The present invention relates to an ophthalmic composition comprising olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients. It further relates to a method of preparing such compositions and their use to treat ocular allergic disorders (e.g. allergic conjunctivitis).

BACKGROUND OF THE INVENTION

Olopatadine, which is a mast cell stabilizer, is chemically known as (11Z)-11-[3-(Dimethylamino) propylidene]-6, 11-dihydrodibenz [b,e]oxepin-2-acetic acid, hydrochloride for topical administration to the eyes. Olopatadine hydrochloride is a white, crystalline, water-soluble powder with a molecular weight of 373.88 and a molecular formula of C21H23NO3•HCl.

Olopatadine is currently marketed in three strengths eq 0.1% base, eq 0.2% base and EQ 0.7% base under brand name of Patanol™, Pataday™ and Pazeo™ respectively. Patanol™ is indicated for the treatment of the signs and symptoms of allergic conjunctivitis. The approved ophthalmic solution of Patanol™ 0.1% contains olopatadine hydrochloride equivalent to 0.1% olopatadine, 0.01% benzalkonium chloride as preservative, dibasic sodium phosphate, sodium chloride, hydrochloric acid and/or sodium hydroxide (to adjust the pH) and purified water. It has a pH of about 7, and osmolality of about 300mOsm/kg.

Pataday™ solution is indicated for the treatment of ocular itching associated with allergic conjunctivitis and the approved ophthalmic solution contains olopatadine hydrochloride equivalent to 0.2% olopatadine, 0.01% benzalkonium chloride as preservative, povidone, dibasic sodium phosphate, sodium chloride, edetate disodium, hydrochloric acid and/or sodium hydroxide (to adjust the pH) and purified water. It has a pH of about 7, and osmolality of about 300mOsm/kg.

Pazeo™ 0.7% contains 7.76 mg of olopatadine hydrochloride, povidone, hydroxypropyl-gamma-cyclodextrin, polyethylene glycol 400, hydroxypropyl methylcellulose, boric acid, mannitol, benzalkonium chloride 0.015% (preservative), hydrochloric acid/sodium hydroxide (to adjust pH), and purified water and is indicated for the treatment of ocular itching associated with allergic conjunctivitis. Pazeo™ solution has a pH of approximately 7.2 and an osmolality of approximately 300 mOsm/kg.

Olopatadine as a compound is known from U.S. 5,116,863 and U.S. 4,871,865 and its use for treating allergy eye diseases is known from U.S. 4,923,892 and U.S. 5,641,805.

U.S. 8,791,154 B2 and U.S. 9,533,053 B2 of Alcon discloses ophthalmic solution for treatment of ocular allergic conjunctivitis, wherein the solution comprises at least 0.67%w/v olopatadine, PEG having a molecular weight of 300 to 500, polyvinylpyrrolidone, hydroxypropyl-gamma-cyclodextrin, benzalkonium chloride, and water.

U.S. 6,995,186 B2 of Alcon discloses topically administrable solution composition for treating allergic or inflammatory disorders of the eye having olopatadine in the solution in amount of 0.17-0.62%(w/v) along with polymeric ingredient consisting essentially of polyvinylpyrrolidone or polystyrene sulfonic acid, wherein the composition does not contain polyvinyl alcohol, polyvinyl acrylic acid, hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose or xanthan gum.

U.S. 7,402,609 B2 of Alcon discloses topically administrable solution composition for treating allergic or inflammatory disorders, wherein the solution has a pH from 6.5-7.5 and a viscosity of 1-2 cps, and wherein the solution consists essentially of: a) 0.18-0.22% (w/v) olopatadine; b) 1.5-2% (w/v) PVP having an average molecular weight of 50,000-60,000; c) a preservative; d) edetate disodium; e) a tonicity-adjusting agent; f) a buffering agent; g) optionally a pH-adjusting agent.

U.S. Patent No. 8,388,941 B2; 8,268,299 and U.S. Patent No. 8,323,630 disclose multi-dose, self-preserved ophthalmic composition, comprising: zinc ions; borate and polyol.

