Claims:1. A pharmaceutical composition of ibuprofen comprising-
a. 75% to 90% by weight of ibuprofen,
b. 0.05% to 0.2% by weight of Sodium lauryl sulfate,
c. 2% to 5% by weight of binder selected from pregelatinized starch, povidone or mixtures thereof,
d. 5-10% of diluent,
e. 3% to 6% by weight of a disintegrant selected from crospovidone, croscarmellose sodium and sodium starch glycolate,
f. 0.2% to 0.8% by weight of glidant and
g. 0.2% to 0.8% by weight of lubricants selected from calcium stearate, magnesium stearate and sodium stearyl fumarate.
where in the total amount of a),b),c),d),e),f) and g) corresponds to 100% by weight of the overall composition.
2. A pharmaceutical composition of ibuprofen according to claim-1, wherein the diluent is microcrystalline cellulose or lactose or mannitol.
3. A pharmaceutical composition of ibuprofen according to claim-1, wherein the glidant is selected from colloidal silicon dioxide, talc, or magnesium carbonate.
4. A process for the preparation of pharmaceutical composition of Ibuprofen according to claim 1, which comprises the steps of ;
(vi) preparing binder solution by mixing water with Sodium lauryl sulfate and binder
(vii) dry mixing Ibuprofen with one or more diluent and binder excipients,
(viii) wet granulating the dry mix of step (ii) using binder solution of step (i) to form granules followed by drying,
(ix) perform blending with disintegrant and glidant in the blender
(x) adding lubricant in the blend of step (iv).
5. A pharmaceutical composition obtained according to claim 1 can be made in to tablets, capsules, Multiple Unit Pellet System (MUPS), granules, solid dispersions, pellets, beads, particles, mini-tablets, orally disintegrating tablets and the like.
6. A pharmaceutical composition comprising
i) 85% by weight of ibuprofen,
j) 6.2% of microcrystalline cellulose,
k) 4.5% by weight of croscarmellose sodium,
l) 0.45% by weight of povidone,
m) 2.5% by weight of pregelatinized starch,
n) 0.15% by weight of Sodium lauryl sulfate,
o) 0.6% by weight of colloidal silicon dioxide and
p) 0.6% by weight of magnesium stearate,
wherein the pharmaceutical composition is prepared by the process of wet granulation. , Description:FIELD OF THE INVENTION
The present invention relates to Pharmaceutical composition of Ibuprofen.

BACKGROUND OF THE INVENTION
Ibuprofen is a medication in the nonsteroidal anti-inflammatory drug (NSAID) class that is used for treating pain, fever, and inflammation. It is chemically termed as (RS)-2-(4-(2-Methylpropyl)phenyl)propanoic acid and structurally represented by the following structure:

Ibuprofen was discovered in 1961 by Stewart Adams and John Nicholson and marketed as Brufen. It is available under a number of trade names, including Advil and Motrin. It was first marketed in 1969 in the United Kingdom and in the United States in 1974. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system
U.S. Patent No. 4,609,675 describes dry granulation process for the preparation of high drug content ibuprofen formulation.
Ho et al in U.S. Patent No. 4,904,477 describes spray dried compositions comprising agglomerates of ibuprofen in a gelatinized starch matrix and to a method for manufacture thereof.
U.S. Patent No. 5,191,114 discloses a process for producing ibuprofen powders for direct tableting, in which powders with improved flowability are said to be obtained by dry mixing of ibuprofen with amorphous silica gel.
WO 2005/037192 describes the production of ibuprofen-containing granules by dry mixing of the active ingredient with pharmaceutical aids and subsequent roll compaction.
Meyer-Boehm et al in U.S. Patent No. 8, 846, 085 discloses process for producing a directly tabletable ibuprofen formulation comprising finely divided excipient with a surface area of at least 100 m2/g, where in At least 50% of the surface of the ibuprofen crystals Is covered with said finely divided excipient.
Sundararajan et al in WO2017060920 disclose a process of preparing ibuprofen composition, which specifically involves the use of glidant in three stages of formulation to obtain free flowing granules that impart better mold release properties and minimize the tablet weight variation
Despite plethora of disclosure on compositions of ibuprofen, the problems associated with the prior art compositions of ibuprofen and processes for preparation include excessive disintegration time, inadequate bulk density; sticking during compression; poor flowing granulation formulation which often becomes difficult to handle on plant scale.

