Title of Invention

A PROCESS FOR THE COMPLEXATION OF SPARINGLY SOLUBLE STEROLDS AND ANTIINFECTIVE AGENTS

Abstract 1. A method to manufacture an Ophthalmic Pharmaceuticai Preparation comprising of (i)anti-inflammatoty agents which are cortico-steroids and (ii) anti-infective agents from the group consisting of derivatives of quinolone, aminoglycoside and theirpharmaceutically acceptable salts such as herein described by a process essentially consisting of: (a) Including the steroid within a solubilizer cum complexing agent to form a solubilser-steroid complex, where in the steroid and solubiliser are in the ratio of lM:2M to 1M:6M. (b) Dispersing or dissolving the anti-infective agent in a suitable solvent, which is subsequently diluted with a complexation enhancing water soluble polymer solution to give an anti-infective agent - polymer solution; (c) Combining the anti-infective agent polymer solution and steroid solubiliser complex to form a water soluble complex; (d) Incorporating the complex in a pharmaceutically acceptable carrier systen; to give a clear, stable, non turbid solution.
Full Text ORIGINAL
1018/MUMNP/2000
FORM 2
THE PATENTS ACT 1970
(39 OF 1970)
(See Section 10, rule 13)
COMPLETE SPECIFICATION
Title: A method to manufacture an Ophthalmic Pharmaceutical Preparation.
Applicants: FDC LIMITED , and Indian Company incroporated within the meaning of the Comany's Act 1956, and having their registered address at B,8, M.I.D.C Industrial Area, Waluj, Maharastra 431135, India
The following specification particularly describes and ascertains the nature of this invention and the manner in which it is to be performned:
GRANTED
29/11/2005



Field of Invention: Tlie invention relates to a method to manufacture opthalmic pharmaceutical
preparation of anti- inflammatory agents in the nature of steroids and an anti-infective agent.
Back ground of invention:
Anti-infective agents, in the form of antibacterial agents or antibiotics, and anti¬inflammatory agents in the nature of steroids, have been used in combination for eflFective control of infection and inflammation.. Use of such combination drugs of appropriate antibacterial agents and steroids helps in increasing patient compliance to therapy as it reduces the number of instillation of different drugs. This is specially true in the case of ophthalmic treatment, when the number of instillation of drags requires to be minimal.
Not only is a combination of steroid and antibiotic or antibacterial agents desirable, but it is also essential that the combination when required for ophthahnic purposes is available a as a clear formulation, either as a solution or a gel.
In formulations, for ophthahnic treatment, a clear formulation is highly desirable, because any formulation in suspension form causes irritation to the eye, as well as causes crust formation around the eye. The U.S. Patent No.5472954 describes a process by which the solubility of lipophilic or sparingly soluble active ingredients (drug/ cosmetic/ agrochemical) is increased by complexing with different derivatives of cyclodextrin. This patent only describes a process by which a single active ingredient can be made soluble by complexing it with cyclodextrin derivatives.
In post operative ophthahnic treatment, where in a combination therapy of antibacterial and anti- inflammatory agent is used, a clear formulation is liighly desired. Even in non-operative cases ophthahnic preparations in clear formulation is preferred to a suspension, as a preferred line of treatment, as it increases the physical and physiological acceptance of the medication.
Ciprofloxacin, which ts a quinolone derivative, and a broad spectrum antibacterial, and considered a 'standard' for the treatment of ocular bacterial infections is currently available in local markets in combination with the steroid dexamethasone only in a suspension form. In addition U.S. Patent No: 6,284,804 describes a suspension