Thus there is a need to develop an alternate olopatadine composition that not only solubilizes sufficient amounts of olopatadine, but also retains desirable pharmaceutical characteristics like stability over the shelf life. The present inventors have developed such compositions wherein olopatadine is solubilized in solution in a stable manner.

SUMMARY OF THE INVENTION

According to one aspect of the present invention, there is provided an ophthalmic composition comprising at least 0.3%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients.

According to another aspect of the present invention, there is provided an ophthalmic composition comprising at least 0.3%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients are selected from the group comprising solubilizer, buffering agent, viscosity enhancing agent, tonicity adjusting agent, pH adjusting agent, vehicle/diluent/solvent, surfactant, preservative and/or combinations thereof.

According to another aspect of the present invention, there is provided an ophthalmic composition comprising at least 0.3%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of polyethylene glycol.

According to another aspect of the present invention, there is provided an ophthalmic composition comprising at least 0.3%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition contains no more than one solubilizer.

According to another aspect of the present invention, there is provided an ophthalmic composition comprising at least 0.3%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of povidone.

According to another aspect of the present invention, there is provided an ophthalmic composition comprising at least 0.3%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition contains no more than one viscosity enhancing agent.

According to another aspect of the present invention, there is provided an ophthalmic composition comprising at least 0.3%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of both polyethylene glycol and povidone.

Still other aspects and advantages of the invention will be apparent from the following detailed description of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an ophthalmic composition comprising olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients.

Unless indicated otherwise, all component concentrations are presented on a % (w/v) basis.

The present invention relates to an ophthalmic composition comprising at least 0.3%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients.

According to one embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients.

According to another preferred embodiment, there is provided an ophthalmic composition comprising 0.7%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients.

According to another embodiment, there is provided an ophthalmic composition comprising at least 0.3%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients are selected from the group comprising solubilizer, buffering agent, viscosity enhancing agent, tonicity adjusting agent, pH adjusting agent, vehicle/diluent/solvent, surfactant, preservative and/or combinations thereof.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of polyethylene glycol.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition contains no more than one solubilizer.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of povidone.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition contains no more than one viscosity enhancing agent.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of both polyethylene glycol and povidone.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the preservative is benzalkonium chloride.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the preservative is other than benzalkonium chloride.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of preservative.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is administered once a day.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is topically administered.

The present invention further relates to an ophthalmic composition comprising olopatadine and one or more pharmaceutically acceptable excipients, wherein the composition has a pH in the range of about 6.0 to 8.0.

The present invention provides an ophthalmic composition comprising olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the olopatadine is present in any known polymorphic form i.e. amorphous or crystalline form.

The present invention provides an ophthalmic composition, wherein the composition is in the form of clear solution, emulsion, suspension, dispersion, gel, and/or nano-dispersion.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is filled into a single-dose container.

According to another embodiment, there is provided an ophthalmic composition comprising 0.3-0.8%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is filled into a multi-dose container.

Suitable containers include, for example, bottles, vials or blow-fill-seal (BFS) containers.

The composition as per the present invention composition is filled in three piece bottle plugged with nozzle and seal with cap.

Pharmaceutically acceptable packaging materials include but are not limited to low density polyethylene ("LDPE"), high density polyethylene ("HDPE"), polypropylene, polystyrene, polycarbonate, polyesters (such as polyethylene terephthalate and polyethylene naphthalate), nylon, polyvinyl chloride, poly(vinylidine chloride), poly(tetrafluoroethylene) and other materials known to those of ordinary skill in the art.

Typically the bottle may be made from Low Density Polyethylene (LDPE), Linear Low Density Polyethylene (LLDPE), High Density Polyethylene (HDPE), Polypropylene (PP) and the like or a combination thereof. Typically the nozzle/cap may be made of low density polyethylene (LDPE), linear low density polyethylene (LLDPE), high density polyethylene (HDPE), polypropylene (PP) and the like or a combination thereof. Alternatively the nozzle may be made of a hydrophobic material or may be coated with a hydrophobic material such as a fluoropolymer like Teflon (polytetrafluoroethylene) and the like.