Hence, there exists a need to explore and provide newer compositions, imporved process conditions, proportions of ingredients in the manufacturing process of ibuprofen or its pharmaceutically acceptable salt to obtain a final formulations (i.e., tablets and capsules or caplets) that may overcome the above cited problems.

Accordingly, the object of the present invention is to provide Ibuprofen compositions, which is consistently stable during its shelf-life so as to minimize the fluctuation in bioavailability of the drug upon administration.

SUMMARY OF INVENTION

One aspect of the present invention relates to pharmaceutical composition of ibuprofen comprising-
a. 75% to 90% by weight of ibuprofen,
b. 0.05% to 0.2% by weight of Sodium lauryl sulfate,
c. 2% to 5% by weight of binder selected from pregelatinized starch, povidone or mixtures thereof,
d. 5-10% of diluent,
e. 3% to 6% by weight of a disintegrant selected from crospovidone, croscarmellose sodium and sodium starch glycolate,
f. 0.2% to 0.8% by weight of glidant and
g. 0.2% to 0.8% by weight of lubricants selected from calcium stearate, magnesium stearate and sodium stearyl fumarate.
Where in the total amount of a),b),c),d),e),f) and g) corresponds to 100% by weight of the overall composition.

In another aspect the present invention relates to process for the preparation of pharmaceutical composition of Ibuprofen, which comprises the steps of;
(i) preparing binder solution by mixing water with Sodium lauryl sulfate and binder
(ii) dry mixing Ibuprofen with one or more diluent and binder excipients,
(iii) wet granulating the dry mix of step (ii) using binder solution of step (i) to form granules followed by drying,
(iv) perform blending with disintegrant and glidant in the blender
(v) adding lubricant in the blend of step (iv).

A Particular aspect of the present invention relates to pharmaceutical composition comprising
a) 85% by weight of ibuprofen,
b) 6.2% of microcrystalline cellulose,
c) 4.5% by weight of croscarmellose sodium,
d) 0.45% by weight of povidone,
e) 2.5% by weight of pregelatinized starch,
f) 0.15% by weight of Sodium lauryl sulfate,
g) 0.6% by weight of colloidal silicon dioxide and
h) 0.6% by weight of magnesium stearate,
Where in the pharmaceutical composition is prepared by the process of wet granulation.

DETAILED DESCRIPTION
As set forth herein, embodiments of the present invention provide a stable pharmaceutical composition comprising Ibuprofen.
The embodiment of the present invention provides a novel pharmaceutical composition, comprising ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof, having various advantageous properties viz, stability, especially regarding compressed tablets dissolution properties, improved bulk density & bioavailability profile besides better processing properties like flowability, non- sticking nature during compression process or filling into capsules etc.

