DESC:Field of the Invention
The present invention relates to novel neutral spherical granules of silica and process for preparing the same for its use as excipients in pharmaceutical, nutraceutical, food, cosmetic and agricultural applications, and particularly as multiunit particulate systems.

Background of the invention
Advancements in the pharmaceutical technology for making solid dosage forms have resulted in the development of complex dosage forms. With the introduction of multiparticulate systems, it is now possible to design dosage forms with multiple active ingredients and ensure their site specific delivery. Multiparticulate systems offer low risk of dose dumping, flexibility in blending to attain different release patterns as well as reproducible and short gastric residence time.

Multi-particulate drug delivery systems are mainly oral dosage forms consisting of a multiplicity of small discrete units, each exhibiting some desired characteristics. In these systems, the dosage of the active ingredient is divided on a plurality of subunits, typically consisting of hundreds of particles with diameter ranging from 0.05-2.00mm. These subunits are roughly spherical in shape. These sub units can be of various types including inert granules coated with active ingredient, or inert particles granulated with active ingredient to form larger pellets etc.

To deliver the recommended total dose of the active ingredient these subunits are compressed into tablets. The release of the active ingredients from the subunits is largely dependent on the properties of inert granules and the amount of active ingredients contained in them.

When using silicon dioxide as inert granules, several problems are encountered in the prior art such as very low density, less drug loading capacity, excessive flow properties, less elasticity, no self-binding etc. which makes it very light and difficult to work with while coating active ingredients on it. The present invention solves this problem by providing a combination that increases the apparent density of silicon dioxide that help in regulating the excessive flow, further increasing the strength of the granule by providing it with some elasticity, to help achieve desirable amount of active ingredient that can be coated onto it. Since uniformity in size and shape that can be achieved with these granules, the problems of segregation are also resolved. Moreover improved flow properties and high stability of these granules over long periods of storage help in their usability.

US5585115 discloses a co-processed particulate agglomerate of microcrystalline cellulose and silicon dioxide in intimate association with each other, wherein silicon dioxide is present in the range from 0.1 to 20% by weight of microcrystalline cellulose. The method of making the excipient as described in the specification is spray drying and alternatively wet granulation. The problem of using more quantity of MCC as excipient is that moisture causes breaking of hydrogen bonding between adjacent bundles of microcrystalline cellulose structure, which may lead separation of particles and non-uniform tablet disintegration. In addition to effect of moisture, the interaction of MCC with ranitidine has raised questions to its inertness. Similarly, instances of difficulty in disintegration or slow or incomplete release of drugs like ketotifen and famotidine have been reported when MCC is used as excipient.

Therefore, formulations that are substantially free of microcrystalline cellulose were developed. US20090311331 discloses a pellet formulation comprising silicon dioxide in combination with one or both of a plasticizer and surfactant. The process of preparation of the pellets as described in the specification includes extrusion and spheronization. Complete removal of microcrystalline cellulose also has its disadvantage as MCC provides for good binding properties and plastic properties while compression of tablets. Another point to note is that extrusion of compositions with high quantity of silicon dioxide in conventional extruding equipment is difficult due to excessive heat generation and it provides products with reduced mechanical strength and very less yield.

From the prior arts it is seen that, even though addition of microcrystalline cellulose has its difficulties, it is still required in small quantities for good binding and plastic properties while making tablets. It is further seen that none of the prior art discloses a process of making silicon dioxide granules where the problems associated with extrusion of high silicon dioxide containing compositions are addressed. The present invention provides solution to this problem by eliminating the step of extrusion and using only spheronization for making the product.

Numerous attempts have been made in prior art to provide an excipient having high drug loading capacity, a small bulk (high apparent density), with improved flow ability, while being capable of providing satisfactory disintegration of the solid dosage form when formulated in multiparticulate systems.

However, we still require an alternative excipient material which is completely inert and capable of replacing earlier high microcrystalline cellulose based excipients. Excipients containing silicon dioxide are one such replacement, but owing to the difficulties of stiffness, heat generation and loss of mechanical strength while extruding high silica containing compositions, there still remains a need for alternate high silicon dioxide based compositions having desirable excipient properties, which are easy to prepare using only spheronization and which eliminate the requirement of extrusion in the process.

Object of the invention
An object of the present invention is to provide neutral, novel, free-flowing non-brittle spherical granules of silica having desirable loading capacity of the active ingredient and optimum stability, a composition of granules of silica and a process for preparing the same.
It is a further object of the present invention to provide a process of preparing spherical silicon dioxide granules by using only spheronization.