The pharmaceutical compositions as per the present invention can be sterilized using any of the known methods but not limited to methods selected from the group comprising filtration, moist heat, dry heat, gas sterilization or irradiation (gamma and electron beam). The container in which composition is filled can be sterilized using gamma irradiation or ethylene oxide or pre-acetic acid or any other conventional method of sterilization.

The present invention further provides an ophthalmic composition comprising olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition has total impurities less than the maximum allowed limit as per ICH guidelines. The proposed composition comprises less than 0.5% olopatadine E-siomer, less than 2% olopatadine related compound B ((Z)-3-{2-(Carboxymethyl) dibenzo [b,e] oxepin-11(6H)- ylidene}-N,N-dimethylpropan-1-amine oxide), less than 0.5% olopatadine carbaldehyde ((Z)-11-[3-(Dimethylamino) propylidene]-6,11-dihydrodibenzo [b,e] oxepine-2-carbaldehyde).

The present invention further provides an ophthalmic composition comprising olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients are selected from the group comprising solubilizer, buffering agent, viscosity enhancing agent, tonicity adjusting agent, pH adjusting agent, vehicle/diluent/solvent, surfactant, preservative and/or combinations thereof.

In an embodiment, the composition as per the present invention includes a solubilizer to ensure good solubilization and/or dissolution of the compound and to minimize precipitation of the compound and thus helps to maintain the composition as a stable or homogeneous solution or dispersion.

Suitable solubilizer to aid in solubilizing the olopatadine include cyclodextrins, such as cyclodextrin, and its derivative preferably hydroxypropyl-gamma-cyclodextrin, hydroxypropyl-beta-cyclodextrin, sulfoalkyl ether beta-cyclodextrin; N-alkylcaprolactam, dimethylacetamide, esters such as ethyl propionate, tributylcitrate, acetyl triethylcitrate, acetyl tributyl citrate, triethylcitrate, ethyl oleate, ethyl caprylate, ethyl butyrate, triacetin, propylene glycol monoacetate, propylene glycol diacetate, epsilon-caprolactone and isomers thereof, delta.-valerolactone and isomers thereof, beta-butyrolactone and isomers thereof; and other solubilizers known in the art, such as polyethylene glycol, dimethyl acetamide, dimethyl isosorbide and diethylene glycol monoethyl ether.

In a preferred embodiment of the present invention, solubilizer may be used in concentrations ranging from about 0.01% to about 50% w/v of the composition.

Suitable buffering agents include, but are not limited to, phosphates, such as sodium phosphate monobasic, sodium phosphate dibasic, citric acid, citrates such as sodium citrate, acetic acid, acetates such as sodium acetate, lactic acid, sodium lactate, tartaric acid, sodium tartrate, borates including boric acid and its salts, such as sodium borate or potassium borate. Borate buffers also include compounds such as potassium tetraborate or potassium metaborate that produce borate acid or its salt in solutions, tartrates, succinates, amino acids such as L-arginine, tromethamine and/or combinations thereof.

In a preferred embodiment of the present invention, buffering agents may be used in concentrations ranging from about 0.01% to about 50% w/v of the composition.

In some embodiments, the compositions can have one or more viscosity enhancing agent. The viscosity enhancing agent typically enhances the viscosity of the ocular solution to increase retention time of the solution on the eye, and in some instances, to provide a protective layer on the eye surface.

According to another embodiment, there is provided an once a day ophthalmic composition comprising 0.7%w/v of olopatadine or pharmaceutically acceptable salts thereof, mannitol, cyclodextrin, hydroxypropyl methylcellulose, benzalkonium chloride, boric acid and one or more pharmaceutically acceptable excipients, wherein the composition is free of polyethylene glycol.

