sign in sign up
<<
Home , Nepafenac

US 2014.0024642A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0024642 A1 Vejarano Restrepo (43) Pub. Date: Jan. 23, 2014

(54) OPHTHALMIC FORMULATION AND A63/545 (2006.01) METHOD FOR AMELORATING A613 L/436 (2006.01) PRESBYOPA A6IP27/02 (2006.01) A613 L/4439 (2006.01) (76) Inventor: Luis Felipe Vejarano Restrepo, (52) U.S. Cl. Popayan (CO) USPC ...... 514/226.5: 514/397: 514/357: 514/343; 514,291 (21) Appl. No.: 13/553,615 (57) ABSTRACT (22) Filed: Jul.19, 2012 An ophthalmic formulation having an effective amount of a parasympathomimetic agent comprising pilocarpine, or a Publication Classification pharmaceutically acceptable salt thereof, and one or more C.1 adrenergic agonists or antagonists is disclosed. The oph (51) Int. Cl. thalmic formulation may enable treatment of conditions A6 IK3I/478 (2006.01) adversely affecting the visual acuity of a patient, including A6 IK3I/4402 (2006.01) presbyopia. A method of using the disclosed ophthalmic for A6IP27/10 (2006.01) mulation to treat or ameliorate symptoms of presbyopia is A6IP 29/00 (2006.01) also disclosed. US 2014/0024642 A1 Jan. 23, 2014

OPHTHALMC FORMULATION AND oxymetazoline, xilometazoline, tramaZoline, and a pharma METHOD FOR AMELORATING ceutically acceptable salt thereof. PRESBYOPA 0007. In some embodiments, a method of ameliorating, reducing or treating presbyopia comprises administering an BACKGROUND OF THE INVENTION effective amount of an ophthalmic formulation to an eye of a 0001 1. Field of the Invention patient. The ophthalmic formulation may include an effective 0002 This application relates to a pharmaceutical prepa amount of pilocarpine, or a pharmaceutically acceptable salt ration comprising a parasympathomimetic drug and an C.1 thereof, and one or more C1 adrenergic agonists or antago (alpha1) adrenergic agonist or antagonist for ameliorating, nists. The C.1 adrenergic agonist may comprise phenyleph reducing or treating presbyopia. rine, or a pharmaceutically acceptable salt thereof. 0003 2. Description of the Related Art DETAILED DESCRIPTION OF SOME 0004 Presbyopia is an age-related reduction in visual acu EMBODIMENTS ity due to a decline in near focusing ability, commonly asso ciated with blurred appearance of objects at nearby distances. 0008. The embodiments described in this application Symptoms of presbyopia often become noticeable by around relate to a pharmaceutical preparation comprising a parasym age 40 to around age 45. Presbyopia is typically associated pathomimetic drug and one or more C.1 (alpha1) adrenergic with the reduced accommodative ability of the eye. For agonists or antagonists. In some embodiment, the pharma example, flexibility or elasticity of the crystalline lens and ceutical preparation described herein is useful for ameliorat strength of the ciliary muscles often decrease with age. A ing, reducing and/or treating presbyopia or symptoms decrease in the flexibility or elasticity of the crystalline lens or thereof. The pharmaceutical preparation may reduce or elimi the strength of ciliary muscles can be associated with a nate the symptoms of presbyopia while maintaining the decrease in the ability of the eye in adjusting the curvature of accommodative function of the eyes, and allow patients Suf the crystalline lens to focus on objects at nearby distances, fering from presbyopia the ability to focus both far and near. including objects at around a normal reading distance. In some embodiments, the pharmaceutical preparation can 0005 Common treatments of presbyopia include use of improve near vision of a patient Suffering from presbyopia eyeglasses, such as reading glasses typically worn for near without affecting the distance vision. In some embodiments, distance vision, and bi-focals or multi-focals to provide both the pharmaceutical preparation may be formulated into an improved near and distance vision for patients who already ophthalmic formulation that can be applied to the eye of a use correction for distance vision. Corrective contact lenses patient Suffering from conditions relating to presbyopia. can also be used to treat presbyopia, including bi-focal, multi 0009. As used herein, the terms ameliorate, treat or treat focal or monovision contact lenses. Monovision contact ment refer to a reduction in the severity of symptoms of an eye lenses typically include a lens for distance vision in one eye, condition adversely affecting visual acuity. In some embodi for example a dominant eye, and a lens for near distance ments, an ophthalmic formulation as described herein is Suit vision in the other eye, for example a non-dominant eye. able for treating, or reducing the severity of the symptoms of Surgical options are also available for treating presbyopia, presbyopia. For example, an ophthalmic formulation as including corrective eye Surgery. For example, refractive eye described herein may be suitable for the treatment of pres Surgery generally involves reshaping of the cornea. Refrac byopia by enabling the patient to visually focus on objects at tive Surgery can allow reshaping of the cornea in one eye a nearby distance, including objects at around a normal read while leaving the other eye untreated, for example correcting ing distance. vision only in a non-dominant eye for improved near vision 0010. As used herein, the terms effective amount include while allowing the dominant eye to maintain distance vision. quantities of one or more active ingredients described herein Implantation of intraocular lenses (IOL) can be another Sur sufficient for the treatment of a condition of the eye adversely gical option in treating presbyopia, generally involving affecting visual acuity, including achieving temporary replacement of the natural lens with a synthetic one. How improvement in the symptoms of presbyopia. For example, ever, eyeglasses or corrective lenses may be cumbersome or effective amounts of an active ingredient when applied to one provide inadequate treatment, while Surgical correction can or both eyes of a patient may enable the patient to visually be invasive and are not without risks. Because these tech focus on objects at a nearby distance, including objects at a niques merely compensate for the loss of accommodation by distance around a normal reading distance. changing the way light enters the eye, patients would have to 0011. Some embodiments describe a pharmaceutical put on the glasses for near vision and remove the glasses for preparation comprising an effective amount of a parasym distance vision, or have only one eye corrected for near vision pathomimetic drug and one or more C.1 adrenergic agonist or while the other eye remains uncorrected in order to maintain antagonist. In some embodiments, the pharmaceutical prepa distance vision. Thus, a way to ameliorate or reduce the ration is an ophthalmic formulation. In some embodiments, symptoms of presbyopia while allowing accommodation is the ophthalmic formulation comprising an effective amount needed. of a parasympathomimetic drug and one or more C.1 adren ergic agonist orantagonist may further comprise one or more SUMMARY OF THE INVENTION of ingredients selected from the group consisting of a vaso 0006. In some embodiments, an ophthalmic formulation constricting agent, an anti-histamine agent, a non-steroid comprises an effective amount of pilocarpine, or a pharma anti-inflammatory drug, and an lubricant. ceutically acceptable salt thereof, and one or more C.1 adren 0012. In some embodiments, the parasympathomimetic ergic agonists orantagonists. The one or more C.1 adrenergic drug is pilocarpine or a pharmaceutically acceptable salt agonists or antagonists may be selected from a group consist thereof. Pilocarpine is a direct acting parasympathomimetic ing of phenylephrine, phenylpropanolamine, etylefrine, agent that acts on M. muscarinic receptor. It can cause the US 2014/0024642 A1 Jan. 23, 2014

ciliary muscle in the eye to contract and provide near focus. 0.004%, about 0.005%, about 0.006%, about 0.007%, about However, it may also cause contraction of the pupil or miosis. 0.008%, about 0.009%, about 0.010%, or about 0.012%, of 0013. In some embodiments, the one or more C1 adrener naphazoline, or a pharmaceutically acceptable salt thereof. gic agonists or antagonists may independently be selected 0018. In some embodiments, an ophthalmic formulation from phenylephrine, phenylpropanolamine, etylefrine, also optionally comprises one or more anti-histamine agents. oxymetazoline, xilometazoline, or tramaZoline, or a pharma A Suitable anti-histamine agent or drug may be independently ceutically acceptable salt thereof. In some embodiments, the selected from pheniramine, chlorpheniramine, dexchlorphe C1 adrenergic agonists or antagonists may be phenylephrine. niramine, dexbrompheniramine, deschlorpheniramine, Phenylephrine may dilate the pupil, and may reduce pupil triprolidine, brompheniramine, iodopheniramine, fluorphe contraction due to pilocarpine. In some embodiments, phe niramine, or a pharmaceutically acceptable salt thereof. In nylephrine may contribute to the normal movement of pupil Some embodiments, the anti-histamine agent is pheniramine, in any light situation, and/or reduces miosis. With proper or a pharmaceutically acceptable salt thereof. Pheniramine concentrations of pilocarpine and phenylephrine, Voluntary may serve to avoid conjunctival injection or congestion and accommodation of the eyes can be maintained or restored reduce red eye. It also has a minimal effect on the ciliary while the presbyopia symptoms are ameliorated or treated. muscle, and may improve accommodation. Pheniramine or a 0014. In some embodiments of the ophthalmic formula pharmaceutically acceptable salt thereof, may be present in tion, pilocarpine or a pharmaceutically acceptable salt an amount of from about 0.01% to about 0.20%, from about thereof, may be present in the amount of from about 0.1% to 0.05% to about 0.15%, from about 0.02% to about 0.10%, about 2.0%, from about 0.1% to about 1.9%, from about 0.2% from about 0.03% to about 0.09%, from about 0.04% to about to about 1.9%, including from about 0.3% to about 1.9%, 0.08%, from about 0.02% to about 0.20%, from about 0.04% from about 0.4% to about 1.9%, from about 0.2% to about to about 0.15%, from about 0.04% to about 0.15%, at about 1.8%, from about 0.3% to about 1.7%, from about 0.1% to 0.01%, about 0.02%, about 0.03%, about 0.04%, about about 1.8%, from about 0.1% to about 1.5%, from about 0.1% 0.05%, about 0.06%, about 0.07%, about 0.08%, about to about 1.3%, from about 0.1% to about 1.2% from about 0.09%, or about 0.10% by weight in the ophthalmic formu 0.1% to about 0.9%, from about 0.1% to about 0.7%, from lation. Alternatively, an ophthalmic formulation may not about 0.4% to about 1.6%, from about 0.5% to about 1.3%, or comprise an anti-histamine agent. at about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0019. In some embodiments, an ophthalmic formulation 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, by may further comprise a non-steroid anti-inflammatory drugs weight. (NSAID). The NSAID may reduce or eliminate anterior seg 0015. In some embodiments of the ophthalmic formula ment inflammation. In some embodiments, a suitable NSAID tion, the phenylephrine or a pharmaceutically acceptable salt is independently selected from the group consisting of thereof, may be present in the amount of from about 0.1% to nepafenac, , , , , about 7%, from about 0.1% to about 6%, from about 0.1% to , , , pranoprofen, about 5.5%, from about 0.1% to about 4.5%, from about 0.1% Surprofen, or indomethacin, and a pharmaceutically accept to about 3%, from about 0.2% to about 3.5%, from about able salt thereof. In some embodiments, an ophthalmic for 0.2% to about 4.5%, from about 0.2% to about 5.5%, from mulation comprises at least one of nepafenac or meloxicam. about 0.2% to about 6%, from about 0.3% to about 5%, from Alternatively, an ophthalmic formulation may not comprise a about 0.4% to about 4%, from about 0.5% to about 3%, from non-steroid anti-inflammatory drug. about 0.6% to about 3%, from about 0.6% to about 2.5%, 0020. In some embodiments, an ophthalmic formulation from about 0.7% to about 2.5%, from about 0.7% to about may beformulated to further comprise an effective amount of 2.0%, or about 0.5%, about 1%, about 1.5%, about 2%, about a NSAID nepafenac. For example, an ophthalmic formula 2.5%, about 3, about 3.5%, about 4%, about 5% by weight. tion formulated to comprise nepafenac may include by 0016. In some embodiments, an ophthalmic formulation weight from about 0.01% to about 0.10%, including from may further comprise a vasoconstricting agent. In some about 0.02% to about 0.09%, including from about 0.03% to embodiments, a Suitable vasoconstricting agent or drug com about 0.08%, including from about 0.04% to about 0.07%, prises naphazoline, or a pharmaceutically acceptable salt including from about 0.01% to about 0.09%, including from thereof. An ophthalmic formulation suitable for the treating a about 0.01% to about 0.08%, including from about 0.01% to condition of the eye adversely affecting the visual acuity of a about 0.07%, including from about 0.01% to about 0.06%, patient, for example presbyopia, may comprise effective including from about 0.01% to about 0.05%, including from amounts of one or more vasoconstricting agents. Alterna about 0.01% to about 0.04%, including from about 0.01% to tively, an ophthalmic formulation may not comprise ea vaso about 0.03%, including from about 0.02% to about 0.08%, constricting agent. including from about 0.02% to about 0.07%, including from 0017 For example, an ophthalmic formulation may about 0.02% to about 0.06%, including from about 0.02% to include by weight from about 0.001% to about 0.020%, about 0.05%, including about 0.02%, about 0.04%, about including from about 0.002% to about 0.018%, including 0.03%, about 0.04%, or about 0.05% of nepafenac, or a phar from about 0.004% to about 0.016%, including from about maceutically acceptable salt thereof. 0.006% to about 0.01%. 2, including from about 0.001% to 0021 Alternatively, the NSAID may be meloxicam. For about 0.015%, including from about 0.001% to about example, the ophthalmic formulation may include by weight 0.012%, including from about 0.001% to about 0.01.1%, from about 0.001% to about 0.015%, including from about including from about 0.001% to about 0.010%, including 0.001% to about 0.014%, including from about 0.001% to from about 0.001% to about 0.009%, including from about about 0.013, including from about 0.001% to about 0.014%, 0.001% to about 0.008%, including from about 0.002% to including from about 0.001% to about 0.014%, including about 0.008%, including from about 0.003% to about from about 0.001% to about 0.012%, including from about 0.009%, including about 0.002%, about 0.003%, about 0.01% to about 0.009%, including from about 0.001% to US 2014/0024642 A1 Jan. 23, 2014

about 0.008%, including from about 0.002% to about patient for improved visual acuity, including for the treatment 0.007%, including from about 0.002% to about 0.006%, of the symptoms of presbyopia. For example, application of including from about 0.003% to about 0.012%, including an ophthalmic formulation comprising an effective amount of from about 0.003% to about 0.01%, including from about a parasympathomimetic agent and an effective amount of an 0.003% to about 0.009%, including from about 0.004% to C1 adrenergic agonist or antagonist may ameliorate symp about 0.012%, including about 0.003%, about 0.004%, about toms of presbyopia while allowing Voluntary accommoda 0.005%, about 0.006%, about 0.007%, about 0.008%, about tion. 0.009%, about 0.010%, or about 0.011% of meloxicam, or a 0028. In some embodiments, an ophthalmic formulation pharmaceutically acceptable salt thereof. as described herein is applied to one or both eyes of a patient 0022. An ophthalmic formulation, as described herein, showing symptoms of presbyopia to improve the ability of the may also further comprise a lubricant or lubricating agent. In patient to focus on objects at a nearby distance, including Some embodiments, the lubricant or lubricating agent may objects at around a normal reading distance. In some embodi facilitate administration of the ophthalmic formulation. Suit ments, application of an ophthalmic formulation as described able lubricants can be independently selected from polyeth herein may sufficiently improve the near distance visual acu yleneglycol 400 or propyleneglycol. In some embodiments, ity of a patient independent of other methods of treatment. For the ophthalmic formulation comprises one or more Suitable example, administration of an ophthalmic formulation as lubricants or lubricating agents. Alternatively, an ophthalmic described herein may enable a patient to focus on objects at a formulation may not comprise a lubricant or lubricating distance around a normal reading distance without use of agent. corrective lenses or corrective eye Surgery. Administration of 0023. In some embodiments, where polyethyleneglycol the ophthalmic formulation may relieve symptoms for a 400 is selected as the lubricant for the ophthalmic formula patient in the early stages of presbyopia, including enabling tion, the ophthalmic formulation may comprise by weight of near distance visual acuity without use of corrective lenses or from about 0.01% to about 0.30%, including from about glasses. 0.02% to about 0.25%, 0.03% to about 0.20%, 0.04% to about 0029. In some embodiments, an ophthalmic formulation 0.15%, 0.05% to about 0.15%, 0.05% to about 0.10%, 0.10% as described herein is administered to a patient having Symp to about 0.30%, 0.10% to about 0.20%, 0.06% to about toms of presbyopia, in addition to symptoms from myopia or 0.20%, 0.05% to about 0.20%, including about 0.05%, about hyperopia to facilitate near distance visual acuity Such that the 0.10%, or about 0.15% of polyethyleneglycol 400 or a phar patient may not need to depend on the corrective treatment maceutically acceptable salt thereof. such as bifocals/multi-focals lenses or monovision contact 0024. In some embodiments, the lubricant may be propy lenses or to remove the glasses to read in myopes. leneglycol. For example, an ophthalmic formulation may include by weight of from about 0.01% to about 0.20%, 0030. In some embodiments, an ophthalmic formulation including from about 0.02% to about 0.10%, including from as described herein is administered to one or both eyes of a about 0.04% to about 0.09%, including from about 0.04% to patient to provide treatment for presbyopia as an alternative to about 0.08%, including from about 0.04% to about 0.06%, corrective eye Surgery. For example, an ophthalmic formula including from about 0.02% to about 0.10%, including from tion as described herein may be administered to a patient about 0.02% to about 0.12%, including from about 0.02% to having symptoms of presbyopia where the patient either pre about 0.14%, including from about 0.05% to about 0.20%, fers not to or cannot receive corrective eye Surgery to treat including from about 0.05% to about 0.15%, including about presbyopia. The ophthalmic formulation as described herein 0.01%, about 0.02%, about 0.03%, about 0.04%, about may also be administered to a myopic or hyperopic patient 0.05%, about 0.06%, about 0.07%, about 0.08%, about (with or without astigmatism) having symptoms of presbyo 0.09%, or about 0.10% of propyleneglycol or a pharmaceu pia, but prefers to receive treatment only for the far vision tically acceptable salt thereof. defect. Alternatively, an ophthalmic formulation as described herein may be administered to a patient who continues to have 0025. In some embodiments, the ophthalmic formulation symptoms of presbyopia after the patient has undergone cor comprises one or more components to facilitate application of rective eye Surgery for presbyopia. The ophthalmic formula the ophthalmic formulation. For example, the ophthalmic tion may be used in conjunction with corrective eye Surgery formulation may also optionally comprise a pharmaceutically for presbyopia to further reduce the symptoms of presbyopia. acceptable carrier, antibacterial agent, or a preservative. In In some embodiments, the ophthalmic formulation as Some embodiments, a pharmaceutically acceptable carrier described herein is applied to one or both eyes of a patient to comprises purified water. reduce a decline in near distance visual acuity after undergo 0026. Some embodiments described herein relate to a method of treating a condition of the eye adversely affecting ing a corrective eye Surgery for far vision at a younger age. near distance visual acuity of a patient, including ameliorat 0031. In some embodiments, administration of an oph ing symptoms of presbyopia. A method of treating the Symp thalmic formulation as described herein facilitates improve toms of presbyopia may include applying to one or both eyes ment in the symptoms of presbyopia for a patient who has of a patient an ophthalmic formulation as described herein. reversed a previously received corrective eye surgery for The ophthalmic formulation may be applied to the eye of a presbyopia. For example, administration of the ophthalmic patient as a liquid, a gel, a solution, a suspension, or any formulation may enable reestablishment of binocularity for a combination thereof. In some embodiments, the ophthalmic patient after a reversal or regression of a previously received formulation is administered to the eye via an ocular route, monovision laser Surgery for treating presbyopia. including topical application to the conjunctiva. 0032. In some embodiments, an ophthalmic formulation 0027. An ophthalmic formulation may comprise one or as described herein is administered to a patient to improve the more components, each component may be administered ability of the patient to focus on nearby objects after the sequentially or simultaneously to the one or both eyes of a patient has undergone corrective Surgery for treatment of US 2014/0024642 A1 Jan. 23, 2014

ocular conditions other than presbyopia, including for 6. The ophthalmic formulation of claim 1, wherein the example a corrective eye Surgery for the treatment of a cata pilocarpine is present in an amount of about 0.1% to about ract. 0.7% by weight. 0033. In some embodiments, an ophthalmic formulation 7. The ophthalmic formulation of claim 1, further com as described herein is used in conjunction with other treat prises a vasoconstricting agent. 8. The ophthalmic formulation of claim 7, the vasocon ments for eye conditions, including treatments for the Symp stricting agent is naphazoline or a pharmaceutically accept toms of presbyopia. For example, an ophthalmic formulation able salt thereof. as described herein may be administered to a patient in con 9. The ophthalmic formulation of claim 7, further com junction with use of mono-focal intraocular lenses, multi prises an anti-histamine. focal intraocular lenses, or accommodative intraocular lenses 10. The ophthalmic formulation of claim 9, wherein the to improve the near focusing ability of the patient. anti-histamine is selected from the group consisting of phe 0034. In some embodiments, application of an ophthalmic niramine, chlorpheniramine, dexchlorpheniramine, dexbro formulation as described herein is suitable for reducing the mpheniramine, deschlorpheniramine, triprolidine, bromphe symptoms of ocular hypertension. The ophthalmic formula niramine, iodopheniramine, fluorpheniramine, and a tion may be administered to an eye of a patient to improve pharmaceutically acceptable salt thereof. symptoms of ocular hypertension through a reduction in 11. The ophthalmic formulation of claim 9, wherein the intraocular pressure. anti-histamine is pheniramine or a pharmaceutically accept 0035 Although this invention has been disclosed in the able salt thereof. context of certain embodiments and examples, it will be 12. The ophthalmic formulation of claim 11, wherein the understood by those skilled in the art that the invention pheniramine is present in an amount of about 0.03% to about extends beyond the specifically disclosed embodiments to 0.09% by weight. other alternative embodiments and/or uses of the invention 13. The ophthalmic formulation of claim 7, further com and obvious modifications and equivalents thereof. In addi prises an non-steroidal anti-inflammatory drug. tion, while several variations of the embodiments of the 14. The ophthalmic formulation of claim 13, wherein the invention have been shown and described in detail, other non-steroidal anti-inflammatory drug is selected from the modifications, which are within the scope of this invention, group consisting of nepafenac, meloxicam, diclofenac, will be readily apparent to those of skill in the art based upon bendazac, ketorolac, oxyphenbutaZone, bromfenac, flurbi this disclosure. It is also contemplated that various combina profen, pranoprofen, Surprofen, indomethacin, and a pharma tions or sub-combinations of the specific features and aspects ceutically acceptable salt thereof. of the embodiments may be made and still fall within the 15. The ophthalmic formulation of claim 13, wherein the scope of the invention. It should be understood that various non-steroidal anti-inflammatory drug is selected from the features and aspects of the disclosed embodiments can be group consisting of nepafenac and meloxicam. combined with, or substituted for, one another in order to 16. A method of ameliorating, reducing or treating pres form varying modes of the embodiments of the disclosed byopia comprising administering an effective amount of an invention. Thus, it is intended that the scope of the invention ophthalmic formulation of claim 1 to an eye of a patient. herein disclosed should not be limited by the particular 17. The method of claim 16, wherein the C1 adrenergic embodiments described above. agonist is phenylephrine or a pharmaceutically acceptable salt thereof. What is claimed is: 18. The method of claim 17, wherein the phenylephrine is 1. An ophthalmic formulation comprising an effective present in an amount of about 0.5% to about 3% by weight amount of pilocarpine or a pharmaceutically acceptable salt and the pilocarpine is present in an amount of about 0.1% to thereof, and one or more C1 adrenergic agonists or antago about 0.7% by weight. nists. 19. The method of claim 17, wherein the ophthalmic for 2. The ophthalmic formulation of claim 1, wherein the one mulation further comprises an anti-histamine selected from or more C.1 adrenergic agonists or antagonists is selected the group consisting of pheniramine, chlorpheniramine, dex from the group consisting of phenylephrine, phenylpropano chlorpheniramine, dexbrompheniramine, deschlorphe lamine, etylefrine, oxymetazoline, xilometazoline, tramaZo niramine, triprolidine, brompheniramine, iodopheniramine, line, and a pharmaceutically acceptable salt thereof fluorpheniramine, and a pharmaceutically acceptable salt 3. The ophthalmic formulation of claim 1, wherein one C.1 thereof. adrenergic agonist is present and the C.1 adrenergic agonist is 20. The method of claim 19, wherein the ophthalmic for phenylephrine or a pharmaceutically acceptable salt thereof. mulation further comprises a non-steroidal anti-inflamma 4. The ophthalmic formulation of claim 3, wherein the tory drug selected from the group consisting of nepafenac, phenylephrine is present in an amount of about 0.5% to about meloxicam, diclofenac, bendazac, ketorolac, oxyphenbuta 3% by weight. Zone, bromfenac, flurbiprofen, pranoprofen, Surprofen, 5. The ophthalmic formulation of claim 3, wherein the indomethacin, and a pharmaceutically acceptable salt phenylephrine is present in an amount of about 0.7% to about thereof. 2.2% by weight.