Summary of Invention
The present invention describes neutral, novel, free-flowing, non-brittle spherical granules of silica having optimum flow properties, with desirable drug loading capacity of the active ingredient and optimum stability when used as inert particles in multiparticulate systems. The silica granules of the present invention may be used as excipients in pharmaceutical, nutraceutical, food, cosmetics and agricultural formulations.

The present invention further describes a process for making silicon dioxide granules by spheronization without the need of extrusion.

Detailed description of the invention
The present invention discloses neutral, novel, free-flowing, non-brittle and spherical granules of silicon dioxide having optimum flow properties, with high loading capacity of the active ingredient and optimum stability for use in multiparticulate systems. The free flowing and non-brittle property may be further enhanced by using cellulosic polymer which imparts waxy feel to the composition and also improves compressibility.

The term "granule", in the context of the present invention, refers to the solid composition of spherical or slightly spherical or slightly elliptical in shape. Further according to the invention it can be dry, free flowing, non- brittle, non-sticky and substantially dust free.

The novel inert spherical granules of silica may have one or more favourable properties such as optimum loading capacity of active ingredient, optimum flow properties and stability. Also the granules of waxy feel substances like silicon based compound could be prepared using a combination of cellulosic polymer, wherein resulting solid substance is dry, free flowing, non-brittle, non-sticky and substantially dust free.

The granular composition of present invention comprises a silicon dioxide, a cellulosic polymer, a surfactant, and a binding solution which further comprises a binder, a plasticizer, a surfactant, a solvent and other pharmaceutically acceptable excipients which may be used as excipients in pharmaceutical, nutraceutical and agricultural formulation.

The silica used in the composition may be selected from the group comprising silicon dioxide of very fine particle size variety. The silicon dioxide may be colloidal silicon dioxide. Colloidal silicon dioxide may be submicron fumed silica prepared by the vapour-phase hydrolysis of a silicon compound.

The amount of silicon dioxide used in the composition may be present in range between
50% to 80% by weight, more preferably 60%to 80% by weight of the composition.

The composition of the present invention includes a cellulosic polymer may be selected from the group comprising hydroxypropyl methylcellulose, hydroxypropyl cellulose (more preferably of the high viscosity type), hydroxyethyl cellulose, methyl cellulose, various water-soluble polysaccharides, carboxymethyl cellulose, ethyl cellulose, microcrystalline cellulose, including salts thereof, more preferably the cellulosic polymer may be microcrystalline cellulose, most preferably the cellulosic polymer may be used in combination.
In an embodiment the cellulosic polymer provides added binding properties to the composition of present invention.

The amount of cellulosic polymer used in the composition may be present in range between 5% to 30% by weight, more preferably 8% to 15% by weight of the composition.

The composition of the present invention also include a surfactant may be selected from the group comprising ammonium lauryl sulfate, sodium lauryl sulfate, polysorbate-80, dioctylsodium sulfo-succinate, alkyl benzene sulfonates, sodium dodecyl sulfate, quaternary ammonium chloride, more preferably sodium lauryl sulfate and most preferably the surfactant may be used in combination.

In another embodiment of the present invention the surfactant may also be used as a constituent of the binding solution.

The total amount of surfactant used in the final composition of the present invention may be present in range between 5% to 20% by weight, more preferably 8% to18% by weight of the composition.

The composition of the present invention may additionally comprise other ingredients such as a binding solution comprising a binder, a plasticizer, a surfactant, a solvent and optionally other pharmaceutically acceptable excipients.

In an embodiment of the present application it is surprisingly seen that granulates having high quantity of silicon dioxide when used in combination with cellulosic polymer in presence of surfactant and plasticizer provide compositions which can directly be spheronized to obtain granules which are neutral, free-flowing, non-brittle having optimum flow properties, improved binding and plastic properties, more uniform disintegration of tablet and desirable drug loading capacity. It is further surprisingly seen that, when silicon dioxide granules are made using only spheronization, the problems associated with extrusion like heat generation, and reduced mechanical strength of products are completely avoided and yield of the granules is improved.

The binder used in the composition of the present invention may be selected from the group comprising Methyl Cellulose, Ethyl Cellulose, Gelatin, Hydroxy Propyl Methyl Cellulose (HPMC), Starch Paste, Hydroxy Propyl Cellulose, Pre-gelatinized Starch, Sodium Carboxy Methyl Cellulose, Polyvinyl Pyrrolidone (PVP), Cellulose, Polyvinyl Alcohols, Polymethacrylates and the like, preferably the binder may be used in combination, more preferably the binder is hydroxy propyl methyl cellulose (HPMC).