According to another embodiment, there is provided an once a day ophthalmic composition comprising 0.7%w/v of olopatadine or pharmaceutically acceptable salts thereof, mannitol, cyclodextrin, hydroxypropyl methylcellulose, benzalkonium chloride, boric acid and one or more pharmaceutically acceptable excipients, wherein the composition is free of povidone.

Suitable viscosity enhancing agent includes, but not limited to cellulose and its derivatives like hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, dextrans, pyrrolidones, polyvinylpyrrolidone, polyvinyl alcohol, glycerin, carbopols, gums or combinations thereof.

In a preferred embodiment of the present invention, viscosity enhancing agent may be used in concentrations ranging from about 0.001% to about 50 % w/v of the composition.

The tonicity agent is used in an amount to maintain the solution’s osmolality compatible with respect to eye fluid. Suitable tonicity adjusting agents include propylene glycol, glycerol/glycerine, sodium chloride, potassium chloride, sodium bromide, calcium chloride, mannitol, sorbitol, dextrose, sucrose, mannose and the like and mixtures thereof.

In a preferred embodiment of the present invention, tonicity adjusting agent may be used in concentrations ranging from about 0.01% to about 50% w/v of the composition.

The pH of the ophthalmic composition can be adjusted by addition of an acid or a base in quantity sufficient to achieve the desired pH. Suitable pH adjusting agents include acids and bases. Suitable acids to adjust the pH of the composition include, but are not limited to, hydrochloric acid, citric acid, sulfuric acid, nitric acid and/or combinations thereof. Suitable bases to adjust the pH of the composition include, but are not limited to, sodium hydroxide, potassium hydroxide, barium hydroxide, amino acid and/or combinations thereof. The aqueous topical solution intended for ophthalmic administration as per the present invention has a pH in the range of 6.0-8.0.

Suitable vehicles/diluents/solvents include water for injection, purified water, Ringer's solution, normal saline solution and oils. Suitable organic diluents include, for example, alcohols.

Suitable chelating/complexing agents include edetate disodium, diethylenetriamine pentaacetic acid, cyclodextrins, citrates and polyphosphates and/or combinations thereof. It may be present in the concentrations ranging from about 0.001% to about 50 % w/v.

Suitable surfactants include but are not limited to, hydrophilic surfactants, lipophilic surfactants, and mixtures thereof. The formulations can contain surface-active agents conventionally employed in topical formulations, such as oleic acid, lecithin, sorbitan trioleate, tyloxapol, cetylpyridinium chloride, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan mono-oleate, polyoxypropylene/polyoxyethylene block copolymers, polyoxypropylene/polyoxyethylene/ethylene diamine block copolymers, polysorbates, poloxamers, ethoxylated castor oil and/or combinations thereof. In some embodiments, the concentration of surfactant, ranges from about 0.01% to about 50% w/v.

Suitable preservatives include, but are not limited to, quaternary ammonium compounds like benzalkonium chloride, benzododecinium bromide (BDD), cetrimide, polyquaternium-1, polyquaternium ammonium chloride; thiomersal, acids and their pharmaceutically acceptable salts such as sorbic acid, potassium sorbate, boric acid, borax, sodium perborate NaBO3, salicylic acid, benzoic acid, lactic acid, acetic acid; S.O.C (stabilized oxychloro complex), S.C.P (stabilized chlorite peroxide), chlorobutanol, phenylethanol, cetrimonium chloride, methyl parahydroxybenzoate, parabens such as methyl paraben, propyl paraben, ethyl paraben, butyl paraben, perborates, phenol and its derivatives such as m-cresol and chlorocresol, benzyl alcohol, halogenated alcohols such as chlorobutanol and/or combinations thereof. The preferred preservative for the aqueous topical solution of the present invention is benzalkonium chloride. In a preferred embodiment of the present invention, preservative may be used in concentrations ranging from about 0.001% to about 25% w/v of the composition.

The present invention provides an ophthalmic composition comprising olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is useful for treatment of ocular itching associated with allergic conjunctivitis.

