FORM 2THE PATENT ACT 1970(39 of 1970)&The Patents Rules, 2003COMPLETE SPECIFICATION(See section 10 and rule 13)
1. TITLE OF THE INVENTIONA PHARMACEUTICAL COMPOSITION CONTAINING ANTIINFLAMMATORY ANTIHISTAMINIC, DECONGESTANT AND METHIONINE FOR TREATING ALLERGIC RHINITIS.
2. APPLICANT (S)(a) NAME: LINCOLN PHARMACEUTICALS LIMITED(b) NATIONALITY: an Indian Company(c) ADDRESS: Nirav complex, Opp Navrang High School, Naranpura, Ahmedabad-380014. Gujarat State, India.
3. PREMABLE TO THE DESCRIPTION
PROVISIONALThe following specification describes the invention. COMPLETEThe following specification particularly describes the invention and the manner in which it is to be performed.

This application is a Patent of Addition of Indian Patent Application No. 763/MUM/2004 filed in India on July 16, 2004, all of which are hereby incorporated herein in their entirety by reference.
The present invention relates to a pharmaceutical composition for the treatment of allergic rhinitis and process for preparation thereof.
More particularly, the present invention relates to a pharmaceutical composition containing anti-inflammatory, anti-histaminic, decongestant and methionine for sustained release in the treatment of allergic rhinitis. Background of the invention
A common cold is an illness caused by a virus infection located in the nose. (Gwaltney, J.M.Jr. 2000. The Common Cold. In Principles and Practices of Infectious Diseases, 5th ed. G.L. Mandell, J.E. Bennett, and R. Dolin, editors. Churchill Livingstone, New York. 651-656.) Colds also involve the sinuses, ears, and bronchial tubes.
The symptoms of a common cold include sneezing, runny nose, nasal obstruction, sore or scratchy throat, cough, hoarseness, and mild general symptoms like headache, feverishness, chilliness, and not feeling well in general. Colds last on average for one week. Mild colds may last only 2 or 3 days while severe colds may last for up to 2 weeks. (Gwaltney, J.M.Jr., J. Hendley, G. Simon, and W.S.J. Jordan. 1967. Rhinovirus infections in an industrial population. II. Characteristics of illness and antibody response. JAMA. 202:494-500.)

A cold is a milder illness than influenza. Influenza typically causes fever, muscle aches, and a more severe cough. However, mild cases of influenza are similar to colds. (Treanor, J.J. 2000. Influenza virus. In Principles and Practice of Infectious Diseases, 5th ed. G.L. Mandell, J.E. Bennett, and R. Dolin, editors. Churchill Livingstone, New York. 1823-1849.)
Cold treatments recommended in www.commoncold.org have been properly tested and found to be effective. Their side effects are known and are acceptable for treating a mild illness like a cold. They include the following:
Older Antihistamines ("first Generation")
Nonsteroidal Antinflammatory Drugs (NSAIDs)
Decongestants (vasoconstrictors)
Cough Suppressants (narcotics)
Anticholinergics (ipratropium)
CA 2555383 disclosed compositions of non-steroidal anti-inflammatory drugs and decongestants or anti-histamine. The dosage forms include an effective amount of each of a non-steroidal anti-inflammatory drug and a decongestant or an antihistamine wherein the effective amount of the decongestant or antihistamine is less than 75% of an approved dose of decongestant or antihistamine relative to an amount of NSAID corresponding to about 100% of the amount present in a normal strength dosage form of the NSAID.
US 4749722, US4749723, US4783465, US4839354 US4749711 US4749721 relates to pharmaceutical compositions of matter comprising one or more non-