formulation containing dexamethasone and ciprofloxacin together with a non-ionic polymer, non-ionic surfactant and an ionic tonicity agent.
Though the above combination is known to be effective against most ocular pathogens, it is not preferred for use in post- operative cases, because it is currently available only in suspension form. An instillation of a drug in suspension form results in crust formation around the eye causing a foreign bodylike feeling in the eye and irritation. Steroids are generally sparingly soluble in aqueous solution which is the reason for most anti-infectiveagent / steroid combinations being available in suspension form. The antibacterial and the steroid in the form of their salts are individually available as a clear solution, but the combination, does not give a stable clear solution. On standing turbidity appears in the mixture of antibacterial- steroid solution.
Further a mere admixture of antibiotic or antibacterial agent in clear solution and the steroid in clear solution, usually results in the crystallization of the antibacterial because of the higher pH used to dissolve the steroid, and the steroid itself degrades in a short time when mixed with the antibacterial.
WO 90/ 01933 describes an invention for an opthalmic preparation consisting of a broad spectrum quinalone and a steroid like dexamethasone. The invention refers to the use of complexing agents like cyclodextrin and viscosity agents like PVA. However the invention does not mention a formulation where because of the critical ratio between the co-complexing agent and the PVA, a clear stable solution is obtained. A clear satble solution is a decided advantage in respect of opthalmic formulations, for use in post operative treatment, since it prevents crust formation around the eye and irritation caused by particulate formation.
The present invention describes for the first time a process by which a steroid and antibacterial could be combined to form a complex which could be used in the preparation of a clear solution, where in the activity and bio-efficacy of the antibacterial and steroid are not m anyway hampered or affected. The process would be particularly ideal in the preparation of fornulations for ophthalmic treatment. The

clear solution or clear gels of anti-bacterials and steroid, would be specially suitable as a preferred form of drug administration in post operative ophthalmic cases.
SUMMARY:
In its main aspect the invention consists of a process to manufacture a combination drug comprising of an anti inflammatory agent and an anti-infective agent. The anti-inflammatory agent in this invention is a cortico-steroid , and the anti-infective agent is either a quinolone derivative, amino-glycoside derivative or their pharmaceutically acceptable salts. The process essentially consists of (i) including the steroid within a solubilizer, which exhibits an inclusion phenomena The steroid is included mthin β-cyclodextrin which acts as a solubilizer cum complexing agent, to form a solubilser-steroid complex, where in the solubiliser and steroid are in the ratio of 1M:2M to 1M:6M; .(ii) dispersing or dissolving the anti infective agent in a suitable solvent which is subsequently or simultaneously diluted with a complexation enhancing water soluble polymer solution to give an anti-infective agent polymer solution; (iii) Controlled addition of anti-infective agent polymer solution to steroid-solubiliser blend to form a water soluble complex of anti-mfective agent, steroid polymer and solubiliser; (iv) Incorporating the complex m a carrier system, to give a stable pharmaceutical preparation.
In another aspect, this invention consists of a process to manufacture a stable pharmaceutical preparation, which is a combination drug of a corticosteroid from the group consisting of fluoromethalone, dexamethasone, beta-methasone, corticosterone, prednisolone, and their derivatives essentially having a common nuclear structure Pregna -1, 4 - diene -3,20 dione. The anti-infective agents are either quinolone derivatives selected from the group consisting of ciprofloxacin, norfloxacm, ofloxacin, sparfloxacin and its salts or tobramycin, gentamicin and their pharmaceutically acceptable derivatives and salts.
In a further aspect of this invention, the solubihser is selected from the group consisting of cyclodextrin and its derivatives preferably Beta cyclodextrin, and the complexation enhancing polymer used is selected from the group consisting of non-ionic polymers like polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose or HPMC (hydroxy propyl methyl cellulose) or hydroxy ethyl cellulose.

In yet another aspect of this invention, the complex that is formed of the anti-infective agent-steroid-solubiliser and polymer is either incorporated in a suitable carrier system or lyophilised and later incorporated in a suitable carrier system, which may be water, gel or ointment base.
In the final aspect of this invention, the complex when incorporated in a carrier system of water or gel together with suitable excipients results in a clear and stable pharmaceutical preparation, suitable for ocular treatment.
DESCRIPTION
A brief description of the invention is as follows:
In its main embodiment, the invention consists of a process of manufacturing a combination drug comprising of i. Anti-inflammatory agents which are cortico¬steroids and ii.Anti-infective agents from the group consisting of quinolone derivatives, aminoglycoside derivatives and their pharmaceutically acceptable salts.
The process consists of the following steps: i. Including the steroid within a solubiliser, which also acts as a complexing agent and exhibits an inclusion phenomena, to form a solubiliser steroid complex. The steroid and solubiliser are taken in desired amounts and mixed thoroughly in a polybag to form a blended complex. The ratio in which the steroid and solubilizer are taken depends on the steroid and the anti-infective agent used. The solubiliser used is cyclodextrin or its derivatives, preferably Beta cyclodextrin. The solubiliser and steroid are used in the critical ratio of 1M:2M to IM:6M.Ths use of Beta cyclodextrin makes this process particularly cost effective.
ii. Dispersing or dissolving the anti-infective agent in a suitable solvent preferably water. The solvent and anti-infective agent are stirred to form a slurry. A complexation enhancing polymer solution is added to the slurry and sufficient water is further added and stirred for 10 to 30 minutes to form a clear anti-