The present invention further relates to a process for preparing an ophthalmic composition comprising olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein said process comprises following steps:

A. Drug solution part:
a) collect 5 to 70% batch quantity of water for injection and add required quantity of buffering agent under continue stirring till clear solution is obtained;
b) add required quantity of solubilizing agent(s) under continue stirring till clear solution is obtained;
c) add required quantity of tonicity agent under continue stirring till clear solution is obtained;
d) add required quantity of preservative under continue stirring till clear solution is obtained;
e) add required quantity of active pharmaceutical ingredient under continue stirring till clear solution is obtained;
f) adjust the pH of the solution, if required;
g) filter sterilized and stored

B. Polymer part:
a) collect 5 to 70% batch quantity of water for injection;
b) add required quantity of viscosity enhancing agents(s) and continue stirring till clear solution is obtained;
c) clarified by filtration;
d) sterilized by autoclaving and stored.

C. Composition:
a) mix batch quantity of sterile drug solution part with required batch quantity of polymer part;
b) adjust the pH of the solution, if required;
c) makeup the volume using water for injection to 100% on weight basis;
d) filling in respective container.

The present invention relates to an ophthalmic composition comprising olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition optionally further comprises one or more additional therapeutic agents. Alternatively, a compound of this invention may be administered to a patient in need thereof in combination with the administration of one or more other therapeutic agents.

The following examples in Table 1-3 will illustrate in more detail the various aspects of the present invention.

The term “q.s.” wherever appears in the tables is an abbreviation for “quantity sufficient” which is the amount of the excipient in such quantities that is just sufficient for its use in the composition of the present invention.

Table 1: Topically Administrable Ophthalmic Solution of Olopatadine

Ingredients Quantity (%w/v)
Example 1 Example 2 Example 3 Example 4 Example 5 Example
6
Olopatadine Hydrochloride 0.7 0.7 0.7 0.7 0.7 0.7
Povidone 0.01% -50% 0.01% - 50% 0.01% - 50% - - -
Hydroxypropyl ? cyclodextrin 0.01% - 50% 0.01% -50% 0.01% -50% 0.01% - 50% 0.01% -50% 0.01% - 50%
Diethylene Glycol Monoethyl Ether - 0.01% - 50% - - - -
Propylene Glycol Diacetate - - 0.01% -50% - - -
Polyethylene glycol 400 - - - 0.01% - 50% 0.01% -50% 0.01% - 50%
Polyvinyl Alcohol - - - - 0.01% - 50% -
Methyl Cellulose - - - - - 0.01% - 50%
Hydroxypropyl Methylcellulose 0.001% -50% 0.001% - 50% 0.001% - 50% 0.001% -50% 0.001% -50% 0.001% -50%
Boric Acid 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% - 50%
Mannitol 0.01% -50% 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% - 50%
Benzalkonium Chloride 0.001% -25% 0.001% - 25% 0.001% -25% 0.001% - 25% 0.001% - 25% 0.001% - 25%
Hydrochloric Acid/ Sodium Hydroxide q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0
Purified Water q.s. to 100 q.s. to 100 q.s. to 100 q.s. to 100 q.s. to 100 q.s. to 100

