Field of the invention

The technical field-of the present invention relates to pharmaceutical compositions of pharmaceuticals for treating rhinitis associated with allergie, cough, cold, cold-like and/or flu symptoms and the discomfort, pain, fever and general malaise associated therewith.

More particularly the present invention relates pharmaceutical compositions comprising one or more non-steroidal anti-inflammatory drugs (NSAID) in combination with at least one antihistamine, sympathomimetic drug (nasal decongestant; bronchodilator) cough suppressant and/or expectorant, optionally in combination with suitable pharmaceutically acceptable non-toxic carriers or excipients.

Background of the invention

Rhinitis refers to an inflammatory disorder of the nasal passages. The symptoms of rhinitis typically consist of sneezing, rhinorrhea, nasal congestion, and increased nasal secretions. Untreated rhinitis may lead to other disorders including infection of the sinuses, ears and lower respiratory tract.

Two types of oral medication are commonly used to treat rhinitis; decongestants and antihistamines. Decongestants and antihistamines differ in mechanism of action, therapeutic effects, and side effects. It is common practice to combine the use of these two to bring about more complete symptom relief of rhinitis than is possible with either entity alone.

Decongestants commonly used to treat rhinitis include the sympatomimetic agents pseudoephedrine and phenylephrine. These agents act to constrict vessels in the nasal mucus membranes and thereby decrease tissue swelling and nasal congestion. Decongestants are found to be better than antihistamines for restoring the patency of congested nasal airways. Nasal decongestants are stimulatory. Decongestants however may produce nervousness, restlessness and insomnia, especially if taken at night.

Histamine is a mediator released from cells which line the walls of the nasal mucous membranes (mast cells). When released, histamine is known to bind to local receptors and thereby cause sneezing, nasal itching, swelling of the nasal membranes, and increased nasal secretions. Antihistamines relieve these effects, albeit by a different mechanism than decongestants. Antihistamines block the binding of histamine to histamine receptors in the nasal membranes. Side effects of antihistamines include impairment of mental acuity and sedation.

Combinations of decongestants and antihistamines employ two mechanistic approaches, and have been shown to offer more complete relief of rhinitis symptoms than therapy with either component alone. Currently, many cold and allergy relief products contain both. Incorporation of decongestant and sedating antihistamine into a single dosage unit balances stimulation and sedation of the components. However, some individuals vary in there sensitivity to either the decongestant or the antihistamine. Consequently, some individuals experience irritability and/or sedation with these combinations.

Non-steroidal anti-inflammatory drugs (NSAIDS) are ideally suited for use in cold formulations for their analgesic, anti-inflammatory, and antipyretic activity and low incidence of untoward side effects. NSAIDS are widely administered orally in the treatment of mild to severe pain.

These combination products provide effective symptom treatment of rhinitis due to cold and allergy. US 4,552,899 discloses pharmaceutical composition of matter for use in the treatment of cough, cold, cold-like and/or flu symptoms in a mammalian organism, comprising a sympathomimetically, analgesically and anti-inflammatorily effective amount of ibuprofen in combinatory immixture with (ii) at least one of the sympathomimetic amines, pseudoephedrine, phenylpropanolamine, phenylephrine, or pharmaceutically acceptable salt thereof.

US 5,025,019 discloses a pharmaceutical composition of matter for use in the treatment of cough, cold, cold-like and/or flu symptoms in a mammalian organism, and adapted for unit dosage oral administration, said composition comprising (i) an analgesically and anti-inflammatoryily effective amount of a non-narcotic constituent consisting essentially of ibuprofen or pharmaceutically acceptable salt thereof, in combinatory immixture with (ii) a sympathomimetically effective amount of at least one of the sympathomimetic amines, pseudoephedrine or pharmaceutically acceptable salt thereof, and (iii) an antihistaminically effective amount of at least one of the antihistamines, chlorpheniramine or pharmaceutically acceptable salt thereof.

US 7,863,287 discloses pharmaceutical composition which includes an effective amount of each of a non-steroidal anti-inflammatory drug (NSAID), a decongestant, and an antihistamine, wherein the effective amount of the decongestant or the antihistamine or both is less than about 75% of an amount present in an approved dose of the decongestant or the antihistamine, or both, relative to an amount of the NSAID corresponding to about 100% of the amount present in a normal strength dosage form of the NSAID.

