Ophthalmic composition containing D2O

Abstract

The present invention provides a stabilized ophthalmic composition containing an atropine preparation that does not require preservatives. [Solution] An ophthalmic composition is provided, comprising approximately 0.001 wt% to approximately 0.5 wt% of atropine or a pharmaceutically acceptable salt of atropine, deuterated water, and water, wherein the pH is approximately 4.2 to approximately 7.9, and the ratio of water to deuterated water is in the range of 10:90 to 99:1.

Description

[Technical Field]

[0001] cross reference This application claims the benefits under U.S. Provisional Patent Application No. 63 / 080,617 filed September 18, 2020, and U.S. Provisional Patent Application No. 62 / 948,761 filed December 16, 2019, which are cited by reference to the entirety of the respective applications. [Background technology]

[0002] Pharmaceutical preparations have an expiration date based on the breakdown of their active ingredients. [Overview of the Initiative]

[0003] This specification provides ophthalmic compositions having a pH of about 4.2 to 7.9, comprising about 0.001 wt% to about 0.5 wt% of a muscarinic antagonist and deuterated water, which are substantially free of benzalkonium chloride preservatives. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions are substantially free of preservatives selected from cetrimonium, sodium perborate, stabilized oxychloro complexes, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions do not contain detectable amounts of benzalkonium chloride preservatives. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions do not contain detectable amounts of benzalkonium chloride. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions do not contain detectable amounts of preservatives. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine. In some embodiments of the ophthalmic compositions described herein, the pH of the ophthalmic composition after long-term storage under storage conditions is one of less than about 7.3, less than about 7.2, less than about 7.1, less than about 7, less than about 6.8, less than about 6.5, less than about 6.4, less than about 6.3, less than about 6.2, less than about 6.1, less than about 6, less than about 5.9, less than about 5.8, less than about 5.2, less than about 4.8, or less than about 4.5. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition contains, based on the initial concentration after long-term storage under storage conditions, at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99% of one muscarinic antagonist.In some embodiments of the ophthalmic compositions described herein, the potency of the ophthalmic composition after long-term storage under storage conditions is one of at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99%. In some embodiments of the ophthalmic compositions described herein, long-term storage is one of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 10 months, about 12 months, about 18 months, about 24 months, about 36 months, about 4 years, or about 5 years. In some embodiments of the ophthalmic compositions described herein, the storage temperature under storage conditions is about 0°C to about 30°C, 2°C to about 10°C, or about 16°C to about 26°C. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in amounts of approximately 0.001 wt% to approximately 0.40 wt%, approximately 0.001 wt% to approximately 0.30 wt%, approximately 0.001 wt% to approximately 0.20 wt%, approximately 0.001 wt% to approximately 0.10 wt%, approximately 0.001 wt% to approximately 0.09 wt%, approximately 0.001 wt% to approximately 0.08 wt%, approximately 0.001 wt% to approximately 0.07 wt%, and approximately 0.001 wt% to approximately 0 The muscarinic antagonist is present in the ophthalmic composition at one of the following concentrations: 0.06 wt%, approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of approximately 0.001 wt% to approximately 0.10 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises 0.004 wt% to about 0.20 wt% citrate. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises a molar osmotic pressure modifier. In some embodiments of the ophthalmic compositions described herein, the molar osmotic pressure modifier is sodium chloride.In some embodiments of the ophthalmic compositions described herein, sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises a buffering agent. In some embodiments of the ophthalmic compositions described herein, the buffering agent is selected from boroates, boroates-polyol complexes, phosphate buffering agents, citrate buffering agents, acetate buffering agents, carbonate buffering agents, organic buffering agents, amino acid buffering agents, or combinations thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is substantially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition has a dose-to-dose muscarinic antagonist concentration variation of one of the following: less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, or less than 5%. In some embodiments of the ophthalmic compositions described herein, the dose-to-dose muscarinic antagonist concentration variation is based on one of 10 consecutive doses, 8 consecutive doses, 5 consecutive doses, 3 consecutive doses, or 2 consecutive doses. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises a pH adjuster. In some embodiments of the ophthalmic compositions described herein, the pH adjuster comprises DCl, HCl, NaOH, NaOD, CD3COOD, C6D8O7, CH3COOH, C6H8O7, or a combination thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition comprises one of less than 5% water (H2O), less than 4% H2O, less than 3% H2O, less than 2% H2O, less than 1% H2O, less than 0.5% H2O, less than 0.1% H2O, or 0% H2O. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is not formulated as an injectable formulation.In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions are formulated as ophthalmic solutions for treating premyopia, myopia, the progression of myopia, or slowing the progression of myopia.

[0004] This specification provides ophthalmic compositions with a pH of about 4.2 to 7.9, comprising about 0.001 wt% to about 0.5 wt% of a muscarinic antagonist, deuterated water, and one or more sodium phosphate buffers. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine. In some embodiments of the ophthalmic compositions described herein, the first sodium phosphate buffer of the one or more sodium phosphate buffers is anhydrous monosodium phosphate. In some embodiments of the ophthalmic compositions described herein, anhydrous monosodium phosphate is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%. In some embodiments of the ophthalmic compositions described herein, the second sodium phosphate buffer of one or more sodium phosphate buffers is anhydrous disodium phosphate. In some embodiments of the ophthalmic compositions described herein, anhydrous disodium phosphate is present in the ophthalmic composition at a concentration of about 0.050 wt% to about 2.0 wt%. In some embodiments of the ophthalmic compositions described herein, the pH of the ophthalmic composition after long-term storage under storage conditions is one of less than about 7.3, less than about 7.2, less than about 7.1, less than about 7, less than about 6.8, less than about 6.5, less than about 6.4, less than about 6.3, less than about 6.2, less than about 6.1, less than about 6, less than about 5.9, less than about 5.8, less than about 5.2, less than about 4.8, or less than about 4.5. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition contains, based on the initial concentration after long-term storage under storage conditions, at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99% of one muscarinic antagonist.In some embodiments of the ophthalmic compositions described herein, the potency of the ophthalmic composition after long-term storage under storage conditions is one of at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99%. In some embodiments of the ophthalmic compositions described herein, long-term storage is one of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 10 months, about 12 months, about 18 months, about 24 months, about 36 months, about 4 years, or about 5 years. In some embodiments of the ophthalmic compositions described herein, the storage temperature under storage conditions is about 0°C to about 30°C, 2°C to about 10°C, or about 16°C to about 26°C. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in amounts of approximately 0.001 wt% to approximately 0.40 wt%, approximately 0.001 wt% to approximately 0.30 wt%, approximately 0.001 wt% to approximately 0.20 wt%, approximately 0.001 wt% to approximately 0.10 wt%, approximately 0.001 wt% to approximately 0.09 wt%, approximately 0.001 wt% to approximately 0.08 wt%, approximately 0.001 wt% to approximately 0.07 wt%, and approximately 0.001 wt% to approximately 0 The muscarinic antagonist is present in the ophthalmic composition at one of the following concentrations: 0.06 wt%, approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of approximately 0.001 wt% to approximately 0.10 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions are substantially free of citrate and acetate buffering agents. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions further include a molar osmotic pressure modifier. In some embodiments of the ophthalmic compositions described herein, the molar osmotic pressure modifier is sodium chloride.In some embodiments of the ophthalmic compositions described herein, sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition does not contain preservatives selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is substantially free of benzalkonium chloride preservatives. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions are substantially free of any preservatives. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions further include a buffering agent. In some embodiments of the ophthalmic compositions described herein, the buffering agent is selected from boroates, boroates-polyol complexes, phosphate buffering agents, citrate buffering agents, acetate buffering agents, carbonate buffering agents, organic buffering agents, amino acid buffering agents, or combinations thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions further include EDTA. In some embodiments of the ophthalmic compositions described herein, EDTA is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.50 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions are substantially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions have inter-dosage muscarinic antagonist concentration variation of one of the following: less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, or less than 5%. In some embodiments of the ophthalmic compositions described herein, the inter-dosage muscarinic antagonist concentration variation is based on one of 10 consecutive doses, 8 consecutive doses, 5 consecutive doses, 3 consecutive doses, or 2 consecutive doses.In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises a pH adjuster. In some embodiments of the ophthalmic compositions described herein, the pH adjuster comprises DCl, HCl, NaOH, NaOD, CD3COOD, C6D8O7, CH3COOH, C6H8O7, or a combination thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition comprises one of less than 5% water (H2O), less than 4% H2O, less than 3% H2O, less than 2% H2O, less than 1% H2O, less than 0.5% H2O, less than 0.1% H2O, or 0% H2O. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is not formulated as an injectable formulation. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is formulated as an ophthalmic solution for treating premyopia, myopia, myopia progression, or slowing myopia progression.

[0005] This specification provides ophthalmic compositions with a pH of about 4.2 to 7.9, comprising about 0.001 wt% to about 0.5 wt% of a muscarinic antagonist, deuterated water, and about 0.01 wt% to about 0.50 wt% of EDTA. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises one or more sodium phosphate buffers. In some embodiments of the ophthalmic compositions described herein, the first sodium phosphate buffer of one or more sodium phosphate buffers is anhydrous monosodium phosphate. In some embodiments of the ophthalmic compositions described herein, anhydrous monosodium phosphate is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%. In some embodiments of the ophthalmic compositions described herein, the second sodium phosphate buffer of one or more sodium phosphate buffers is anhydrous disodium phosphate. In some embodiments of the ophthalmic compositions described herein, anhydrous disodium phosphate is present in the ophthalmic composition at a concentration of about 0.050 wt% to about 2.0 wt%. In some embodiments of the ophthalmic compositions described herein, the pH of the ophthalmic composition after long-term storage under storage conditions is one of the following: less than about 7.3, less than about 7.2, less than about 7.1, less than about 7, less than about 6.8, less than about 6.5, less than about 6.4, less than about 6.3, less than about 6.2, less than about 6.1, less than about 6, less than about 5.9, less than about 5.8, less than about 5.2, less than about 4.8, or less than about 4.5. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition contains at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99% of a muscarinic antagonist, based on the initial concentration after long-term storage under storage conditions.In some embodiments of the ophthalmic compositions described herein, the potency of the ophthalmic composition after long-term storage under storage conditions is one of at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99%. In some embodiments of the ophthalmic compositions described herein, long-term storage is one of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 10 months, about 12 months, about 18 months, about 24 months, about 36 months, about 4 years, or about 5 years. In some embodiments of the ophthalmic compositions described herein, the storage temperature under storage conditions is about 0°C to about 30°C, 2°C to about 10°C, or about 16°C to about 26°C. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in amounts of approximately 0.001 wt% to approximately 0.40 wt%, approximately 0.001 wt% to approximately 0.30 wt%, approximately 0.001 wt% to approximately 0.20 wt%, approximately 0.001 wt% to approximately 0.10 wt%, approximately 0.001 wt% to approximately 0.09 wt%, approximately 0.001 wt% to approximately 0.08 wt%, approximately 0.001 wt% to approximately 0.07 wt%, and approximately 0.001 wt% to approximately 0 The muscarinic antagonist is present in the ophthalmic composition at one of the following concentrations: 0.06 wt%, approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of approximately 0.001 wt% to approximately 0.10 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises 0.004 wt% to about 0.20 wt% citrate. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises a molar osmotic pressure modifier. In some embodiments of the ophthalmic compositions described herein, the molar osmotic pressure modifier is sodium chloride.In some embodiments of the ophthalmic compositions described herein, sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition does not contain preservatives selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is substantially free of benzalkonium chloride preservatives. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions are substantially free of any preservatives. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions further include a buffering agent. In some embodiments of the ophthalmic compositions described herein, the buffering agent is selected from boroates, boroates-polyol complexes, phosphate buffering agents, citrate buffering agents, acetate buffering agents, carbonate buffering agents, organic buffering agents, amino acid buffering agents, or combinations thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions are substantially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions have an inter-administration muscarinic antagonist concentration variation of one of less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, or less than 5%. In some embodiments of the ophthalmic compositions described herein, inter-dosing muscarinic antagonist concentration variability is based on one of 10 consecutive doses, 8 consecutive doses, 5 consecutive doses, 3 consecutive doses, or 2 consecutive doses. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises a pH adjuster.In some embodiments of the ophthalmic compositions described herein, the pH adjuster includes DCl, HCl, NaOH, NaOD, CD3COOD, C6D8O7, CH3COOH, C6H8O7, or a combination thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition includes one of less than 5% water (H2O), less than 4% H2O, less than 3% H2O, less than 2% H2O, less than 1% H2O, less than 0.5% H2O, less than 0.1% H2O, or 0% H2O. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is not formulated as an injectable formulation. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is formulated as an ophthalmic solution for treating premyopia, myopia, myopia progression, or slowing myopia progression.

[0006] This specification provides ophthalmic compositions having a pH of about 4.2 to about 7.9, comprising about 0.001 wt% to about 0.5 wt% of a muscarinic antagonist, deuterated water, and water, wherein the ratio of water to deuterated water is in the range of about 99:1 to about 1:99. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine. In some embodiments of the ophthalmic compositions described herein, the pH of the ophthalmic composition after long-term storage under storage conditions is one of the following: less than about 7.3, less than about 7.2, less than about 7.1, less than about 7, less than about 6.8, less than about 6.5, less than about 6.4, less than about 6.3, less than about 6.2, less than about 6.1, less than about 6, less than about 5.9, less than about 5.8, less than about 5.2, less than about 4.8, or less than about 4.5. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition contains at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99% of a muscarinic antagonist, based on the initial concentration after long-term storage under storage conditions. In some embodiments of the ophthalmic compositions described herein, the potency of the ophthalmic composition after long-term storage under storage conditions is one of at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99%. In some embodiments of the ophthalmic compositions described herein, long-term storage is one of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 10 months, about 12 months, about 18 months, about 24 months, about 36 months, about 4 years, or about 5 years.In some embodiments of the ophthalmic compositions described herein, the storage conditions include a storage temperature of about 0°C to about 30°C, 2°C to about 10°C, or about 16°C to about 26°C. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in concentrations of about 0.001 wt% to about 0.40 wt%, about 0.001 wt% to about 0.30 wt%, about 0.001 wt% to about 0.20 wt%, about 0.001 wt% to about 0.10 wt%, about 0.001 wt% to about 0.09 wt%, about 0.001 wt% to about 0.08 wt%, about 0.001 wt% to about 0.07 wt%, and about 0.001 wt% to about 0. The muscarinic antagonist is present in the ophthalmic composition at one of the following concentrations: 0.06 wt%, approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of approximately 0.001 wt% to approximately 0.10 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises 0.004 wt% to about 0.20 wt% citrate. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises one or more sodium phosphate buffers. In some embodiments of the ophthalmic compositions described herein, the first sodium phosphate buffer of the one or more sodium phosphate buffers is anhydrous monosodium phosphate. In some embodiments of the ophthalmic compositions described herein, anhydrous monosodium phosphate is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%. In some embodiments of the ophthalmic compositions described herein, the second sodium phosphate of the one or more sodium phosphate buffers is anhydrous disodium phosphate. In some embodiments of the ophthalmic compositions described herein, anhydrous disodium phosphate is present in the ophthalmic composition at a concentration of about 0.050 wt% to about 2.0 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises a molar osmotic concentration modifier.In some embodiments of the ophthalmic compositions described herein, the molar osmotic pressure modifier is sodium chloride. In some embodiments of the ophthalmic compositions described herein, sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition does not contain preservatives selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is substantially free of the benzalkonium chloride preservative. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions are substantially free of any preservatives. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions further include a buffering agent. In some embodiments of the ophthalmic compositions described herein, the buffering agent is selected from boroates, boroates-polyol complexes, phosphate buffering agents, citrate buffering agents, acetate buffering agents, carbonate buffering agents, organic buffering agents, amino acid buffering agents, or combinations thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions further include EDTA. In some embodiments of the ophthalmic compositions described herein, EDTA is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.50 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions are substantially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition has an inter-administration muscarinic antagonist concentration variation of one of the following: less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, or less than 5%.In some embodiments of the ophthalmic compositions described herein, inter-dosing muscarinic antagonist concentration variation is based on one of 10 consecutive doses, 8 consecutive doses, 5 consecutive doses, 3 consecutive doses, or 2 consecutive doses. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition further comprises a pH adjuster. In some embodiments of the ophthalmic compositions described herein, the pH adjuster comprises DCl, HCl, NaOH, NaOD, CD3COOD, C6D8O7, CH3COOH, C6H8O7, or a combination thereof. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is not formulated as an injectable formulation. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is formulated as an ophthalmic solution for treating premyopia, myopia, myopia progression, or slowing myopia progression. In some embodiments of the ophthalmic compositions described herein, the ratio of water to deuterated water is in the range of about 95:5 to about 5:95, about 90:10 to about 10:90, about 80:20 to about 20:80, about 80:20 to about 30:70, about 80:30 to about 40:60, about 90:10 to about 50:50, or about 80:20 to about 60:40. In some embodiments of the ophthalmic compositions described herein, the ratio of water to deuterated water is about 50:50. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.03 wt%. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.05 wt%. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 wt%. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.03 wt%. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition is substantially free of benzalkonium chloride preservatives. In some embodiments of the ophthalmic compositions described herein, the ophthalmic composition does not contain any detectable amount of benzalkonium chloride preservative.In some embodiments of the ophthalmic compositions described herein, the ophthalmic compositions do not contain any detectable amount of preservatives. In some embodiments of the ophthalmic compositions described herein, the pH of the ophthalmic compositions is about 5.1 to about 6.0. In some embodiments of the ophthalmic compositions described herein, the pH of the ophthalmic compositions is about 5.54 to about 5.59.