The amount of binder used in the composition may be present in range between 0.5% to 5% by weight, more preferably 1% to 4% by weight of the composition.

The plasticizer used in the composition of the present invention may be selected from the group comprising glycerides, including monoglycerides, diglycerides and triglycerides and mixtures thereof, preferably the plasticizer is glycerine.

The amount of plasticizer used in the composition may be present in range between 2% to 15% by weight, more preferably 5% to 13% by weight of the composition.

The surfactant used in the binding solution of the present invention may be selected from the group comprising ammonium lauryl sulfate, sodium lauryl sulfate, polysorbate-80, dioctylsodium sulfosuccinate, alkyl benzene sulfonates, sodium dodecyl sulfate, quaternary ammonium chloride and combinations thereof, preferably the surfactant is polysorbate-80.

The solvent may be selected from the group comprising ethanol, isopropyl alcohol and water, more preferably water.

The granular composition of the present invention comprising silicon dioxide present in the amount in the range of 50% to 80% by weight, and cellulosic polymer in amount in the range of 5% to 30% by weight, more preferably 8% to 15% by weight. The cellulosic polymer and silicon dioxide present in the composition of the present invention being in intimate association with each other.

In an embodiment the composition of the present invention may be prepared by a process comprising the steps of:
i. sieving of dry components,
ii. Granulation of the dry components of step (i) with binding solution,
iii. spheronization of wet solid material of step (i ii),
iv. drying of the granules of step ( iii),
v. optionally sieving the granules of step ( iv) to obtain the granules of present invention.

The dry components of step (i) include silicon dioxide in combination with cellulosic polymer and other pharmaceutically acceptable excipients.

The dry components of step (i) may be sieved to achieve homogenization at every stage of dry composition preparation to generate uniform clump free physical forms. Other size sieves may also be used in plurality of order and time to obtain similar results.

The binding solution may be prepared by combining binder, surfactant, and plasticizer with a suitable solvent. To enable homogenous component distribution, all ingredients may be mixed in suitable sized container with manual or automated stirring mechanism depending on requirement. Binding solution may be used for granulation step in plurality of volumes and ways to facilitate wet solid material formation.

Sieved and homogenized powdered ingredients of step (i) may then be combined into wet solid material with the help of binding solution of step (ii). The binding solution may be prepared with solvent or combination of solvents. The solvent may be selected from the group comprising ethanol, isopropyl alcohol and water, more preferably water. The binding solution may additionally comprise sieved and powdered binder(s) to make slurry like liquid and can be filtered through suitable sieves.

The dry components and binding solution may be mixed for a time period of 55 to 60 minutes at high speed. The binding solution may be added in small batches.

The wet solid material of step (iii) may further be spheronized using rapid mixing granulator and standard spheronizer. Further the granules thus produced may be passed through spheronizer to obtain uniform textured spherical granules.

The granules of step (iv) may be dried using dryers selected from group comprising fluid bed dryers, tray dryer, belt dryer, vacuum tray dryer, spray dryer and rotary dryer, more preferably tray dryer and dried at a temperature in range of60-80°C, preferably at 75-80°C for time period in range of5-12 hours, preferably for 7-10 hours.

The granules thus obtained may be checked for desired size, strength, moisture content etc. as per desired specifications. The moisture content may be measured by IR moisture balance and various methods as illustrated in pharmacopoeias.

In case of granules of uneven sizes, multi-mill step may optionally be used to generate granules of lower and somewhat uniform size and sifted with appropriate screen. The granules may further be sifted through screen of #60mesh to obtain similar size granules.

The granules of the present invention may be used an excipient with one or more active pharmaceutical ingredients (APIs) and other pharmaceutically acceptable excipients.Suitable APIs that may be used with the present invention include, but are not limited to and renergic blocking agent; acetyl-cholinesterase inhibitor; analgesic or antipyretics; angiotensin modulator; anthelmintic agents; anti anxiety agent; antibacterial; antibiotic; anticoagulant; anticonvulsant; antidepressant; antifungal; antihistamine; antimalarial; antimicrobial agent; antipsychotic agent; Antiviral agents; blood glucose lowering drug; calcium channel modulator; diuretic; erectile dysfunction; gastric acid secretion inhibitor; histamine H2-receptor antagonist; inhibitor of steroid Type II 5[alpha]-reductase including; lipid regulating agents; selective Hl- receptor antagonist; vasodilator; vitamins.