infective agent polymar sohition. Dispertion is usually earned out at a tamperature between 20° to 50° C, preferably ambient temperature. The sohition is maitained at a pH range between 4 to 7,
iii. Controlled addition of anti-infective agent polymer solution to steroid solubiliser blend with constant stirring to form a water soluble complex of anti-infective agent-staroid -polymer and solubiliser. The addition can even be done at room tamperature. The clarity of the final solution is dependant on the crucial ratio of the anti-infective agent polymer solution to the steroid-solubiliser blend. The ratio depends upon the type of anti-infective agent and anti-inflamatory agent used. If the ratio is disturbed the clarity of the final solution is affected. The comlexation usually occurs within 30 minutes. The compex formed is stable up to a temperature of 50°C.
iv. Incorporating the complex in a carrier system The complex may be incorporated in water, ointment base or a gel togethw with suitable excipients, depending upon the final purpose of its use.
The complex when dissolved in water, along with excipients, forms a clear stable solution which is very suitable for ocular treatment. A geling polymer may be used as a carrier system, if the final commercial product is desired in a gel fonn. Geling polymer that are used may be one or more among hydroxy propylmethyl cellulose, carbomer or its derivatives, carboxy methyl cellulose or methyl cellulose or hydroxyethyl cellulose. The excipients used are benzalkonium chloride as preservative, disodium EDTA as chelating agent, mono or dibasic sodium phosphate as a buffering agent, and sodium chloride as tonicity adjustor. NaCl is added in such a proportion so as to obtain an osmolality of about 270-320 mOsm in the final composition .In respect of gel preparations sorbitol is used as tonicity adjustor. In its preferred embodiment the steroids used are selected from the group having a general nuclear structure Pregna - 1, 4 - diene - 3, 20 dione which could be dexamethasone, fluoromethalone, Betamethasone, corticosterone, prednisolone and such ohers . The anti-infective agents are slected from the group consisting of derivatives of Ciprofloxacin, , Ofloxacin, sparfloxadn. Norfloxacin, Tobramycin sulphate gentamicin sulphate and their pharmaceutically acceptable salts. The concentration of the anti-infective in the final solution ranges from 3 to 5% weight by

volume, and that of steroid ranges from .l%to .3% weight by volume in the final ftnal solution.
The following examples specifically describe the process for the different combinations of steroids and anti-infective agents used in the various carrier systems.
MANUFACTURING PROCESS OF THE EYE DROPS:
Example: 1
Steroid - Dexamethasone
Anti'infective agent ~ Ciprofloxacin Hydrochloride
1. 0.1% of Dexamethasone and 1% of Betacyclodextrin are accurately weighed.
2. Betacyclodextrin and Dexamethasone are blended thoroughly for 5 minutes.
3. 0.35% of Ciprofloxacin Hydrochloride is dispersed in water and stirred for 5 minutes to form a slurry
4. 1% of Polyvinyl alcohol solution is slowly added as a complexation enhancing agent.
Sufficient water is added and stirred for 10-30 minutes to form a clear solution.
5. Blend of solubilized Dexamethasone and Betacyclodextrin are gradually added to Step No. 4 by stirring it for 10-30 minutes.
6. 0.0005% of Sodium Phosphate is added to Step 5 as a buffering agent and stirred for 5 minutes.
7. 0.1% of Disodium Edetate is added to Step No. 6 as a cnelating agent.
8. 0.01% of Benzalkonium Chloride is added as a preservative to Step No. 7.
9. 0.8% of Sodium Chloride is added to Step No.8 as a tonicity adjuster.
10. The solution is stirred for 10 minutes and pH of the solution is checked. Sodium
Hydroxide solution is used to adjust the pH of solution between 4.5 and 5.0
* All the steps from 1 to 9 are carried out in class 100 area.
11. The solution is filtered through 0.2 μfilter to get a sterile ophthalmic solution.
The solution is filled in a suitable container