steroidal anti-inflammatory drugs (NSAID) in combination with at least one antihistamine, sympathometic drug (nasal decongestant, bronchodilator) cough suppressant and/or expectorant, optionally in combination with suitable pharmaceutically acceptable non-toxic carriers and excipients.
US 5025019 teaches pharmaceutical compositions and methods of using a composition containing a non-steroidal anti-inflammatory drug in combination with at least one other active component selected from an antihistamine, decongestant, cough suppressant or expectorant.
US2004/0253311 Al disclosed a combination of a non-steroidal antiinflammatory drugs, decongestants and antihistamine (preferably non-sedating anitihistamine) in a solid dosage form, preferably a multi-layer tablet comprising an immediate release layer and an extended release layer, to provide a matched duration of action of the active agents such that their durations of effect are substantially equal.
While these combination products provide effective symptom treatment of rhinitis due to cold and allergy, they do not alleviate the side effects of non-steroidal anti-inflammatory drugs in patients. NSAIDs have been known for there idiosyncratic hepatotoxicity in susceptible patients, though the exact molecular mechanisms underline this toxicity have not yet been fully elucidated. However, experimental evidences suggest that binding of their metabolites with sulphydryl groups with hepatocytes causes cell damage, increased concentration of the drugs in the hepatobiliary compartment, formation of reactive metabolites that covalently modify proteins and produce oxidative stress, and mitochonondrial injury.

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 activates.
Object of Invention:
The main object of the present invention is to develop a pharmaceutical composition for the treatment of rhinitis containing aniti-inflammatory, antihistamines, decongested and methionine in single dosage form.
Another object of the invention is to provide pharmaceutical formulation, wherein the dosage is reduced to maximum of two per day.
A further object of the instant invention is to provide pharmaceutical formulation for the treatment of rhinitis which does not show hepatotoxicity.
An additional object of the invention is to provide pharmaceutical composition in the form of tablet, hard gelatin capsule or oral liquid suspension.
An additional object of the invention is to provide synergistic admixture showing improved properties of being administrable in single form and with reduced per diem dosage and not a mere aggregate of the properties of the individual ingredients.
Detailed description of the invention:
As explained in the background of the invention, allergic rhinitis is a common disorder occurring normally during change of seasons. The patient normally shows symptoms like sneezing, headache, running nose, congestion, body ache and infection of upper respiratory system. The symptomatic cure to provide relief from these

symptoms normally comprises administering antihistamine, anti-inflammatory, decongestant drugs to the patient, either alone or in a combination of any two thereof. It has been observed that the time taken for the patient to obtain relief can be quite long and the dosage can be quite high- as much as 9 tablets per day. Missing a single dose in a regimen of treatment can result in slowing down of the efficacy of the treatment process.
The present invention provides a novel pharmaceutical composition containing an anti-inflammatory, an antihistamine, a decongestant and methionine in a single dose. The composition can be in the form of tablet, capsule or oral liquid suspension. The maximum dose per day of the dosage form is two.
When the cells are damaged, they release chemical called histamine. Histamine acts like a messenger to nearby cells, to initiate their own defenses. This makes the site where the germ entered the body (the site of infection) red, swollen and sore. If person is allergic then his body mistakenly generates an immune response to something that's not really harmful. Antihistamines work by blocking the binding of histamine to histamine receptor, and so easing the symptoms of allergic reactions.
Decongestants work by narrowing blood vessels in the lining of the nose. This reduces nasal congestion and allows drainage of sinus passages so air can pass through more easily. It makes some people feel nervous or dizzy. It can cause palpitations (feeling like your heart is racing) or problems sleeping. It can also raise blood pressure in some people, (www. Familydoctor.org)

Inhibition of cyclooxygenase (COX), the enzyme responsible for the biosynthesis of the prostaglandins and certain related autacoids, generally is thought to be a major facet of the mechanism of NSAIDs.
Methionine is metabolized in the liver and converted to S-adenosyl-1-methionine (SAMe). SAMe is a methyl group donor and is an enzyme activator in a number of biochemical reactions. In patients with liver diseases, these pathways are impaired because of the decreased contents of glutathione, the major abnormality being a reduction in SAMe synthetase activity. Exogenous SAMe may overcome the results of impaired SAMe synthetase activities. (Kaohsiung J. Med. Sci. 2001,Sep 17(9); 455-60).
Oral administration of SAMe resulted in its hepatic repletion with a corresponding attenuation of the ethanol-induced oxidative stress and liver injury, with significantly less GSH depletion, less increases in plasma aspartate aminotransferase (AST) levels, less leakage of mitochondrial glutamic dehydrogenase into the plasma, and fewer megamitochondria. (Alcohol. 2002 Jul; 27(3); 173-7).
In the present invention non-steroidal anti-inflammatory drug is selected from the group of diclophenac, fenflofenac, nimesulide; aspirine; indomethacin, sulindac, tolmetin, ibuprofen, ketoprofen, fenoprofen, flubiprofen, naxproxen, meclofenamic acid, flufenamic acid, piroxicam, tenoxicam, meloxicam, celicoxib, roficoxib, nabumetone, effective salts thereof, derivatives thereof and combination thereof. More preferably nimesulide is used as a nonsteroidal anti-inflammatory drug.