The surface area of silicon dioxide used in the present invention may be in the range of 50 m2/gm to 500 m2/gm, more preferably 100 m2/gm to 400 m2/gm.

The average primary particle diameter of silicon dioxide used in the present invention may be in the range of 5 nm to 50 nm, more preferably in the range of 10 nm to 40 nm. The particle size of the silicon dioxide granules made according to the present invention is 200µ to 400µ.

The bulk density of silicon dioxide used in the present invention may be in the range of 20 g/l to 100 g/l, more preferably the bulk density may be in the range of 25 g/l to 80 g/l. The tapped bulk density of silicon dioxide granules made according to the current invention is 500 g/l to 800 g/l.

Without being limited by the theory, the present invention provides a novel, free-flowing non-brittle granules of silica, a composition comprising silicon dioxide, cellulosic polymer, surfactant and optionally binder, plasticizer and other pharmaceutically acceptable excipients. The composition of the present invention may be used as an excipient with one or more active pharmaceutical ingredient and other pharmaceutically acceptable excipients in pharmaceutical, nutraceuticals and agricultural formulations.

ADVANTAGES OF THE INVENTION
1. The novel spherical granules of silica of the present invention are free-flowing, non-brittle, having good binding and plastic properties, with high active ingredient loading capacity and improved stability.
2. The granules can be used as an excipient with wide range of APIs.
3. Better flow properties of the granules due to their spherical shape provide easy usability.
4. Even distribution of the drug in drug layered granules in oral dosage forms like tablets, etc.
5. The granules as such may also be used as excipients in capsules, oral and topical suspensions, etc.
6. Easy manipulation of the formulation depending upon the specific site for delivery of the drug. The drug layered granules may be coated with immediate release or enteric release coating to assist in their release at specific site i.e from oral cavity to gastrointestinal tract or stomach or intestine.
7. The process of the present invention does not require extrusion thus problems like heat generation, reduced mechanical strength of products are avoided. It further also saves time, energy and cost of production.

The invention is described in detail herein below with respect to the following examples, which are provided merely for illustration and are not intended to restrict scope of invention in any manner. Any embodiments that may be apparent to a person skilled in the art are deemed to fall within the scope of present invention.

EXAMPLES
Example 1: Illustrative composition of the Present Invention
Table A: Composition of the present invention
Ingredients Std. Formula as % w/w
Colloidal Silicon Dioxide (Aerosil) 65
HPMC 15 cps 3
Sodium Lauryl Sulphate 10
Glycerin 10
Polysorbate 80 5
Microcrystalline Cellulose 7
Purified water Q.S.
Total 100

Example 2: Process for Preparation of Silicon Dioxide Granules
The cellulosic polymer e.g. microcrystalline cellulose (7%) and surfactant like sodium lauryl sulphate (10%) are sifted through suitable mesh. The binding solution is prepared by mixing 3% of hydroxyl propyl methyl cellulose (15 cps), 10% of glycerine, 5% of polysorbate 80 in adequate amount of water in an appropriate size tank and this mixture is stirred at 20 rpm for 1 hours and filtered. During the granulation step, 65% kg of colloidal silicon dioxide and binding solution are mixed intermittently with sifted cellulosic polymer and surfactant in rapid mixture granulator. The material is mixed at high speed for one hour to get the wet solid material.
In some of the cases where oversized granules are obtained, they may be broken optionally using appropriate device (e.g. multi-mill, etc). Generated granules are then sifted through suitable screen to obtain granules of desired size. Further spheronization is performed by using a suitable chequer plate of spheronizer. Generated granules are then loaded in tray dryer by spreading them uniformly, on the trays and dried at 80°C. The granules obtained after spheronization are mostly spherical in shape and these spherical granules were dried for 10 hrs and after which temperature of tray dryer is lowered down to obtain ambient temperature and then spherical granules are removed from dryer.
Generated spherical granules are then checked for loss on drying test by using IR moisture balance. Alternately, above dried 1gm granules are placed in oven at 105°C for 2hr.Loss of moisture is calculated as per pharmacopeial guidelines.
Further in order to sort our generated granules in proper manner, they are required to be sieved with the help of Mechanical Sifter. To achieve desired size of spherical granules, arrange sieves and collect retention on sieves.

