in the case of waxy material based tablet, the main characteristics of the Povidone K30 is soluble in water and in many organic solvents and it forms hard, transparent, glossy film on granules. It is compatible with most of the excipients. It is 100% powder. Povidone K-30 stabilizes dispersions. It simply passes through the body when taken orally. Povidone K-30 is used as a binder in the range between 4% to 6 % more preferably in 5%.
In another embodiment, the present invention discloses Crosspovidone used as a Disintegrant. Disintegrant is an excipient which is added to a tablet blend to aid in the breakup of the compacted mass by capillary forming action when it is put into a fluid environment. This is especially important for immediate release products where rapid release of drug substance is required. A disintegrant can be added to a powder blend for direct compression. It can also be used with products that are wet granulated. In wet granulation formulations, the disintegrant is normally effective when incorporated into the granule (intragranularly), if added in appropriate percentage. However, it may be more effective if added in appropriate percentage intragranularly, and extra-granularly (i.e., in the final dry mixture).
Crosspovidone is used as a Disintegrant intragranularly, in the range between 1.5 % to 2.5 % more preferably in 2.5%., and extra-granularly the range between 6.5 % to 7.5 % more preferably in 7.5%.
Other disintegrants may be used in this invention are selected from Crosscaramellose sodium, Sodium starch glycolate, and potassium salt of methacrylic acid. The purpose of use of Crosscaramellose sodium, sodium starch glycolate and potassium salt of methacrylic acid in the instant tablets is to assist the tablet in disintegrating in the gastro intestinal tract at the required location. The cross-linking reduces water solubility while

still allowing the material to swell and absorb many times its weight in water. As a result, it provides superior drug dissolution and disintegration characteristics, thus improving the formulation's subsequent bioavailability. More preferably Croscarmellose sodium is used as a Disintegrant intragranularly, in the range between 1.5 % to 2.5 % more preferably in 2.5%., and extra-granularly in the range between 6.5 % to 7.5 % more preferably in 7.5% and Potassium salt of methacrylic acid is used in the range between 3% to 6% more preferably in 5 %.
In another embodiment, the present invention comprises colloidal silicon dioxide wherein it used as an adsorbent for dissolved lipid.
"An adsorbent is a substance, usually porous in nature and with a high surface area that can adsorb substances onto its surface by intermolecular forces." Colloidal sillicon dioxide is used as a inert absorbent in the range between 25% to 30% more preferably in 26%.
In another embodiment, the present invention comprises sodium lauryl sulfate, Tween-80 and Sodium deoxycholate wherein, these are used to improve the solubility and dissolution of essential phospholipid. It is used as a solubiliser to increase water solubility. The more preferably Sodium lauryl sulfate is used as solubilizer in the range between 1 % to 4% more preferably in 3%.
The medication of the invention comprises essential phospholipids (EPL -substance) specially derived from soya lecithin which represent a highly purified fraction of phosphatidylcholine. Essential phospholipids work by regulating permeability of cellular wall, improve membranous function and the process of intracellular perspiration and biological oxidation. Essential phospholipid eliminates fatty infiltration of hepatocytes, stabilizes physicochemical bile properties, activates RNA synthesis and normalizes protein metabolism.
In another embodiment, the present invention utilizes a solvent, preferably ethanol in the range between 90 % to 100% of total amount of essential phospholipid most preferably 100% to dissolve essential phospholipid to form solution which is easy to adsorb on inert

