AU2015252082B2 - Povidone iodine, a novel alternative preservative for ophthalmic compositions - Google Patents

Abstract

The invention includes a preserved ophthalmic preparation comprising povidone iodine (PVP-J) at a concentration sufficient to preserve the ophthalmic preparation, and at least 5 one member selected from the group consisting of a steroidal anti-inflammatory compound, a non-steroidal anti-inflammatory compound, an antibacterial compound, an anti-allergy compound, and an anti-glaucoma compound. The invention also includes adding PVP-J to an ophthalmic composition in order to preserve the composition, wherein the PVP-J is added at a concentration sufficient to preserve the composition.

Description

2015252082 04 Nov 2015 10 15 20 25

Povidone Iodine. Λ Novel Alterative Preservative For Opiltlialiilic Compositions CR^S-REFERENCE TO RELATED ,APPLICATION.؟

This application is a divisional of Australian Applieation No. 200925814? filed on 10 June 2009, die contents of wilieh arc to be taken as incorporated herein by reference. Australian Ajnplication No. 2009258145 elainns priority to U.S. Provisional Pittenl Application No. 61/129.222, filed on June 12. 2008, and to as. Provisional Patent Application No. 61/201.854. filed oil December 15, 2008. both ol'which are also incorporated by reference herein in their entirety.

BACKGROUND

Preservatives are cuirently an integral part o؛' oplithalniic preparations. Suilalnle antimicrobial preservatives are typically added to prevent multi-dose package contannination. Sucln agents may include benzalkonium chloride, thimerosal. cliloiobutainol. methyl paraben. propyl paraben. phenylethyl alcohol. EDTA. sorbic acid. Onanner M. other agents disclosed to tlnose skilletl in tlie art. or a combination thereof. Benzalkonium chloride (also referred to as BAK or BACl is the most common preservative used in ophtlialnnic preparations. Typically, sucln preservatives arc employed at a level of 1'ronn 0.1)111% to 1.0% by wciglnt. However, recent evidence liiglilight the potential corneal and conjunctival toxicity of BAK. wilieh lead to serious medical issues such as ocular nicdicamcntosa. decreased success of glaucotnna surgery, or reduced coinnpliance with ocular medications.

The discussion of doermnents. acts, materials, devices, articles and tine like is included in this specification solely for tine purpose of providing a context for the present invention. It is not suggested or represented tlnat any or all of these nnatlcrs fornned part of tine prior art hase or were coinnnnon general knowledge in tine fieltl relevant to tine present invention as it existed before tine priority date of each clainn of tlnis application.

Wlnere tine ternns “comprise", "comprises'', “connprised" or “comprising” are used in tlnis specification (including the elainns.) llney are t،n be interpreted as specifying line presence of tine slated features, integers, steps or components, but not precluding tine presence of one. Ol. innorc other features, integers, steps or connponents, or gioup thereof.

M BRIEF SUMMARY OF THE INVENTION 2015252082 20Jul

The invention includes a preserved ophthalmic preparation comprising povidone-iodine (PVP-1) at a concentration sufficient to preserve the ophthalmic preparation, and at least 5 one member selected from the group consisting ofa steroidal anti-inllammatory conrpound, a non-steroidal anti-inflammatory compound, an antibacterial compound, an anti-allergy compound, and an anti-glaucoma compound.

In one aspect, the present invention provides an ophthalmic composition suitable for topical administration to the eye, comprising a mixture of a. povidone-iodine (PVP-1) at a 10 concentration between about 0.01% and about 10%, and b. a steroid, wherein the steroid is dexamethasone, wherein the pH of the composition is in the range of 3 to 4.

In an embodiment, PVP-1 is present at a concentration selected from the group consisting of O.Ol./o to 10%, 0.1% to 2.5%, 0.2 to 1.5%, 0.3% to 1.0%. In another embodiment, PVP-1 is present at a concentration of0.5%. la I521/<؛PCT/US200 واة1?ا/را٠اأ2 vvo 2015252082 04 Nov 2015

In an embodiment, the P٧P-I concentration is measured on a weight/weight basis with respect to the overall preparation. In another embodiment, the PVP-1 concentration is measured on a weight/volume basis with respect to the overall preparation.