In the present invention antihistamine is selected from the group of astemizole, azatadine, brompheniramine, centizine, levocentirizine, chlorpheniramine, clemastine, cyproheptadine, dexchlorpheniramine, direnhydrinate, diphinhydramine, doxylamine, hydroxyzine, loratadine, phenindamine, terfenadine, tripelennamine, effective salts thereof, derivatives thereof and mixture thereof. More preferably centirizine and levocentirizine are used as antihistamine.
In the present invention decongestants is selected from ephedrine, phenylephirine, phenylpropanolamine and pseudoephdrine. More preferably psedoehidrine is used as decongestant.
The methionine is selected from the L isomer, and D isomer or a racemic mixture thereof.
Symptoms of allergic rhinitis occur as a result of direct and indirect action of histamine acting largely on the HI receptors in target tissues. Along with histamine a range of other vasoactive mediators such as kinins cause vasodilaton resulting in congestion. Nimesulide apart from its analgesic, antipyretic and anti-inflammatory activity it is a mast cell inhibitor i.e. in turn inhibits the release of histamines. Centrizine or Levocentrizine in combination with Nimesulide as a synergistic effect and acts as an antihistamine by selective HI histamine receptor antagonistic. Combination of Nimesulide and Cetirizine however does not relieve nasal congestion. Therefore, the present invention relies on the addition of Psedoehedrine as decongestant. Pseudoephedrine acts as predominantly on alfa receptors without central nervous system stimulation. Combination of Nimesulide,

Cetirizine/levocentirizine, Pseudoephedrine and methionine in the single formulation helps in relieving the signs and symptoms of allergic rhinitis within three days without showing any hepatotoxicity.
The composition has been clinically studied at multiple locations. Clinical studies have shown that the combination of Nimesulide Centizine or levoentirizine Psudoephedrine, and methionine in a single dosage form gives much better results in terms of relieving of signs of symptoms of allergic rhinitis. Patients administered with above combinations have been shown faster recovery form allergic rhinitis than the patients administered with drugs with individual dosage forms.
It has been also observed that failure by patient to take the dosage is reduced since number of doses per day is less (with sustained release Pseudoephedrine). This has also helped in maintaining the drug-serum level in the body.
Accordingly, the present invention provides a pharmaceutical composition for the treatment of allergic rhinitis comprising an anti-inflammatory, an anti-histamine and a decongestant in a single dosage form, the amount of the anti-inflammatory being in the range of 50 mg to 200 mg, the amount of anti-histamine being in the rang of 2.5 to 10 mg and the amount of the decongestant being in the range of 30 mg to 120 mg. All amounts being expressed in terms of weight per dose of the composition, the balance if any comprising one or more conventional additives and pharmaceutically acceptable excipients.

In the invention, the conventional ingredients are selected from the group consisting of diluents, binders, lubricants, disintegrants and other conventional excipients.
The binder is selected from the group consisting of starch paste, gelatin, pregelatinised starch, polyvinyl pyrrolidone- various grades like K-30, K-90, VA- 64, etc., sodium carboxymethyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, gum acacia, carbopol and other acrylic resins, and polyethylene glycols.
The diluent is selected from the group consisting of starch and modified starches, microcrystalline cellulose, lactose, sorbitol, dicalcium phosphate, calcium carbonate, hydroxyl propyl cellulose, aluminium magnesium silicate and cyclodextrins.
The lubricant and disintegrants are selected from the group consisting of starch, sodium starch glycolate, colloidal silicondioxide, guar gum, sodium carboxymethyl cellulose, stearic acid and its salts, purified talc and modified silica.
The conventional additive comprises sweetening agents, suspending agents, and preservatives.
The diluent for an oral liquid suspension comprises purified water, glycerin, propylene glycol, polyethylene glycol-200 and polyethylene glycol- 400.
The sweetening agent is selected from the group consisting of mannitol, sugar, invert sugar, liquid glucose, sorbitol malt extract, aspartame, saccharine and salt thereof.