absorbent like Colloidal silicon dioxide.
This essential phospholipid medication is also indicated for the treatment of fatty degeneration of the liver, hepatitis (including toxic hepatitis, liver damage caused by medicines or alcohol abuse), cirrhosis of the liver, disturbances in liver function associated with different illnesses. It can be useful in the treatment of various diseases, for example fatty degeneration of the liver of various etiologies (including diabetes), Acute and chronic hepatitis, Liver cirrhosis , Necrosis of liver cells, Hepatic coma and precoma, Toxic liver damage, Gestational toxicosis pre-and postoperative care, especially during surgeries on hepatobiliary system, Psoriasis (in complex treatment) and Radiation Syndrome.
Essential phospholipid plays an important role in various diseases, which are as follows: In the case of Lung Surfactant the therapeutic possibilities of EPL in this indication field consist first of all in the prophylactic substitution of phosphatidylcholine molecules in the decisive pregnancy weeks to support the formation of surfactant in the unborn child. Another possibility is the compensation of membrane damages, e.g. in the presence of inflammatory processes in the lung, or in atherosclerotically changed blood flow properties and erythrocyte flexibility. In the case of Geriatrics where age-related physiological changes in the organism are often combined with specific diseases, the membrane therapeutic EPL may prove to be useful. The effects described for various indications can be summarized as follows: enhanced memory performance of the aging brain, promotion of gastrointestinal function by mucosa restoration, activation of the liver metabolism and detoxication, activation of renal function, influence on the lipid metabolism and on atherosclerosis by cholesterol mobilization, improvement of the coronary, peripheral and cerebral blood flow and, finally,correction of the increased cholesterol/phospholipid ratio in cellular membranes in general, often multimorbidity is present In old age and the elderly mostly have to take different drugs, it is essential that geriatric disorders be treated with a preparation that does not provoke additional side-effects or which even alleviates the adverse reactions of the accompanying medication. "Essential" phospholipids are a phytotherapeutic product without noteworthy side- effects even in long-term application, and without contraindications.

In the case of gastrointestinal inflammation the mucosa quality, membrane structures, membrane-dependent immunological reactions and the local prostaglandin synthesis are altered.
In the case of Membrane Therapeutic, EPL acts primarily by its influence on membranes. As membrane changes and damages occur in many disturbances and diseases the therapeutic approach with EPL in man is a holistic one. The possibilities of application reside, on the one hand, in the kind and severity of membrane damage and, on the other, in the influence on membrane fluidity and thus on membrane-dependent metabolic processes by the incorporation of the special molecule 1,2-dilinoleoylphosphatidylcholine. In addition, the membrane pool of substrates for the endogenous metabolism is increased.
The application of EPL as a membrane therapeutic seems to be limited by the attempt of the cell to maintain normal membrane homeostasis which allows only certain variations. although the cell is also active to eliminate damages. EPL can be applied (in general as adjuvant medication) in membrane-associated damages and diseases, and, in specific cases, to enhance membrane-related physiological processes.
In the case of cardiovascular diseases, EPL works on coronary heart disease, stable stenocardia post-infarction condition, disturbance of the cerebral and peripheral circulation, Hypertension, thrombembolia prophylaxis, atherosclerosis, diabetic angiopathy, thrombembolia prophylaxis and fat embolism.
In the case of alcoholic liver damage, EPL accelerates elimination of fatty deposits from hepatic tissue.
In the case of Drug-Induced Hepatic Injury wherein EPL can prevent, or at least substantially diminish, hepatic injury due to anti-tuberculous agents and even ameliorates hepatic function in patients with pre-existing liver damage.
In the case of Acute Viral Hepatitis wherein EPL Incorporation into the damaged membrane structures of the liver cell, facilitates the rapid normalization of the metabolic