US '287 further discloses that the addition of a non-steroidal anti-inflammatory agent to a composition containing an antihistamine and/or a decongestant enchances the i efficacy of the antihistamine and decongestant, thus permitting a reduction in the total dose of either or both.

US 2004/0253311 discloses a pharmaceutical composition comprising an effective amount of each of (a) a non-steroidal anti-inflammatory drug (NSAID), (b) a decongestant; and (c) an antihistamine, wherein the composition is a multi-layer tablet; and at least one of the NSAID, the decongestant and the antihistamine is in a first layer of the multi-layer tablet and at least one other of the NSAID, the decongestant and the antihistamine is in a second layer of the multi-layer tablet.

Thus, there remains a need in the art for improved compositions and methods for treating symptoms of rhinitis with reduced side effects from the treatment and/or with improved release characteristics of the pharmaceutical actives.

Objective of the invention

Accordingly, the main objective of the present invention is to provide a pharmaceutical composition comprising an effective amount of non-steroidal anti-inflammatory drug (NSAID), an antihistamine, a decongestant and one or more pharmaceutically acceptable excipient in such a way that the dosage form will comply with the reference product in terms of in vitro parameters like dissolution, disintegration and etc.

Summary of the invention

Accordingly, the present invention provides a pharmaceutical composition which includes an effective amount of each of a non-steroidal anti-inflammatory drug (NSAID), a decongestant, and an antihistamine and one or more pharmaceutically acceptable excipient.

In an embodiment, the present invention also provides the pharmaceutical composition comprising an effective amount of each of (a) a non-steroidal anti-inflammatory drug (NSAID), (b) a decongestant; and (c) an antihistamine, wherein the composition is a mono-layer tablet.

In an embodiment, the present invention also provides process for the preparation Df pharmaceutical composition comprising an effective amount of each of (a) a non-steroidal anti-inflammatory drug (NSAID), (b) a decongestant; and (c) an antihistamine, wherein the composition is a mono-layer tablet.

In another embodiment, the present invention also provides the granules comprising an effective amount of each of (a) a non-steroidal anti-inflammatory drug (NSAID), (b) a decongestant; and (c) an antihistamine.

In another embodiment, the present invention also provides the pharmaceutical composition comprising an effective amount of each of (a) a non-steroidal anti-inflammatory drug (NSAID), (b) a decongestant; and (c) an antihistamine, wherein the composition is a mono-layer tablet, and atleast one of the NSAID, decongestant and antihistamine is in one granular portion of the mono-layer tablet and at least one other of the NSAID, decongestant and antihistamine is in a second granular portion of the mono-layer tablet.

Detailed description of the invention

\The present invention provides a pharmaceutical composition which includes an effective amount of each of a non-steroidal anti-inflammatory drug (NSAID), a decongestant, and an antihistamine and one or more pharmaceutically acceptable excipient.

In an embodiment, the present invention also provides the pharmaceutical composition comprising an effective amount of each of (a) a non-steroidal anti-inflammatory drug (NSAID), (b) a decongestant; and (c) an antihistamine, wherein the composition is a mono-layer tablet.
 
In another embodiment, the present invention also provides the granules comprising an effective amount of each of (a) a non-steroidal anti-inflammatory drug (NSAID), (b) a decongestant; and (c) an antihistamine.

In another embodiment, the present invention also provides the pharmaceutical composition comprising an effective amount of each of (a) a non-steroidal anti- inflammatory drug (NSAID), (b) a decongestant; and (c) an antihistamine, wherein the composition is a mono-layer tablet, and atleast one of the NSAID, decongestant and antihistamine is in one granular portion of the mono-layer tablet and at least one other of the NSAID, decongestant and antihistamine is in a second granular portion of the mono-layer tablet.

NSAIDs suitable for use in the practice of the invention include, but are not limited to ibuprofen, naproxen, flurbiprofen, fenoprofen, ketoprofen, suprofen, fenbufen, and fluprofen or pharmaceutically acceptable salt thereof. The amount of NSAID used in the present invention may range from about 50 mg to 400 mg.