Table 2: Topically Administrable Ophthalmic Solution of Olopatadine

Ingredients Quantity (%w/v)
Example
7 Example
8 Example
9 Example 10 Example 11 Example 12
Olopatadine Hydrochloride 0.7 0.7 0.7 0.7 0.7 0.7
Povidone - - - - - -
Hydroxypropyl ? cyclodextrin 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% -50%
Diethylene Glycol Monoethyl Ether - 0.01% - 50% - - 0.01% - 50% 0.01% -50%
Propylene Glycol Diacetate - - 0.01% - 50% 0.01% - 50% - -
Polyethylene glycol 400 0.01% - 50% - - - - -
Polyvinyl Alcohol - 0.01% - 50% 0.01% - 50% - - -
Methyl Cellulose - - - 0.01% - 50% 0.01% - 50% -
Sodium Carboxymethyl cellulose 0.01% - 50% - - - - 0.01% - 50%
Hydroxypropyl Methylcellulose 0.001% - 50% 0.001% - 50% 0.001% -50% 0.001% -50% 0.001% -50% 0.001% - 50%
Boric Acid 0.01% -50% 0.01% - 50% 0.01% - 50% 0.01% -50% 0.01% - 50% 0.01% - 50%
Mannitol 0.01% -50% 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% - 50% 0.01% - 50%
Benzalkonium Chloride 0.001% -25% 0.001% - 25% 0.001% -25% 0.001% -25% 0.001% - 25% 0.001%-25%
Hydrochloric Acid/ Sodium Hydroxide q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0 q.s. to pH 6.0-8.0
Purified Water q.s. to 100 q.s. to 100 q.s. to 100 q.s. to 100 q.s. to 100 q.s. to 100

Table 3: Topically Administrable Ophthalmic Solution of Olopatadine

Ingredients Quantity (%w/v)
Example 13 Example 14 Example 15
Olopatadine Hydrochloride 0.7 0.7 0.7
Povidone - - -
Hydroxypropyl ? cyclodextrin 0.01% - 50% 0.01% - 50% 0.01% - 50%
Diethylene Glycol Monoethyl Ether - - -
Propylene Glycol Diacetate 0.01% - 50% - -
Polyethylene glycol 400 - - -
Polyvinyl Alcohol - - -
Methyl Cellulose - - -
Sodium Carboxymethyl cellulose 0.01% - 50% 0.01% - 50% 0.01% - 50%
Propylene Glycol - 0.01% - 50% -
Tyloxapol - - 0.01% - 50%
Hydroxypropyl Methylcellulose 0.001% -50% 0.001% - 50% 0.001% - 50%
Boric Acid 0.01% - 50% 0.01% - 50% 0.01% - 50%
Mannitol 0.01% - 50% 0.01% - 50% 0.01% - 50%
Benzalkonium Chloride 0.001% - 25% 0.001% - 25% 0.001% - 25%
Hydrochloric Acid/ Sodium Hydroxide q.s. to
pH 6.0-8.0 q.s. to
pH 6.0-8.0 q.s. to
pH 6.0-8.0
Purified Water q.s. to 100 q.s. to 100 q.s. to 100

Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only.

WE CLAIM

1.An ophthalmic composition comprising 0.7%w/v of olopatadine or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of polyethylene glycol.

2. The ophthalmic composition as claimed in claim 1, wherein the composition is free of povidone.

3. The ophthalmic composition as claimed in claim 1, wherein the composition is free of both polyethylene glycol and povidone.

4. The ophthalmic composition as claimed in claim 1, wherein the composition contains no more than one solubilizer.

5. The ophthalmic composition as claimed in claim 1, wherein the composition contains no more than one viscosity enhancing agent.

6. The ophthalmic composition as claimed in claim 1, wherein the composition is filled into a single-dose container or multi-dose container.

7. The ophthalmic composition as claimed in claim 1, wherein the one or more pharmaceutically acceptable excipients are selected from the group comprising solubilizer, buffering agent, viscosity enhancing agent, tonicity adjusting agent, pH adjusting agent, vehicle/diluent/solvent, surfactant, preservative and/or combinations thereof.

8. An once a day ophthalmic composition comprising 0.7%w/v of olopatadine or pharmaceutically acceptable salts thereof, mannitol, cyclodextrin, hydroxypropyl methylcellulose, benzalkonium chloride, boric acid and one or more pharmaceutically acceptable excipients, wherein the composition is free of polyethylene glycol.

9. An once a day ophthalmic composition comprising 0.7%w/v of olopatadine or pharmaceutically acceptable salts thereof, mannitol, cyclodextrin, hydroxypropyl methylcellulose, benzalkonium chloride, boric acid and one or more pharmaceutically acceptable excipients, wherein the composition is free of povidone.