processes in the liver and will reduce the susceptibility of the hepatocytes to cytotoxic
agents.
In some other cases according to clinical evidence, some positive effects in certain diseases, such as involutional dementias and multiple sclerosis, improvements of subjective wellbeing, such as headache, dizziness, memory, concentration, endurance, irritability, insomnia, angina attacks thereof.
In the case of neurological diseases the reduction of choline a precursor of the neurotransmitter acetylcholine, the deficiency in unsaturated fatty acids, or increased rigidity of neuronal membranes may influence metabolic processes and functions of the nerves.
The amount of the phospholipids added is equal to between about 20% and 100%, or preferably from 30% to 100% by weight of the essential phospholipid composition wherein the essential phospholipids can be compressed to continually form solid essential phospholipid extrusions.
The solid essential phospholipid composition can be formed into a variety of sizes and shapes as per the need of administration.
Some other features are following
The active pharmaceutical ingredient for the formulation of oral/tablet of essential phospholipid is preferably derived from soya lecithin.
The gastrointestinal tract provides sufficient fluid to facilitate disintegration of the dosage form and dissolution of the drug. The large surface area of gastric mucosa favors the drug absorption.
Essential phospholipid derived from soya lecithin is used to produce systemic effect are administered orally the drug dissolution is facilitated by the tablets' quick disintegration. The simplest way to achieve quick disintegration is to use a super-Disintegrant in concert with suitable diluents, Super-Disintegrants such as croscarmellose sodium, crospovidone,

another superdisintegrant like Potassium salt of methacrylic acid are frequently used in tablet formulations to improve the rate and extent of tablet disintegration and thereby increase the rate of drug dissolution.
The tablets of crospovidone exhibit significantly higher hardness in the present invention as Crospovidone acts by wicking action and croscarmellose sodium acts mainly by swelling action. Therefore, the Super-Disintegrants complement each other, accelerating the disintegration process when used together.
The water uptake by the tablet is facilitated by the wicking action of crospovidone, while the tablet disintegration is facilitated by the swelling force exhibited by croscarmellose sodium. Povidone K-30 and sodium lauryl sulphate are used with a view to increase its water solubility.
In addition, the essential phospholipid composition can be compressed into a tablet in a size suitable for ingestion so as to prepare a high potency oral essential phospholipid tablet. When taken orally without other ingredients, phospholipids impart many benefits to the consumer including, among others: they act as antioxidants, reduce platelet aggregation, improve elasticity of blood vessels, dissolve gall stones, aid in memory retention, enhance physical endurance, and detoxify the liver thereof.
The compositions according to the present invention exhibit an effective therapeutic action in the treatment of various diseases for example liver, kidneys, brain, lung thereof.
It has now surprisingly been found that the pharmaceutical compositions of the invention display remarkable therapeutic effects by virtue of unforeseeable synergistic essential phospholipid derived from soya lecithin.
Accordingly, the present invention in one of its preferred embodiment provides stable solid oral free flowable granule based essentialphospholipid formulation including essential phospholipid derived from soyalecithin, or physiologically acceptable salts, together with an adsorbent, binder, solubilizer, disintegrant and other pharmaceutical excipients with enhanced bioavailability.

The most important advantages of the present invention can be summarized as follows:
1. The formulation can be prepared by employing easy, economical and non-sticky tablet manufacturing process.
2. The process according to the invention can be continuously carried out, and allows the large scale preparation of the tablets.
Accordingly, in a preferred embodiment, the present invention provides a process for the preparation of solid oral free flowing granules of essential phospholipids to achieve optimum dissolution and enhanced bioavailability, where the process manufacturing steps are as below:
STEP 1-ADSORPTION OF ESSENTIAL PHOSPHOLIPID
Added and dissolved with continuous stirring Povidone K-30 in suitable solvent like
ethanol 99% to form solution.
Dissolved the essential phospholipid in above solution to form clear solution.
Dispersed sodium lauryl sulfate in above solution under continuous stirring and added
slowly colloidal sillicon dioxide to above dispersion with continuous shear mixing to
form free flowable solid granules.
STEP 2 DRY MIXING
Weighed Croscarmellose sodium, Crospovidone, Mannitol another superdisintegrant like Potassium salt of methacrylic acid and mixed uniformly with Step-I Mixture.
STEP 3 LUBRICATION
Mixed the granules of Step-I and Step-II and lubricated with magnesium stearate
STEP 4 COMPRESSION
Compressed the blend in to tablet using capsule shaped suitable punches on rotary compression machine.
The following are working examples demonstrating the production and use of solid essential phospholipid compositions of the present invention.