Example 3: Illustrative composition of the present invention

Table B: Composition of the present invention
Ingredients Std. Formula as % w/w
Colloidal Silicon Dioxide (Aerosil) 60
HPMC 15 cps 3
Sodium Lauryl Sulphate 12.5
Glycerin 12.5
Polysorbate 80 5
Microcrystalline Cellulose 7
Purified water Q.S.
Total 100

Dry ingredients i.e60 % of Colloidal Silicon Dioxide, 7 % of microcrystalline cellulose and 12.5 % of sodium lauryl sulphate are sieved through a suitable mesh. The binding solution is prepared by mixing the binder i.e 3% of hydroxylpropyl cellulose with 12.5 % glycerine and 5% of Polysorbate 80 in appropriate quantity of water. The binding solution is added intermittently to the dry ingredients and the mass is granulated in a rapid mixer granulator. The granules are then subjected to spheronization by using a 2mm chequer plate. The spherical granules obtained are subjected to drying in a tray dryer for 10 hours. The spherical granules then pass through a mechanical sifter to sort and separate spherical granules of different dimensions.

Example 4: Illustrative composition of the present invention

Table C: Composition of the present invention
Ingredients Std. Formula as % w/w
Colloidal Silicon Dioxide 70
HPMC 15 cps 3
Sodium Lauryl Sulphate 7.5
Glycerin 7.5
Polysorbate 80 5
Microcrystalline Cellulose 7
Purified water Q.S.
Total 100

Dry ingredients i.e70 % of Colloidal Silicon Dioxide 70 %, 7 % of microcrystalline cellulose and 7.5 % of sodium lauryl sulphate are sieved through a suitable mesh. The binding solution is prepared by mixing the binder i.e 3% of hydroxyl propyl cellulose with 7.5 % glycerine and 5% of Polysorbate 80 in appropriate quantity of. The binding solution is added intermittently to the dry ingredients and the mass is granulated in a rapid mixer granulator. The granules are then subjected to spheronization by using a 2mm chequer plate. The spherical granules obtained are subjected to drying using a fluid bed drier. The spherical granules then pass through a mechanical sifter to sort and separate spherical granules of different dimensions.

Example 5: Illustrative composition of the present invention

Table D: Composition of the present invention
Ingredients Std. Formula as % w/w
Colloidal Silicon Dioxide 75
HPMC 15 cps 3
Sodium Lauryl Sulphate 5
Glycerin 5
Polysorbate 80 5
Microcrystalline Cellulose 7
Purified water Q.S.
Total 100

Dry ingredients i.e75 % of Colloidal Silicon Dioxide, 7 % of microcrystalline cellulose and 5% of sodium lauryl sulphate are sieved through a suitable mesh. The binding solution is prepared by mixing the binder i.e 3% of hydroxyl propyl cellulose with 5 % glycerine and 5% of Polysorbate 80 in appropriate quantity of water. The binding solution is added intermittently to the dry ingredients and the mass is granulated in a rapid mixer granulator. . The granules obtained are subjected to drying using a suitable drying technique. The spherical granules then pass through a mechanical sifter to sort and separate spherical granules of different dimensions. These dried granules can be used as bulk filler for compressed tablets and capsules.

Example 6: Illustrative composition of the present invention

Table E: Composition of the present invention
Ingredients Std. Formula as % w/w
Colloidal Silicon Dioxide 80
HPMC 15 cps 3
Sodium Lauryl Sulphate 2.5
Glycerin 2.5
Polysorbate 80 5
Microcrystalline Cellulose 7
Purified water Q.S.
Total 100

Dry ingredients i.e80 % of Colloidal Silicon Dioxide, 7 % of microcrystalline cellulose and 2.5 % of sodium lauryl sulphate are sieved through a suitable mesh. The binding solution is prepared by mixing the binder i.e 3% of hydroxyl propyl cellulose with 2.5 % glycerine and 5% of Polysorbate 80 in appropriate quantity of water. The binding solution is added intermittently to the dry ingredients and the mass is granulated in a rapid mixer granulator. The granules obtained are subjected to drying in a tray dryer for 10 hours. The granules then pass through a mechanical sifter to sort and separate granules of different dimensions.

Example 7: Preparation of tablets containing sustained release Multi –Unit Particulate Systems (MUPS) by using granules made as per example 1 to 6.