Decongestants suitable for use in the practice of the invention include, but are not limited to, pseudoephedrine, phenylephedrine and phenylpropanolamine or pharmaceutically acceptable salt thereof. The amount of decongestant used in the present invention may range from about 30 mg to 120 mg.

Antihistamines suitable for use in the practice of the invention include, but are not limited to, astemizole, azatadine, azelastine, acrivastine, brompheniramine, chlorpheniramine, clemastine, cyclizine, carebastine, cyproheptadine, carbinoxamine, descarboethoxyloratadine (also known as SCH-34117), desloratadine doxylamine, dimethindene, ebastine, epinastine, efletirizine, fexofenadine, hydroxyzine, ketotifen, loratadine, levocabastine, mizolastine, mequitazine, mianserin, noberastine, meclizine, norastemizole, picumast, pyrilamine, promethazine, terfenadine, tripelennamine, temelastine, trimeprazine and triprolidine or pharmaceutically acceptable salt thereof. The amount of antihistamine used in the present invention may range from about 2 mg to 12 mg.

The term "effective amount" as provided herein is defined as an amount of the agent at least sufficient to provide the desired therapeutic effect.
 
"Pharmaceutically acceptable excipient/s" are the components added to pharmaceutical formulation to facilitate manufacture, enhance stability, control release, enhance product characteristics, enhance bioavailability, enhance patient acceptability, etc. Pharmaceutically acceptable excipients includes, but not limited to, diluents/fillers, binders, disintegrants, sugars, lubricants, glidants, compression aids, colors, sweeteners, preservatives, surfactants, suspending agents, dispersing agents, film formers, flavors, printing inks, etc.

Diluents increase the bulk of the composition. Diluents according to the present invention include, but not limited to, sugars such as lactose, sucrose, dextrose; sugar alcohols such as mannitol, sorbitol, xylitol, lactitol; Starlac® (co-processed mixture of Starch and lactose), Microcelac® (co-processed mixture of microcrystalline cellulose and lactose), starch, corn starch, modified starches, pregelatinized starch, dibasic calcium phosphate, tribasic calcium phosphate, powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose and the like or combinations thereof. The diluent may be used in the range of 5-99%, preferably 10-70% by weight of the dosage form.

Binders hold the ingredients in the composition together. Exemplary binders include, but not limited to, cellulose and its derivatives including, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose and hydroxyethyl cellulose, carboxymethyl cellulose; starch and its derivatives; pregelatinized starch, hydrocolloids; sugars; polyvinyl pyrrolidone, copovidone, methacrylic acid copolymers and combinations comprising one or more of the foregoing binders. The binder may be used in the range of 0.1-40%, preferably 1-20% by weight of the dosage form.

Disintegrants according to the present invention include, but not limited to, water swellable substances, for example, cellulose and its derivatives including low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose; cross-linked polyvinylpyrrolidone; cross-linked sodium carboxymethylcellulose, cross-linked calcium carboxymethylcellulose, sodium carboxymethylcellulose, calcium carboxy methylcellulose, microcrystalline cellulose; sodium starch glycolate; ion-exchange resins; starch and modified starches including pregelatinized starch; formalin-casein; alginates, gums, and combinations comprising one or more of the foregoing water swellable substances. The disintegrant may be used in the range of 0-30%, preferably 1-20% by weight of the dosage form.

Surfactants are compounds which are capable of improving the wetting of the drug and/or enhancing the dissolution. The surfactants can be selected from hydrophilic surfactants or lipophilic surfactants or mixtures thereof. The surfactants can be anionic, nonionic, cationic, and zwitterionic surfactants. Surfactants according to the present invention include, but not limited to, polyoxyethylene alkylaryl ethers such as polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether; polyethylene glycol fatty acid esters such as PEG monolaurate, PEG dilaurate, Polyethylene glycol 660 12- hydroxyl Stearate Ph.Eur. or Polyoxyl 15 hydroxystearate NF (Solutol HS 15), PEG distearate, PEG dioleate; polyoxyethylene sorbitan fatty acid ester such as polysorbate 40, polysorbate 60, polysorbate 80; sorbitan fatty acid mono esters such as sorbitan monolaurate, sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, polyoxyethylene castor oil derivates such as polyoxyl castor oil, polyoxyl hydrogenated castor oil, sodium lauryl sulphate, monooleate, monolaurate, monopalmitate, monostearate, sodium dioctyl sulfosuccinate (DOSS), lecithin, stearylic ^ alcohol, cetostearylic alcohol, cholesterol, polyoxyethylene ricin oil, polyoxyethylene fatty acid glycerides, poloxamer, cremophore RH 40, polyoxyethylene stearates (Macrogol-stearate) and the like or combinations thereof. The surfactant may be used in the range of 0.001-5% by weight of the dosage form.