EXAMPLE 1
In this example, a tablet composition for free flowable, nonsticky granules of essential phospholipid is prepared as per the process described above. The composition comprising essentia! phospholipid derived from soya lecithin 300 mg as an active ingredient, colloidal sillicon dioxide-275mg as a Adsorbent, Povidone K-30 -45mg as a Binder, Tween 80—lO.OOmg, Sodium lauryl sulphate-20.00mg, Ethanol 99%-q,s as a Solvent, Sodium starch glycolate -50.00mg as a disintegrant, Crosspovidone-50.00mg as a disintegrant, Mannito!-172.38mg as a Diluent, Magnesium stearate-5.Q0mg as a Lubricant.
The test results for the above described solid oral tablet composition for the Essential phospholipid is found to be satisfactory.
EXAMPLE 2
In this example, tablet composition for free flowable nonsticky granules of essentia! phospholipid is prepared as per the invention. The composition comprising essential phospholipid derived from soya lecithin -300 mg as an active ingredients, colloidal sillicon dioxide- 260 mg as a adsorbent, Povidone K-30 -45mg as a binder, Sodium deoxycholate (by Sigma)-25mg as a solubilizer, Sodium lauryl sulphate-20.mg as a Solubiliser, Ethanol 99%-q.s. as a Solvent, Dis'mtegrant like Crosscaramellose sodium-lOO.OOmg, Crosspovidone-lOO.OOmg, another superdisintegrant like Potassium salt of methacrylic acid - 20mg, mannitol-72.38mg as a diliuent, Magnesium stearate 5.00mg as a lubricant.
The test results for the above described solid oral tablet composition for the Essential phospholipid is found to be satisfactory.
EXAMPLE 3
In this example, a tablet composition for free flowable, nonsticky granules of essentia! phospholipid is prepared as per the invention. The composition comprising essential phospholipid derived form soya lecithin 300 mg as a active ingredients ,colloidal sillicon

dioxide- 275 mg as a Adsorbent, Povidone K-30 -45mg as a Binder ,Ethanol 99% q.s. as a
Solvent.
Disintegrant like Croscarmellose sodium-85.00mg, Crosspovidone-85.00mg and another
superdisintegrant like Potassium salt of methacrylic acid - 30mg, Mannitol-112.38mg as a
Diluent , Sodium Lauryl Sulphate-20.00mg as a Solubiliser, Magnesium streate-5.00mg
as a Lubricant.
The test results for the above described solid oral tablet composition for the Essential
phospholipid is found to be satisfactory.
EXAMPLE 4
In this example, a tablet composition for free flowable, nonsticky granules of essential
phospholipid is prepared as per the invention. The composition comprising essential
phospholipid derived from soya lecithin 300 mg as an active ingredient ,colloidal sillicon
dioxide-260 mg as a Adsorbent, Povidone K-30 -45mg as a Binder ,Sodium lauryl
sulphate-30mg as a Solubilizer ,Ethanol 99%-q.s. As a Solvent, Disintegrant like
Croscarmellose sodium-lOO.OOmg and Crosspovidone-lOO.OOmg another
superdisintegrant like Potassium salt of methacrylic acid - 50mg, Mannitol-87.38mg as a
Diluent, Magnesium stearate-5.00mg as a Lubricant.
The test results for the above described solid oral tablet composition for the Essential
Phospholipid is found to be satisfactory.
All the above batches subjected for the stability studies % as per ICH guidelines and found
that almost all formulation resulted into satisfactory dissolution (90 - 70%) therefore oral
bioavailability of Essential phospholipid tablets are successfully proven.
The bellow table depicting the stability data of best formulation packed in PVC Blister
packing