Example: 2
Steroid - Dexamethasone
Anti-infective agent - Tobramycin Sulphate
1. 0.1 % of Dexamethasone and 1 % of Betacyclodextrin are accurately weighed.
2. Betacyclodextrin and Dexamethasone are blended thoroughly for 5 minutes.
3. 0.3% of Tobramycin Sulphate is dispersed in water and stirred for 5 minutes fo form a slurry
4. 1% of Polyvinyl alcohol solution is slowly added as a co-complexing agent; Sufficient water is added and stirred for 10-30 minutes to form a clear solution.
5. Blended solublized steriod Of Dexamethasone and Betacyclodextrin are gradually added to Step No. 4 by stirring it for 10-30 minutes.
6. 0,0005% of Sodium Phosphate is added to Step 5 as a buffering agent.
7. 0.1% ofDisodium Edetate is added to Step No. 6 as a chelating agent.
8. 0.01% of Benzalkonium Chloride is added as a preservative to Step No. 7.
9. 0.8% of Sodium Chloride is added to Step No. 8 as a tonicity adjustor.
10. The solution is stirred for 10 minutes and pH of the solution is checked. Sodium Hydroxide solution is used to adjust the pH of solution between 7.0 and 7.5.
* All the steps from 1 to 9 are carried out in class 100 area.
11. The solution is filtered through 0.2 μ filter to get a sterile ophthalmic solution.
The solution is filled in a suitable container.
Example : 3
Steroid - Dexamethasone Anti-infective agent - Ofloxacin
1. 0.1 % of Dexamethasone and 1% of Betacyclodextrin are accurately weighed.
2. Betacyclodextrin and Dexamethasone are blended thoroughly for S minutes
3. 0.3% of Ofloxacin is dispersed m water and stirred for 5 minutes to from a slurry

4. 1% of Polyvinyl alcohol solution is slowly added as a co-complexing agent. Sufficient water is added and stirred for 10-30 minutes to form a clear solution.
5. Blend of solublized Dexamethasone and Betacyclodextrin is gradually added to Step No. 4 by stirring it for 10-30 minutes.
6. 0.0005% of Sodium Phosphate is added to Step 5 as a buffering agent and stirred for 5 minutes.
7. 0.1 % of Disodium Edetate is added to Step No. 6 as a chelating agent.
8. 0.01% of Benzalkonium Chloride is added as a preservative to Step No. 7.
9. 0.8% of Sodium Chloride is added to Step No. 8 as a tonicity adjustor.
10. The solution is stirred for 10 minutes and pH of the solution is checked. Sodium Hydroxide solution is used to adjust the pH of solution between 6.5 and 7,
* All the steps from 1 to 9 are carried out in class 100 area.
11. The solution is filtered through 0.2 μ filter to get a sterile ophthalmic solution.
The solution is filled in a suitable container.
Example: 4
Steroid - Dexamethasone Anti-infective agent - Sparfloxacin
1. 0,1% of Dexamethasone and 1% of Betacyclodextrin are accurately weighed.
2. Betacyclodextrin and Dexamethasone are blended thoroughly for 5 minutes.
3. 0.3% of Sparfloxacin is dispersed in water and stirred for 5 minutes to form a slurry
4. 1% of Polyvinyl alcohol solution is slowly added as a complexing agent. Sufficient water is added and stirred for 10-30 minutes to form a clear solution.
5. Blended solubtlized steriod of Dexamethasone and Betacyclodextrin are gradually-added to Step No. 4 by stirring it for 10-30 minutes.
6. 0.0005% of Sodium Phosphate is added to Step 5 as a buffering agent and stirred for 5 minutes.
7 0 1% of Disodium Edetate is added to Step No. 6 as a chelating agent
8. 0.01% of Benzalkonium Chloride is added as a preservative to Step No. 7
9. 0.8% of Sodium Chloride is added to Step No. 8 as a tonicity adjuster.