A- Seal Coating: Silicon dioxide granules made as per composition and method of example 1 to 6, having particle size in range of 250 – 400 microns are seal coated with a seal coating solution comprising hydroxyl propyl methyl cellulose (6cps), talc and water. The seal coating had 11% solids content. Weight gain after the seal coating was noted as 5%.
B- Drug Loading: An aqueous solution of active pharmaceutical ingredient like metoprolol succinate alongwith povidone K-30, talc and titanium dioxide was coated onto the seal coated granules. The weight gain after the drug loading was 37-40%.
C-Seal Coating: The drug loaded granules were again seal coated with Ideal Cures product INSTACOAT™ UNIVERSAL-3521 reconstituted in water at 11% solids content, so that the granules have a weight gain of 5-7%.
D-Sustained Release Coating: The granules obtained after following the above mentioned steps are then coated with a sustained release coating containing ethyl cellulose as the sustained release polymer and diethyl phthalate as the plasticizer in a mixture of organic solvents like isopropyl alcohol and dichloromethane, until the weight gained is around 40%.
E- Colour Coating: The granules are lastly colour coated to obtain a weight gain of 5% with Ideal Cures product INSTACOAT™ UNIVERSAL (A05R02598).Colour coating was done using PamGlatt's R&D model GPCG 1.1.
The sustained release pellets of metoprolol succinate obtained after the above mentioned steps are sieved through a suitable mesh to obtain particles with similar size dimensions and then mixed with other suitable pharmaceutical excipients like Aerosil and Cross Povidone XL-10 and compressed with suitable pressure in a tablet press to obtain tablets with sustained release pellets of metoprolol succinate.
The disintegration time of the MUPS was tested using USP standard disintegration test and it was found to be 25-27 mins.
,CLAIMS:1. A free flowing granular composition comprising silicon dioxide, a cellulosic polymer, a surfactant and a binding solution.
2. The granular composition as claimed in claim 1, wherein the silicon dioxide is preferably colloidal silicon dioxide and is present in the range of 50% to 80% by weight of the composition.
3. The granular composition as claimed in claim 1, wherein cellulosic polymer is selected from the group comprising microcrystalline cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, ethyl cellulose, and combinations thereof.
4. The granular composition as claimed in claim 3, wherein the cellulosic polymer is microcrystalline cellulose and is present in the range of 5% to 30% by weight of composition.
5. The granular composition as claimed in claim 1, wherein the surfactant is selected from a group comprising ammonium lauryl sulfate, sodium lauryl sulfate, polysorbate-80, dioctylsodium sulfosuccinate, alkyl benzene sulfonates, sodium dodecyl sulfate, quaternary ammonium chloride and combinations thereof.
6. The granular composition as claimed in claim 5, wherein the surfactant is sodium lauryl sulfate and is present in the range of 5% to 20% by weight of the composition.
7. The granular composition as claimed in claim 1, wherein the binding solution further comprises a binder, a plasticizer, a surfactant and solvent.
8. The granular composition as claimed in claim 7, wherein the binder is selected from a group comprising methyl Cellulose, ethyl Cellulose, gelatin, hydroxy propyl methyl cellulose (HPMC), starch paste, hydroxy propyl cellulose, pregelatinized starch, sodium carboxy methyl cellulose, polyvinyl pyrrolidone (PVP), cellulose, polyvinyl alcohols polymethacrylates and combination thereof.
9. The granular composition as claimed in claim 8, wherein the binder is hydroxy propyl methyl cellulose (HPMC) and is present in range of 0.5% to 5% by weight of composition.
10. The granular composition as claimed in claim 7, wherein the plasticizer is selected from group comprising glycerides like monoglycerides, diglycerides, triglycerides and combination thereof.
11. The granular composition as claimed in claim 10, wherein the plasticizer is glycerine and is present in range of 2% to 15% by weight of composition.
12. The granular composition as claimed in claim 7, wherein the surfactant is selected from the group comprising ammonium lauryl sulfate, sodium lauryl sulfate, polysorbate-80, dioctylsodium sulfosuccinate, alkyl benzene sulfonates, sodium dodecyl sulfate, quaternary ammonium chloride and combinations thereof.
13. The granular composition as claimed in claim 12, wherein the surfactant is polysorbate-80 and is present in range of 5% to 20% by weight of composition.
14. The granular composition as claimed in claim 7, wherein the solvent is selected from the group comprising ethanol, isopropyl alcohol and purified water or mixtures thereof, preferably, purified water.
15. A process of preparation of free flowing granular composition comprising steps of:
a) sieving and homogenization of dry components,
b) Granulation of the dry components of step (a) with binding solution,
c) spheronization of wet solid material of step (b),
d) drying of the granules of step (c),
e) optionally sieving the granules of step (d) to obtain the granules of present invention.