The ingredients and processes set forth herein allow for the manufacture of tablets and capsules with advantageous characteristics including faster dissolution profile and improved tablet strength.
As used herein, the term ‘about’, or ‘approximately’ means a particular value can have a range acceptable to those of skilled in the art given the nature of the value and method by which it is determined.
In one embodiment according to present invention, it provides a pharmaceutical composition of ibuprofen comprising-
a. 75% to 90% by weight of ibuprofen,
b. 0.05% to 0.2% by weight of Sodium lauryl sulfate,
c. 2% to 5% by weight of binder selected from pregelatinized starch, povidone or mixtures thereof,
d. 5-10% of diluent,
e. 3% to 6% by weight of a disintegrant selected from crospovidone, croscarmellose sodium and sodium starch glycolate,
f. 0.2% to 0.8% by weight of glidant and
g. 0.2% to 0.8% by weight of lubricants selected from calcium stearate, magnesium stearate and sodium stearyl fumarate.
where in the total amount of a),b),c),d),e),f) and g) corresponds to 100% by weight of the overall composition.
In this embodiment according to present application for an Ibuprofen pharmaceutical composition, it comprisethe Ibuprofen in an amount ranging from 75 to 90% and one or more pharmaceutically acceptable excipient(s)..The Ibuprofen may be present as Ibuprofen or its pharmaceutically acceptable salt, enantiomers thereof.
Further specific embodiment according to present invention includes Sodium lauryl sulfate present as wetting agent in the composition in an amount ranging between 0.05% to 0.2% by weight based on the total weight of composition. The role of Sodium lauryl sulfate(SLS) to aid in improved permeation of drug through biological membrane as it destroys the path through which drug has to pass and thus minimizing the path length for the drug to travel.
Wetting agents are mainly added when hydrophobic drug is to be formulated into tablet. SLS, Sodium diisobutyl sulfosuccinate are used as wetting agent in tablet formulation.
In another embodiment according to present invention, it provides use of binder selected from pregelatinized starch, povidone or mixtures thereof are present as binder in the amount of ranging 2% to 5% by weight based on the total weight of composition. Binders are useful in holding the ingredients in tablets together to give volume to low active tablets.
In yet another embodiment according to present invention, diluent is utilized in an amount ranging between 5-10% based on the total weight of composition. Diluents are selected from microcrystalline cellulose or lactose or mannitol. In a particular embodiment according to present invention, it used Microcrystalline cellulose (MCC) as diluent, which is found highly compressible diluent.
In another embodiment according to present invention, the disintegrant utilized in the composition in an amount ranging between 3% to 6% based on the total weight of composition. The disintegrant is selected crospovidone, croscarmellose sodium and sodium starch glycolate.
In a specific embodiment, inventors of the present application used Croscarmellose sodium, or sodium CMC as disintegrant, which is a cross-linked polymer of carboxymethylcellulose sodium. Cross-linking allows apparently enhanced bioavailability of the drug through superior drug dissolution.
In yet another embodiment according to present invention, the glidant used in the composition in an amount ranging between 0.2% to 0.8% based on the total weight of composition. Glidants are added to the formulation to improve the flow properties of the material which is to be fed into the die cavity and aid in particle rearrangement within the die during the early stages of compression. The glidant in the present invention are selected from colloidal silicon dioxide, talc, or magnesium carbonate.
In a specific embodiment, inventors of the present application used colloidal silicon dioxide as glidant.
In yet another embodiment according to present invention, the lubricants in the composition used in an amount ranging between 0.2% to 0.8% based on the total weight of composition. As lubricants found to reduce friction between, and wear of one or both, surfaces in proximity and moving relative to each other, by interposing a substance, they are selected in the composition from calcium stearate, magnesium stearate and sodium stearyl fumarate.
In yet another embodiment according to the present invention, it provide the process for the preparation of pharmaceutical composition of Ibuprofen comprises the steps of;
(i) preparing binder solution by mixing water with Sodium lauryl sulfate and binder
(ii) dry mixing Ibuprofen with one or more diluent and binder excipients,
(iii) wet granulating the dry mix of step (ii) using binder solution of step (i) to form granules followed by drying,
(iv) perform blending with disintegrant and glidant in the blender
(v) adding lubricant in the blend of step (iv).
In a more specific and particular embodiment the pharmaceutical composition of Ibuprofen comprising:
a) 85% by weight of ibuprofen,
b) 6.2% of microcrystalline cellulose,
c) 4.5% by weight of croscarmellose sodium,
d) 0.45% by weight of povidone,
e) 2.5% by weight of pregelatinized starch,
f) 0.15% by weight of Sodium lauryl sulfate,
g) 0.6% by weight of colloidal silicon dioxide and
h) 0.6% by weight of magnesium stearate,
where in the pharmaceutical composition is prepared by the process of wet granulation.
The present invention embodiment also includes specific features of the process of preparing the said pharmaceutical composition of Ibuprofen; wherein disintegrant & glidant were used together before blending and lubrication in order to improve the granules therapeutic performance.
Also the process of preparing the said pharmaceutical composition of Ibuprofen includes wherein disintegrant, glidant and lubricants were used together before subjecting to blending in order to improve the granules therapeutic performance.
All necessary steps in the excipients use include conventional sifting of them before adding into the specific processing stage.
In the process of preparing the granulation according to present invention, it was carried out as a wet granulation method, which comprises, sifting the composition components of the present invention selected from binder, diluent, disintegrant, wetting agent etc, including Ibuprofen or its pharmaceutically acceptable salts and dry mixing for not less than 5 minutes. Granulating the dry mix in RMG using binder solution prepared using specifically water. Drying the resulting granules using FBD followed by milling/sizing and mixing the granules with a part of glidant for not more than 20 minutes. Further blending with diluent, disintegrant and glidant of not less than 5- 10 minutes. Lubricant in the final blend was added and performed for not more than 10 minutes.
The manufacturing process of the present invention involves the use of glidant in single stage of formulation and specifically along with distinitgrant followed by lubricant process.
The amounts of the added excipients are preferably the minimum amounts necessary to accomplish their purposes. For example, the lubricant component is present in a lubricating amount sufficient to impart mold release properties to tablets formed from the formulation and preferably insufficient to increase disintegration time and dissolution time of such tablets, and preferably insufficient to decrease the hardness obtainable for tablets formed from a formulation having no additional lubricant.