The suspending agent for that oral liquid suspension is selected from the group consisting of carboxymethyl cellulose and salt thereof, cellulose dilutes, guar gum, xanthan gum, precipitated silicone, colloidal silicone dioxide, alginic acid and salt thereof.
The preservative is selected from the group consisting of benzoic acid, and salt thereof, methyl paraben and salt thereof, propyl paraben and salt thereof, and bronoppol.
The composition is in the form of a tablet, hard gelatin capsule or oral liquid suspension.
A process for preparation of pharmaceutical composition comprises admixing of non-steroidal anti-inflammatory drug, antihistamine, decongestant, methionine, one or more conventional additives and pharmaceutical acceptable excipients; and subjecting said mixture to conventional methods of tableting, capsule formation or suspension.
(A) Pharmaceutical combination has been developed in tablet form containing: (i) Each tablet contains:
1. Nimesulide 50 to 200 mg
2. Centirizine Dihydrochloride 2.5 to 10 mg
3. Psedoephedrine Hydrochloride 30 to 120 mg
(Sustained Release Form)
4. Methionine 25 to 100 mg
5. Excipients Q. S.

(ii) Each tablet contains:
1. Nimesulide 50 to 200 mg
2. Levocentirizine Dihydrochloride 2.5 to 5 mg
3. Psedoephedrine Hydrochloride 30 to 120 mg
(Sustained Release Form)
4. Methionine 25 to 100 mg
5. Excipients Q. S.
Tablet form was developed with different combinations of diluents (i.e. starch and modified starches, microcrystalline cellulose, lactose, sorbitol, dicalcium phosphate, calcium carbonate, hydroxypropyl cellulose, alumimium magnesium silicate), Binders (i.e. starch paste, gelatin, pregelatinized starch, polyvinyl pyrrolidoen - various grades like K-30, K-90, VA-64, etc. sodium carboxymethyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, gum acacia, carbopol and other acrylic resins, polyethylene glycols) and lubricants and disintegrants (i.e. starch, sodium starch, glycolate, colloieal silicodioxide, guar gum, sodium carboxymethyl cellulose, stearic acid and its salts, purified talc and modified silica).
The invention is illustrated more in detail in the following examples. The examples describe and demonstrate embodiments within the scope of the present invention. These examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope.

Example 1:
INGREDIENT Nimesulide
Cetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose Starch
Hydroxypropyl methyl cellulose Microcrystalline cellulose Dicalcium phosphate Purified Talc Colloidal silicon dioxide Colour

QUANTITY PER TABLET 100 mg
5mg 120 mg 50 mg 30 mg 137 mg 50 mg 50 mg 50 mg 70 mg 10 mg
5mg
Q.S.

Example 2:
INGREDIENT Nimesulide
Levocetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose
Starch
Hydroxypropyl methyl cellulose Dicalcium phosphate
Purified Talc

QUANTITY PER TABLET 100 mg
5mg
120 mg
50 mg
15 mg
100 mg
50 mg
50 mg
50 mg
10 mg

Example 3:
INGREDIENT Nimesulide
Cetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose
Starch
Hydroxypropyl methyl cellulose Dicalcium phosphate Purified Talc

QUANTITY PER TABLET 100 mg
10 mg
120 mg
50 mg
15 mg
100 mg
95 mg
50 mg
100 mg
10 mg

Example 4:
INGREDIENT Nimesulide
Cetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose Starch
Hydroxypropyl methyl cellulose Dicalcium phosphate Purified Talc

QUANTITY PER TABLET
50 mg
5mg
60 mg
25 mg
15 mg
200 mg
100 mg
50 mg
110 mg
10 mg

Example 5:
INGREDIENT Nimesulide
Cetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose
Starch
Hydroxypropyl methyl cellulose Dicalcium phosphate Purified Talc

QUANTITY PER TABLET
50 mg
2.5 mg
30 mg
25 mg
15 mg
200 mg
100.5 mg
92 mg
100 mg
10 mg

Example 6:
INGREDIENT Nimesulide
Levocetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose
Starch
Hydroxypropyl methyl cellulose Dicalcium phosphate Purified Talc

QUANTITY PER TABLET
50 mg
2.5 mg
30 mg
25 mg
15 mg
200 mg
100.5 mg
92 mg
100 mg
10 mg

Hard gelatin capsule form was developed with different combinations of Diluents and Excipients (i.e. starch and modified starches, microcrystalline cellulose,

lactose, sorbitol, dicalcium phosphate, calcium carbonate, starch, gelatin, pregelatinised starch, polyvinyl pyrrolidone - various grades like K-30, K-90, VA-64 etc., sodium carboxymethyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose and other acrylic resins, polyethylene glycols) and Lubricants (i.e. stearic acid and its salts purified talc and modified silica).