[0007] This specification provides ophthalmic compositions having a pH of about 4.2 to 7.9, comprising about 0.001 wt% to about 0.5 wt% of a muscarinic antagonist and deuterated water, which are substantially free of benzalkonium chloride preservatives. In some embodiments, the ophthalmic compositions are substantially free of preservatives selected from cetrimonium, sodium perborate, stabilized oxychloro complexes, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof. In some embodiments, the ophthalmic compositions do not contain detectable amounts of benzalkonium chloride preservatives. In some embodiments, the ophthalmic compositions do not contain detectable amounts of benzalkonium chloride. In some embodiments, the ophthalmic compositions do not contain detectable amounts of preservatives. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or combinations thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine. In some embodiments, the muscarinic antagonist is present in amounts of approximately 0.001 wt% to 0.40 wt%, approximately 0.001 wt% to 0.30 wt%, approximately 0.001 wt% to 0.20 wt%, approximately 0.001 wt% to 0.10 wt%, approximately 0.001 wt% to 0.09 wt%, approximately 0.001 wt% to 0.08 wt%, approximately 0.001 wt% to 0.07 wt%, approximately 0.001 wt% to 0.06 wt%, The muscarinic antagonist is present in the ophthalmic composition at one of the following concentrations: approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%. In some embodiments, the muscarinic antagonist is present in the ophthalmic composition at a concentration of approximately 0.001 wt% to approximately 0.10 wt%.In some embodiments, the ophthalmic composition further comprises 0.004 wt% to about 0.20 wt% of citrate. In some embodiments, the ophthalmic composition further comprises a molar osmotic pressure modifier. In some embodiments, the molar osmotic pressure modifier is sodium chloride. In some embodiments, sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%. In some embodiments, the ophthalmic composition further comprises a buffering agent. In some embodiments, the buffering agent is selected from boroate, boroate-polyol complex, phosphate buffering agent, citrate buffering agent, acetate buffering agent, carbonate buffering agent, organic buffering agent, amino acid buffering agent, or a combination thereof. In some embodiments, the ophthalmic composition is essentially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some embodiments, the ophthalmic composition further comprises a pH adjuster. In some embodiments, the pH adjuster comprises DCl, HCl, NaOH, NaOD, CD3COOD, C6D8O7, CH3COOH, C6H8O7, or a combination thereof. In some embodiments, the ophthalmic composition contains less than 10% of muscarinic antagonist degradation products resulting from the degradation of muscarinic antagonists.

[0008] This specification provides ophthalmic compositions having a pH of about 4.2 to about 7.9, comprising about 0.001 wt% to about 0.5 wt% of a muscarinic antagonist, deuterated water, and one or more sodium phosphate buffers, wherein at least one of the sodium phosphate buffers is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine. In some embodiments, the first sodium phosphate buffer of the one or more sodium phosphate buffers is anhydrous monosodium phosphate. In some embodiments, anhydrous monosodium phosphate is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%. In some embodiments, the second sodium phosphate buffer of one or more sodium phosphate buffers is anhydrous disodium phosphate. In some embodiments, anhydrous disodium phosphate is present in the ophthalmic composition at a concentration of about 0.050 wt% to about 2.0 wt%. In some embodiments, the muscarinic antagonist is present in amounts of approximately 0.001 wt% to 0.40 wt%, approximately 0.001 wt% to 0.30 wt%, approximately 0.001 wt% to 0.20 wt%, approximately 0.001 wt% to 0.10 wt%, approximately 0.001 wt% to 0.09 wt%, approximately 0.001 wt% to 0.08 wt%, approximately 0.001 wt% to 0.07 wt%, approximately 0.001 wt% to 0.06 wt%, It is present in ophthalmic compositions at one of the following concentrations: approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%.In some embodiments, a muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.001 wt% to about 0.10 wt%. In some embodiments, the ophthalmic composition is essentially free of citrate and acetate buffering agents. In some embodiments, the ophthalmic composition further comprises a molar osmotic concentration modifier. In some embodiments, the molar osmotic concentration modifier is sodium chloride. In some embodiments, sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%. In some embodiments, the ophthalmic composition does not contain preservatives selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complexes, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof. In some embodiments, the ophthalmic composition is substantially free of benzalkonium chloride preservatives. In some embodiments, the ophthalmic composition is substantially free of any preservatives. In some embodiments, the ophthalmic composition further comprises a buffering agent. In some embodiments, the buffering agent is selected from boroates, boroate-polyol complexes, phosphate buffering agents, citrate buffering agents, acetate buffering agents, carbonate buffering agents, organic buffering agents, amino acid buffering agents, or combinations thereof. In some embodiments, the ophthalmic composition further comprises EDTA. In some embodiments, EDTA is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.50 wt%. In some embodiments, the ophthalmic composition is essentially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some embodiments, the ophthalmic composition further comprises a pH adjuster. In some embodiments, the pH adjuster comprises DCl, HCl, NaOH, NaOD, CD3COOD, C6D8O7, CH3COOH, C6H8O7, or a combination thereof.

[0009] This specification provides ophthalmic compositions having a pH of about 4.2 to 7.9, comprising about 0.001 wt% to about 0.5 wt% of a muscarinic antagonist, deuterated water, and about 0.01 wt% to about 0.50 wt% of EDTA. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine. In some embodiments, the ophthalmic composition further comprises one or more sodium phosphate buffers. In some embodiments, the first sodium phosphate buffer of the one or more sodium phosphate buffers is anhydrous monosodium phosphate. In some embodiments, anhydrous sodium phosphate is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%. In some embodiments, the second sodium phosphate buffer of one or more sodium phosphate buffers is anhydrous disodium phosphate. In some embodiments, anhydrous disodium phosphate is present in the ophthalmic composition at a concentration of about 0.050 wt% to about 2.0 wt%. In some embodiments, the muscarinic antagonist is present in amounts of approximately 0.001 wt% to 0.40 wt%, approximately 0.001 wt% to 0.30 wt%, approximately 0.001 wt% to 0.20 wt%, approximately 0.001 wt% to 0.10 wt%, approximately 0.001 wt% to 0.09 wt%, approximately 0.001 wt% to 0.08 wt%, approximately 0.001 wt% to 0.07 wt%, approximately 0.001 wt% to 0.06 wt%, The muscarinic antagonist is present in the ophthalmic composition at one of the following concentrations: approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%. In some embodiments, the muscarinic antagonist is present in the ophthalmic composition at a concentration of approximately 0.001 wt% to approximately 0.10 wt%.In some embodiments, the ophthalmic composition further comprises 0.004 wt% to about 0.20 wt% of citrate. In some embodiments, the ophthalmic composition further comprises a molar osmotic pressure modifier. In some embodiments, the molar osmotic pressure modifier is sodium chloride. In some embodiments, sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%. In some embodiments, the ophthalmic composition does not contain a preservative selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or a combination thereof. In some embodiments, the ophthalmic composition is substantially free of the benzalkonium chloride preservative. In some embodiments, the ophthalmic composition is substantially free of any preservatives. In some embodiments, the ophthalmic composition further comprises a buffering agent. In some embodiments, the buffering agent is selected from boroates, boroates-polyol complexes, phosphate buffering agents, citrate buffering agents, acetate buffering agents, carbonate buffering agents, organic buffering agents, amino acid buffering agents, or combinations thereof. In some embodiments, the ophthalmic composition is essentially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some embodiments, the ophthalmic composition further comprises a pH adjuster. In some embodiments, the pH adjuster includes DCl, HCl, NaOH, NaOD, CD3COOD, C6D8O7, CH3COOH, C6H8O7, or combinations thereof.

[0010] This specification provides ophthalmic compositions having a pH of about 4.2 to about 7.9, comprising about 0.001 wt% to about 0.5 wt% of a muscarinic antagonist, deuterated water, and water, wherein the ratio of water to deuterated water is in the range of 60:40 to about 99:1. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or combinations thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine. In some embodiments, the muscarinic antagonist is present in amounts of approximately 0.001 wt% to 0.40 wt%, approximately 0.001 wt% to 0.30 wt%, approximately 0.001 wt% to 0.20 wt%, approximately 0.001 wt% to 0.10 wt%, approximately 0.001 wt% to 0.09 wt%, approximately 0.001 wt% to 0.08 wt%, approximately 0.001 wt% to 0.07 wt%, approximately 0.001 wt% to 0.06 wt%, The muscarinic antagonist is present in the ophthalmic composition at one of the following concentrations: approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%. In some embodiments, the muscarinic antagonist is present in the ophthalmic composition at a concentration of approximately 0.001 wt% to approximately 0.10 wt%. In some embodiments, the ratio of water to deuterated water is in the range of approximately 80:20 to approximately 60:40. In some embodiments, the ratio of water to deuterated water is about 65:35. In some embodiments, the ratio of water to deuterated water is about 90:10. In some embodiments, the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.05 wt%. In some embodiments, the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.03 wt%. In some embodiments, the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 wt%.In some embodiments, a muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.03 wt%. In some embodiments, the ophthalmic composition is substantially free of benzalkonium chloride preservative. In some embodiments, the ophthalmic composition does not contain a detectable amount of benzalkonium chloride preservative. In some embodiments, the ophthalmic composition does not contain a detectable amount of preservative. In some embodiments, the pH of the ophthalmic composition is about 5.1 to about 6.0. In some embodiments, the pH of the ophthalmic composition is about 5.54 to about 5.59. In some embodiments, the ophthalmic composition further comprises 0.004 wt% to about 0.20 wt% citrate. In some embodiments, the ophthalmic composition further comprises one or more sodium phosphate buffers. In some embodiments, the first sodium phosphate buffer of the one or more sodium phosphate buffers is anhydrous monosodium phosphate. In some embodiments, anhydrous monosodium phosphate is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%. In some embodiments, the second sodium phosphate buffer of one or more sodium phosphate buffers is anhydrous disodium phosphate. In some embodiments, anhydrous disodium phosphate is present in the ophthalmic composition at a concentration of about 0.050 wt% to about 2.0 wt%. In some embodiments, the ophthalmic composition further comprises a molar osmotic concentration modifier. In some embodiments, the molar osmotic concentration modifier is sodium chloride. In some embodiments, sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%. In some embodiments, the ophthalmic composition does not contain preservatives selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof. In some embodiments, the ophthalmic composition is substantially free of the benzalkonium chloride preservative. In some embodiments, the ophthalmic composition is substantially free of any preservatives.In some embodiments, the ophthalmic composition further comprises a buffering agent. In some embodiments, the buffering agent is selected from boroates, boroates-polyol complexes, phosphate buffering agents, citrate buffering agents, acetate buffering agents, carbonate buffering agents, organic buffering agents, amino acid buffering agents, or combinations thereof. In some embodiments, the ophthalmic composition further comprises EDTA. In some embodiments, EDTA is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.50 wt%. In some embodiments, the ophthalmic composition is essentially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some embodiments, the ophthalmic composition further comprises a pH adjuster. In some embodiments, the pH adjuster comprises DCl, HCl, NaOH, NaOD, CD3COOD, C6D8O7, CH3COOH, C6H8O7, or combinations thereof. In some embodiments, the ophthalmic composition contains less than 10% of muscarinic antagonist degradation products resulting from the breakdown of muscarinic antagonists.

[0011] This specification provides ophthalmic compositions that are formulated as ophthalmic solutions for treating premyopia, myopia, the progression of myopia, or slowing the progression of myopia. [Brief explanation of the drawing]

[0012] Novel features of the invention disclosed herein are described in particular in conjunction with the appended claims. The features and advantages of the invention will be better understood by referring to the following detailed description, which specifies exemplary embodiments in which the principles of the invention are utilized, and to the accompanying drawings. [Figure 1] This figure shows the plot of the primary velocity. [Figure 2] This figure shows the monthly tropic acid formation rate in ophthalmic compositions at 25°C (black bar) or 40°C (white bar). [Figure 3] This figure shows the ratio of tropic acid formation rate constants at 25°C and 40°C, and the relationship between the ratio of deuterated water to water (v / v) in the ophthalmic composition. [Figure 4] A diagram showing the experimentally determined relationship between tropic acid formation and pH of an ophthalmic composition according to an embodiment. [Figure 5] A diagram showing the experimentally determined relationship between the rate of tropic acid formation and the ratio (v / v) of water to deuterated water in an ophthalmic composition according to an embodiment. [Figure 6] A diagram showing the relationship between the grasped pH and the ratio (v / v) of water to deuterated water in an ophthalmic composition according to an embodiment. [Figure 7] A diagram showing the relationship between the rate constant (k / mol) of tropic acid formation at 25 °C and the ratio (v / v) of water to deuterated water in an ophthalmic composition according to an embodiment. [Figure 8] A diagram showing the experimentally determined rate constant of tropic acid formation (k / mol) of an ophthalmic composition according to an embodiment. [Figure 9] A diagram showing the effects of pH and temperature on the tropic acid formation rate (100% D2O).

Embodiments for Carrying Out the Invention

[0013] The present disclosure recognizes the need for a stabilized ophthalmic composition with a long shelf life during storage. The present disclosure also recognizes the need to stabilize an ophthalmic composition by preventing or reducing at least partial hydrolysis of the active agent of the ophthalmic composition. The present disclosure further recognizes the need for an ophthalmic composition that provides convenient and effective delivery of a muscarinic antagonist such as atropine to a patient's eye.

[0014] Furthermore, the present disclosure recognizes the need for a stabilized ophthalmic composition that does not require a preservative. The present disclosure recognizes the need for an ophthalmic composition that is substantially free of preservatives.

[0015] This disclosure recognizes that muscarinic antagonists (e.g., atropine or a pharmaceutically acceptable salt thereof) prevent or inhibit the development of myopia in humans, as demonstrated, for example, by the reduced rate of myopia progression in young people. This disclosure also recognizes the effects of muscarinic antagonists (e.g., atropine or a pharmaceutically acceptable salt thereof) on axial length elongation and myopia reduction in visually impaired chick eyes, and on eye growth and muscarinic cholinergic receptors in young rhesus monkeys.

[0016] In addition, this disclosure acknowledges that undesirable side effects may occur due to the absorption of muscarinic antagonists (e.g., atropine) into the body, and that such systemic exposure may be reduced or prevented by topical delivery of muscarinic antagonists (e.g., atropine or a pharmaceutically acceptable salt thereof).

[0017] Furthermore, this disclosure recognizes that some liquid muscarinic antagonists (e.g., atropine) are formulated in a relatively low pH range (e.g., below 4.5) for the stability of the muscarinic antagonist (e.g., atropine or a pharmaceutically acceptable salt thereof). In some cases, lower pH ranges may cause discomfort or other side effects, such as eye irritation or burning, in some individuals, which can be prevented or mitigated by formulating the muscarinic antagonist (e.g., atropine) composition in a higher pH range. In some cases, lower pH may induce a tear response in some individuals, reducing efficacy by decreasing drug absorption in the eye.

[0018] Furthermore, this disclosure recognizes that some muscarinic antagonist (e.g., atropine) liquid compositions formulated at lower concentrations (e.g., 0.001% to 0.50%) present stability issues that are less frequently observed at higher concentrations. While we do not wish to be bound by any particular theory, some muscarinic antagonists (e.g., atropine) contribute to the stability of ophthalmic compositions, such as aqueous solutions. For example, in some embodiments, the concentration of a muscarinic antagonist (e.g., atropine) affects the pH of an ophthalmic composition, including the muscarinic antagonist acting as a buffering agent. Furthermore, in some embodiments, the concentration of a muscarinic antagonist (e.g., atropine) affects the interaction between the muscarinic antagonist and other components of the ophthalmic composition, thereby affecting the stability of the ophthalmic composition.

[0019] Finally, this disclosure recognizes that deuterated water stabilizes ophthalmic compositions. In some cases, deuterated water is weaker acidic than H2O, and therefore contains low concentrations of reactive species (e.g., -OD) that, in some examples, cause base-catalyzed hydrolysis of the active agent in the ophthalmic composition. Thus, in some examples, compositions containing deuterated water undergo lower base-catalyzed hydrolysis compared to compositions containing H2O. In some examples, deuterated water reduces the tear reflex in the eye by further decreasing the buffering capacity of the ophthalmic composition.

[0020] Myopia, or elongation of the eyeball, affects the majority of people. Myopia typically develops during elementary school age and progresses until eye growth is complete. This disclosure recognizes the importance of compositions and treatments for preventing or inhibiting the progression of myopia, specifically compositions and treatments that allow for convenient administration, reduce possible side effects, have adequate stability, and / or provide relatively consistent therapeutic effects.