10. The solution is stirred for 10 minutes and pH of the solution is checked. Sodium
Hydroxide solution is used to adjust the pH ;
* All the steps from 1 to 9 are carried out in class 100 area.
11. The solution is filtered through 0.2 μ filter to get a sterile ophthalmic solution.
The solution is filled in a suitable container.
Example: 5
Steroid - Dexamethasone
Anti-infective agent - Gentamicin Sulphate
1. 0.1 % of Dexamethasone and 1 % of Betacyclodextrin are accurately weighed.
2. Betacyclodextrin and Dexamethasone are blended thoroughlly for 5 minutes.
3. 0.3% of Gentamicin Sulphate is dispersed in water and stirred for 5 minutes to form a slurry
4. 1% of Polyvinyl alcohol solution is slowly added as a co-complexing agent. Sufficient water is added and stirred for 10-30 minutes to form a clear solution.
5. Blend of solublized Dexamethasone and Betacyclodextrin is gradually added to Step No. 4 by stirring it for 10-30 minutes.
6. 0.0005% of Sodium Phosphate is added to Step 5 as a buffering agent and stirred for 5 minutes.
7.. 0 1% of Disodium Edetate is added to Step No. 6 as a chelating agent.
8. 0.01% of Benzalkonium Chloride is added as a preservative to Step No. 7.
9. 0.8% of Sodium Chloride is added to Step No. 8 as a tonicity adjustor.
10. The solution is stirred for 10 minutes and pH of the solution is checked. Sodium Hydroxide solution is used to adjust the pH of solution between 4.5 and 5.0.
* All the steps from 1 to 9 are carried out in class 100 area. .
11. The solution is filtered through 0.2 μ filter to get a sterile ophthalinic solution.
The solution is filled in a suitable container.
Example 6: .
Steroid: Dexamethasone Anti-infective Agent: Ciprofloxacin

Polymer: Polyvinyl Pyrollidone (PVP) MANUFACTURING PROCESS OF EYE DROPS: Example No. 1/A
1. Accurately weigh . 1 % of Dexamethasone and 1 % of Betacyclodextrin.
2. Blend thoroughly Betacyclodextrin and Dexamethasone for 5 minutes.
3. Disperse 0.35% of Ciprofloxacin Hydrochloride in water to form a slurry and stir for 5 minutes.
4. Add 1% of Polyvinyl Pyrollidone (PVP) solutions as a co-complexing agent slowly. Add sufficient water and stir for 10-30 minutes to form a clear solution.
5. Add solubliized blend of Dexamethasone and Betacyclodextrin to Step No.4 gradually under stirring for 10 -30 minutes.
6. Add 0.0005% Sodium Phosphate as a buffering agent to Step No.5 and stir for 5 minutes.
7. Add 0.1 % of Disodium Edetate in Step No.6 as chelating agent.
8. Add 0.01% of Benzalkonium Chloride as preservative in Step No.7
9. Add 0.8% ofSodium Chloride in Step No.8 as a tonicity adjustor.
10. Stir the solution for 10 minutes and check pH of the solution. Adjust the pH of
solution between 4.5 to 5.0 using Sodium Hydroxide solution.
• Carry out all the steps 1 to 9 in class 100 area.
11. Filter the solution through 0.2 u filter to get a sterile ophthalmic solution.
Fill the solution in suitable container.
MANUFACTURING PROCESS OF OPHTHALMIC GEL:
Example: 7
Steroid - Dexamethasone
Anti-infective agent - Ciprofloxacin Hydrochloride
1 0 1 % of Dexamethasone and 1 % of Bctacyclodcxtrm arc accurately' weighed