Lubricants and glidants aids in the processing of powder materials. Exemplary lubricants include, but not limited to, calcium stearate, glycerol behenate, magnesium stearate, mineral oil, polyethylene glycol, fumaric acid, sodium stearyl fiimarate, stearic acid, talc, vegetable oil, zinc stearate, castor wax and combinations comprising one or more of the foregoing lubricants. The lubricant may be used in the range of 0.01-5%, preferably 0.1-2% by weight of the dosage form. Exemplary glidants include, but not limited to, talc, silicon dioxide, silicic acid, cornstarch, calcium silicate, magnesium carbonate, magnesium oxide, magnesium silicate, colloidal silicon dioxide, starch, castor wax and the like. The glidant may be used in the range of 0.01-5%, preferably 0.1-2% by weight of the dosage form.

In another embodiment, the present invention provides the pharmaceutical composition comprising an effective amount of each of (a) ibuprofen or pharmaceutically acceptable salt thereof, (b) pseudoephedrine or pharmaceutically acceptable salt thereof and (c) chlorpheniramine or pharmaceutically acceptable salt thereof, wherein the composition is a mono-layer tablet.

In another embodiment, the present invention also provides the granules comprising an effective amount of each of (a) ibuprofen or pharmaceutically acceptable salt thereof, (b) pseudoephedrine or pharmaceutically acceptable salt thereof and (c) chlorpheniramine or pharmaceutically acceptable salt thereof.

In another embodiment, the present invention also provides the pharmaceutical composition comprising an effective amount of each of (a) ibuprofen or pharmaceutically acceptable salt thereof, (b) pseudoephedrine or pharmaceutically acceptable salt thereof and (c) chlorpheniramine or pharmaceutically acceptable salt thereof, wherein the composition is a mono-layer tablet, and atleast one of ibuprofen or pharmaceutically acceptable salt thereof, pseudoephedrine or pharmaceutically acceptable salt thereof and chlorpheniramine or pharmaceutically acceptable salt thereof is in one granular portion of the mono-layer tablet and at least one other of ibuprofen or pharmaceutically acceptable salt thereof, pseudoephedrine or pharmaceutically acceptable salt thereof and chlorpheniramine or pharmaceutically acceptable salt thereof is in a second granular portion of the mono-layer tablet.

In a preferred embodiment, the present invention also provides a monolayer tablet comprising the granules comprising an effective amount of each of (a) ibuprofen or pharmaceutically acceptable salt thereof, (b) pseudoephedrine or pharmaceutically acceptable salt thereof and (c) chlorpheniramine or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein said granules are prepared by wet granulation process.

In another embodiment, the present invention also provides a monolayer tablet comprising the granules comprising based on the weight of tablet; about 30% to about 60% of ibuprofen or pharmaceutically acceptable salt thereof, (b) about 2%. to about 10% of pseudoephedrine or pharmaceutically acceptable salt thereof and (c) about 0.1% to about 2% of chlorpheniramine or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients selected from diluent, binder, disintegrant and lubricant, wherein said granules are prepared by wet granulation process.

In a preferred embodiment, the present invention also provides a monolayer tablet comprising:
(a) first granules comprising ibuprofen or its pharmaceutically acceptable salts thereof and one or more excipients,
(b) second granules comprising pseudoephedrine or pharmaceutically acceptable salt thereof and chlorpheniramine or pharmaceutically acceptable salt thereof and one or more excipients,
(c) one or more pharmaceutically acceptable excipients, wherein said granules are prepared by wet granulation process.

In another embodiment, first granules comprises based on weight of tablet; about 30% to about 60% of ibuprofen or pharmaceutically acceptable salt thereof 10% to about 50% of diluent, 0% to about 10% of disintegrant, 0.5% to about 5.0% of binder.