[0021] Ophthalmic composition This specification provides ophthalmic compositions containing low concentrations of ophthalmic agents. In some embodiments, the ophthalmic composition comprises about 0.001 wt% to about 0.50 wt% or about 0.001 wt% to about 0.10 wt% of an ophthalmic agent for the treatment of an ophthalmic disorder or disease, and a pharmaceutically acceptable carrier, wherein the ophthalmic agent is substantially uniformly distributed throughout the pharmaceutically acceptable carrier. In some examples, the ophthalmic agent is a muscarinic antagonist.

[0022] This specification provides ophthalmic compositions containing low concentrations of muscarinic antagonists. In some embodiments, the ophthalmic composition comprises about 0.001 wt% to about 0.50 wt% or about 0.001 wt% to about 0.10 wt% of a muscarinic antagonist for the treatment of an ophthalmic disorder or disease, and a pharmaceutically acceptable carrier, wherein the muscarinic antagonist is substantially uniformly distributed throughout the pharmaceutically acceptable carrier.

[0023] In some examples, muscarinic antagonists include atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, methylatropine nitrate, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, tropicamide, cyclopentolate, pirenzepine, homatropin, solifenacin, dalifenacin, benzatropin, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, or combinations thereof. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or combinations thereof. In some embodiments, the muscarinic antagonist is atropine, or a pharmaceutically acceptable salt or prodrug thereof. In some embodiments, the muscarinic antagonist is atropine sulfate.

[0024] In some embodiments, the ophthalmic composition comprises a muscarinic antagonist selected from atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, methylatropine nitrate, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, tropicamide, cyclopentolate, pirenzepine, homatropin, solifenacin, dalifenacin, benzatropin, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, or a combination thereof. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, or homatropin. In some embodiments, the muscarinic antagonist is atropine, or a pharmaceutically acceptable salt or prodrug thereof.

[0025] In some embodiments, the ophthalmic composition comprises two or more muscarinic antagonists, the two or more muscarinic antagonists include atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, methylatropine nitrate, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, tropicamide, cyclopentolate, pirenzepine, homatropin, solifenacin, dalifenacin, benzatropin, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, or a combination thereof. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or any combination thereof. In some embodiments, the muscarinic antagonist is atropine, or a pharmaceutically acceptable salt or prodrug thereof.

[0026] In some embodiments, the ophthalmic composition comprises one or more muscarinic antagonists in combination with one or more sympathetic agonists. In some embodiments, the sympathetic agonists are selected from phenylephrine or hydroxyamphetamine. In some embodiments, the ophthalmic composition comprises one or more of the following as muscarinic antagonists: atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, methylatropine nitrate, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, tropicamide, cyclopentolate, pirenzepine, homatropin, solifenacin, dalifenacin, benzatropin, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, or tolterodine, in combination with one or more of the following as sympathetic agonists: phenylephrine or hydroxyamphetamine.

[0027] In other aspects of this disclosure, ophthalmic compositions comprising one or more ophthalmic agents are described herein. In some examples, the first ophthalmic agent of the one or more ophthalmic agents is a muscarinic antagonist. In some embodiments, the second ophthalmic agent of the one or more ophthalmic agents is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin Syn, bacitracin, besifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sulfacetamide sodium, sulfisoxyl Sazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sulfacetamide sodium, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / Zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide,Dorzolamide / Timolol, Ecothiopart iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, Unoprostone, Artificial tears, Dexamethasone, Difluprednate, Fluocinolone, Fluorometholone, Loteprednol, Medlison, Prednisolone, Rimexolone, Triamcinolone, Fluorometholone / Sodium sulfacetoamide, Dexamethasone / Neomycin, Dexamethasone / Tobramycin, Dexamethasone / Neomycin / Polymyxin b, Loteprednol / Tobramycin, Prednisolone / Sodium sulfacetoamide, Bacitraci These include chloramphenicol / hydrocortisone / neomycin / polymyxin b, chloramphenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b / prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, acequanizine, or any combination thereof. In some embodiments, the ophthalmic agent is acequanizine, tropicamide, pilocarpine, or a combination thereof.

[0028] In another aspect of this disclosure, this specification includes ophthalmic compositions comprising an ophthalmic agent, the ophthalmic agent being aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacaine, tetracaine, benoxynate, azithromycin, bacitracin, be Ciprofloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sulfacetamide sodium, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetrasulfate Ikurin / Polymyxin b, Phenylephrine / Sulfacetamide sodium, Vidarabine, Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc sulfate, Tetrahydrozoline, Tetrahydro Rozoline / zinc sulfate, fluorescein, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopat iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol,Physostigmine, pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medlison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocortisone / neomycin / polymyxin b An ophthalmic composition is described, which is chloramphenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b / prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, asecidin, or any combination thereof. In some embodiments, the ophthalmic agent is asecidin, tropicamide, pilocarpine, or a combination thereof.

[0029] In some embodiments, the ophthalmic composition is essentially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some embodiments, the ophthalmic composition is substantially free of procaine and benactidine, or pharmaceutically acceptable salts thereof. In some examples, the ophthalmic composition does not have detectable amounts of procaine and benactidine, or pharmaceutically acceptable salts thereof.

[0030] This specification provides ophthalmic compositions containing low concentrations of atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the ophthalmic composition comprises about 0.001 wt% to about 0.50 wt% or about 0.001 wt% to about 0.10 wt% of atropine or a pharmaceutically acceptable salt thereof for the treatment of an ophthalmic disorder or disease, and a pharmaceutically acceptable carrier, wherein the ophthalmic agent is substantially uniformly distributed throughout the pharmaceutically acceptable carrier.

[0031] This specification provides ophthalmic compositions containing low concentrations of atropine or a pharmaceutically acceptable salt or prodrug thereof. In some embodiments, the ophthalmic composition comprises about 0.001 wt% to about 0.50 wt% or about 0.001 wt% to about 0.10 wt% of atropine or a pharmaceutically acceptable salt or prodrug thereof for the treatment of an ophthalmic disorder or disease, and a pharmaceutically acceptable carrier, wherein the ophthalmic agent is substantially uniformly distributed throughout the pharmaceutically acceptable carrier.

[0032] In some embodiments, the ophthalmic disorder or disease is premyopia, myopia, or progression of myopia.

[0033] This disclosure further acknowledges that the clinical use of atropine as a therapeutic agent is limited due to ocular side effects, including glare due to pupillary dilation and blurred vision due to loss of accommodation. While we do not wish to be bound by any particular theory, the limitations on the use of atropine for the development of myopia include ocular side effects resulting from the concentrations of atropine used in known ophthalmic formulations (e.g., ≥1 wt%).

[0034] This disclosure further recognizes that there are problems with formulations of compositions containing ophthalmic agents, such as muscarinic antagonists (e.g., atropine or a pharmaceutically acceptable salt thereof), at low concentrations, specifically very low concentrations (e.g., about 0.001 wt% to about 0.50 wt% or about 0.001 wt% to about 0.10 wt%). Specifically, pharmaceutical compositions containing such low concentrations of ophthalmic agents are difficult to maintain between doses in terms of the content and / or distribution of the ophthalmic agent.

[0035] In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in amounts of approximately 0.001 wt% to approximately 0.40 wt%, approximately 0.001 wt% to approximately 0.30 wt%, approximately 0.001 wt% to approximately 0.20 wt%, approximately 0.001 wt% to approximately 0.10 wt%, approximately 0.001 wt% to approximately 0.09 wt%, approximately 0.001 wt% to approximately 0.08 wt%, approximately 0.001 wt% to approximately 0.07 wt%, and approximately 0.001 wt% to approximately 0 The muscarinic antagonist is present in the ophthalmic composition at one of the following concentrations: 0.06 wt%, approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of approximately 0.001 wt% to approximately 0.10 wt%. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof.

[0036] In some embodiments of the ophthalmic compositions described herein, atropine or a pharmaceutically acceptable salt thereof is present in concentrations of approximately 0.001 wt% to approximately 0.40 wt%, approximately 0.001 wt% to approximately 0.30 wt%, approximately 0.001 wt% to approximately 0.20 wt%, approximately 0.001 wt% to approximately 0.10 wt%, approximately 0.001 wt% to approximately 0.09 wt%, approximately 0.001 wt% to approximately 0.08 wt%, approximately 0.001 wt% to approximately 0.07 wt%, and approximately 0.001 wt%. Atropine is present in the ophthalmic composition at one of the following concentrations: approximately 0.06 wt%, approximately 0.001 wt% to approximately 0.05 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%. In some embodiments of the ophthalmic compositions described herein, atropine or a pharmaceutically acceptable salt thereof is present in the ophthalmic composition at a concentration of approximately 0.001 wt% to approximately 0.10 wt%.

[0037] In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in concentrations of approximately 0.001 mg / g to approximately 0.40 mg / g, approximately 0.001 mg / g to approximately 0.30 mg / g, approximately 0.001 mg / g to approximately 0.20 mg / g, approximately 0.001 mg / g to approximately 0.10 mg / g, approximately 0.001 mg / g to approximately 0.09 mg / g, approximately 0.01 mg / g to approximately 0.40 mg / g, approximately 0.01 mg / g to approximately 0.30 mg / g, approximately 0.01 mg / g to approximately 0.20 mg / g, approximately 0.01 mg / g to approximately 0.10 mg / g, approximately 0.01 mg / g to approximately 0.09 mg / g, and approximately 0.01 mg / g to approximately 0.08 mg / g. It is present in the ophthalmic composition at one of the following concentrations: g / g, approximately 0.01 mg / g to approximately 0.07 mg / g, approximately 0.01 mg / g to approximately 0.06 mg / g, approximately 0.01 mg / g to approximately 0.05 mg / g, approximately 0.01 mg / g to approximately 0.04 mg / g, approximately 0.01 mg / g to approximately 0.03 mg / g, approximately 0.01 mg / g to approximately 0.025 mg / g, approximately 0.01 mg / g to approximately 0.02 mg / g, approximately 0.01 mg / g to approximately 0.1 mg / g, approximately 0.01 mg / g to approximately 0.25 mg / g, approximately 0.01 mg / g to approximately 0.5 mg / g, approximately 0.01 mg / g to approximately 0.75 mg / g, and approximately 0.01 mg / g to approximately 1.0 mg / g. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 mg / g to about 0.5 mg / g.

[0038] In some embodiments of the ophthalmic compositions described herein, atropine or a pharmaceutically acceptable salt thereof is present in concentrations of approximately 0.001 mg / g to approximately 0.40 mg / g, approximately 0.001 mg / g to approximately 0.30 mg / g, approximately 0.001 mg / g to approximately 0.20 mg / g, approximately 0.001 mg / g to approximately 0.10 mg / g, approximately 0.001 mg / g to approximately 0.09 mg / g, approximately 0.01 mg / g to approximately 0.40 mg / g, approximately 0.01 mg / g to approximately 0.30 mg / g, approximately 0.01 mg / g to approximately 0.20 mg / g, approximately 0.01 mg / g to approximately 0.10 mg / g, approximately 0.01 mg / g to approximately 0.09 mg / g, and approximately 0.01 mg / g to approximately 0. It is present in the ophthalmic composition at one of the following concentrations: 0.08 mg / g, approximately 0.01 mg / g to approximately 0.07 mg / g, approximately 0.01 mg / g to approximately 0.06 mg / g, approximately 0.01 mg / g to approximately 0.05 mg / g, approximately 0.01 mg / g to approximately 0.04 mg / g, approximately 0.01 mg / g to approximately 0.03 mg / g, approximately 0.01 mg / g to approximately 0.025 mg / g, approximately 0.01 mg / g to approximately 0.02 mg / g, approximately 0.01 mg / g to approximately 0.1 mg / g, approximately 0.01 mg / g to approximately 0.25 mg / g, approximately 0.01 mg / g to approximately 0.5 mg / g, approximately 0.01 mg / g to approximately 0.75 mg / g, and approximately 0.01 mg / g to approximately 1.0 mg / g. In some embodiments of the ophthalmic compositions described herein, atropine or a pharmaceutically acceptable salt thereof is present in the ophthalmic composition at a concentration of about 0.01 mg / g to about 0.5 mg / g.

[0039] In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in amounts of approximately 0.0001 mg to approximately 0.040 mg, approximately 0.0001 mg to approximately 0.030 mg, approximately 0.0001 mg to approximately 0.020 mg, approximately 0.0001 mg to approximately 0.010 mg, approximately 0.0001 mg to approximately 0.009 mg, approximately 0.001 mg to approximately 0.040 mg, approximately 0.001 mg to approximately 0.030 mg, approximately 0.001 mg to approximately 0.020 mg, approximately 0.001 mg to approximately 0.010 mg, approximately 0.001 mg to approximately 0.009 mg, and approximately 0.001 mg to approximately 0. It is present in the ophthalmic composition at one of the following concentrations: 0.08 mg, approximately 0.001 mg to approximately 0.007 mg, approximately 0.001 mg to approximately 0.006 mg, approximately 0.001 mg to approximately 0.005 mg, approximately 0.001 mg to approximately 0.004 mg, approximately 0.001 mg to approximately 0.003 mg, approximately 0.001 mg to approximately 0.0025 mg, approximately 0.001 mg to approximately 0.002 mg, approximately 0.001 mg to approximately 0.01 mg, approximately 0.001 mg to approximately 0.025 mg, approximately 0.001 mg to approximately 0.05 mg, approximately 0.001 mg to approximately 0.075 mg, and approximately 0.001 mg to approximately 1.0 mg. In some embodiments of the ophthalmic compositions described herein, the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.0003 mg to about 0.025 mg or about 0.001 mg to about 0.05 mg.

[0040] In some embodiments of the ophthalmic compositions described herein, atropine or a pharmaceutically acceptable salt thereof is present in amounts of approximately 0.0001 mg to approximately 0.040 mg, approximately 0.0001 mg to approximately 0.030 mg, approximately 0.0001 mg to approximately 0.020 mg, approximately 0.0001 mg to approximately 0.010 mg, approximately 0.0001 mg to approximately 0.009 mg, approximately 0.001 mg to approximately 0.040 mg, approximately 0.001 mg to approximately 0.030 mg, approximately 0.001 mg to approximately 0.020 mg, approximately 0.001 mg to approximately 0.010 mg, approximately 0.001 mg to approximately 0.009 mg, and approximately 0.001 mg It is present in the ophthalmic composition at one of the following concentrations: approximately 0.008 mg, approximately 0.001 mg to approximately 0.007 mg, approximately 0.001 mg to approximately 0.006 mg, approximately 0.001 mg to approximately 0.005 mg, approximately 0.001 mg to approximately 0.004 mg, approximately 0.001 mg to approximately 0.003 mg, approximately 0.001 mg to approximately 0.0025 mg, approximately 0.001 mg to approximately 0.002 mg, approximately 0.001 mg to approximately 0.01 mg, approximately 0.001 mg to approximately 0.025 mg, approximately 0.001 mg to approximately 0.05 mg, approximately 0.001 mg to approximately 0.075 mg, and approximately 0.001 mg to approximately 1.0 mg. In some embodiments of the ophthalmic compositions described herein, atropine or a pharmaceutically acceptable salt thereof is present in the ophthalmic composition at a concentration of about 0.0003 mg to about 0.025 mg or about 0.001 mg to about 0.05 mg.

[0041] In some embodiments, formulations or solutions of muscarinic antagonists (e.g., atropine) formulated in deuterated water are described herein. In some embodiments, formulations or solutions of muscarinic antagonists (e.g., atropine) formulated in deuterated water are stable with at least 80% potency at various temperatures, various relative humidities, acid pDs, and for ophthalmic preparations. In further embodiments, the buffering capacity of formulations or solutions of muscarinic antagonists (e.g., atropine) formulated in deuterated water is reduced. In such examples, the reduced buffering capacity of the ophthalmic preparation or solution upon administration to the eye allows the ophthalmic preparation or solution to reach physiological pH at a faster rate compared to equivalent ophthalmic preparations or solutions formulated in H2O.

[0042] In some embodiments, formulations of low-concentration muscarinic antagonists (e.g., atropine) that exhibit no inter-dosing variation are described herein. In some embodiments, formulations of low-concentration muscarinic antagonists (e.g., atropine) that are stable with at least 80% efficacy against various temperatures, various relative humidities, acid pDs, and ophthalmic agents are described herein.

[0043] In other embodiments, this specification describes the formulation of ophthalmic compositions as ophthalmic gels or ophthalmic ointments. For example, some of the ophthalmic gels or ophthalmic ointments described herein allow for desired uniformity between doses, reduction or limitation of systemic exposure, or a combination thereof.

[0044] In some embodiments of this specification, ophthalmic compositions that are substantially free of preservatives are described. In some examples, the compositions are substantially free of benzalkonium chloride preservatives. In some examples, the compositions do not contain detectable amounts of benzalkonium chloride preservatives. In some examples, the compositions do not contain detectable amounts of benzalkonium chloride. In some examples, the compositions are substantially free of preservatives selected from cetrimonium, sodium perborate, stabilized oxychloro complexes, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof. In some examples, the compositions do not contain detectable amounts of preservatives. In some examples, the compositions are substantially free of any preservatives.

[0045] In some embodiments, the ophthalmic composition comprises one or more sodium phosphate buffers. In some examples, the sodium phosphate in one or more sodium phosphate buffers is anhydrous monosodium phosphate. In some examples, the sodium phosphate in one or more sodium phosphate buffers is anhydrous disodium phosphate. In some embodiments, the concentration of sodium phosphate is between about 0.001% to about 0.20% by weight, about 0.004% to about 0.20% by weight, about 0.005% to about 0.20% by weight, about 0.010% to about 0.20% by weight, about 0.015% to about 0.20% by weight, about 0.020% to about 0.20% by weight, about 0.025% to about 0.20% by weight, about 0.030% to about 0.20% by weight, about 0.035% to about 0.20% by weight, about 0.040% to about 0.20% by weight, or about 0.045% to about 0.20% by weight of the composition. In some embodiments, the amount of sodium phosphate is between about 0.01% to about 2.0% by weight, about 0.04% to about 2.0% by weight, about 0.05% to about 2.0% by weight, about 0.010% to about 2.0% by weight, about 0.015% to about 2.0% by weight, about 0.020% to about 2.0% by weight, about 0.025% to about 2.0% by weight, about 0.030% to about 2.0% by weight, about 0.035% to about 2.0% by weight, about 0.040% to about 2.0% by weight, or about 0.045% to about 2.0% by weight of the composition. In some examples, sodium phosphate is present in the composition at least or about 0.001% by weight, 0.002% by weight, 0.003% by weight, 0.004% by weight, 0.005% by weight, 0.006% by weight, 0.007% by weight, 0.008% by weight, 0.009% by weight, 0.010% by weight, 0.020% by weight, 0.030% by weight, 0.040% by weight, 0.050% by weight, and 0. It is present in ophthalmic compositions at concentrations of 0.60% by weight, 0.070% by weight, 0.080% by weight, 0.090% by weight, 0.10% by weight, 0.20% by weight, 0.30% by weight, 0.40% by weight, 0.50% by weight, 0.60% by weight, 0.70% by weight, 0.80% by weight, 0.90% by weight, 1.0% by weight, 2.0% by weight, 3.0% by weight, 4.0% by weight, or greater than 4.0% by weight.

[0046] In some embodiments of this specification, ophthalmic compositions comprising EDTA are described. In some embodiments, EDTA is present in the composition at approximately 0.001%, 0.005%, 0.010%, 0.015%, 0.020%, 0.025%, 0.030%, 0.035%, 0.040%, 0.045%, 0.050%, 0.055%, 0.060%, 0.065%, 0.070%, 0.075%, 0.080%, 0.085%, 0.090%, 0.095%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.5%, 2.0%, 2.5%, or 3.0%. In some embodiments, EDTA is present in the composition at approximately 0.01% to 0.05%, 0.01% to 0.04%, 0.01% to 0.03%, 0.01% to 0.025%, 0.01% to 0.02%, 0.001% to 0.01%, 0.001% to 0.008%, or 0.001% to 0.005%. In some cases, the percentages are weight percentages.

[0047] In some embodiments of this specification, ophthalmic compositions comprising a variable ratio of water (H2O) to deuterated water (D2O) are described. In some examples, the ratio of water to deuterated water is in the range of about 99:1 to about 1:99. In some examples, the ratio of water to deuterated water is in the range of about 99:1 to about 5:95, about 99:1 to about 10:90, about 99:1 to about 20:80, about 99:1 to about 30:70, about 99:1 to about 40:60, about 99:1 to about 50:50, about 99:1 to about 60:40, about 99:1 to about 70:30, about 99:1 to about 80:20, or about 99:1 to about 90:10. In some examples, the ratio of water to deuterated water is in the range of approximately 5:95 to 1:99, 10:90 to 1:99, 20:80 to 1:99, 30:70 to 1:99, 40:60 to 1:99, 50:50 to 1:99, 60:40 to 1:99, 70:30 to 1:99, 80:20 to 1:99, or 90:10 to 1:99.In some examples, the ratio of water to deuterated water is approximately 99:1, 98:2, 97:3, 96:4, 95:5, 94:6, 93:7, 92:8, 91:9, 90:10, 89:11, 88:12, 87:13, 86:14, 85:15, 84:16, 83:17, 82:18, 81:19, 80:20, 79:21, 78:22, 77:23, and 7 6:24, approx. 75:25, approx. 74:26, approx. 73:27, approx. 72:28, approx. 71:29, approx. 70:30, approx. 69:31, approx. 68:32, approx. 67:33, approx. 66:34, approx. 65:35, approx. 64:36, approx. 63:37, approx. 62:38, approx. 61:39, approx. 60:40, approx. 59:41, approx. 58:42, approx. 57:43, approx. 56:44, approx. 55:45, approx. 54:46, approx. 53:47, approx. 52:48, approx. 51 :49, approx. 50:50, approx. 49:51, approx. 48:52, approx. 47:53, approx. 46:54, approx. 45:55, approx. 44:56, approx. 43:57, approx. 42:58, approx. 41:59, approx. 40:60, approx. 39:61, approx. 38:62, approx. 37:63, approx. 36:64, approx. 35:65, approx. 34:66, approx. 33:67, approx. 32:68, approx. 31:69, approx. 30:70, approx. 29:71, approx. 28:72, approx. 27:73, approx. 26 :74, approximately 25:75, approximately 24:76, approximately 23:77, approximately 22:78, approximately 21:79, approximately 20:80, approximately 19:81, approximately 18:82, approximately 17:83, approximately 16:84, approximately 15:85, approximately 14:86, approximately 13:87, approximately 12:88, approximately 11:89, approximately 10:90, approximately 9:91, approximately 8:92, approximately 7:93, approximately 6:94, approximately 5:95, approximately 4:96, approximately 3:97, approximately 2:98, or approximately 1:99.

[0048] eye drop composition In some embodiments of this specification, ophthalmic compositions formulated as aqueous solutions are disclosed. In some embodiments, the ophthalmic composition comprises about 0.001 wt% to about 0.50 wt% or about 0.001 wt% to about 0.10 wt% of a muscarine antagonist and deuterated water. As used herein, deuterated water represents D2O, DHO, heavy water, and / or deuterium oxide. DHO comprises a mixture of H2O and D2O.

[0049] In some embodiments, the composition contains at least about 80% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 80% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 81% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 82% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 83% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 84% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 85% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 86% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 87% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 88% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 89% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 90% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 91% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 92% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 93% ophthalmic agent (e.g., muscarinic antagonist) over a long period of time under storage conditions.In some embodiments, the composition contains at least about 94% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 95% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 96% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 97% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 98% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the composition contains at least about 99% of an ophthalmic agent (e.g., a muscarinic antagonist) over a long period of time under storage conditions. In some embodiments, the concentration of the ophthalmic agent (e.g., a muscarinic antagonist) is based on the initial concentration after a long period of time under storage conditions.

[0050] In some embodiments, the efficacy of the composition is at least about 80% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 81% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 82% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 83% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 84% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 85% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 86% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 87% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 88% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 89% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 90% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 91% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 92% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 93% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 94% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 95% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 96% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 97% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 98% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition is at least about 99% after a long period of time under storage conditions.

[0051] In some embodiments, the duration is at least one week. In some embodiments, the duration is at least two weeks. In some embodiments, the duration is at least three weeks. In some embodiments, the duration is at least one month. In some embodiments, the duration is at least two months. In some embodiments, the duration is at least three months. In some embodiments, the duration is at least four months. In some embodiments, the duration is at least five months. In some embodiments, the duration is at least six months. In some embodiments, the duration is at least seven months. In some embodiments, the duration is at least eight months. In some embodiments, the duration is at least nine months. In some embodiments, the duration is at least ten months. In some embodiments, the duration is at least eleven months. In some embodiments, the duration is at least twelve months (i.e., one year). In some embodiments, the duration is at least eighteen months (i.e., 1.5 years). In some embodiments, the duration is at least twenty-four months (i.e., two years). In some embodiments, the duration is at least thirty-six months (i.e., three years). In some embodiments, the duration is at least three years. In some embodiments, the long term is at least 5 years or more.

[0052] In some embodiments, the storage temperature is between approximately 20°C and approximately 70°C. In some embodiments, the storage temperature is between approximately 25°C and approximately 65°C, approximately 30°C and approximately 60°C, approximately 35°C and approximately 55°C, or approximately 40°C and approximately 50°C. In some embodiments, the storage temperature is between approximately 0°C and approximately 30°C, approximately 2°C and approximately 10°C, or approximately 16°C and approximately 26°C. In some embodiments, the storage temperature is approximately 25°C. In some embodiments, the storage temperature is approximately 40°C. In some embodiments, the storage temperature is approximately 60°C.

[0053] In some embodiments, the relative humidity of the storage conditions is between approximately 50% and 80%, or between approximately 60% and 75%. In some embodiments, the relative humidity of the storage conditions is approximately 60%. In some embodiments, the relative humidity of the storage conditions is approximately 75%.

[0054] In some embodiments, the composition contains less than 60% H2O. In some embodiments, the composition contains less than 55% H2O. In some embodiments, the composition contains less than 50% H2O. In some embodiments, the composition contains less than 45% H2O. In some embodiments, the composition contains less than 40% H2O. In some embodiments, the composition contains less than 35% H2O. In some embodiments, the composition contains less than 30% H2O. In some embodiments, the composition contains less than 25% H2O. In some embodiments, the composition contains less than 20% H2O. In some embodiments, the composition contains less than 15% H2O. In some embodiments, the composition contains less than 10% H2O.

[0055] In some embodiments, the composition contains less than 5% H2O to 0% H2O. In some embodiments, the composition contains less than 5% H2O. In some embodiments, the composition contains less than 4.5% H2O. In some embodiments, the composition contains less than 4% H2O. In some embodiments, the composition contains less than 3.5% H2O. In some embodiments, the composition contains less than 3% H2O. In some embodiments, the composition contains less than 2.5% H2O. In some embodiments, the composition contains less than 2% H2O. In some embodiments, the composition contains less than 1.5% H2O. In some embodiments, the composition contains less than 1% H2O. In some embodiments, the composition contains less than 0.5% H2O. In some embodiments, the composition contains less than 0.4% H2O. In some embodiments, the composition contains less than 0.3% H2O. In some embodiments, the composition contains less than 0.2% H2O. In some embodiments, the composition contains less than 0.1% H2O. In some embodiments, the composition contains 0% H2O.

[0056] In some embodiments, the pH of the composition is between approximately 4 and 8, approximately 4.2 and 7.9, approximately 4.5 and 7.8, approximately 5 and 7.5, approximately 4.9 and 6.1, approximately 5.0 and 6.0, approximately 5.2 and 6.1, approximately 5.5 and 7, or approximately 5.5 and 5.6, when measured, for example, at approximately 40°C. In some embodiments, the pH of the composition is between approximately 4 and 8, approximately 4.2 and 7.9, approximately 4.5 and 7.8, approximately 5 and 7.5, approximately 4.9 and 6.1, approximately 5.0 and 6.0, approximately 5.2 and 6.1, approximately 5.5 and 7, or approximately 5.5 and 5.6, when measured, for example, at approximately 40°C. In some embodiments, the pH of the composition is approximately 8.0. In some embodiments, the pH of the composition is approximately 7.9. In some embodiments, the pH of the composition is approximately 7.8. In some embodiments, the pH of the composition is about 7.7. In some embodiments, the pH of the composition is about 7.6. In some embodiments, the pH of the composition is less than about 7.5. In some embodiments, the pH of the composition is less than about 7.4. In some embodiments, the pH of the composition is less than about 7.3. In some embodiments, the pH of the composition is less than about 7.2. In some embodiments, the pH of the composition is less than about 7.1. In some embodiments, the pH of the composition is less than about 7. In some embodiments, the pH of the composition is less than about 6.9. In some embodiments, the pH of the composition is less than about 6.8. In some embodiments, the pH of the composition is less than about 6.7. In some embodiments, the pH of the composition is less than about 6.6. In some embodiments, the pH of the composition is less than about 6.5. In some embodiments, the pH of the composition is less than about 6.4. In some embodiments, the pH of the composition is less than about 6.3. In some embodiments, the pH of the composition is less than about 6.2. In some embodiments, the pH of the composition is less than about 6.1. In some embodiments, the pH of the composition is less than about 6. In some embodiments, the pH of the composition is less than about 5.9. In some embodiments, the pH of the composition is less than about 5.8. In some embodiments, the pH of the composition is less than about 5.7. In some embodiments, the pH of the composition is less than about 5.6.In some embodiments, the pH of the composition is less than about 5.5. In some embodiments, the pH of the composition is less than about 5.4. In some embodiments, the pH of the composition is less than about 5.3. In some embodiments, the pH of the composition is less than about 5.2. In some embodiments, the pH of the composition is less than about 5.1. In some embodiments, the pH of the composition is less than about 5. In some embodiments, the pH of the composition is less than about 4.9. In some embodiments, the pH of the composition is less than about 4.8. In some embodiments, the pH of the composition is less than about 4.7. In some embodiments, the pH of the composition is less than about 4.6. In some embodiments, the pH of the composition is less than about 4.5. In some embodiments, the pH of the composition is less than about 4.4. In some embodiments, the pH of the composition is less than about 4.3. In some embodiments, the pH of the composition is less than about 4.2. In some embodiments, the pH of the composition is less than about 4.1. In some embodiments, the pH of the composition is less than about 4.

[0057] In some embodiments, the pD of the composition, when measured, for example at about 25°C, is between about 4 and about 8, about 4.2 and about 7.9, about 4.5 and about 7.8, about 5 and about 7.5, about 5.5 and about 7, about 5.3 and about 6.5, about 5.4 and about 6.4, about 5.6 and about 6.6, or about 5.9 and about 6.0. In some embodiments, the pD of the composition, when measured, for example at about 40°C, is between about 4 and about 8, about 4.2 and about 7.9, about 4.5 and about 7.8, about 5 and about 7.5, about 5.5 and about 7, about 5.3 and about 6.5, about 5.4 and about 6.4, about 5.6 and about 6.6, or about 5.9 and about 6.0. In some embodiments, the pD of the composition is about 8.0. In some embodiments, the pD of the composition is about 7.9. In some embodiments, the pD of the composition is about 7.8. In some embodiments, the pD of the composition is about 7.7. In some embodiments, the pD of the composition is about 7.6. In some embodiments, the pD of the composition is less than about 7.5. In some embodiments, the pD of the composition is less than about 7.4. In some embodiments, the pD of the composition is less than about 7.3. In some embodiments, the pD of the composition is less than about 7.2. In some embodiments, the pD of the composition is less than about 7.1. In some embodiments, the pD of the composition is less than about 7. In some embodiments, the pD of the composition is less than about 6.9. In some embodiments, the pD of the composition is less than about 6.8. In some embodiments, the pD of the composition is less than about 6.7. In some embodiments, the pD of the composition is less than about 6.6. In some embodiments, the pD of the composition is less than about 6.5. In some embodiments, the pD of the composition is less than about 6.4. In some embodiments, the pD of the composition is less than about 6.3. In some embodiments, the pD of the composition is less than about 6.2. In some embodiments, the pD of the composition is less than about 6.1. In some embodiments, the pD of the composition is less than about 6. In some embodiments, the pD of the composition is less than about 5.9. In some embodiments, the pD of the composition is less than about 5.8. In some embodiments, the pD of the composition is less than about 5.7. In some embodiments, the pD of the composition is less than about 5.6.In some embodiments, the pD of the composition is less than about 5.5. In some embodiments, the pD of the composition is less than about 5.4. In some embodiments, the pD of the composition is less than about 5.3. In some embodiments, the pD of the composition is less than about 5.2. In some embodiments, the pD of the composition is less than about 5.1. In some embodiments, the pD of the composition is less than about 5. In some embodiments, the pD of the composition is less than about 4.9. In some embodiments, the pD of the composition is less than about 4.8. In some embodiments, the pD of the composition is less than about 4.7. In some embodiments, the pD of the composition is less than about 4.6. In some embodiments, the pD of the composition is less than about 4.5. In some embodiments, the pD of the composition is less than about 4.4. In some embodiments, the pD of the composition is less than about 4.3. In some embodiments, the pD of the composition is less than about 4.2. In some embodiments, the pD of the composition is less than about 4.1. In some embodiments, the pD of the composition is less than about 4.

[0058] In some embodiments, the buffering capacity of compositions containing deuterated water is lower than that of equivalent compositions containing H2O. As described elsewhere in this specification, in some embodiments, the lower buffering capacity allows compositions containing deuterated water to normalize to physiological pH at a faster rate than compositions containing H2O. In some embodiments, the lower buffering capacity means that the compositions do not induce the tear reflex as much as equivalent compositions containing H2O.

[0059] In some examples, compositions containing deuterated water stabilize muscarinic antagonists (e.g., atropine). In some embodiments, this stabilization is due to the lower concentration of reactive species (e.g., -OD) in the D2O / aqueous system than the lower concentration of reactive species (e.g., -OH) in an equivalent pure aqueous system. In some cases, base-catalyzed hydrolysis leads to the presence of tropine degradation products from atropine. In some cases, at lower concentrations of the reactive species that cause tropine degradation product formation, the atropine solution is more stable in the D2O / aqueous system than in an equivalent pure aqueous system. In some embodiments, ophthalmic compositions formulated with deuterated water enable more stable ophthalmic compositions compared to ophthalmic compositions formulated with H2O.

[0060] In some embodiments, the composition contains less than 20% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 15% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions.

[0061] In some embodiments, the composition contains less than 10% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 5% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 2.0% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 1.5% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 1.0% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 0.5% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 0.4% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 0.3% of the main degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 0.2% of the main degradation product, based on the concentration of the ophthalmic preparation after prolonged storage under certain conditions. In some embodiments, the composition contains less than 0.1% of the main degradation product, based on the concentration of the ophthalmic preparation after prolonged storage under certain conditions. In some embodiments, the main degradation product is tropic acid.

[0062] In some embodiments, the efficacy of the composition is at least 80% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition is at least 85% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition is at least 90% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition is at least 93% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition is at least 95% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition is at least 97% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition is at least 98% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition is at least 99% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition is at least 80%, at least 85%, at least 90%, at least 93%, at least 95%, at least 97%, at least 98%, or at least 99% at temperatures of about 0°C to about 30°C, 2°C to about 10°C, or about 16°C to about 26°C.

[0063] In some cases, the efficacy of the composition is at least 80% for at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months. In some cases, the efficacy of the composition is at least 85% for at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months. In some cases, the efficacy of the composition is at least 90% for at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months. In some cases, the potency of the composition is at least 93% for at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months. In some cases, the potency of the composition is at least 95% for at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months.In some cases, the efficacy of the composition is at least 97% for at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months. In some cases, the efficacy of the composition is at least 98% for at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months. In some cases, the efficacy of the composition is at least 99% for at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months.

[0064] In some embodiments, the composition contains less than 20% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 15% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 10% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 5% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions.

[0065] In some embodiments, the composition contains less than 2.5% to less than 0.1% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 2.5% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 2.0% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 1.5% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 1.0% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 0.5% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 0.4% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 0.3% primary degradation products, based on the concentration of the ophthalmic agent after prolonged storage under certain conditions. In some embodiments, the composition contains less than 0.2% primary degradation products, based on the concentration of the ophthalmic agent after a long period of time under storage conditions. In some embodiments, the composition contains less than 0.1% primary degradation products, based on the concentration of the ophthalmic agent after a long period of time under storage conditions. In some examples, the storage conditions include temperatures of about 25°C, about 40°C, or about 60°C. In some embodiments, the storage conditions include temperatures between about 0°C and about 30°C, about 2°C and about 10°C, or about 16°C and about 26°C. In some embodiments, the long period is at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 18 months, or at least 24 months.

[0066] In some embodiments, the composition contains less than 20% primary degradation products based on the concentration of the ophthalmic agent at temperatures of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 15% primary degradation products based on the concentration of the ophthalmic agent at temperatures of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 10% primary degradation products based on the concentration of the ophthalmic agent at temperatures of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 5% primary degradation products based on the concentration of the ophthalmic agent at temperatures of about 25°C, about 40°C, or about 60°C.

[0067] In some embodiments, the composition contains less than 2.5% to less than 0.1% of primary degradation products, based on the concentration of the ophthalmic agent at a temperature of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 2.5% of primary degradation products, based on the concentration of the ophthalmic agent at a temperature of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 2.0% of primary degradation products, based on the concentration of the ophthalmic agent at a temperature of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 1.5% of primary degradation products, based on the concentration of the ophthalmic agent at a temperature of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 1.0% of primary degradation products, based on the concentration of the ophthalmic agent at a temperature of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 0.5% primary degradation products based on the concentration of the ophthalmic agent at temperatures of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 0.4% primary degradation products based on the concentration of the ophthalmic agent at temperatures of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 0.3% primary degradation products based on the concentration of the ophthalmic agent at temperatures of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 0.2% primary degradation products based on the concentration of the ophthalmic agent at temperatures of about 25°C, about 40°C, or about 60°C. In some embodiments, the composition contains less than 0.1% primary degradation products based on the concentration of the ophthalmic agent at temperatures of about 25°C, about 40°C, or about 60°C.

[0068] In some embodiments, the primary degradation product is an early eluting related substance with an RRT of 0.87–0.89 as measured by the UPLC method described herein. In some examples, the early eluting related substance is represented as RRT 0.87–0.89. In some embodiments, the primary degradation product is RRT 0.87–0.89.

[0069] In some embodiments of this specification, ophthalmic compositions comprising various ratios of water (H2O) to deuterated water (D2O) are described. In some examples, the ratio of water to deuterated water is in the range of about 99:1 to about 1:99. In some examples, the ratio of water to deuterated water is in the range of about 99:1 to about 5:95, about 99:1 to about 10:90, about 99:1 to about 20:80, about 99:1 to about 30:70, about 99:1 to about 40:60, about 99:1 to about 50:50, about 99:1 to about 60:40, about 99:1 to about 70:30, about 99:1 to about 80:20, or about 99:1 to about 90:10. In some examples, the ratio of water to deuterated water is in the range of approximately 5:95 to 1:99, 10:90 to 1:99, 20:80 to 1:99, 30:70 to 1:99, 40:60 to 1:99, 50:50 to 1:99, 60:40 to 1:99, 70:30 to 1:99, 80:20 to 1:99, or 90:10 to 1:99. In some cases, the ratio of water to deuterated water is in the range of approximately 95:5 to 5:95, approximately 90:10 to 10:90, approximately 80:20 to 20:80, approximately 80:20 to 30:70, approximately 80:30 to 40:60, approximately 90:10 to 50:50, or approximately 80:20 to 60:40.In some examples, the ratio of water to deuterated water is approximately 99:1, 98:2, 97:3, 96:4, 95:5, 94:6, 93:7, 92:8, 91:9, 90:10, 89:11, 88:12, 87:13, 86:14, 85:15, 84:16, 83:17, 82:18, 81:19, 80:20, 79:21, 78:22, 77:23, and 7 6:24, approx. 75:25, approx. 74:26, approx. 73:27, approx. 72:28, approx. 71:29, approx. 70:30, approx. 69:31, approx. 68:32, approx. 67:33, approx. 66:34, approx. 65:35, approx. 64:36, approx. 63:37, approx. 62:38, approx. 61:39, approx. 60:40, approx. 59:41, approx. 58:42, approx. 57:43, approx. 56:44, approx. 55:45, approx. 54:46, approx. 53:47, approx. 52:48, approx. 51 :49, approx. 50:50, approx. 49:51, approx. 48:52, approx. 47:53, approx. 46:54, approx. 45:55, approx. 44:56, approx. 43:57, approx. 42:58, approx. 41:59, approx. 40:60, approx. 39:61, approx. 38:62, approx. 37:63, approx. 36:64, approx. 35:65, approx. 34:66, approx. 33:67, approx. 32:68, approx. 31:69, approx. 30:70, approx. 29:71, approx. 28:72, approx. 27:73, approx. 26 The ratios are approximately 74, 25:75, 24:76, 23:77, 22:78, 21:79, 20:80, 19:81, 18:82, 17:83, 16:84, 15:85, 14:86, 13:87, 12:88, 11:89, 10:90, 9:91, 8:92, 7:93, 6:94, 5:95, 4:96, 3:97, 2:98, or 1:99. In some examples, the ratio of water to deuterated water is in the range of approximately 100:0. In some examples, the ratio of water to deuterated water is in the range of approximately 0:100.

[0070] In another aspect of this disclosure, this specification describes ophthalmic compositions having a pH of about 3.8 to about 7.5, comprising about 0.001% to about 0.05% by weight of a muscarinic antagonist and water.

[0071] In some examples, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or combinations thereof. In some cases, the muscarinic antagonist is atropine. In some cases, the muscarinic antagonist is atropine sulfate. In some embodiments, the muscarinic antagonist is atropine, or a pharmaceutically acceptable salt or prodrug thereof.

[0072] In some examples, the ophthalmic composition contains, based on the initial concentration after long-term storage under storage conditions, at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99% of one muscarinic antagonist.

[0073] In other aspects of this disclosure, ophthalmic compositions comprising one or more ophthalmic agents are described herein. In some examples, the first ophthalmic agent of the one or more ophthalmic agents is a muscarinic antagonist. In some embodiments, the second ophthalmic agent of the one or more ophthalmic agents is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin Syn, bacitracin, besifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sulfacetamide sodium, sulfisoxyl Sazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sulfacetamide sodium, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / Zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide,Dorzolamide / Timolol, Ecothiopart iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, Unoprostone, Artificial tears, Dexamethasone, Difluprednate, Fluocinolone, Fluorometholone, Loteprednol, Medlison, Prednisolone, Rimexolone, Triamcinolone, Fluorometholone / Sodium sulfacetoamide, Dexamethasone / Neomycin, Dexamethasone / Tobramycin, Dexamethasone / Neomycin / Polymyxin b, Loteprednol / Tobramycin, Prednisolone / Sodium sulfacetoamide, Bacitraci These include chloramphenicol / hydrocortisone / neomycin / polymyxin b, chloramphenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b / prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, acequanizine, or any combination thereof. In some embodiments, the ophthalmic agent is acequanizine, tropicamide, pilocarpine, or a combination thereof.

[0074] In another aspect of this disclosure, this specification includes ophthalmic compositions comprising an ophthalmic agent, the ophthalmic agent being aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacaine, tetracaine, benoxynate, azithromycin, bacitracin, be Ciprofloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sulfacetamide sodium, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetrasulfate Ikurin / Polymyxin b, Phenylephrine / Sulfacetamide sodium, Vidarabine, Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc sulfate, Tetrahydrozoline, Tetrahydro Rozoline / zinc sulfate, fluorescein, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopat iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol,Physostigmine, pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medlison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocortisone / neomycin / polymyxin b An ophthalmic composition is described, which is chloramphenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b / prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, asecidin, or any combination thereof. In some embodiments, the ophthalmic agent is asecidin, tropicamide, pilocarpine, or a combination thereof.

[0075] In some cases, the pH of the ophthalmic composition, after long-term storage under storage conditions, is one of the following: less than approximately 7.3, less than approximately 7.2, less than approximately 7.1, less than approximately 7, less than approximately 6.8, less than approximately 6.5, less than approximately 6.4, less than approximately 6.3, less than approximately 6.2, less than approximately 6.1, less than approximately 6, less than approximately 5.9, less than approximately 5.8, less than approximately 5.2, less than approximately 4.8, or less than approximately 4.2.

[0076] In some cases, the potency of an ophthalmic composition after long-term storage under storage conditions is one of at least about 80%, at least about 85%, at least about 90%, at least about 93%, at least about 95%, at least about 97%, at least about 98%, or at least about 99%.

[0077] In some examples, a long period of time is one of the following: approximately 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 8 months, 10 months, 12 months, 18 months, 24 months, 36 months, 4 years, or 5 years.

[0078] In some cases, the storage temperature is one of approximately 25°C, 40°C, or 60°C. In other cases, the storage temperature is approximately 2°C to 10°C, or approximately 16°C to 26°C. In other cases, the relative humidity is approximately 60% or 75%.

[0079] In some cases, ophthalmic compositions are in the form of aqueous solutions. In some cases, muscarinic antagonists are present in the composition at one of the following concentrations: approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%.

[0080] In some cases, the ophthalmic composition further includes a molar osmotic pressure modifier. In some cases, the molar osmotic pressure modifier is sodium chloride.

[0081] In some cases, the ophthalmic composition further includes a preservative. Depending on the circumstances, the preservative may be selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or a combination thereof.

[0082] In some cases, the ophthalmic composition further comprises a buffer. Depending on the case, the buffer may be selected from boroates, boroates-polyol complexes, phosphate buffers, citrate buffers, acetate buffers, carbonate buffers, organic buffers, amino acid buffers, or combinations thereof.

[0083] In some cases, the ophthalmic composition further comprises a tonicity adjusting agent. Depending on the circumstances, the tonicity adjusting agent may be selected from sodium chloride, sodium nitrate, sodium sulfate, sodium bisulfate, potassium chloride, calcium chloride, magnesium chloride, zinc chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, dextrose, mannitol, sorbitol, dextrose, sucrose, urea, propylene glycol, glycerin, or a combination thereof.

[0084] In some cases, the ophthalmic composition further includes a penetration agent. In some cases, the penetration agent is benzalkonium chloride.

[0085] In some cases, ophthalmic compositions are stored in plastic containers. In some instances, the material of the plastic containers includes low-density polyethylene (LDPE).

[0086] In some cases, ophthalmic compositions have inter-dosage muscarinic antagonist concentration variability of less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, or less than 5%. In some cases, inter-dosage muscarinic antagonist concentration variability is based on one of 10 consecutive doses, 8 consecutive doses, 5 consecutive doses, 3 consecutive doses, or 2 consecutive doses.

[0087] In some examples, the pH of an ophthalmic composition, when measured at, for example, 25°C, is one of the following: approximately 3.8 to 7.5, approximately 4.2 to 7.5, approximately 4.8 to 7.3, approximately 5.2 to 7.2, approximately 5.8 to 7.1, approximately 6.0 to 7.0, or approximately 6.2 to 6.8, approximately 4.9 to 6.1, approximately 5.0 to 6.0, approximately 5.2 to 6.1, or approximately 5.5 to 5.6. In some examples, the pH of an ophthalmic composition, when measured at, for example, 40°C, is one of the following: approximately 3.8 to approximately 7.5, approximately 4.2 to approximately 7.5, approximately 4.8 to approximately 7.3, approximately 5.2 to approximately 7.2, approximately 5.8 to approximately 7.1, approximately 6.0 to approximately 7.0, or approximately 6.2 to approximately 6.8, approximately 4.9 to approximately 6.1, approximately 5.0 to approximately 6.0, approximately 5.2 to approximately 6.1, or approximately 5.5 to 5.6.

[0088] In some cases, the ophthalmic composition further includes a pH adjuster. In some cases, the pH adjuster includes HCl, NaOH, CH3COOH, or C6H8O7.

[0089] In some cases, ophthalmic compositions contain one of the following: less than 5% D2O, less than 4% D2O, less than 3% D2O, less than 2% D2O, less than 1% D2O, less than 0.5% D2O, less than 0.1% D2O, or 0% D2O. In some cases, ophthalmic compositions contain essentially no D2O.

[0090] In some cases, the ophthalmic composition further comprises a pharmaceutically acceptable carrier.

[0091] In some cases, ophthalmic compositions are formulated as eye drops to treat eye disorders. In some cases, the ophthalmic disorder or disease is premyopia, myopia, or the progression of myopia. In some cases, ophthalmic compositions are formulated to slow the progression of myopia.

[0092] In some cases, ophthalmic compositions are not formulated as injectable formulations.

[0093] Ophthalmic agent concentration In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.5% by weight, about 0.005% to about 0.5% by weight, about 0.010% to about 0.5% by weight, about 0.015% to about 0.5% by weight, about 0.020% to about 0.5% by weight, about 0.025% to about 0.5% by weight, about 0.030% to about 0.5% by weight, about 0.035% to about 0.1% by weight, about 0.040% to about 0.5% by weight, or about 0.045% to about 0.5% by weight. In some examples, the prodrug of the ophthalmic agent (e.g., a muscarinic antagonist) is chemically converted to the ophthalmic agent (e.g., a muscarinic antagonist) after administration of the ophthalmic composition. In non-limiting examples, muscarinic antagonist prodrugs have a chemical bond that can be cleaved by one or more enzymes in the tear fluid. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or combinations thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. As described herein, the ophthalmic agent includes optically pure stereoisomers, optically rich stereoisomers, and racemic mixtures of stereoisomers. For example, some ophthalmic compositions disclosed herein contain atropine sulfate, in which atropine is a racemic mixture of D-isomers and L-isomers, and some ophthalmic compositions disclosed herein contain atropine or atropine sulfate, in which the more optically active L-isomer is optically abundant in atropine. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine,Hydroxyamphetamine / tropicamide, cysteamine, occliplasmin, mitomycin, dapiprazole, lidocaine, propalacaine, tetracaine, benoxynate, azithromycin, bacitracin, besifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / Limethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine , rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brimonidine / brizolamide, carbachol, carteolol, demecalli Um bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopat iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol, physostigmine, pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium,Dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocortisone / neomycin / polymyxin b, chloramphenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b / prednisolone, gentamicin / prednisolone These include ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, asecidine, or any combination thereof. In some embodiments, the ophthalmic agent is asecidine, tropicamide, pilocarpine, or a combination thereof.

[0094] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.45% by weight, about 0.005% to about 0.45% by weight, about 0.010% to about 0.45% by weight, about 0.015% to about 0.45% by weight, about 0.020% to about 0.45% by weight, about 0.025% to about 0.45% by weight, about 0.030% to about 0.45% by weight, about 0.035% to about 0.45% by weight, or about 0.040% to about 0.45% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol Cole, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sulfacetamide sodium, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b,Phenylephrine / sulfacetamide sodium, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, f Luolethene, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopat iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol, physostigmine, Pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medlison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / Neomycin / Polymyxin b, Hydrocortisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine,These are procyclidine, aclidinium bromide, trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0095] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.40% by weight, about 0.005% to about 0.40% by weight, about 0.010% to about 0.40% by weight, about 0.015% to about 0.40% by weight, about 0.020% to about 0.40% by weight, about 0.025% to about 0.40% by weight, about 0.030% to about 0.40% by weight, or about 0.035% to about 0.40% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, Erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine,Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Proparacaine, Benox Synate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Trabo Prost, Unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocor Tizone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium Bromide,The ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0096] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.35% by weight, about 0.005% to about 0.35% by weight, about 0.010% to about 0.35% by weight, about 0.015% to about 0.35% by weight, about 0.020% to about 0.35% by weight, about 0.025% to about 0.35% by weight, about 0.030% to about 0.35% by weight, or about 0.035% to about 0.35% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, Erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine,Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Proparacaine, Benox Synate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Trabo Prost, Unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocor Tizone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium Bromide,The ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0097] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.30% by weight, about 0.005% to about 0.30% by weight, about 0.010% to about 0.30% by weight, about 0.015% to about 0.30% by weight, about 0.020% to about 0.30% by weight, about 0.025% to about 0.30% by weight, about 0.030% to about 0.30% by weight, or about 0.030% to about 0.30% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, Erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine,Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Proparacaine, Benox Synate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Trabo Prost, Unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocor Tizone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium Bromide,The ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0098] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.25% by weight, about 0.005% to about 0.25% by weight, about 0.010% to about 0.25% by weight, about 0.015% to about 0.25% by weight, about 0.020% to about 0.25% by weight, about 0.025% to about 0.25% by weight, about 0.030% to about 0.25% by weight, or about 0.035% to about 0.25% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, Erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine,Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Proparacaine, Benox Synate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Trabo Prost, Unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocor Tizone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium Bromide,The ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0099] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.20% by weight, about 0.005% to about 0.20% by weight, about 0.010% to about 0.20% by weight, about 0.015% to about 0.20% by weight, about 0.020% to about 0.20% by weight, about 0.025% to about 0.20% by weight, about 0.030% to about 0.20% by weight, or about 0.035% to about 0.20% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, Erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine,Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Proparacaine, Benox Synate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Trabo Prost, Unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocor Tizone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium Bromide,The ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0100] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.15% by weight, about 0.005% to about 0.15% by weight, about 0.010% to about 0.15% by weight, about 0.015% to about 0.15% by weight, about 0.020% to about 0.15% by weight, about 0.025% to about 0.15% by weight, about 0.030% to about 0.15% by weight, or about 0.035% to about 0.15% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, Erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine,Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Proparacaine, Benox Synate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Trabo Prost, Unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocor Tizone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium Bromide,The ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0101] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.1% by weight, about 0.005% to about 0.1% by weight, about 0.010% to about 0.1% by weight, about 0.015% to about 0.1% by weight, about 0.020% to about 0.1% by weight, about 0.025% to about 0.1% by weight, about 0.030% to about 0.1% by weight, about 0.035% to about 0.1% by weight, about 0.040% to about 0.1% by weight, or about 0.045% to about 0.1% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol Cole, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sulfacetamide sodium, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b,Phenylephrine / sulfacetamide sodium, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, f Luolethene, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopat iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol, physostigmine, Pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medlison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / Neomycin / Polymyxin b, Hydrocortisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine,These are procyclidine, aclidinium bromide, trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0102] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.95% by weight, about 0.005% to about 0.95% by weight, about 0.010% to about 0.95% by weight, about 0.015% to about 0.95% by weight, about 0.020% to about 0.95% by weight, about 0.025% to about 0.95% by weight, about 0.030% to about 0.95% by weight, about 0.035% to about 0.95% by weight, or about 0.040% to about 0.95% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol Cole, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sulfacetamide sodium, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b,Phenylephrine / sulfacetamide sodium, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, f Luolethene, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopat iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol, physostigmine, Pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medlison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / Neomycin / Polymyxin b, Hydrocortisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine,These are procyclidine, aclidinium bromide, trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0103] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at ophthalmic agent concentrations between about 0.001% to about 0.090% by weight, about 0.005% to about 0.090% by weight, about 0.010% to about 0.090% by weight, about 0.015% to about 0.090% by weight, about 0.020% to about 0.090% by weight, about 0.025% to about 0.090% by weight, about 0.030% to about 0.090% by weight, and about 0.035% to about 0.090% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin Syn, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide,Vidarabine, bromfenac, nepafenac, ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydro Lutisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium BromideThe ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0104] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at ophthalmic agent concentrations between about 0.001% to about 0.085% by weight, about 0.005% to about 0.085% by weight, about 0.010% to about 0.085% by weight, about 0.015% to about 0.085% by weight, about 0.020% to about 0.085% by weight, about 0.025% to about 0.085% by weight, about 0.030% to about 0.085% by weight, and about 0.035% to about 0.085% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin Syn, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide,Vidarabine, bromfenac, nepafenac, ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydro Lutisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium BromideThe ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0105] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at ophthalmic agent concentrations between about 0.001% to about 0.080% by weight, about 0.005% to about 0.080% by weight, about 0.010% to about 0.080% by weight, about 0.015% to about 0.080% by weight, about 0.020% to about 0.080% by weight, about 0.025% to about 0.080% by weight, about 0.030% to about 0.080% by weight, and about 0.035% to about 0.080% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin Syn, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide,Vidarabine, bromfenac, nepafenac, ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydro Lutisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium BromideThe ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0106] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at ophthalmic agent concentrations between about 0.001% to about 0.075% by weight, about 0.005% to about 0.075% by weight, about 0.010% to about 0.075% by weight, about 0.015% to about 0.075% by weight, about 0.020% to about 0.075% by weight, about 0.025% to about 0.075% by weight, about 0.030% to about 0.075% by weight, and about 0.035% to about 0.075% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin Syn, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide,Vidarabine, bromfenac, nepafenac, ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydro Lutisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium BromideThe ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0107] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at ophthalmic agent concentrations between about 0.001% to about 0.070% by weight, about 0.005% to about 0.070% by weight, about 0.010% to about 0.070% by weight, about 0.015% to about 0.070% by weight, about 0.020% to about 0.070% by weight, about 0.025% to about 0.070% by weight, about 0.030% to about 0.070% by weight, and about 0.035% to about 0.070% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin Syn, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide,Vidarabine, bromfenac, nepafenac, ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydro Lutisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium BromideThe ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0108] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at ophthalmic agent concentrations between about 0.001% to about 0.065% by weight, about 0.005% to about 0.065% by weight, about 0.010% to about 0.065% by weight, about 0.015% to about 0.065% by weight, about 0.020% to about 0.065% by weight, about 0.025% to about 0.065% by weight, about 0.030% to about 0.065% by weight, and about 0.035% to about 0.065% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin Syn, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide,Vidarabine, bromfenac, nepafenac, ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydro Lutisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium BromideThe ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0109] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at ophthalmic agent concentrations between about 0.001% to about 0.060% by weight, about 0.005% to about 0.060% by weight, about 0.010% to about 0.060% by weight, about 0.015% to about 0.060% by weight, about 0.020% to about 0.060% by weight, about 0.025% to about 0.060% by weight, about 0.030% to about 0.060% by weight, and about 0.035% to about 0.060% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin Syn, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide,Vidarabine, bromfenac, nepafenac, ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydro Lutisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium BromideThe ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0110] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at ophthalmic agent concentrations between about 0.001% to about 0.055% by weight, about 0.005% to about 0.055% by weight, about 0.010% to about 0.055% by weight, about 0.015% to about 0.055% by weight, about 0.020% to about 0.055% by weight, about 0.025% to about 0.055% by weight, about 0.030% to about 0.055% by weight, and about 0.035% to about 0.055% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin Syn, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide,Vidarabine, bromfenac, nepafenac, ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydro Lutisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium BromideThe ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0111] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between approximately 0.001% to approximately 0.050% by weight, approximately 0.005% to approximately 0.050% by weight, approximately 0.010% to approximately 0.050% by weight, approximately 0.015% to approximately 0.050% by weight, approximately 0.020% to approximately 0.050% by weight, approximately 0.025% to approximately 0.050% by weight, approximately 0.030% to approximately 0.050% by weight, approximately 0.035% to approximately 0.050% by weight, approximately 0.040% to approximately 0.050% by weight, or approximately 0.045% to approximately 0.050% by weight of the composition. In some examples, the prodrug of an ophthalmic agent (e.g., a muscarinic antagonist) is chemically converted to the ophthalmic agent (e.g., a muscarinic antagonist) after administration of the ophthalmic composition. In non-limiting examples, the prodrug of a muscarinic antagonist has a chemical bond that can be cleaved by one or more enzymes in the tear fluid. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. As described herein, ophthalmic preparations include optically pure stereoisomers, optically rich stereoisomers, and racemic mixtures of stereoisomers. For example, some ophthalmic compositions disclosed herein contain atropine sulfate, in which atropine is a racemic mixture of D-isomers and L-isomers, and some ophthalmic compositions disclosed herein contain atropine or atropine sulfate, in which the more optically active L-isomer is optically abundant in atropine. In some embodiments, the ophthalmic preparations include aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine,Tropicamide, Ketorolac / Phenylephrine, Hydroxyamphetamine / Tropicamide, Cysteamine, Ocliplasmin, Mitomycin, Dapiprazole, Lidocaine, Proparacaine, Tetracaine, Benoxynate, Azithromycin, Bacitracin, Becifloxacin, Boric acid, Chloramphenicol, Ciprofloxacin, Erythromycin, Ganciclovir, Gatifloxacin, Gentamicin, Idoxuridine, Levofloxacin, Moxifloxacin, Natamycin, Norfloxacin, Ofloxacin, Bacitracin / Polymi Polymyxin b, Tobramycin, Polymyxin b / Trimethoprim, Povidone-iodine, Trifluridine, Gramicidin / Neomycin / Polymyxin b, Sulfacetamide sodium, Sulfisoxazole, Bacitracin / Neomycin / Polymyxin b, Oxytetracycline / Polymyxin b, Phenylephrine / Sulfacetamide sodium, Vidarabine, Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Propalacaine, Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizo Lamide, Carbachol, Carteolol, Demepotassium bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopart iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, Unoprostone, Artificial tears, Dexamethasone, Difluprednate, Fluocinolone, Fluorometholone, Loteprednol, Medrison, Prednisolone, Rimexolone, Triamcinolone,Fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocortisone / neomycin / polymyxin b, chloramphenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b / prednisolone, Gen These include tamycin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, asecidine, or any combination thereof. In some embodiments, the ophthalmic agent is asecidine, tropicamide, pilocarpine, or a combination thereof.

[0112] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.045% by weight, about 0.005% to about 0.045% by weight, about 0.010% to about 0.045% by weight, about 0.015% to about 0.045% by weight, about 0.020% to about 0.045% by weight, about 0.025% to about 0.045% by weight, about 0.030% to about 0.045% by weight, about 0.035% to about 0.045% by weight, or about 0.040% to about 0.045% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol Cole, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sulfacetamide sodium, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b,Phenylephrine / sulfacetamide sodium, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, f Luolethene, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopat iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol, physostigmine, Pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medlison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / Neomycin / Polymyxin b, Hydrocortisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine,These are procyclidine, aclidinium bromide, trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0113] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at ophthalmic agent concentrations between about 0.001% to about 0.040% by weight, about 0.005% to about 0.040% by weight, about 0.010% to about 0.040% by weight, about 0.015% to about 0.040% by weight, about 0.020% to about 0.040% by weight, about 0.025% to about 0.040% by weight, about 0.030% to about 0.040% by weight, and about 0.035% to about 0.040% by weight. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin Syn, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide,Vidarabine, bromfenac, nepafenac, ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimonidine, Brizolamide, Brimonidine / Brizolamide, Carbachol, Carteolol, Demepotassium Bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopat Iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydro Lutisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Darifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium BromideThe ophthalmic agent is trihexyphenidyl / benzhexol, tolterodine, aceline, or any combination thereof. In some embodiments, the ophthalmic agent is aceline, tropicamide, pilocarpine, or a combination thereof.

[0114] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.035% by weight, about 0.005% to about 0.035% by weight, about 0.010% to about 0.035% by weight, about 0.015% to about 0.035% by weight, about 0.020% to about 0.035% by weight, about 0.025% to about 0.035% by weight, or about 0.030% to about 0.035% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacaine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin Ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine, bromfenac, nepafenac,Ketrolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkaftazine, azelastine, bepotastine, cromolyn, emedastine, epinastine, ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine Ninggreen, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopate iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol, physostigmine, pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexa Metasone, difluprednate, fluocinolone, fluorometholone, loteprednol, medrisone, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocortisone / neomycin / polymyxin b, chloramf Phenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b / prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine,Acephedrine, or any combination thereof. In some embodiments, the ophthalmic agent is acephedrine, tropicamide, pilocarpine, or a combination thereof.

[0115] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.030% by weight, about 0.005% to about 0.030% by weight, about 0.010% to about 0.030% by weight, about 0.015% to about 0.030% by weight, about 0.020% to about 0.030% by weight, or about 0.025% to about 0.030% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, gancyclo Viru, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine,Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Proparacaine, Benoxynate / Fluorescein, Indocyanine Green, Trypanb Lu, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopate iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol, physostigmine, pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, diflupre Donato, fluocinolone, fluorometholone, loteprednol, medrison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocortisone / neomycin / polymyxin b, chloramphenicol / hydro Cortisone / Polymyxin b, Neomycin / Polymyxin b / Prednisolone, Gentamicin / Prednisolone, Ketorolac / Phenylephrine, Diphenhydramine, Dimenhydrinate, Dicyclomine, Flavoxate, Oxybutynin, Tiotropium, Hyostine, Scopolamine (L-Hyostine), Hydroxyzine, Ipratropium, Pirenzepine, Solifenacin, Dalifenacin, Benzatropine, Mebeberine, Procyclidine, Acridinium Bromide, Trihexyphenidyl / Benzhexol, Tolterodine, Acelyzine,or any combination thereof. In some embodiments, the ophthalmic agent is acecidin, tropicamide, pilocarpine, or a combination thereof.

[0116] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.025% by weight, about 0.005% to about 0.025% by weight, about 0.010% to about 0.025% by weight, about 0.015% to about 0.025% by weight, or about 0.020% to about 0.025% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, ge Ntamycin, Idoxuridine, Levofloxacin, Moxifloxacin, Natamycin, Norfloxacin, Ofloxacin, Bacitracin / Polymyxin B, Tobramycin, Polymyxin B / Trimethoprim, Povidone-iodine, Trifluridine, Gramicidin / Neomycin / Polymyxin B, Sulfacetamide Sodium, Sulfisoxazole, Bacitracin / Neomycin / Polymyxin B, Oxytetracycline / Polymyxin B, Phenylephrine / Sulfacetamide Sodium, Vidarabine, Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac,Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Propalacaine, Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxanthin Solol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopat iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol, physostigmine, pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone Loteprednol, Medrison, Prednisolone, Rimexolone, Triamcinolone, Fluorometholone / Sulfacetoamide sodium, Dexamethasone / Neomycin, Dexamethasone / Tobramycin, Dexamethasone / Neomycin / Polymyxin b, Loteprednol / Tobramycin, Prednisolone / Sulfacetoamide sodium, Bacitracin / Hydrocortisone / Neomycin / Polymyxin b, Hydrocortisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b, Neomycin The ophthalmic agents are: ¹ / polymyxin b / prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, acezine, or any combination thereof. In some embodiments, the ophthalmic agent is:These are acecidin, tropicamide, pilocarpine, or a combination thereof.

[0117] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.020% by weight, about 0.005% to about 0.020% by weight, about 0.010% to about 0.020% by weight, or about 0.015% to about 0.020% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idox Uridine, levofloxacin, moxifloxacin, natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine, flurbiprofen, suprofen, diclofenac, alkafatazine, azelastine, bepotastine,Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Propalacaine, Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine, Betaxolol, Bimatoprost, Brimoni Zin, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopate iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobunolol, levobetaxolol, metipranolol, physostigmine, pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, fluorometholone, loteprednol, me Dolison, prednisolone, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocortisone / neomycin / polymyxin b, chloramphenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b Xynxin b / prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, acequazine, or any combination thereof. In some embodiments, the ophthalmic agent is acequazine, tropicamide, pilocarpine,Or a combination of those.

[0118] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.015% by weight, about 0.005% to about 0.015% by weight, or about 0.010% to about 0.015% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin Sacin, Moxifloxacin, Natamycin, Norfloxacin, Ofloxacin, Bacitracin / Polymyxin B, Tobramycin, Polymyxin B / Trimethoprim, Povidone-iodine, Trifluridine, Gramicidin / Neomycin / Polymyxin B, Sulfacetamide Sodium, Sulfisoxazole, Bacitracin / Neomycin / Polymyxin B, Oxytetracycline / Polymyxin B, Phenylephrine / Sulfacetamide Sodium, Vidarabine, Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine,Ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine Brizolamide, Carbachol, Carteolol, Demepotassium bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopart iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, Unoprostone, Artificial tears, Dexamethasone, Difluprednate, Fluocinolone, Fluorometholone, Loteprednol, Medrison, Prednisolone Lon, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocortisone / neomycin / polymyxin b, chloramphenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b / These include prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, asecidine, or any combination thereof. In some embodiments, the ophthalmic agent is asecidine, tropicamide, pilocarpine, or a combination thereof.

[0119] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration between about 0.001% to about 0.010% by weight, about 0.005% to about 0.010% by weight, or about 0.008% to about 0.010% by weight of the composition. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropine, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, becifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin Sacin, Moxifloxacin, Natamycin, Norfloxacin, Ofloxacin, Bacitracin / Polymyxin B, Tobramycin, Polymyxin B / Trimethoprim, Povidone-iodine, Trifluridine, Gramicidin / Neomycin / Polymyxin B, Sulfacetamide Sodium, Sulfisoxazole, Bacitracin / Neomycin / Polymyxin B, Oxytetracycline / Polymyxin B, Phenylephrine / Sulfacetamide Sodium, Vidarabine, Bromfenac, Nepafenac, Ketrolac, Cyclosporine, Flurbiprofen, Suprofen, Diclofenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine,Ketotifen, levocabastine, rhodoxamide, nedocromil, naphazoline, naphazoline / pheniramine, naphazoline / zinc sulfate, olopatadine, oxymetazoline, pemirolast, phenylephrine / zinc sulfate, tetrahydrozoline, tetrahydrozoline / zinc sulfate, fluorescein, fluorescein / propalacaine, benoxynate / fluorescein, indocyanine green, trypan blue, acetylcholine, apraclonidine, betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine Brizolamide, Carbachol, Carteolol, Demepotassium bromide, Dipibufrine, Dorzolamide, Dorzolamide / Timolol, Ecothiopart iodide, Epinephrine, Epinephrine / Pilocarpine, Latanoprost, Levobunolol, Levobetaxolol, Metipranolol, Physostigmine, Pilocarpine, Tafluprost, Timolol, Travoprost, Unoprostone, Artificial tears, Dexamethasone, Difluprednate, Fluocinolone, Fluorometholone, Loteprednol, Medrison, Prednisolone Lon, rimexolone, triamcinolone, fluorometholone / sulfacetoamide sodium, dexamethasone / neomycin, dexamethasone / tobramycin, dexamethasone / neomycin / polymyxin b, loteprednol / tobramycin, prednisolone / sulfacetoamide sodium, bacitracin / hydrocortisone / neomycin / polymyxin b, hydrocortisone / neomycin / polymyxin b, chloramphenicol / hydrocortisone / polymyxin b, neomycin / polymyxin b / These include prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, asecidine, or any combination thereof. In some embodiments, the ophthalmic agent is asecidine, tropicamide, pilocarpine, or a combination thereof.

[0120] In some embodiments, the compositions described herein contain an ophthalmic agent or a pharmaceutically acceptable prodrug or salt thereof at an ophthalmic agent concentration of about 0.001% by weight, 0.005% by weight, 0.010% by weight, 0.015% by weight, 0.020% by weight, 0.025% by weight, 0.030% by weight, 0.035% by weight, 0.040% by weight, 0.045% by weight, 0.050% by weight, 0.055% by weight, 0.060% by weight, 0.065% by weight, 0.070% by weight, 0.075% by weight, 0.080% by weight, 0.085% by weight, 0.090% by weight, 0.095% by weight, or 0.1% by weight of the composition. In some embodiments, the ophthalmic agent concentration of the compositions described herein is about 0.001% to about 0.05%, about 0.001% to about 0.04%, about 0.001% to about 0.03%, about 0.001% to about 0.025%, about 0.001% to about 0.02%, about 0.001% to about 0.01%, about 0.001% to about 0.008%, or about 0.001% to about 0.005%. In some embodiments, the ophthalmic agent is a muscarinic antagonist. In some embodiments, the muscarinic antagonist includes atropine, atropine sulfate, noatropine, atropine-N-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof. In some embodiments, the muscarinic antagonist is atropine or a pharmaceutically acceptable salt thereof. In some embodiments, the muscarinic antagonist is atropine sulfate. In some embodiments, the ophthalmic agent is aflibercept, ranibizumab, pegaptanib, cyclopentolate, phenylephrine, homatropin, scopolamine, cyclopentolate / phenylephrine, phenylephrine / scopolamine, tropicamide, ketorolac / phenylephrine, hydroxyamphetamine / tropicamide, cysteamine, ocliplasmin, mitomycin, dapiprazole, lidocaine, propalacine, tetracaine, benoxynate, azithromycin, bacitracin, besifloxacin, boric acid, chloramphenicol, ciprofloxacin, erythromycin, ganciclovir, gatifloxacin, gentamicin, idoxuridine, levofloxacin, moxifloxacin,Natamycin, norfloxacin, ofloxacin, bacitracin / polymyxin b, tobramycin, polymyxin b / trimethoprim, povidone-iodine, trifluridine, gramicidin / neomycin / polymyxin b, sodium sulfacetamide, sulfisoxazole, bacitracin / neomycin / polymyxin b, oxytetracycline / polymyxin b, phenylephrine / sodium sulfacetamide, vidarabine, bromfenac, nepafenac, ketorolac, cyclosporine, flurbiprofen, suprofen, dichloro Fenac, Alkaftazine, Azelastine, Bepotastine, Cromolyn, Emedastine, Epinastine, Ketotifen, Levocabastine, Rhodoxamide, Nedocromil, Naphazoline, Naphazoline / Pheniramine, Naphazoline / Zinc Sulfate, Olopatadine, Oxymetazoline, Pemirolast, Phenylephrine / Zinc Sulfate, Tetrahydrozoline, Tetrahydrozoline / Zinc Sulfate, Fluorescein, Fluorescein / Propalacaine, Benoxynate / Fluorescein, Indocyanine Green, Trypan Blue, Acetylcholine, Apraclonidine Betaxolol, bimatoprost, brimonidine, brizolamide, brimonidine / brizolamide, carbachol, carteolol, demepotassium bromide, dipibufrine, dorzolamide, dorzolamide / timolol, ecothiopate iodide, epinephrine, epinephrine / pilocarpine, latanoprost, levobonolol, levobetaxolol, metipranolol, physostigmine, pilocarpine, tafluprost, timolol, travoprost, unoprostone, artificial tears, dexamethasone, difluprednate, fluocinolone, flu Lometholone, Loteprednol, Medrison, Prednisolone, Rimexolone, Triamcinolone, Fluorometholone / Sulfacetoamide sodium, Dexamethasone / Neomycin, Dexamethasone / Tobramycin, Dexamethasone / Neomycin / Polymyxin b, Loteprednol / Tobramycin, Prednisolone / Sulfacetoamide sodium, Bacitracin / Hydrocortisone / Neomycin / Polymyxin b, Hydrocortisone / Neomycin / Polymyxin b, Chloramphenicol / Hydrocortisone / Polymyxin b,Neomycin / polymyxin b / prednisolone, gentamicin / prednisolone, ketorolac / phenylephrine, diphenhydramine, dimenhydrinate, dicyclomine, flavoxate, oxybutynin, tiotropium, hyostine, scopolamine (L-hyostine), hydroxyzine, ipratropium, pirenzepine, solifenacin, dalifenacin, benzatropine, mebeberine, procyclidine, acridinium bromide, trihexyphenidyl / benzhexol, tolterodine, acequazine, or any combination thereof. In some embodiments, the ophthalmic agent is acequazine, tropicamide, pilocarpine, or a combination thereof.

[0121] While it is not desirable to be bound by any particular theory, this specification intends that low concentrations of ophthalmic agents (e.g., muscarinic antagonists such as atropine or atropine sulfate) in the disclosed ophthalmic compositions provide sufficient and consistent therapeutic benefits to individuals in need, while reducing or avoiding ocular side effects associated with ophthalmic formulations containing higher concentrations of ophthalmic agents (e.g., muscarinic antagonists such as atropine or atropine sulfate), including glare due to pupillary dilation and blurred vision due to loss of accommodation.

[0122] Solution stability In some embodiments, the compositions described herein include a buffer. In some embodiments, the buffer is selected from boroates, boroates-polyol complexes, phosphate buffers, citrate buffers, acetate buffers, carbonate buffers, organic buffers, amino acid buffers, or combinations thereof. In some embodiments, the compositions described herein include a buffer containing deuterated water. In some embodiments, the deuterated buffer is selected from boroates, boroates-polyol complexes, phosphate buffers, citrate buffers, acetate buffers, carbonate buffers, organic buffers, amino acid buffers, or combinations thereof, which are formulated in deuterated water.

[0123] In some cases, boroates include boric acid, salts of boric acid, other pharmaceutically acceptable boroates, and combinations thereof. In some cases, boroates include boric acid, sodium borate, potassium borate, calcium borate, magnesium borate, manganese borate, and other borates.

[0124] As used herein, the term polyol includes any compound having at least one hydroxyl group on each of two adjacent carbon atoms that are not in a trans configuration with respect to each other. In some embodiments, polyols are linear or cyclic, substituted or unsubstituted, or a combination thereof, as long as the resulting complex is water-soluble and pharmaceutically acceptable. Examples of polyols include sugars, sugar alcohols, sugar acids, and uronic acids. Examples of polyols include, but are not limited to, mannitol, glycerin, xylitol, and sorbitol.

[0125] In some embodiments, the phosphate buffering agent may be phosphoric acid; alkali metal phosphates such as disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, or tripotassium phosphate; alkaline earth metal phosphates such as calcium phosphate, calcium hydrogen phosphate, calcium dihydrogen phosphate, monomagnesium phosphate, dimagnesium phosphate (magnesium hydrogen phosphate), or trimagnesium phosphate; ammonium phosphate such as diammonium hydrogen phosphate or ammonium dihydrogen phosphate; or combinations thereof. In some examples, the phosphate buffering agent is an anhydrous. In some examples, the phosphate buffering agent is a hydrate.

[0126] In some embodiments, the boroate-polyol complex includes those described in U.S. Patent No. 6,503,497. In some examples, the boroate-polyol complex comprises boroate in an amount of about 0.01 to about 2.0% w / v and one or more polyols in an amount of about 0.01% w / v to about 5.0% w / v.

[0127] In some cases, the citrate buffering agent comprises citric acid and sodium citrate. In some examples, the citrate buffering agent comprises citrate. In some embodiments, citrate is present in the ophthalmic composition at concentrations between about 0.001% to about 0.20% by weight, about 0.004% to about 0.20% by weight, about 0.005% to about 0.20% by weight, about 0.010% to about 0.20% by weight, about 0.015% to about 0.20% by weight, about 0.020% to about 0.20% by weight, about 0.025% to about 0.20% by weight, about 0.030% to about 0.20% by weight, about 0.035% to about 0.20% by weight, about 0.040% to about 0.20% by weight, or about 0.045% to about 0.20% by weight. In some examples, citrate is present in the ophthalmic composition at concentrations of at least or about 0.001% by weight, 0.002% by weight, 0.003% by weight, 0.004% by weight, 0.005% by weight, 0.006% by weight, 0.007% by weight, 0.008% by weight, 0.009% by weight, 0.010% by weight, 0.020% by weight, 0.030% by weight, 0.040% by weight, 0.050% by weight, 0.060% by weight, 0.070% by weight, 0.080% by weight, 0.090% by weight, 0.10% by weight, 0.20% by weight, 0.30% by weight, or 0.40% by weight.

[0128] In some cases, acetate buffering agents include acetic acid, potassium acetate, and sodium acetate.

[0129] In some cases, carbonate buffering agents include sodium bicarbonate and sodium carbonate.

[0130] Depending on the case, organic buffering agents may include, for example, 2-(N-morpholino)ethanesulfonic acid (MES), N-(2-acetamide)iminodiacetic acid, N-(carbamoylmethyl)iminodiacetic acid (ADA), piperazine-N,N'-bis(2-ethanesulfonic acid) (PIPES), N-(2-acetamide)-2-aminoethanesulfonic acid (ACES), β-hydroxy-4-morpholinepropanesulfonic acid, 3-morpholino -2-hydroxypropanesulfonic acid (MOPSO), cholamine chloride, 3-(N-morpholino)propanesulfonic acid (MOPS), N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), 2-[(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)amino]ethanesulfonic acid (TES), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) The Good Buffers include 3-(N,N-bis[2-hydroxyethyl]amino)-2-hydroxypropanesulfonic acid (DIPSO), acetamidoglycine, 3-{[1,3-dihydroxy-2-(hydroxymethyl)-2-propanyl]amino}-2-hydroxy-1-propanesulfonic acid (TAPSO), piperazine-1,4-bis(2-hydroxypropanesulfonic acid) (POPSO), 4-(2-hydroxyethyl)piperazine-1-(2-hydroxypropanesulfonic acid) hydrate (HEPPSO), 3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid (HEPPS), tricine, glycinamide, bicine, or sodium N-tris(hydroxymethyl)methyl-3-aminopropanesulfonate (TAPS); glycine; and diethanolamine (DEA).

[0131] In some cases, amino acid buffering agents include taurine, aspartic acid and its salts (e.g., potassium salts), and E-aminocaproic acid.

[0132] In some embodiments of this specification, compositions are described that are essentially free of citrate buffers, acetate buffers, or combinations thereof. In some embodiments, the compositions are substantially free of citrate buffers, acetate buffers, or combinations thereof. In some embodiments, the compositions do not have detectable amounts of citrate buffers, acetate buffers, or combinations thereof.

[0133] In some cases, the compositions described herein further comprise tonic modifiers. Tonic modifiers are agents introduced into preparations such as ophthalmic compositions to reduce local irritation by preventing osmotic shock at the application site. In some cases, buffer solutions and / or pH modifiers that broadly maintain eye drops at specific ionic concentrations and pH are considered tonic modifiers. In some cases, tonic modifiers comprise various salts, such as monovalent cation halide salts. In some cases, tonic modifiers comprise mannitol, sorbitol, dextrose, sucrose, urea, and glycerin. In some cases, suitable tonic modifiers comprise sodium chloride, sodium nitrate, sodium sulfate, sodium bicarbonate, potassium chloride, calcium chloride, magnesium chloride, zinc chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, dextrose, mannitol, sorbitol, dextrose, sucrose, urea, propylene glycol, glycerin, or combinations thereof.

[0134] In some cases, the concentration of the tension modifier in the compositions described herein is between about 0.5% and about 2.0%. In some cases, the concentration of the tension modifier in the compositions described herein is between about 0.7% and about 1.8%, about 0.8% and about 1.5%, or about 1% and about 1.3%. In some cases, the concentration of the tension modifier is about 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or 1.9%. Where applicable, the percentages are weight percentages.

[0135] In some cases, the compositions described herein further include pH adjusters. In some embodiments, the pH adjuster used is an acid or a base. In some embodiments, the base is an oxide, hydroxide, carbonate, bicarbonate, etc. In some examples, the oxide is a metal oxide such as calcium oxide or magnesium oxide, the hydroxide is an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide, calcium hydroxide, or their deuterated equivalents, and the carbonate is sodium carbonate, sodium bicarbonate, potassium bicarbonate, etc. In some examples, the acid is a mineral acid or organic acid such as hydrochloric acid, nitric acid, phosphoric acid, acetic acid, citric acid, fumaric acid, malic acid, tartaric acid, or their deuterated equivalents. In some examples, pH adjusters include, but are not limited to, acetates, bicarbonates, ammonium chloride, citrates, phosphates, pharmaceutically acceptable salts thereof, combinations thereof, or mixtures thereof. In some embodiments, the pH adjuster includes DCl and NaOD. In some embodiments, the pH adjuster includes DCl, HCl, NaOH, NaOD, CD3COOD, C6D8O7, CH3COOH, C6H8O7, or a combination thereof.

[0136] In some embodiments, the pH adjuster is present in the ophthalmic composition at a concentration between about 0.001% to about 0.20% by weight, about 0.004% to about 0.20% by weight, about 0.005% to about 0.20% by weight, about 0.010% to about 0.20% by weight, about 0.015% to about 0.20% by weight, about 0.020% to about 0.20% by weight, about 0.025% to about 0.20% by weight, about 0.030% to about 0.20% by weight, about 0.035% to about 0.20% by weight, about 0.040% to about 0.20% by weight, or about 0.045% to about 0.20% by weight. In some examples, pH adjusters are present in the ophthalmic composition at concentrations of at least or about 0.001% by weight, 0.002% by weight, 0.003% by weight, 0.004% by weight, 0.005% by weight, 0.006% by weight, 0.007% by weight, 0.008% by weight, 0.009% by weight, 0.010% by weight, 0.020% by weight, 0.030% by weight, 0.040% by weight, 0.050% by weight, 0.060% by weight, 0.070% by weight, 0.080% by weight, 0.090% by weight, 0.10% by weight, 0.20% by weight, 0.30% by weight, or 0.40% by weight. Examples of pH adjusters include, but are not limited to, acetates, bicarbonates, ammonium chloride, citrates, phosphates, pharmaceutically acceptable salts thereof, combinations or mixtures thereof. In some embodiments, the pH adjuster includes DCl and NaOD.