2. Betacyclodextrin and Dexamethasone are blended thoroughly for 5 minutes.
3. 0.3% of Ciprofloxacin Hydrochloride is dispersed in water to form a solution and stirred for 5 minutes.
4. Blend of solublized Dexamethasone and Betacyclodextrin is gradually added by stirring it for 10-30 minutes.
5. 0.01% of Benzalkonium Chloride is dissolved as a preservative in hot water and added to Step No. 4.
6. The solution of step 5 is filtered through 0.2 μ membrane filter and given a wash with water.
7. HPMC 2% is dispersed as viscofying agent in hot water with continuous stirring till a uniform gel without any lumps formation.
8. 12% of sorbitol is added to Step 6 as tonicity adjuster / Humactant under constant stirring.
9. The gel is autoclaved at 121° C for about 15 minutes.
10. The autoclaved gel is aseptically mixed (at room temperature) with the solution from Step 6 under continuous stirring till clear gel forms.
MANUFACTURING PROCESS OF OPHTHALMIC GEL:
Example: 8
Steroid - Dexamethasone
Anti-infective agent - Tobramycin Sulphate
1. 0.1 % of Dexamethasone and 1 % of Betacyclodextrin are accurately weighed.
2. Betacyclodextrin and Dexamethasone are blended thoroughly for 5 minutes.
3. 0.3% of Tobramycin Sulphate is dispersed in water to fonn a solution and stirred for 5 minutes.
4. Blend of solublized Dexamethasone and Betacyclodextrin is gradually added by stirring it for 10-30 minutes
5 0 01% of Benzalkomum Chloride is dissolved as a preservative in hot water and added to Step No 4

6. The solution of step 5 is filtered through 0.2 μ membrane filter and given a wash with water.
7. HPMC 2% is dispersed as viscofying agent in hot water with continuous stirring till a uniform gel without any lumps formation.
8. 12% of sorbitol is added to Step 6 as tonicity adjustor / Humactant under constant stirring.
9. The gel is autoclaved at 1210 C for about 15 minutes.
10. The autoclaved gel is aseptically mixed (at room temperature) with the" solution from Step 6 under continuous stirring till clear gel forms.
EXAMPLE 9:
Steroid: Dexamethasone Anti-infective Agent: Norfloxacin
1. Accurately weigh 0.1% of Dexamethasone and 1% of Betacyclodextrin.
2. Blend thoroughly Betacyclodextrin and Dexamethasone for 5 minutes.
3 Disperse 0.3% of Norfloxacin in water to form a slurry and stir for 5 minutes.
4. Add 1% of Polyvinyl alcohol solution as a co-complexing agent slowly. Add sufficient water and stir for 10 - 30 minutes to form a clear solution.
5. Add solubilized steroid blend of Dexamethasone and Betacyclodextrin to Step No. 4 gradually under stirring for 10 - 30 minutes.
6. Add 0.0005% Sodium Phosphate as a buffering agent to Step No. 5 and stir for 5 minutes
7. Add 0.1 % of Disodium Edetate in Step No. 6 as chelating agent.
8. Add 0.01 % of Benzalkonium Chloride as preservative in Step No. 7.
9. Add 0.8% of Sodium Chloride in Step No. 8 as a tonicity adjustor.
10. Stir the solution for 10 minutes and check pH of the solution. Adjust the pH of solution between 4.5 to 5.0 using Sodium Hydroxide solution.
* Cany out all the steps 1 to 9 in class 100 area. 11 Filte the sotution through 0.2 μ filter to get a sterile ophthalmic solution. Fill the solution in suitable container.

WE CLAIM:
1. A method to manufacture an Ophthalmic Pharmaceuticai Preparation comprising
of (i)anti-inflammatoty agents which are cortico-steroids and (ii) anti-infective agents from the group consisting of derivatives of quinolone, aminoglycoside and theirpharmaceutically acceptable salts such as herein described by a process essentially consisting of:
(a) Including the steroid within a solubilizer cum complexing agent to form a solubilser-steroid complex, where in the steroid and solubiliser are in the ratio of lM:2M to 1M:6M.
(b) Dispersing or dissolving the anti-infective agent in a suitable solvent, which is subsequently diluted with a complexation enhancing water soluble polymer solution to give an anti-infective agent - polymer solution;
(c) Combining the anti-infective agent polymer solution and steroid solubiliser complex to form a water soluble complex;
(d) Incorporating the complex in a pharmaceutically acceptable carrier systen; to give a clear, stable, non turbid solution.

2. A process as claimed in claim 1, where in the steroid has a common nuclear structure Pregna -1,4 - diene - 3,20 dione;
3. A process as claimed in claim 2, where in the steroid is selected from the group consisting of Fluorometholone, Dexamethasone, Betnethasone, prednisolone, corticosterone and their derivatives
4. A process as claimed in claim 3 where in the anti-infective agents are quinolone derivatives selected from a the group consisting of ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin and their pharmaceutically acceptale derivatives and
salts.