Example 7:
INGREDIENT QUANTITY PER TABLET
Nimesulide 100 mg
Cetirizine dihydrochloride 5mg Pseudoephedrine Hydrochloride 120 mg
Methionine 50 mg
Polyvinyl pyrrolidone (K- 30) 15 mg
Lactose 100 mg
Starch 100 mg
Hydroxypropyl methyl cellulose 50 mg Dicalcium phosphate 100 mg
Purified Talc 10 mg

Example 8:
INGREDIENT QUANTITY PER TABLET
Nimesulide 200 mg
Levocetirizine dihydrochloride 10 mg
Pseudoephedrine Hydrochloride 120 mg
Methionine 100 mg
Polyvinyl pyrrolidone (K- 30) 15 mg
Lactose 100 mg


Starch
Hydroxypropyl methyl cellulose Dicalcium phosphate Purified Talc

50 mg 50 mg 50 mg 10 mg

Example 9:
INGREDIENT Nimesulide
Cetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose
Starch
Hydroxypropyl methyl cellulose Dicalcium phosphate Purified Talc

QUANTITY PER TABLET
100 mg
10 mg
120 mg
50 mg
15 mg
100 mg
95 mg
50 mg
100 mg
10 mg

Example 10:
INGREDIENT Nimesulide
Cetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose
Starch
Hydroxypropyl methyl cellulose

QUANTITY PER TABLET
50 mg
5mg
60 mg
25 mg
15 mg 200 mg 100 mg
50 mg

Calcium carbonate Purified Talc

110 mg 10 mg

Example 11:
INGREDIENT Nimesulide
Cetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose
Starch
Hydroxypropyl methyl cellulose Calcium carbonate
Purified Talc

QUANTITY PER TABLET
50 mg
2.5 mg
30 mg
25 mg
15 mg
200 mg
100.5 mg
92 mg
100 mg
10 mg

Example 12:
INGREDIENT Nimesulide
Levocetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Polyvinyl pyrrolidone (K- 30) Lactose
Starch
Hydroxypropyl methyl cellulose Calcium carbonate Purified Talc

QUANTITY PER TABLET
50 mg
2.5 mg
30 mg
25 mg
15 mg
200 mg
100.5 mg
92 mg
100 mg
10 mg

(c) Pharmaceutical combination has been developed in oral Liquid Suspension form containing:
(i) Each 5 ml contains
1. Nimesulide 50 to 200 mg
2. Centrizine Dihydrochloride 2.5 to 10 mg
3. Psedoephedrine Hydrochloride 30 to 120 mg
4. Methionine 25 to 100 mg
5. Excipients Q. S.
(ii) Each 5 mg contains
1. Nimesulide 50 to 200 mg
2. Levocentrizine Dihydrochloride 2.5 to 5 mg
3. Psedoephedrine Hydrochloride 30 to 120 mg
4. Methionine 25 to 100 mg
5. Excipients Q. S.
Oral liquid suspension form was developed with different combinations of Diluents (i.e. purified water, glycerin, propylene glycol, polyethylene glycol -200 & 400), Sweetners (i.e. sugar, invert sugar, liquid glucose, sorbitol, mannitol, malt extract, aspartame, saccharine and its salts), Suspending Agents (i.e. carboxymethyl cellulose and its salts, cellulose dilutes, guar gum, xantham gum, precipitated silicone, colloidal silicone, dioxide, alginic acid and its salt) an Preservatives (i.e. benzoic acid and its salt, sorbic acid and its salt, methyl paraben and its salts, propyl paraben and its salt, bronopol)

Example 13:
INGREDIENT Nimesulide
Cetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Liquid Glucose
Sugar
Sorbitol Solution 70% Glycerin
Propylene Glycol Aspartame
Propyl Paraben sodium Bronopol
Citric Acid
Xantham Gum
Colour
Purified water

EACH 100 ML CONTAINS
1.0 gm
0.1 gm
1.2 gm
0.5 gm
25 gm
35 gm
10 gm
5.0 gm
5.0 gm 0.05 gm 0.05 gm 0.02 gm 0.04 gm 0.15 gm
Q.S.
Q.S.

