FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION
A NOVEL ORAL LIQUID DOSAGE FORM COMPOSITION AND PROCESS THEREOF
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, India.
3. PREMABLE TO THE DESCRIPTION

PROVISIONAL
The following specification describes the invention.

0 COMPLETE
The following specification particularly describes the invention and the manner in which it is to be performed.

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The present invention relates to a novel oral liquid dosage form composition of paracetamol alone or paracetamol in combination with nasal decongestant, and anti-allergic agent and process of preparation thereof.
More particularly the present invention relates to a novel oral liquid dosage form composition of paracetamol alone or paracetamol in combination with pseudoephedrine and chlorpheniramine. Background Art:
Infants and children are generally sensitive towards common disease. Moreover infants and children generally suffer from fever and cold. There are drugs available in the market which cure fever and cold. However these drugs are not suitable for effective treatment of fever and cold in infants and children. Also these drugs are available in the form of tablet or soft gel which are not suitable for children and infants. Present invention is in the solution form. The solution form of the product further assists accuracy and precision in dose delivery compared to suspension form of the liquid products. The particles present in suspension form also block the nozzle of the dropper whereas in solution form the problem of the blockage does not arise. In solution form, drug bio-availability will be more compared to suspension form.
Chinese patent number CN1850083 discloses a dispersion tablet for curing common cold and its preparation process. Said invention is formed from main medicine including paracetamol, pseudoephedrine hydrochloride, dextromethorphan and chlorpheniramine maleate and auxiliary ingredients
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including avicel, low-substituted hydroxypropyl cellulose, povidone K30, cross-linked povidone, aspartame, micropowder silica gel and magnesium stearate. However solvents used in the present invention are quite different and also quantity of paracetamol, pseudoephedrine hydrochloride and chlorpheniramine maleate are in very large amount. Though the paracetamol content (125 mg per ml) is very high, composition remains in solution form even at very low temperature. Object of the Invention:
Main object of the present invention is to provide a unique drug composition containing of paracetamol alone or paracetamol in combination with nasal decongestant, and anti-allergic agent.
Another object of the present invention is to provide novel liquid dosage form composition containing of paracetamol alone or paracetamol in combination with pseudoephedrine and chlorpheniramine maleate for management of fever and cold in pediatrics.
Other object of the present invention is to provide a unique drug combination of paracetamol, pseudoephedrine and chlorpheniramine maleate in solution form even at very low temperature and large drug content.
Yet another object is to provide dose with accuracy and precision and this can be achieved if the preparation is in solution form rather than in suspension form. The dose of paracetamol is 20 to 30 mg to infants weighing 5 to 10 pounds and the liquid to be administered will be 4 to 6 drops of liquid preparation
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containing 125 mg per ml. For delivery of the drops narrow mouth nozzle fitted on to the bottle will be the right choice. The passage of suspension through narrow mouth nozzle will be difficult and hence solution form is must.
Further object is also to provide a preparation which will remain in solution form even when stored at minus 10 degree centigrade temperature. Summery of the Invention:
The present invention relates to a novel oral liquid dosage form composition of paracetamol alone or paracetamol in combination with nasal decongestant, and anti-allergic agent and process of preparation thereof. More particularly present invention includes a novel oral liquid dosage form composition containing paracetamol alone or paracetamol in combination with pseudoephedrine and chlorpheniramine maleate and process of preparation thereof. This composition is in the solution form though the drug contents are very high. Also present composition remains in solution form even when stored at minus 10° centigrade. This quality of the product makes it more useful as it can be stored in any coldest part of the world. Also the solution form of the product further assists accuracy and precision in dose delivery compared to suspension form of the liquid products. Also in solution form the problem of the blockage of nozzle of the dropper does not arise,
The method of preparation of novel liquid dosage form composition involves dissolving paracetamol, pseudoephedrine and chlorpheniramine maleate in solublizer then adding one or more sweeteners, preservatives, chelating agents,
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colours and flavours to the solution and finally making up the volume with
purified water.
Detailed Description of the Invention:
The present invention relates to a novel oral liquid dosage form composition of paracetamol alone or paracetamol in combination with nasal decongestant, anti-allergic agent and process of preparation thereof. Present pharmaceutical composition is recommended especially for pediatric use for the management of fever and cold. It contains relatively large amount of paracetamol (125 mg per ml), even though the taste is palatable. It remains in solution form even at minus 10° centigrade.
In the present invention decongestants is selected from ephedrine, phenylephirine, phenylpropanolamine and pseudoephdrine. More preferably psedoehidrine is used as decongestant.
In the present invention anti-allergic agent is selected from chlorpheniramine maleate and derivatives, pheniramine maleate and derivatives, diphenhydramine,promethazine, dimethindene, azatadine, astemizole, terfenadine, ketotifen, cetirizine, levocetirizine, clemastine, hydroxyzine, loratadine, desloratadine, fexofenadine, ebastinerupatadine, azelastine, mizolastine, flunisolide etc. More preferably chlorpheniramine maleate is used as an anti¬allergic agent.
The present invention includes a novel liquid oral liquid dosage form composition containing paracetamol 125 mg /ml, pseudoephedrine 15 mg /ml and
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chlorpheniramine maleate 1 mg /ml and process of preparation thereof. This composition is made using solublizers, preservatives, sweeteners, chelating agents, colours and flavours. In this composition Solublizers are selected from the group consisting of propylene glycol, polyoxyethylene castor oil derivatives (brand names: Acrysol k-150, Acrysol k-140, Cremophor RH 40 and other varieties of Cremophor) and polyethylene glycol and mixture thereof and preservatives are selected from the group consisting of sodium methyl paraben and sodium propyl paraben also neotame is used as sweetener and disodium edetate is used as chelating agent. In one embodiment of the invention propylene glycol is in the range of 50% to 90% of the total volume of the composition. In other embodiment of the invention polyoxyethylene castor oil derivatives is in the range of 15% to 90% of the total volume of the composition. The combination of propylene glycol and polyoxyethylene castor oil derivatives in different proportion can also be used to achieve the object.
Method for preparation of novel oral dosage form composition of comprises series of steps. First of, all paracetamol 125 mg /ml, pseudoephedrine 15 mg /ml and chlorpheniramine maleate 1 mg /ml are dissolved in solublizers. Solublizers are selected from the group consisting of propylene glycol, polyoxyethylene castor oil derivatives (brand names: acrysol k-150, acrysol k-140) and polyethylene glycol and mixture thereof. Then the preservatives, sweeteners, chelating agents, colours and flavours are added into the solution. Preservatives are selected from the group consisting of sodium methyl paraben and sodium
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propyl paraben. Neotame is used as sweetener and disodium edetate is used as chelating agent. In one embodiment of the invention propylene glycol is in the range of 50% to 90% of the total volume of the composition. In other embodiment of the invention polyoxyethylene castor oil derivatives is in the range of 15% to 90% of the total volume of the composition. Example 1:

Serial No. Ingredients
1 Paracetamol
2 Pseudoephedrine hydrochloride
3 Chlorpheniramine maleate
4 Propylene glycol
5 Polyoxyethylene castor derivative( Acrysol)
6 Sodium methyl paraben
7 Sodium propyl paraben
8 Disodium edetate
9 Neotame
10 Colour ponceu 4R
11 Flavour pipermint
12 Purified water

mg/ml grams/1000ml
125 125
15 15
1 1
600 600
oil 250 250

0.5 0.5
0.1 0.1
1.74 1.74
0.35 0.35
0.02 0.02
3 3
Q.S. Q.S.

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Manufacturing Process
1. Dissolve paracetamol, pseudoephedrine, and chlorpheniramine maleate in mixture of propylene glycol and acrosyl k-150.
2. Add neotame, sodium methyl paraben, sodium propyl paraben, disodium edetate, colour and flavour to that solution.
3. make up the volume with purified water
Example 2:
Serial No. Ingredients mg/ml grams/1000ml
1 Paracetamol 125 125
2 Propylene glycol 600 600
3 Polyoxyethylene castor oil 250 250 derivatie( Acrysol)
Sodium methyl paraben 0.5 0.5
Sodium propyl paraben 0.1 0.1
Disodium edetate 1.74 1.74
Neotame 0.35 0.35
Colour ponceu 4R 0.02 0.02
Flavour pipermint 3 3
Purified water Q.S. Q.S.
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Manufacturing Process
1. Dissolve paracetamol, maleate in mixture of propylene glycol and acrosylk-150.
2. Add neotame, sodium methyl paraben, sodium propyl paraben, disodium edetate, colour and flavour to that solution.
3. make up the volume with purified water
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We claim:
1. A novel oral liquid dosage form composition comprises of paracetamol alone or paracetamol in combination with nasal decongestant, and anti¬allergic agent.
2. The novel oral liquid dosage form composition as claimed in claim 1 wherein decongestants is selected from ephedrine, phenylephirine, phenylpropanolamine and pseudoephdrine.
3. The pharmaceutical composition as claimed in claim 2 wherein decongestant is pseudoephidrine.
4. The novel oral liquid dosage form composition as claimed in claim 1 wherein anti-allergic agent is selected from group consisting of chlorpheniramine maleate and derivatives, pheniramine maleate and derivatives, diphenhydramine, promethazine, dimethindene, azatadine, astemizole, terfenadine, ketotifen, cetirizine, levocetirizine, clemastine, hydroxyzine, loratadine, desloratadine, fexofenadine, ebastinerupatadine, azelastine, mizolastine, flunisolide etc.
5. A novel oral liquid dosage form composition as claimed in claim 1 wherein anti-allergic agent is chlorpheniramine maleate.
6. A novel oral liquid dosage form composition as claimed in claim 1 wherein the amount of the paracetamol is 125 mg /ml.
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7. A novel oral liquid dosage form composition as claimed in claim 1 wherein 125 mg/ml paracetamol, 15 mg/ml decongestant and 1 mg/ml anti allergic agent is used.
8. A novel oral liquid dosage form composition as claimed in claim 7 wherein pseudoephedrine hydrochloride as decongestant and chlorpheniramine maleate as anti allergic agent is used.
9. A novel oral liquid dosage form composition as claimed in claim 1, 6 or 7 further comprises of one or more solublizers, preservatives, sweeteners, chelating agents, colours and flavours.
10. A novel oral liquid dosage form composition as claimed in claim 9 wherein the solublizers are selected from the group consisting of propylene glycol, polyoxyethylene castor oil derivatives and polyethylene glycol and mixture thereof.
11. A novel oral liquid dosage form composition as claimed in claim 9 wherein the preservatives are selected from the group consisting of sodium methyl paraben and sodium propyl paraben.
12. A novel oral liquid dosage form composition as claimed in claim 9 wherein the sweetener is neotame and chelating agent is disodium edetate.
13. A novel oral liquid dosage form composition as claimed in claim 9 or claim 10 wherein propylene glycol is in the range of 50% to 90% of the total volume of the composition.
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14. A novel oral liquid dosage form composition as claimed in claim 9 or claim 10 wherein polyoxyethylene castor oil derivatives is in the range of 15% to 90% of the total volume of the composition.
15. A method for preparation of novel oral dosage form composition comprises of
(i) dissolving paracetamol, pseudoephedrine and chlorpheniramine
maleate in solublizer; (ii) adding one or more sweeteners, preservatives, chelating agents,
colours and flavours to the solution; (iii) making up the volume with purified water.
16. A method for preparation of novel oral liquid dosage form composition as claimed in claim 15 wherein the solublizers are selected from the group consisting of propylene glycol, polyoxyethylene castor oil derivatives and polyethylene glycol and mixture thereof.
17. A method for preparation of novel oral liquid dosage form composition as claimed in claim 15 wherein the preservatives are selected from the group consisting of sodium methyl paraben and sodium propyl paraben.
. A method for preparation of novel oral liquid dosage form composition as claimed in claim 15 wherein the sweetener is neotame and chelating agent is disodium edetate.
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19. A method for preparation of novel oral liquid dosage form composition as claimed in claim 15 or claim 16 wherein propylene glycol is in the range of 50% to 90% of the total volume of the composition.
20. A method for preparation of novel oral liquid dosage form composition as claimed in claim 15 or claim 16 wherein polyoxyethylene castor oil derivatives is in the range of 15% to 90% of the total volume of the composition.
21. A novel oral liquid dosage form composition substantially as described herein before and with reference to the foregoing examples.
22. A method for preparation of novel oral liquid dosage form composition substantially as described herein before and with reference to the foregoing examples.
Dated this 12th day of May 2008.
Dr. Rajeshkumar H. Acharya
Advocate & Patent Agent
For & on behalf of the Applicant.
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