The final drug forms (resulting from the new granulation formulations) will be having various advantageous properties viz, stability, especially regarding compressed tablets dissolution properties, improved bulk density & bioavailability profile besides better processing properties like flowability, non- sticking nature during compression process or filling into capsules etc.

The composition of the present invention obtained by the process exhibits a significant improvement in dissolution profile and assay during stability in stress and accelerated condition as compared to marketed formulation.
In yet another embodiment according to present invention, the obtained pharmaceutical composition of Ibuprofen can be suitably converted in to tablets, capsules, Multiple Unit Pellet System (MUPS), granules, solid dispersions, pellets, beads, particles, mini-tablets, orally disintegrating tablets and the like.
The invention is further exemplified with following examples which are not intended to limit the scope of the invention.

EXAMPLES:
The following examples further describe and demonstrate particular embodiments within the scope of the present invention. It will be apparent to those skilled in the art that many modifications, both to materials and methods, may be practiced without departing from the scope of the invention.

Table 1:
Example 1-3:
S.No. Ingredients Example 1 Example 2 Example 3
In % In % In %
1. Ibuprofen 85.0 81.5% 87.8
2. Microcrystalline cellulose 6.20 8.0 5.8
3. Pregelatinized starch 2.50 3.2 1.8
4. Povidone (K – 90) 0.45 0.8 0.3
5. Sodium Lauryl Sulphate 0.15 0.1 0.2
6. Croscarmellose Sodium 4.50 5.0 3.2
7. Magnesium stearate 0.60 0.7 0.4
8. Colloidal Silicon Dioxide 0.60 0.7 0.5
9. Purified water Q.S Q.S Q.S

Manufacturing process:
1. Binder solution is prepared by mixing povidone in Purified water having a temperature of NLT 65°C
2. Sodium lauryl sulfate is dispersed in purified water separately in a small vessel and added to above binder solution of step (1) slowly by avoiding excess stirring
3. Ibuprofen, Pregelatinised starch and microcrystalline cellulose are loaded into Rapid Mixer Granulator and sprayed using binder solution of step (2) to form wet granules.
4. The obtained wet granules are dried using Fluid bed dryer and dried at 55 – 650C till required LOD 0.6 - 1.0 % is achieved.
5. The obtained granules of step (4) were milled, sifted and blended with sifted croscarmellose sodium and colloidal silicon dioxide for about 10 minutes.
6. The granules of step (5) were finally lubricated with sifted magnesium stearate (through #40 mesh).
7. The blending process was performed in octagonal blender for about 5 minutes.
The granules composition so obtained may then be compressed in to tablets by a conventional process known in the art.
Suitable Coating may also be carried out with known coating agents.
Similar procedure was conducted to obtain the pharmaceutical granules of example 2 and example 3 respectively.
The said pharmaceutical composition according to invention can also be suitably converted to dosage forms like, capsules, Multiple Unit Pellet System (MUPS), solid dispersions, pellets, beads, particles, mini-tablets, orally disintegrating tablets and the like.

All documents cited in the specification are incorporated herein by reference; the citation of any document is not to be construed as an admission that it is prior art with respect to the present invention.
While particular embodiments of the present invention have been illustrated and described, it would be obvious to one skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended and construed to cover in the appended claims all such changes and modifications that are within the scope of this invention.