In an embodiment, a preparation includes an anti-inflammatory compound 5 selected from the group consisting ofketotifen ftrmarate, diclofenac sodium, nepafenac, bromfenac, flurbiprofen sodium, suprofen, celecoxib, naproxen, rofecoxib, and any combination thereof.

In an embodiment, a preparation includes an antiinflammatory «impound selected from the group consisting of dexamethasone, dexamethasone alcohol, 10 dexametliasone sodium phosphate, fluromethalone acetate, fluromethalone alcohol, lotoprendol etabonate, medrysane, prednisolone acetate, prednisolone sodium phosphate, difluprednate, rimexolone, hydrocortisone, hydrocortisone acetate, lodoxamide tromethamine, and any combination thereof.

In an embodiment, a preparation farther includes an antimicrobial preservative 15 selected from the ^oup consisting of benzalkonium chloride, thimerosal, chlorobutanol, methjvl paraben, propyl paraben, phenylcthyl alcohol, EDTA, sorbic acid, Onamer M and any combination therwf.

In an embodiment, a preparation farther includes a viscosity increasing agent. In an embodiment, a viscosity increasing agent is selected from the group consisting of 20 polyvinyl alcohol, pol۴inylp۴olidone, methyl cellulose, hydroxypropylmethylcellulose, bydroxyethylcellulose, carboximiethylcellulose, hydroxypropylcellulose, and any combination thereof.

In an embodiment, a preparation farther com includes prises at least one artificial tears-based lubricant. 25 The invention also includes a method of presejwing an ophthalmic preparation, the method comprising adding to an ophthalmic preparation PVP-1 in an amount sufficient to preserve the ophthalmic preparation. In an embodiment, the method includes adding PVP-1 to exist at a concentration selected from the group consisting ofo.01% to 10%, 0.1% to 2.5%, 0.2 to 1.5%, and 0.3% to 1.0%. In an embodiment, PVP-1 is present at a 30 concentration of 0.5%. ا2وواا٠ا/رأا٠ا2$(ا/1')اا ر٠ا6ا?ا/را٠أا2 ١١0 2015252082 04 Nov 2015

DETAILED DESCRIPTION

As used herein, the term “about" means plus or minus 10% of a referenced value, inclusive ofthe value.

Ranges set forth herein are intended to include every value between the two referenced endpoints, inclusive ofthe endpoint values.

Herein, it is now shown tliat povidone iodine can seive as a preseivative for variety of phamiaceutical compositions. In an aspect ofthe invention, povidone iodine is shown to be a preservative for ophthalmic preparations. Therefore, in an embodiment, the invention provides a preserved ophthalmic imposition comprising a povidone iodine composition.

In an embodiment, povidone iodine fimetions as at least a preservative for variety of pharmaceutical impositions. In an embodiment, povidone iodine is a preservative in an ophthalmic composition. The concentration of povidone-iodine as a preservative in ophthalmic compositions can range from 0.01% - 10% (weight/weight or weight/volume), and alt concentrations in between. In an embodiment, the povidone-iodine concentration is bertveen 0.1% and 2.5%, in another embodiment, between 0.2 and 1.5%, and in yet another embodiment, between 0.3% and 1.0%. In an embodiment, the povidone-iodine concentration is about 0.5%.

In an aspect ofthe invention, povidone iodine provides an antimicrobial property to an oplrthalmic preparation. In another aspect, povidone iodine provides an ophthalmic preparation with one or more non-antimicrobial preservative properties (e.g., antioxidant).

In an embodiment, the invention also provides povidone-iodine compositions comprising one or more components in addition to the povidone-iodine component, as set forth herein.

In an aspect, the invention provides a broad spectrum of povidone-iodine ophthalmic compositions, for example, comprising povidone iodine as a preservative to be used in cases of ocular conjunctival or corneal infection caused by mycobacteria, vimses, fongi, and amoeba. In another aspect, compositions ofthe invention are usefiil in the infectious prophylaxis of patients recovering from recent ophthalmic surgery, among ofoer ophthalmic procedures.

In various embodiments, povidone-iodine ophthalmic compositions according to the invention include, but are not limited to the following: 1. Artificial-tears preparations comprising povidone iodine as a preservative. Artificial-tear based constihrents include, but are not limited to, ophthalmically- 3 acceptable lubricants, propylene glycol, glycerin, polyethylene glycol, dextran. blended polyvinyl alcoliols. polyvinyl alcohol, polyethylene glycol, light mineral oil. hydroxypropyl methylcellulose. hypromellose. carbopol. carbotner 940 (polyacrylic acid), polyvinyl pyrrolidone. wliitc petrolatum, soy lecitliin. and sodium carboxyl metliylcclliilosc, as well as otlier agents tlisclosed to those skilled in the art. or any combination thereof. Typically, such constituents are employed at a level of from 0.1% to 2% by weight. In an embodiment, the constituents are 1.0% Propylene glycol. 0.3% glycerin. 2.7% blended polyvinyl alcohols. 1% Polyvinyl Alcolrol, 1% Polyethylene Glycol, light mineral oil, 0.3% hydroxypropyl methylcellulose. 1.0% Soy lecitliin. 0.25% or 0.5% sodium cai'boxyl imethylcellulosc. In anotlicj- embotliment. tlie total weiglil of tlie p٧p-l. artificial-tcar based constituents is lielwccn 0.1 % and 4.5% of tlie totitl weiglit ol' tlie composition. 2015252082 04 Nov 2015 2. Anti-inllanimaiory and steroid preparations coniprising povidone iodine preservative. Ntin-limiting examples ol' suitable, anti-inflammatories ineltide: kettitifen Umaralc. diclofenac sotlium. ncpilfe.nac. bromfenac. flurbiprofen sotlitim. suprofen. cclecoxib. naproxen or rofecoxib. Νοη-limiting examples of suitable steroids include: Dexametliasone alcoliol. dexamethasone sodium pliospliate. fluromelhalone acetate, flurometlialtme alcoliol. loloprcndol etabonate. medrysone. prednisolone acetate, prednisolone sodium pliosphate. difluprednate, rimcxolone. hydrocortisone. hydiOcortisone acetate, lodoxamide tromctliamine. Tlie anti-inflammatory and steroid constituent's arc typically used at a concentration of 0.01% to 2.0% by weight of tlie total composition. In an aspect, about 0.1% dexamethasone is used in a preserved ophthalmic preparation. 3. BAK-1'ree ophthalmic compositions to treat glauconia comprising povidone iodine as a preservative. Non-limiting examples of suitable glaucoma medicines include: Beta Blockers (levobunolol. timolol hemihydratc. betaxolol hydrochloride, timolol maleatc, and related salts thereof)؛ prostaglandin analogs (for example bimatoprost. travoprost, Latanoprost); Alplia Agonists (brimonidine. Iopidine, apraclonidine)؛ Carbonic Anhydrase Inhibitors (brinzolamidc. dorzolamide). Sucli constituents are used at concentrations typically usetl in tire art. 4. Antibiotic/Antiniicrobialophthalmics comprising povidone iodine as a preservative. Non-linriting examples of suitable include fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin, nroxifloxacin, gatifloxacin, etc...)؛ Aminoglycosides (tobramycin, gentamicin, neomycin, etc...); Polymyxin B Combinations (polymyxin B/trimetlioprim, Polysporin polymyxin B/bacitracin Neosporin polymyxin B/ncomycin/ gramicidin, etc.) and 4

Ollier antibiotics (azithromycin, ilolycin. erythromycin, bacitracin, etc...). Typically, sucli antiliiotic anti antimicrobial constituents are employed at a level of from 0.001% to 1.0% by weiglit of time total composition. 2015252082 04Νο٧2015 5. Anti-Allergic preparations comprising povidone iodine as a preservative. Non-limiting examples of suitable components include cpinasline. emedastin'c 'difumarate azelasline hydrochloride, olopatadine hydrochloride, olopaladine. ketotifen fumarate, pemiiolast potassitmi. ncdocroniil. lodoxaniide. cromolyn anti cromolyn salts. Such constituents are used at concentralitmns typically used in the art. 6. Multiple preservative ophthahmmic prcparalioims comprising povidone i^^ preservative. Non-limiting examples of suitable components inclutle atm antimicrobial preservative. Iim itn enmbodiment. itim antimicrobial preservative is selected from time group consistiimg of benzafkonium chloride, tlminmerosal. chlorobutanol. immetlmyl paraben. propyl paraben. plmcnyletlmyl alcohol. EDTA, sorbic acid. Onaimmei- M and coimmbinatioims thereol'. Such constituents are used at concentrations typically used iim the art.

Additionally, non-limiting exaimmples of suitable excipients for povidone-iodine compositions of the itmvetmliotm itmcludc co-solvenlsAurfactants. viscosity-altering agctmls. and/or bioadlmesive agents. Sucli constituents are used at concentrations typically used iim the art.

Iim aim asjmect. time compositions of time invention immay optionally include a co-solvent or surfactant. In an enmbotliimmcnt. a co-solvent may be time satmme or dill'ercimt than a surfactant. In an cimmbodimcimt, time solubility of time coimmponenls of the compositions nmay be enhanced by inclusion of a surfactant or appropriimte co-solvent in the composition. Such CO-solvents/surfactants include, but are not linmited to. polysorbate-20. -60, atmd -80, polyoxyethylene /polyoxypropylene surfactants (c.g. Pluronic F-68. F-84 and Ρ-105), cyclodcxtrin. lyloxapol, PEG 55 Castci" oil (Creimmoplmor EL), polyoxyl 40 Stearate (Myrj 52). as well as ollmct- agents disclosed to those skilled in the art. or any conmbination tlmercof. Typically, such co-solvents are employed at tm level of front 0.01% to 2% by weight.

Iim anollmcr aspect, time cotmmposilions of time iimvetmlioim may optionitlly comprise an optional viscosity-increasing or viscosity-decreasing itgemmt. Viscosity increased above tlmat of sinmple aqueous solutioims nmay be desirable to increase ocular absorptiomm of the active coimmpoutmd. to decrease vaiiability in dispensing time forimmulation. to decrease plmysical separatioim of coimmponcnts ،if a suspension or enmulsion of the formnulatioim and/or to otherwise itmtprove the ophthalmic forimmulation. Such viscosity-cnlmaimcing agents include, but are not limited to, polyvinyl alcohol. polyvinylpyrrolidone. methyl cellulose. 5 hydioxypropylmelhylccllulose, Inydroxycthylcellulosc. carboxymethylcellulosc. 2015252082 04 Nov 2015 liydroxypropylceJlulose, olhcj. agents disclosed to those skilled ill the art. and/or any combination tliercof. Such agents are typically eniployetl at' a level of from 0.01% to 2% by wciglmt.

In another aspect, bioadhcsivc agents may conmpris'c llic compositions, in order to increase the retention lime of the diug gradient over a biological substrate. The bioadlmesive agents include, but ai'e not limited to: polyvinylpyrrolidone (PVP). xanthan gum. locust bean gum. acacia gum, hydroxypropyl methylcellulosc (HPMC). sodiunm alginate, pectin, gelatin, carbomer. polyvinylalcohol, gellan gum. tragaeanlh. acacia, and sodium carboxynietlmyl cellulose, as well as other agents disclose،, to tliose skilled in the art. or any combination thereof.

Furthermore, time compositions can lie combined witlm 111؛ effective amount of a chemical agent ttm piovide a cooling sensation to relieve mild ocular irritation, enlnance oc.ula.1. comfort, provitle a refreshing effect, and ؛improved sensation, wlien the povidone-iodine solutitnn is applied to tine eyes. Sucln an ؛igent encompasses varitnus chemicals and chemical classes, including, but not limited to. cooling agents sucln as mcnnthol. nncnthol derivatives including methonc glycerin acetyl atid meintliyl esters, carboxamides, nnentlianc glycet'ol ketals, alkyl substituted ureas, sulfonamitlcs. tenpenc analogs, furanoncs. and pliosphinc oxides; or cannplnor. and borncol.

The povidonc-iodine-connprising composition may be in the form of a solution, a suspension, an emulsion, an ointnnent. a cream, a gel. or a controlled-release/sustain-release vehicle. For example, the composition nnay be in the form of a contact lens solution, eyewash, eyedrop, and tine like.

In any of the compositions o 1. this disclosure foj- topical administration, such as tojnical administration to tine eye. tine mixtures can be formulated as aqueous solutions at a pH in the range of 3.5 to 6.5. It will be understootl that a range listed herein is intended to enneonnpass the upper and lower bounds of the range, inclusively. In inn ennbodiment. the pH is in tine range of 4 to 5. Tlnis pH range may be achieved by the addition of acids/bases to the solution. In another ennbodinnent. the pH is in the range of 3 to 7.

Tine invention also provides nnethods of using a povidone-iodine-comprising composition. In an ennbodinnent. tine dose volume administered to a sulnject nnay be between about 1(.1 microliters and about 200 nnicroliters. in anotlncr cinnbodifnnent. between ١؛ PCT/IS2009/.HI352ا

9ل6ل?ا/٠9)ا2٠ VVO 2015252082 04 .Nov 2015 about 20 microliters and about 00 ل microliters, and in another embodiment, between about 50 microliters and about 80 microliters, and in another embodiment, about one drop per eye. In an aspect, one drop may be between about 50 and about 80 microliters.

In an embodiment, administration frequency may be anywhere in the range of 1 to 100 times a day. In another embodiment, adminisfration frequency may be between 2 and 24 times a day. In another embodiment, administration frequency may be between 2 and 4 times a day. While the precise regimen can be identified by the skilled artisan, the composition may be topically applied by placing one drop in each eye about 1 to about 24 times daily. For example, the solution may be applied 1,2,3, 4, 5, 6, 7, 8, 9, 10,11,12, 13, 14,15, 16, 17, 18, 19, 20, 21,22, 23, 24, 48, or 96 times a day.

EXAMPLES

The invention is now described with reference to the following Examples. These Examples are provided for the putyose of illustration only and the invention should in no way be constnred as being limited to these Examples, but rather should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.

Example 1: Antimicrobial Preservative Effectiveness Tests of PVP-1 preserved artificial tears A composition including at least one artificial tear constituent according to the invention, fiirther comprising PVP-1, may be used as a preservative. The preservative properties of a composition of the invention, such as an ophthalmic preparation comprising PVP-1, can be tested, for example, using USP <51>, or by any method known in the art to determine the effectiveness of an antimiCTobial preservative. PVP-1 solutions having concenfrations of about 0.36% by weight are prepared as set forth herein. By way of a non-limiting example, a PVP-1 containing solution is prepared using about 0.36% PVP-1, by weight, as desired in the final product, and combining the PVP-1 with 0.01% edentate disodium, 1.2% sodium sulfate, 0.25% hydroxyethylcellulose, 0.5% tyloxapol, 0.35% sodium chloride to adjust osmolality within 300-350 mOsm/kg, sodium hydroxide and/or sulfirric acid to adjust the pH to about 4.0, and enough purified water to bring the total volume up to 100% total. 7 PCT/IJS2009/003521 ل٠ا516ا/9ا٠اا2 ١١0 2015252082 04 Nov 2015

The test solutions are challenged with known numbers of standard laboratory strains selected. At periodic integrals: 0, 7, 14, and 28 days, samples are removed and assayed to detennine survival.

Example 2: Antimicrobial Preservative Effectiveness Tests of ΡΥΡ-Ι preserved 0.1% dexamethasone suspension

The preservative properties of a composition of the invention, such as an ophthalmic preparation comprising PVP-Ι, can be tested, for example, using USP <51>, or by any method known in the art to deteiminc the effectiveness of an antimicrobial preservative. PVP-1 solutions having concentrations of about 0.18% and about 0.36% by weight are prepared as set forth herein. By way of a non-limiting example, a PVP-1 containing solution is prepared using 0.18%, or 0.36% PVP-Ι, by weight, as desired in the final product, and combining the PVP-Ι with 0.1% dexamethasone, 0.01% edentate disodium, 1.2% sodium sulfate, 0.25% hydroxyethylcellulose, 0.5% tyloxapol, 0.35٠/α sodium chloride to adjust osmolality within 300-350 mOsm/kg, sodium hydroxide and/or sulfirric acid to adjust the pH to 4,0, and enough purified water to bring the total volume up to 100% total. The test solutions are challenged with known numbers of standard laboratory strains selected. At periodic intervals: 0, 7, 14, and 28 days, samples are removed and assayed to determine survival.

Example 3: Antimicrobial Activity of Preserved PVP-Ι Solutions

By way of a non-limiting example, PVP-Ι solutions having concentrations of about 0.36% by weight are prepared as set forth herein. By way of a non-limiting example, a PVP-Ι containing solution is prepared using 0.36% PVP-Ι, by weight, as desired in the final product, and combining the PVP-Ι with 0.1% dexamethasone, 0.01% edentate disodium, 1.2% sodium sulfete, 0.25% hydroxyethylcellulose, 0.5./. tyloxapol, 0.35% sodium chloride to adjust osmolalitjv within 300-350 mOsm/kg, sodium hjvdroxide and/or sulfilric acid to adjust the pH to 4.0, and enough purified water to bring the total volume up to 100% total. These solutions are then tested for in-vitro microbiological activity. Microbiological activity can be tested for antimicrobial activity against, for example, bacteria found in the mouth (P. gingivalis), or against other bacteria. In another example, killing time tests are conducted with a series of log phase culmres of gram negative and gram positive organisms including Gentamicin resistant Pseudomonas aeruoinosa, methicilin-resistant staph aureus, E, coll, chlamydia trachoma ةج١حة\حة ةااًه PCT/IIS2009/00352ا

ؤا6ا?ا/ذ٠ا٠ا2 VVO 2015252082 04 Nov 2015 viruses. ControJs used may include ophthalmic preparations of commercially available antimicrobial products. Bacterial samples are taken at 30 seconds, 1, 2, 5, 10 and 15 minutes and transfemed into culture media containing inactivators for iodine. Similarly, virus killing time tests are sampled at one minute and transferred into inactivating media. The results obtained with the experimental samples are compared with the control samples to assess the level of antimicrobial activity of a composition of the invention.

Example 4: Preparation of ΡΥΡ-Ι preserved 0.3% tobramycin and 0.1% dexamethasone suspension ΒΑΚ-frce Tobradcx® ophthalmic suspension preserved with PVPI concentration ranging from about 0.36% to about 0.6% by weight is prepared as set forth herein. By way of a non-limiting example, a composition is prepared using 0.36%, 0.48%, or 0.6% P٧P-I, by weight, as desired in the final product, and combining witli 0.3% tobramycin, 0.1% dexamethasone, 0.01% edentate disodium, 1.2% sodium sulfate, 0.25% hydroxyethylcellulose, 0.5% tyloxapol, 0.35% sodium chloride to adjust osmolality within 300-350 mOsm/kg, sodium hydroxide and/or sulforic acid to adjust the pH to about 4.0, and enough purified water to bring the total volume up to 100% total.

Example 5: Preparation of p٧p-l preserved 0.3% tobramycin solution ΒΑΚ-free tobramycin ophthalmic solution preserved with PVP-Ι in a concentration range of about 0.36% to about 0.6% by weight is prepared as set forth herein. By way of a non-limiting example, an composition is prepared using 0.36%, 0.48%, or 0.6% PVP-Ι, by weight, as desired in the final product, and combining with 0.3% tobramycin, boric acid, sodium sulfote, sodium chloride, tyloxapol, sodium hydroxide and/or sulfilric acid (to adjust pH) and purified water.

Example 6: Preparation of PVP-1 preserved 0.5% moxifloxacin hydrochloride ophthalmic solution ΒΑΚ-free moxifloxacin hydrochloride ophthalmic solution preserved with P٧P-I in a concentration range of about 0.36% to about 0.6% by weight is prepared as set forth herein. By way of a non-limiting example, a composition is prepared using 0.36%, 0.48%, or 0.6% PVP-Ι, by weight, as desired in the final product, and combining with 0.5% moxifloxacin hydrochloride, boric acid, sodium chloride, and purified water. In an 9 PCT/US2009/.J03521 VVO 2009/9ل6ل5ا 2015252082 04 Nov 2015 embodiment, a preserved ophthalmic solution comprises hydrochloric acid and/or sodium hydroxide to adjust pH.

Example 7: Preparation of PVP-1 preserved 1.0% prednisolone acetate suspension 5 ΒΑΚ-free prednisolone acetate suspension preserved with PVP-1 in a concentration range of about 0.36% to about 0.6% by weight is prepared as set forth herein. By way of a non-limiting example, a composition is prepared using 0.36%, 0.48%, or 0.6% PVP-1, by weight, as desired in the final product, and combining with 1.0% prednisolone acetate, boric acid, edetate disodium, hypromellose, polysorbate 80, 10 sodium bisulfite, sodium citrate, sodium ctiloride, and purified water.

The invention has been described herein by reference to certain embodiments. However, as variations thereof will become apparent to those skilled in the art, when armed with the disclosure set fortli herein, the invention is not to be considered as limited 15 thereto. All patents, patent applications, and references cited herein are hereby incorporated by reference in their entirety. 10

Claims (17)

1. The claims defining the invention are as follows:

   1. An ophthalmic composition suitable for topical administration to the eye, comprising a mixture of: a. povidone-iodine (PVP-I) at a concentration between about 0.01% and about 10%, and b. a steroid, wherein the steroid is dexamethasone, and wherein the pH of the composition is in the range of 3 to 4.
2. 2. The ophthalmic composition of claim 1, wherein the PVP-I is present at a concentration selected from the group consisting of 0.1% to 2.5%, 0.2 to 1.5%, and 0.3% to 1.0%.
3. 3. The ophthalmic composition of claim 1, wherein the PVP-I is present at a concentration of 0.5%.
4. 4. The ophthalmic composition of claim 2, wherein the PVP-I concentration is measured on a weight/weight basis with respect to the overall composition.
5. 5. The ophthalmic composition of claim 2, wherein the PVP-I concentration is measured on a weight/volume basis with respect to the overall composition.
6. 6. The ophthalmic composition of any one of claims 1 to 5, wherein said composition further comprises an antimicrobial preservative selected from the group consisting of benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, EDTA, sorbic acid, and any combination thereof.
7. 7. The ophthalmic composition of any one of claims 1 to 6, wherein said composition further comprises a viscosity increasing agent.
8. 8. The ophthalmic composition of claim 7, wherein said viscosity increasing agent is selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, hydroxypropylcellulose, and any combination thereof.
9. 9. The ophthalmic composition of any one of claims 1 to 8, wherein the composition comprises at least one artificial tears-based lubricant.
10. 10. The ophthalmic composition of claim 1, wherein the PVP-I is present at a concentration of 0.6%.
11. 11. The ophthalmic composition of any one of claims 1 to 10, wherein said steroid is present at a concentration between 0.01 and 2%.
12. 12. The ophthalmic composition of any one of claims 1 to 11, wherein said steroid is present at a concentration of 0.1%.
13. 13. The ophthalmic composition of any one of claims 1 to 12, wherein said composition further comprises a co-solvent/surfactant.
14. 14. The ophthalmic composition of claim 13, wherein said co-solvent/surfactant is selected from the group consisting of polysorbate 20, polysorbate 60, polysorbate 80, polyoxyethylene /polyoxypropylene surfactants, cyclodextrin, tyloxapol and a combination thereof.
15. 15. The ophthalmic composition of claim 13 or claim 14, wherein said co-solvent/surfactant is at a concentration of about 0.01% to 2% by weight in said composition.
16. 16. The ophthalmic composition of claim 1, comprising: 0.6% (w/w) polyvinylpyrrolidinone-iodine complex; 0.1% (w/w) steroid; 0.01% (w/w) EDTA; 0.35% (w/w) sodium chloride; 0.01 to 2% (w/w) tyloxapol; 1.2% (w/w) sodium sulfate; and 0.25% (w/w) hydroxyethylcellulose.
17. 17. The ophthalmic composition of any one of claims 1 to 16, wherein said pH is pH 4.