In another embodiment, second granules comprises based on weight of tablet; about 2% to about 10% of pseudoephedrine or pharmaceutically acceptable salt thereof and about 0,1% to about 2% of chlorpheniramine or pharmaceutically acceptable salt thereof, 10% to about 25% of diluent, 0% to about 10% of disintegrant, 1% to about 10% of binder and 0% to about 5% of glidant.

In another embodiment, first granules and second granules are then blended with one or more excipients such as disintegrant, glidant and lubricant.

In another embodiment, there is provided a process for the preparation of a mono layer tablet comprising ibuprofen or pharmaceutically acceptable salt thereof, pseudoephedrine or pharmaceutically acceptable salt thereof and chlorpheniramine or pharmaceutically acceptable salt thereof prepared by the process comprising the steps of: i) granulating ibuprofen or pharmaceutically acceptable salt thereof, pseudoephedrine or pharmaceutically acceptable salt thereof and chlorpheniramine or pharmaceutically acceptable salt thereof and one or more excipients using aqueous/nonaqueous binder solution, ii) drying the granules of step (i),
iii) blending the dried granules of step (ii) with one or more excipients and vi) compressing the blend into mono layer tablets.

In another embodiment, there is provided a process for the preparation of a mono layer tablet comprising ibuprofen or pharmaceutically acceptable salt thereof, pseudoephedrine or pharmaceutically acceptable salt thereof and chlorpheniramine or pharmaceutically acceptable salt thereof prepared by the process comprising the steps of: i) granulating ibuprofen or pharmaceutically acceptable salt thereof and one or more excipients using aqueous/nonaqueous binder solution, ii) drying the granules of step (i),
iii) granulating pseudoephedrine or pharmaceutically acceptable salt thereof and chlorpheniramine or pharmaceutically acceptable salt thereof and one or more excipients using aqueous/nonaqueous binder solution,

iv) drying the granules of step (iii),
v) blending the dried granules of step (ii) & step (iv) with one or more excipients and
vi) compressing the blend into mono layer tablets.
The solvents used for granulation include methylene chloride, isopropyl alcohol, acetone, methanol, ethanol, water and the like or mixtures thereof.
In another embodiment, the solid dosage form according to the present invention may be presented in any dosage form including, but not limited to, capsule, tablet, , granules, pellets, mini-tablets, beads or the like.

The tablet according to the present invention may be uncoated or optionally - coated with film coating/moisture barrier coating composition.

The film coating composition comprises a solution / suspension of film coating polymers and one or more excipients such as lactose, titanium dioxide, solubilizing agent, plasticizer.and antisticking agent.

Suitable film coating polymers used according to the present invention are selected from ethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose and the like or mixture thereof.

The solubilizing agent of the present invention may be selected from anionic or non-ionic surfactants such as sodium lauryl sulphate, polyethylene-propylene glycol copolymer (poloxamer), polyoxyethylene stearates (Macrogol-stearate), polysorbates, propylene glycol, and the like or mixture thereof.

Suitable anti-sticking agents used according to the present invention are selected from talc, magnesium stearate and the like or a mixture thereof.

In yet another embodiment, the present invention also provides a method for the treatment of cough, cold, cold-like and/or flu symptoms by administering compositions of the present invention.

The following examples further exemplify the invention and are not intended to limit the scope of the invention. It is obvious to those skilled in the art to find out the composition for other dosage forms and substitute the equivalent excipients as described in this specification or with the one known to the industry.

J The processing steps involved in manufacturing composition as given in example -1 are given below:
i i) Ibuprofen, Pseudoephedrine Hydrochloride and Chlorpheniramine maleate, microcrystalline cellulose, croscarmellose sodium and corn starch were sifted and blended,
ii) the blend of step (i) was granulated using a solution of povidone in purified water,
iii) the granules of step (ii) were dried and then blended with croscarmellose sodium and colloidal silicon dioxide,
iv) the granules of step (iii) were lubricated with stearic acid and
v) the lubricated granules were compressed to obtain tablets.

The processing steps involved in manufacturing composition as given in example -2 are given below:
i) Ibuprofen, microcrystalline cellulose, croscarmellose sodium and corn starch were sifted and blended,
ii) binder solution of povidone in water was prepared,
iii) granulated the blended material of step (i) with binder solution of step (ii),
iv) dried the granules obtained in step (iii),
v) Pseudoephedrine Hydrochloride, Chlorpheniramine maleate, microcrystalline cellulose and croscarmellose sodium was sifted and blended,
vi) granulated the blended material of step (v) with an aqueousof povidone in water,
vii) dried the granules obtained in step (vi),
viii) the granules of step (iv) and step (vii) were then blended with croscarmellose sodium and colloidal silicon dioxide,
ix) lubricated the blend of step (viii) with stearic acid and
x) the lubricated blend was compressed to obtain mono layer tablets.

Claims:

1. A mono layered tablet comprising an effective amount of each of a non-steroidal anti-inflammatory drug (NSAID), a decongestant, and an antihistamine and one or more pharmaceutically acceptable excipients.

2. The tablet as claimed in claim 1, comprising an effective amount of each of (a) a non-steroidal anti-inflammatory drug (NSAID), (b) a decongestant; and (c) an antihistamine, and atleast one of the NSAID, decongestant and antihistamine is in one granular portion of the mono-layer tablet and at least one other of the NSAID, decongestant and antihistamine is in a second granular portion of the mono-layer tablet.

3. The tablet as claimed in claim 1, wherein one or more pharmaceutically acceptable excipients is selected from the group comprising diluents, binders, disintegrants, surfactants, glidants and lubricants.

4. The tablet as claimed in claim I, wherein non-steroidal anti-inflammatory drug is selected from the group comprising ibuprofen, naproxen, flurbiprofen, fenoprofen, ketoprofen, suprofen, fenbufen, and fluprofen or its pharmaceutically acceptable salt.

5. The tablet as claimed in claim 1, wherein decongestant is selected from the group comprising pseudoephedrine, phenylephedrine and phenylpropanolamine or its pharmaceutically acceptable salt.

6. The tablet as claimed in claim 1, wherein antihistamine is selected from the group comprising astemizole, azatadine, azelastine, acrivastine, brompheniramine, chlorpheniramine, clemastine, cyclizine, carebastine, cyproheptadine, carbinoxamine, , desloratadine doxylamine, dimethindene, ebastine, epinastine, efletirizine, fexofenadine, hydroxyzine, ketotifen, loratadine, levocabastine, mizolastine, mequitazine, mianserin, noberastine, meclizine, norastemizole, picumast, pyrilamine, promethazine, terfenadine,
■ tripelennamine, temelastine, trimeprazine and triprolidine or its pharmaceutically acceptable salt.

7. The tablet as claimed in claim 1, comprising an effective amount of each of (a) ibuprofen or pharmaceutically acceptable salt, (b) pseudoephedrine or pharmaceutically acceptable salt and (c) chlorpheniramine or pharmaceutically acceptable salt.

8. The tablet as claimed in claim 1, comprising an effective amount of each of (a) ibuprofen or pharmaceutically acceptable salt, (b) pseudoephedrine or pharmaceutically acceptable salt and (c) chlorpheniramine or pharmaceutically acceptable salt, and atleast one of ibuprofen or pharmaceutically acceptable salt, pseudoephedrine or pharmaceutically acceptable salt and chlorpheniramine or pharmaceutically acceptable salt is in one granular portion of the mono-layer tablet and at least one other of ibuprofen or pharmaceutically acceptable salt, pseudoephedrine or pharmaceutically acceptable salt and chlorpheniramine or pharmaceutically acceptable salt is in a second granular portion of the mono-layer tablet.

9. The tablet as claimed in claim 1, comprising the granules comprising an effective amount of each of (a) ibuprofen or pharmaceutically acceptable salt, (b) pseudoephedrine or pharmaceutically acceptable salt and (c) chlorpheniramine or pharmaceutically acceptable salt and one or more pharmaceutically acceptable excipients, wherein said granules are prepared by wet granulation process.

10. The tablet as claimed in claim 1, comprising:
(a) first granules comprising ibuprofen or its pharmaceutically acceptable salts thereof and one or more excipients,
(b) second granules comprising pseudoephedrine or pharmaceutically acceptable salt thereof and chlorpheniramine or pharmaceutically acceptable salt thereof and one or more excipients,
(c) one or more pharmaceutically acceptable excipients, wherein said granules are prepared by wet granulation process.