Example 14:
INGREDIENT Nimesulide
Levocetirizine dihydrochloride Pseudoephedrine Hydrochloride Methionine
Liquid Glucose
Sugar
Sorbitol Solution 70%

EACH 100 ML CONTAINS 2.0 gm
0.1 gm
1.2 gm
1.0 gm
20 gm
45 gm
10.0 gm

Glycerin 5.0 gm
Propylene Glycol 5.0 gm
Propyl Paraben sodium 0.05 gm
Bronopol 0.02 gm
Citric Acid 0.04 gm
Sodium Carboxymethyl Cellulose 2.0 gm
Colour Q.S.
Purified water Q. S.
Example 15:
INGREDIENT EACH 100 ML CONTAINS
Nimesulide 1.0 gm
Cetirizine dihydrochloride 0.1 gm
Pseudoephedrine Hydrochloride 1.2 gm
Methionine 0.5 gm
Liquid Glucose 30 gm
Sugar 45 gm
Glycerin 5.0 gm
Propylene Glycol 5.0 gm
Aspartame 0.05 gm
Propyl Paraben sodium 0.05 gm
Methyl Paraben sodium 0.2 gm
Citric Acid 0.04 gm
Xantham Gum 0.15 gm
Colour Q. S.
Purified water Q. S.

Example 16:
INGREDIENT EACH 100 ML CONTAINS
Nimesulide 1.0 gm
Levocetirizine dihydrochloride 0.1 gm
Pseudoephedrine Hydrochloride 1.2 gm
Methionine 0.5 gm
Liquid Glucose 30 gm
Sugar 45 gm
Glycerin 5.0 gm
Propylene Glycol 5.0 gm
Aspartame 0.05 gm
Propyl Paraben sodium 0.05 gm
Methyl Paraben sodium 0.2 gm
Citric Acid 0.04 gm
Xantham Gum 0.15 gm
Colour Q.S.
Purified water Q.S.
Example 17:
INGREDIENT EACH 100 ML CONTAINS
Nimesulide 0.5 gm
Cetirizine dihydrochloride 0.1 gm
Pseudoephedrine Hydrochloride 0.6 gm
Methionine 0.25 gm
Liquid Glucose 30.0 gm
Sugar 45.0 gm
Glycerin 5.0 gm
Propylene Glycol 5.0 gm

Aspartame 0.05 gm
Propyl Paraben sodium 0.05 gm
Methyl Paraben Sodium 0.2 gm
Citric Acid 0.04 gm
Xantham Gum 0.15 gm
Colour Q. S.
Purified water Q. S.
Example 18:
INGREDIENT EACH 100 ML CONTAINS
Nimesulide 0.5 gm
Cetirizine dihydrochloride 0.05 gm
Pseudoephedrine Hydrochloride 0.3 gm
Methionine 0.25 gm
Liquid Glucose 30 gm
Sugar 45 gm
Glycerin 5 gm
Propylene Glycol 5.0 gm
Aspartame 0.05 gm
Propyl Paraben sodium 0.05 gm
Bronopol 0.02 gm
Citric Acid 0.04 gm
Sodium Carboxymethyl Cellulose 2.0 gm
Colour Q. S.
Purified water Q. S.

Claim:
1. A pharmaceutical composition for the treatment of allergic rhinitis comprising 50 mg to 200 mg non-steroidal anti-inflammatory drug, 2.5 to 10 mg antihistamine, 30 to 120 mg decongestant, 25 to 100 mg methionine, one or more conventional additives and pharmaceutical acceptable excipients.
2. A pharmaceutical composition as claimed in claim 1 wherein non-steroidal anti-inflammatory drug is selected from the group of diclophenac, fenflofenac, nimesulide; aspirine; indomethacin, sulindac, tolmetin, ibuprofen, ketoprofen, fenoprofen, flurbiprofen, naxproxen, meclofenamic acid, flufenamic acid, piroxicam, tenoxicam, meloxicam, celicoxib, roficoxib, nabumetone, effective salts thereof, derivatives thereof and combination thereof.
3. A pharmaceutical composition as claimed in claim 2 wherein non-steroidal anti-inflammatory drug is nimesulide.
4. A pharmaceutical composition as claimed in claim 1 wherein antihistamine is selected from the group of astemizole, azatadine, brompheniramine, centizine, levocentirizine, chlorpheniramine, clemastine, cyproheptadine, dexchlorpheniramine, direnhydrinate, diphinhydramine, doxylamine, hydroxyzine, loratadine, phenindamine, terfenadine, tripelennamine, effective salts thereof, derivatives thereof and mixture thereof.
5. A pharmaceutical composition as claimed in claim 4 wherein antihistamine is centirizine or levocentirizine.