5. A process as claimed in claim 3 where in the anti-infective agents are aminoglycoside derivatives selected from among tobramycin, gentamicin and its salts, preferably sulphates.
6. A process as claimed in claim 4 or S, where in the solubiliser is selected from the group consisting of cyclodextrin and its derivatives.
7. A process as claimed in claim 6, where in the solubiliser is Beta-cyclodextrim.

8. A process as claimed in claim 7, where in the solvent used for dissolving or dispersing anti-infective agent is water.
9. A process as claimed in claim 8, wherein the complexation enhancing polymer used is non-ionic slected from the group consisting of polyvinyl alcohol, polyvinyl pyrrolidone, mettiyl cellulose, hydroxyethyl cellulose, hydroxy propyl mettiy cdhilose.
10. A process as daimed in claim 1, where in the water soluble complex is optionally lyophilised before being incorporated in a suitable carrier system.
11. A process as claimed in claim 9 or 10, where in the carrier system is water with suitable exdpients resulting in a non~turbid pharmaceutical preparation for ocular treatment.
12. A process as claimed in claim 9 or 10, where in the carrier system consist of water, gelling polymer together with suitable excipients.
13. A process as claimed in claim 12, where in the gelling polymer is selected from among hydroxy propylmethyl cellulose, carbomer or its derivatives, carboxy methyl cdhilose or methyl cellulose or hydroxyethy cellulose.
14. A process as daimed in claim 9 or 10 , where in the carrier systen consists of ointment base and exciptents.
15. A process as claimed in claim 11, 12 and 14 , where the excipients used are a buffering agent, chclating agentt, preservative and a tonicity adjustor.

16. A process as claimed in claim15, where in the excipients are benzalkonium choride as preservatives, Edetate disodium (EDTA) as chelating agent, mono or dibasic sodium phosphate as a buffeting agent and sodium chloride as tonicity adjustor, all in pharmnaceutically acceptable concentrations.
17. A process as claimed in claim 16, where in the carrier system is water and the sodium chloride is in amounts sufficient to cause the composition to have an osmolality of about 270 -320 mOsm.
18. A process as claimed in daim 17, where in the coocentniticffis of the and-infetive agent ranges from 0.3% to 0.5% wt by volume and steroid ranges from 0.1% to 0.3% wt by volume in the final preparation
Dated this 2nd day of November 2001

USHA ACHANDRASEKHAR PATENT AGENT AND ATTORNEY

For FDC limited

Documents:

1018-mum-2000-cancelled page(29-11-2005).pdf

1018-mum-2000-claim(granted)-(29-11-2005).doc

1018-mum-2000-claim(granted)-(29-11-2005).pdf

1018-mum-2000-correspondence(29-11-2005).pdf

1018-mum-2000-correspondence(ipo)-(22-11-2004).pdf

1018-mum-2000-form 1(29-11-2005).pdf

1018-mum-2000-form 2(granted)-(29-11-2005).doc

1018-mum-2000-form 2(granted)-(29-11-2005).pdf

1018-mum-2000-form 26(15-11-2000).pdf

1018-mum-2000-form 3(09-11-2001).pdf

1018-mum-2000-form 3(22-03-2005).pdf


Patent Number 204373
Indian Patent Application Number 1018/MUM/2000
PG Journal Number 43/2008
Publication Date 24-Oct-2008
Grant Date 19-Feb-2007
Date of Filing 15-Nov-2000
Name of Patentee FDC LIMITED
Applicant Address B-8, M.I.D.C., INDUSTRIAL AREA, WALUJ.
Inventors:
# Inventor's Name Inventor's Address
1 DR. MAINDE CHANDRASHEKHAR 603/B, MAROL HILL VIEW MITIETARY ROAD, MAROL ANDHERI (EAST), MUMBAI-400 059.
2 CHANDAVARKAR MOHAN A 7A, CHAND TERRACES, ST. ANDREWS ROAD, BANDRA (W), MUBBAI-400 050.
3 CHANDAVARKAR NANDAN MOHAN 7A, CHAND TERRACES, ST. ANDREWS ROAD, BANDRA (W), MUBBAI-400 050.
PCT International Classification Number A 61 K 9/20
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA