FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)
1. TITLE OF THE INVENTION:
OPHTHALMIC COMPOSITION COMPRISING NAPHAZOLINE OR SALT THEREOF
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Towers, Bandra-Kurla Complex, Bandra
(East), Mumbai - 400 051.
3. PREAMBLE TO THE DESCRIPTION
The present invention provides ophthalmic composition comprising of naphazoline or salt thereof along with ophthalmically acceptable carriers.
The following specification particularly describes the invention and the manner in which it is to be performed.
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4. DESCRIPTION
The present invention provides ophthalmic composition comprising of naphazoline or salt thereof along with ophthalmically acceptable carriers.
Naphazoline hydrochloride, an ocular vasoconstrictor, is an imidazoline
derivative sympathomimetic amine. It occurs as a white, odorless crystalline
powder having a bitter taste and is freely soluble in water and in alcohol.
Naphazoline chemically is 2-(1-Naphthylmethyl)-2-imidazoline
monohydrochloride of formula 1. It is indicated for use as a topical ocular vasoconstrictor.
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FORMULA 1
US Patent No 6,982,079 provide a composition comprising an ophthalmically acceptable carrier component; a vasoconstrictor component, and a polyanionic component. The composition is in the form of solution.
US Application No 20050267088 provide a composition comprising an ophthalmically acceptable carrier component; a chlorine dioxide precursor component; and a vasoconstrictor component in an amount effective to treat hyperemia when the composition is administered to an eye.
US Patent No 7,022,740 discloses ophthalmic solution having a pH of between about 7.0 and about 8.0, consisting of monographed polyol, borate,
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monographed polysorbate, monographed preservative a buffer and water to 100% wt.
The present invention now provides a stable aqueous ophthalmic composition comprising naphazoline or salt thereof along with other ophthalmically acceptable carriers. The invention provides comfort to the eye without any irritation. The emollient, demulcent or polyanionic components are "substantially absent" from the composition.
In one of the aspects of the present invention there is provided an ophthalmic composition comprising naphazoline or salt thereof along with ophthalmically acceptable carrier component, characterised by the fact that the polyanionic component is "substantially absent" from the composition.
The therapeutically effective amount of naphazoline or salt thereof is added to the composition. The term "substantially absent" refers to the amount of polyanionic component, which does not impart any lubrication to the eye surface. The composition can be easily and cost effectively manufactured. The composition can be prepared by using aqueous carrier components, which helps to impart emollient property to the eye. This aqueous carrier component further helps to facilitate convenient, consistent and effective use of the composition.
The composition may be in the form of solution, ointments, gels, and the like. Ophthalmically acceptable carriers can be preservative, chelating agent, tonicity adjusting agent, buffering agent.
The term preservative has the meaning commonly understood in the ophthalmic art. Preservatives are used to prevent bacterial contamination in multiple-use ophthalmic preparations and examples include benzalkonium chloride, phenylmercuric acetate, chlorobutanol, benzyl alcohol, parabens, and thimerosal. Preferably, the preservative is benzalkonium chloride.
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The chelating agent is a compound that is capable of complexing a metal, as understood by those of ordinary skill in the chemical art. Chelating agents are used in ophthalmic compositions to enhance preservative effectiveness. Some useful chelating agents for the purposes of this invention are edetate salts like edetate disodium, edetate calcium disodium, edetate sodium, edetate trisodium, and edetate dipotassium. In this invention edetate disodium is used as the chelating agent.
Tonicity adjusting agents are used in ophthalmic compositions to adjust the concentration of dissolved material to the desired isotonic range. Some examples include mannitol, sorbitol, sodium chloride, sodium borate, and the like and the mixtures thereof.
The present ophthalmic composition may be prepared by mixing all the carrier components into a suitable solvent. Further adding naphazoline or salt thereof into this mixture. Adjusting the pH of the composition with suitable pH adjusting agent and further filtering the solution with membrane filter.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Examples- Following formulations are representatives of the preferred compositions of the present invention. The preparation of example 1 & 2 is detailed below.
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Example 1
Table 1 - Ophthalmic composition comprising Naphazoline hydrochloride.

Sr.No Ingredients Qty in %
1 Naphazoline Hydrochloride 0.1
2 Benzalkonium chloride 0.01-0.02
3 Disodium edetate 0.01 -0.1
4 Boric acid 0.05-1.5
5 Potassium chloride 0.05-1.5
6 Sodium chloride 0.1 -0.6
7 Sodium carbonate/Hydrochloric acid Qs to adjust pH
8 Water for Injection Qsto100
Procedure:
Benzalkonium chloride, Disodium edetate, Boric acid, Potassium chloride and Sodium chloride were mixed together in solvent and stirred well. Naphazoline hydrochloride was added to the above mixture. pH was adjusted to 5.5 to 7.0 using suitable pH adjusting agent. The solution was filtered through 0.45 micron and 0.22 micron and filled in the suitable container.
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Example 2
Table 2 - Ophthalmic composition comprising Naphazoline hydrochloride.

Sr.No Ingredients Qty in %
1 Naphazoline Hydrochloride 0.1
2 Benzalkonium chloride 0.01 -0.1
3 Disodium edetate 0.01-0.1
4 Boric acid 0.05-1.5
5 Borax 0.05-2.0
6 Sodium chloride 0.1 -0.9
7 Water for Injection Qsto100
Procedure:
Benzalkonium chloride, Disodium edetate, Boric acid, Borax and Sodium chloride were mixed together in solvent and stirred well. Naphazoline hydrochloride was added to the above mixture. pH was adjusted to 5.5 to 7.0 using suitable pH adjusting agent. The solution was filtered through 0.45 micron and 0.22 micron and filled in the suitable container.
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WE CLAIM:
1. An ophthalmic composition comprising naphazoline or salt thereof along with ophthalmically acceptable carrier component, characterised by the fact that the polyanionic component is "substantially absent" from the composition.
2. Ophthalmic composition according to claim 1, wherein the naphazoline is present in the form of naphazoline hydrochloride.
3. Ophthalmic composition according to claim 1, wherein the carrier component comprises water.
4. Ophthalmic composition according to claim 1 further comprises chelating agent, tonicity adjusting agent, buffer component and a preservative.
5. Ophthalmic composition according to claim 1, wherein the chelating agents comprises of edetate disodium, edetate calcium disodium, edetate sodium, edetate trisodium, edetate dipotassium and the like.
6. Ophthalmic composition according to claim 1, wherein the tonicity adjusting agents comprises of mannitol, sorbitol, sodium chloride, potassium chloride other electrolytes and the like.
7. Ophthalmic composition according to claim 1, wherein the buffer component comprises of boric acid, borax and the like.
8. Ophthalmic composition according to claim 1, wherein the preservative comprises of benzalkonium chloride, phenylmercuric acetate, chlorobutanol, benzyl alcohol, parabens, thimerosal and the like.
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9. Ophthalmic composition according to claim 1 in which the solution has a pH between 5.5 to 7.0.
Dated this 23th ay of September, 2006 For Wockhardt Limited
(Mandar ftodgule) Authorized Signatory
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