SR.
Parameters STD Limit
no

Initial 1M 3M 6M

RT 30°C RT 30° C RT 30° C 40° C
1. Description Brown coloured capsule shaped biconvex tablets with break! ine on one side and plain on another side same@ same@ Same@ same@ same@ same@ same@ same@
2 Average weight in mg 1020mg 1022mg 1020 1020 1020 1020 1020 1020 1020
3 Assay 90 to 110% 103.59 104.96 105.09 103.20 100.01 101.30 99.83 98.37
4 Dissolution NLT 70% 98.33 76.36 93.83 77.59% 83.30 80.13 78.10 67.32
5 Disintegration NMT30Min 12 13min 12 min lOmin 12 min 11 min 13 min 13 min
6 Hardness (kg/cm'' NLT 5 Kg/cm2 5 Kg/cm2 5 Kg/cm2 5 K.g/cnr 5 Kg/cm2 5 Kg/cm2 5 Kg/cm2 5 Kg/cm2 5 Kg/cm2
7 Weight Variation To comply CompJie Complie Complie Compile Complie Complie Complie Complie
@: Brown coloured capsule shaped biconvex tablets with breakline on one side and plain
on another side
Conclusion:
Phospholipid tablets developed with this novel method showed successful compliance at
RT and intermediate condition (30oC/65%RH) throughout 6 months.
Dissolution of the poorly water insoluble lipid proved to be bioavailable for oral route
according to the invention as the same are found to have remarkable invitro dissolution.

We claim,
1. Stable solid oral free flowable granules based essential Phospholipid with optimum stability and enhanced bioavailability comprising essential phospholipid, or physiologically acceptable salts derived from soyalecithin, together with an adsorbent, binder, solubilizer, lubricant, disintegrant and other pharmaceutical excipients.
2. Stable solid oral free flowable granule based essential phospholipid formulation as claimed as claim 1, wherein, the essential phospholipid is present in an amount of 30%, adsorbent in an amount of 25% to 30%., binder in an amount of 4% to 6%; solubilizer in an amount of 1% to 5%, disintegrant in an amount of 8% to 10%, super disintegrant in amount of 3% to 6%, together with other pharmaceutical excipients.
3. Stable solid oral free flowable granules based essential phospholipid formulation as claimed as claim 1, wherein, the essential phospholipid present in an amount of 30%, adsorbant in an amount of 25% to 30%; binder in an amount of 4% to 6%; solubilizer in an amount of 1% to 5% with appropriate amount of solvent.
4. Stable solid oral free flowable granules based essential Phospholipid formulation as claimed as claim I, wherein the Adsorbent is colloidal sillicon dioxide present in the amount of 25% to 30%.
5. Stable solid oral free flowable granules based essential phospholipid formulation as claimed as claim I, wherein Binder is Povidone K-30 present in the amount of 4 % to 6%.
6. Stable solid oral free flowable granules based essential phospholipid formulation as claimed as claim 1 wherein Solubilizer is Sodium Laury] sulphate present in the amount of 1% to 4%.
7. Stable solid oral free flowable granule based essentialphospholipid formulation as claimed as claim 1, wherein, Disintegrant is Crosscaramellose present in the amount of 8% to 10%.

8. Stable solid oral free flowable granules based essential phospholipid formulation as claimed as claim 1, wherein Disintegrant is Crosspovidone present in the amount of 8% to 10%.
9. Stable solid oral free flowable granule based essential phospholipid formulation as claimed as claim 1 wherein, the superdisintegrant, Potassium salt of methacrylic acid present in the amount of 2 % to 6%.
10. Stable solid oral free flowable granule based essential phospholipid formulation as claimed as claim 1 wherein, Diluent is Mannitol present in the amount of 5 % to 10%.
11. Stable solid oral free flowable granules based essential phospholipid formulation as claimed as claim 1 wherein, a solvent is used to aid dissolution of the essential phospholipid in the manufacturing process of free flowable granules of essential Phospholipid.