6. A pharmaceutical composition as claimed in claim 1 wherein decongestants is selected from ephedrine, phenylephirine, phenylpropanolamine and pseudoephdrine.
7. A pharmaceutical composition as claimed in claim 6 wherein decongestant is pseudoephidrine.
8. A pharmaceutical composition as claimed in claim 1 wherein the methionine is selected from the L isomer, and D isomer or a racemic mixture thereof.
9. A pharmaceutical composition as claimed in claim 1 wherein the conventional ingredients are selected from the group consisting of diluents, binders, lubricants, disintegrants and conventional excipients.
10. A pharmaceutical composition as claimed in claim 9 wherein diluent is selected from the group consisting of starch and modified starches, microcrystalline cellulose, lactose, sorbitol, dicalcium phosphate, calcium carbonate, hydroxyl propyl cellulose, aluminium magnesium silicate and cyclodextrins.
11. A pharmaceutical composition as claimed in claim 9 the binder is selected from the group consisting of starch paste, gelatin, pregelatinised starch, polyvinyl pyrrolidone- various grades like K-30, K-90, VA- 64, etc., sodium carboxymethyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, gum acacia, carbopol and other acrylic resins, and polyethylene glycols.

12. A pharmaceutical composition as claimed in claim 9 wherein the lubricant and disintegrants are selected from the group consisting of starch, sodium starch glycolate, colloidal silicondioxide, guar gum, sodium carboxymethyl cellulose, stearic acid and its salts, purified talc and modified silica.
13. A pharmaceutical composition as claimed in claim 1 wherein pharmaceutical acceptable excipients comprise sweetening agents, suspending agents and preservatives.
14. A pharmaceutical composition as claimed in claim 13 the sweetening agent is selected from the group consisting of mannitol, sugar, invert sugar, liquid glucose, sorbitol malt extract, aspartame, saccharine and salt thereof.
15. A pharmaceutical composition as claimed in claim 13 the suspending agent for that oral liquid suspension is selected from the group consisting of carboxymethyl cellulose and salt thereof, cellulose dilutes, guar gum, xanthan gum, precipitated silicone, colloidal silicone dioxide, alginic acid and salt thereof.
16. A pharmaceutical composition as claimed in claim 13 the preservative is selected from the group consisting of benzoic acid, and salt thereof, methyl paraben and salt thereof, propyl paraben and salt thereof, and bronoppol.
17. A pharmaceutical composition as claimed in claim 1 wherein the composition is in the form of a tablet, hard gelatin capsule or oral liquid suspension.
18. A process for preparation of pharmaceutical composition comprises (i) admixing of:

a. 50 mg to 200 mg non-steroidal anti-inflammatory drug,
b. 2.5 to 10 mg antihistamine,
c. 30 to 120 mg decongestant,
d. 25 to 100 mg methionine,
e. one or more conventional additives and pharmaceutical acceptable
excipients.
(ii) subjecting said mixture to conventional methods of tableting, capsule formation or suspension.
19. A pharmaceutical composition substantially as described herein before and with reference to the foregoing examples.
20. A method for the preparation of a pharmaceutical composition substantially as described herein before and with reference to the forgoing examples.

ABSTRACT
The present invention relates to a pharmaceutical composition for the treatment of allergic rhinitis comprising non-steroidal anti-inflammatory drug, antihistamine, decongestant, methionine, one or more conventional additives and pharmaceutical acceptable excipients. The invention is to provide pharmaceutical formulation for the treatment of rhinitis which does not show hepatotoxicity. A provide pharmaceutical composition available in the form of tablet, hard gelatin capsule or oral liquid suspension.