[0137] In some examples, the pH adjuster is citrate. In some embodiments, citrate is present in the ophthalmic composition at concentrations between about 0.001% to about 0.20% by weight, about 0.004% to about 0.20% by weight, about 0.005% to about 0.20% by weight, about 0.010% to about 0.20% by weight, about 0.015% to about 0.20% by weight, about 0.020% to about 0.20% by weight, about 0.025% to about 0.20% by weight, about 0.030% to about 0.20% by weight, about 0.035% to about 0.20% by weight, about 0.040% to about 0.20% by weight, or about 0.045% to about 0.20% by weight. In some examples, citrate is present in the ophthalmic composition at concentrations of at least or about 0.001% by weight, 0.002% by weight, 0.003% by weight, 0.004% by weight, 0.005% by weight, 0.006% by weight, 0.007% by weight, 0.008% by weight, 0.009% by weight, 0.010% by weight, 0.020% by weight, 0.030% by weight, 0.040% by weight, 0.050% by weight, 0.060% by weight, 0.070% by weight, 0.080% by weight, 0.090% by weight, 0.10% by weight, 0.20% by weight, 0.30% by weight, or 0.40% by weight.

[0138] In some cases, the compositions described herein further comprise one or more sodium phosphate buffers. Examples of exemplary sodium phosphate buffers include, but are not limited to, monosodium phosphate (sodium dihydrogen phosphate), disodium phosphate, trisodium phosphate, anhydrous monosodium phosphate, anhydrous disodium phosphate, and anhydrous trisodium phosphate. In some examples, the sodium phosphate in one or more sodium phosphate buffers is monosodium phosphate. In some examples, the sodium phosphate in one or more sodium phosphate buffers is disodium phosphate. In some examples, the sodium phosphate in one or more sodium phosphate buffers is anhydrous. In some examples, the sodium phosphate in one or more sodium phosphate buffers is anhydrous monosodium phosphate. In some examples, the sodium phosphate in one or more sodium phosphate buffers is anhydrous disodium phosphate.

[0139] In some embodiments, the concentration of sodium phosphate is between about 0.001% to about 0.20% by weight, about 0.004% to about 0.20% by weight, about 0.005% to about 0.20% by weight, about 0.010% to about 0.20% by weight, about 0.015% to about 0.20% by weight, about 0.020% to about 0.20% by weight, about 0.025% to about 0.20% by weight, about 0.030% to about 0.20% by weight, about 0.035% to about 0.20% by weight, about 0.040% to about 0.20% by weight, or about 0.045% to about 0.20% by weight of the composition. In some embodiments, the amount of sodium phosphate is between about 0.01% to about 2.0% by weight, about 0.04% to about 2.0% by weight, about 0.05% to about 2.0% by weight, about 0.010% to about 2.0% by weight, about 0.015% to about 2.0% by weight, about 0.020% to about 2.0% by weight, about 0.025% to about 2.0% by weight, about 0.030% to about 2.0% by weight, about 0.035% to about 2.0% by weight, about 0.040% to about 2.0% by weight, or about 0.045% to about 2.0% by weight of the composition. In some examples, sodium phosphate is present in the composition at least or about 0.001% by weight, 0.002% by weight, 0.003% by weight, 0.004% by weight, 0.005% by weight, 0.006% by weight, 0.007% by weight, 0.008% by weight, 0.009% by weight, 0.010% by weight, 0.020% by weight, 0.030% by weight, 0.040% by weight, 0.050% by weight, and 0. It is present in ophthalmic compositions at concentrations of 0.60% by weight, 0.070% by weight, 0.080% by weight, 0.090% by weight, 0.10% by weight, 0.20% by weight, 0.30% by weight, 0.40% by weight, 0.50% by weight, 0.60% by weight, 0.70% by weight, 0.80% by weight, 0.90% by weight, 1.0% by weight, 2.0% by weight, 3.0% by weight, 4.0% by weight, or greater than 4.0% by weight.

[0140] In some embodiments, the concentration of anhydrous monosodium phosphate is between about 0.001% to about 0.20% by weight, about 0.004% to about 0.20% by weight, about 0.005% to about 0.20% by weight, about 0.010% to about 0.20% by weight, about 0.015% to about 0.20% by weight, about 0.020% to about 0.20% by weight, about 0.025% to about 0.20% by weight, about 0.030% to about 0.20% by weight, about 0.035% to about 0.20% by weight, about 0.040% to about 0.20% by weight, or about 0.045% to about 0.20% by weight of the composition. In some embodiments, the amount of anhydrous monosodium phosphate is between about 0.01% to about 2.0% by weight, about 0.04% to about 2.0% by weight, about 0.05% to about 2.0% by weight, about 0.010% to about 2.0% by weight, about 0.015% to about 2.0% by weight, about 0.020% to about 2.0% by weight, about 0.025% to about 2.0% by weight, about 0.030% to about 2.0% by weight, about 0.035% to about 2.0% by weight, about 0.040% to about 2.0% by weight, or about 0.045% to about 2.0% by weight of the composition. In some examples, anhydrous monosodium phosphate is present in the composition at least or about 0.001% by weight, 0.002% by weight, 0.003% by weight, 0.004% by weight, 0.005% by weight, 0.006% by weight, 0.007% by weight, 0.008% by weight, 0.009% by weight, 0.010% by weight, 0.020% by weight, 0.030% by weight, 0.040% by weight, 0.050% by weight, 0. It is present in ophthalmic compositions at concentrations of 0.060% by weight, 0.070% by weight, 0.080% by weight, 0.090% by weight, 0.10% by weight, 0.20% by weight, 0.30% by weight, 0.40% by weight, 0.50% by weight, 0.60% by weight, 0.70% by weight, 0.80% by weight, 0.90% by weight, 1.0% by weight, 2.0% by weight, 3.0% by weight, 4.0% by weight, or greater than 4.0% by weight.

[0141] In some embodiments, the concentration of anhydrous disodium phosphate is between about 0.001% to about 0.20% by weight, about 0.004% to about 0.20% by weight, about 0.005% to about 0.20% by weight, about 0.010% to about 0.20% by weight, about 0.015% to about 0.20% by weight, about 0.020% to about 0.20% by weight, about 0.025% to about 0.20% by weight, about 0.030% to about 0.20% by weight, about 0.035% to about 0.20% by weight, about 0.040% to about 0.20% by weight, or about 0.045% to about 0.20% by weight of the composition. In some embodiments, the amount of anhydrous disodium phosphate is between about 0.01% to about 2.0% by weight, about 0.04% to about 2.0% by weight, about 0.05% to about 2.0% by weight, about 0.010% to about 2.0% by weight, about 0.015% to about 2.0% by weight, about 0.020% to about 2.0% by weight, about 0.025% to about 2.0% by weight, about 0.030% to about 2.0% by weight, about 0.035% to about 2.0% by weight, about 0.040% to about 2.0% by weight, or about 0.045% to about 2.0% by weight of the composition. In some examples, anhydrous disodium phosphate is present in the composition at least or about 0.001% by weight, 0.002% by weight, 0.003% by weight, 0.004% by weight, 0.005% by weight, 0.006% by weight, 0.007% by weight, 0.008% by weight, 0.009% by weight, 0.010% by weight, 0.020% by weight, 0.030% by weight, 0.040% by weight, 0.050% by weight, 0. It is present in ophthalmic compositions at concentrations of 0.060% by weight, 0.070% by weight, 0.080% by weight, 0.090% by weight, 0.10% by weight, 0.20% by weight, 0.30% by weight, 0.40% by weight, 0.50% by weight, 0.60% by weight, 0.70% by weight, 0.80% by weight, 0.90% by weight, 1.0% by weight, 2.0% by weight, 3.0% by weight, 4.0% by weight, or greater than 4.0% by weight.

[0142] In some examples, the pH of the composition is between approximately 4 and 8, approximately 4.2 and 7.9, approximately 4.5 and 7.8, approximately 5 and 7.5, or approximately 5.5 and 7. In some embodiments, the pH of the composition is approximately 8.0. In some embodiments, the pH of the composition is approximately 7.9. In some embodiments, the pH of the composition is approximately 7.8. In some embodiments, the pH of the composition is approximately 7.7. In some embodiments, the pH of the composition is approximately 7.6. In some embodiments, the pH of the composition is less than approximately 7.5. In some embodiments, the pH of the composition is less than approximately 7.4. In some embodiments, the pH of the composition is less than approximately 7.3. In some embodiments, the pH of the composition is less than approximately 7.2. In some embodiments, the pH of the composition is less than approximately 7.1. In some embodiments, the pH of the composition is less than approximately 7. In some embodiments, the pH of the composition is less than approximately 6.9. In some embodiments, the pH of the composition is less than approximately 6.8. In some embodiments, the pH of the composition is less than about 6.7. In some embodiments, the pH of the composition is less than about 6.6. In some embodiments, the pH of the composition is less than about 6.5. In some embodiments, the pH of the composition is less than about 6.4. In some embodiments, the pH of the composition is less than about 6.3. In some embodiments, the pH of the composition is less than about 6.2. In some embodiments, the pH of the composition is less than about 6.1. In some embodiments, the pH of the composition is less than about 6. In some embodiments, the pH of the composition is less than about 5.9. In some embodiments, the pH of the composition is less than about 5.8. In some embodiments, the pH of the composition is less than about 5.7. In some embodiments, the pH of the composition is less than about 5.6. In some embodiments, the pH of the composition is less than about 5.5. In some embodiments, the pH of the composition is less than about 5.4. In some embodiments, the pH of the composition is less than about 5.3. In some embodiments, the pH of the composition is less than about 5.2. In some embodiments, the pH of the composition is less than about 5.1. In some embodiments, the pH of the composition is less than about 5.In some embodiments, the pH of the composition is less than about 4.9. In some embodiments, the pH of the composition is less than about 4.8. In some embodiments, the pH of the composition is less than about 4.7. In some embodiments, the pH of the composition is less than about 4.6. In some embodiments, the pH of the composition is less than about 4.5. In some embodiments, the pH of the composition is less than about 4.4. In some embodiments, the pH of the composition is less than about 4.3. In some embodiments, the pH of the composition is less than about 4.2. In some embodiments, the pH of the composition is less than about 4.1. In some embodiments, the pH of the composition is less than about 4. In some embodiments, the pH is the pH of the composition after a long period of time under storage conditions.

[0143] In some examples, the pD of the composition is between approximately 4 and approximately 8, approximately 4.2 and approximately 7.9, approximately 4.5 and approximately 7.8, approximately 5 and approximately 7.5, or approximately 5.5 and approximately 7. In some embodiments, the pD of the composition is approximately 8.0. In some embodiments, the pD of the composition is approximately 7.9. In some embodiments, the pD of the composition is approximately 7.8. In some embodiments, the pD of the composition is approximately 7.7. In some embodiments, the pD of the composition is approximately 7.6. In some embodiments, the pD of the composition is less than approximately 7.5. In some embodiments, the pD of the composition is less than approximately 7.4. In some embodiments, the pD of the composition is less than approximately 7.3. In some embodiments, the pD of the composition is less than approximately 7.2. In some embodiments, the pD of the composition is less than approximately 7.1. In some embodiments, the pD of the composition is less than approximately 7. In some embodiments, the pD of the composition is less than approximately 6.9. In some embodiments, the pD of the composition is less than about 6.8. In some embodiments, the pD of the composition is less than about 6.7. In some embodiments, the pD of the composition is less than about 6.6. In some embodiments, the pD of the composition is less than about 6.5. In some embodiments, the pD of the composition is less than about 6.4. In some embodiments, the pD of the composition is less than about 6.3. In some embodiments, the pD of the composition is less than about 6.2. In some embodiments, the pD of the composition is less than about 6.1. In some embodiments, the pD of the composition is less than about 6. In some embodiments, the pD of the composition is less than about 5.9. In some embodiments, the pD of the composition is less than about 5.8. In some embodiments, the pD of the composition is less than about 5.7. In some embodiments, the pD of the composition is less than about 5.6. In some embodiments, the pD of the composition is less than about 5.5. In some embodiments, the pD of the composition is less than about 5.4. In some embodiments, the pD of the composition is less than about 5.3. In some embodiments, the pD of the composition is less than about 5.2. In some embodiments, the pD of the composition is less than about 5.1. In some embodiments, the pD of the composition is less than about 5.In some embodiments, the pD of the composition is less than about 4.9. In some embodiments, the pD of the composition is less than about 4.8. In some embodiments, the pD of the composition is less than about 4.7. In some embodiments, the pD of the composition is less than about 4.6. In some embodiments, the pD of the composition is less than about 4.5. In some embodiments, the pD of the composition is less than about 4.4. In some embodiments, the pD of the composition is less than about 4.3. In some embodiments, the pD of the composition is less than about 4.2. In some embodiments, the pD of the composition is less than about 4.1. In some embodiments, the pD of the composition is less than about 4. In some embodiments, the pD of the composition is less than 4. In some embodiments, pD is the pD of the composition after a long period of time under storage conditions.

[0144] In some examples, the initial pH of the composition is between approximately 4 and 8, approximately 4.2 and 7.9, approximately 4.5 and 7.8, approximately 5 and 7.5, or approximately 5.5 and 7. In some embodiments, the initial pH of the composition is approximately 8.0. In some embodiments, the initial pH of the composition is approximately 7.9. In some embodiments, the initial pH of the composition is approximately 7.8. In some embodiments, the initial pH of the composition is approximately 7.7. In some embodiments, the initial pH of the composition is approximately 7.6. In some embodiments, the initial pH of the composition is approximately 7.5. In some embodiments, the initial pH of the composition is approximately 7.4. In some embodiments, the initial pH of the composition is approximately 7.3. In some embodiments, the initial pH of the composition is approximately 7.2. In some embodiments, the initial pH of the composition is approximately 7.1. In some embodiments, the initial pH of the composition is approximately 7. In some embodiments, the initial pH of the composition is approximately 6.9. In some embodiments, the initial pH of the composition is approximately 6.8. In some embodiments, the initial pH of the composition is about 6.7. In some embodiments, the initial pH of the composition is about 6.6. In some embodiments, the initial pH of the composition is about 6.5. In some embodiments, the initial pH of the composition is about 6.4. In some embodiments, the initial pH of the composition is about 6.3. In some embodiments, the initial pH of the composition is about 6.2. In some embodiments, the initial pH of the composition is about 6.1. In some embodiments, the initial pH of the composition is about 6. In some embodiments, the initial pH of the composition is about 5.9. In some embodiments, the initial pH of the composition is about 5.8. In some embodiments, the initial pH of the composition is about 5.7. In some embodiments, the initial pH of the composition is about 5.6. In some embodiments, the initial pH of the composition is about 5.5. In some embodiments, the initial pH of the composition is about 5.4. In some embodiments, the initial pH of the composition is about 5.3. In some embodiments, the initial pH of the composition is about 5.2. In some embodiments, the initial pH of the composition is about 5.1. In some embodiments, the initial pH of the composition is about 5.In some embodiments, the initial pH of the composition is about 4.9. In some embodiments, the initial pH of the composition is about 4.8. In some embodiments, the initial pH of the composition is about 4.7. In some embodiments, the initial pH of the composition is about 4.6. In some embodiments, the initial pH of the composition is about 4.5. In some embodiments, the initial pH of the composition is about 4.4. In some embodiments, the initial pH of the composition is about 4.3. In some embodiments, the initial pH of the composition is about 4.2. In some embodiments, the initial pH of the composition is about 4.1. In some embodiments, the initial pH of the composition is about 4.

[0145] In some examples, the initial pD of the composition is between approximately 4 and 8, approximately 4.2 and 7.9, approximately 4.5 and 7.8, approximately 5 and 7.5, or approximately 5.5 and 7. In some embodiments, the initial pD of the composition is approximately 8.0. In some embodiments, the initial pD of the composition is approximately 7.9. In some embodiments, the initial pD of the composition is approximately 7.8. In some embodiments, the initial pD of the composition is approximately 7.7. In some embodiments, the initial pD of the composition is approximately 7.6. In some embodiments, the initial pD of the composition is approximately 7.5. In some embodiments, the initial pD of the composition is approximately 7.4. In some embodiments, the initial pD of the composition is approximately 7.3. In some embodiments, the initial pD of the composition is approximately 7.2. In some embodiments, the initial pD of the composition is approximately 7.1. In some embodiments, the initial pD of the composition is approximately 7. In some embodiments, the initial pD of the composition is approximately 6.9. In some embodiments, the initial pD of the composition is about 6.8. In some embodiments, the initial pD of the composition is about 6.7. In some embodiments, the initial pD of the composition is about 6.6. In some embodiments, the initial pD of the composition is about 6.5. In some embodiments, the initial pD of the composition is about 6.4. In some embodiments, the initial pD of the composition is about 6.3. In some embodiments, the initial pD of the composition is about 6.2. In some embodiments, the initial pD of the composition is about 6.1. In some embodiments, the initial pD of the composition is about 6. In some embodiments, the initial pD of the composition is about 5.9. In some embodiments, the initial pD of the composition is about 5.8. In some embodiments, the initial pD of the composition is about 5.7. In some embodiments, the initial pD of the composition is about 5.6. In some embodiments, the initial pD of the composition is about 5.5. In some embodiments, the initial pD of the composition is about 5.4. In some embodiments, the initial pD of the composition is about 5.3. In some embodiments, the initial pD of the composition is about 5.2. In some embodiments, the initial pD of the composition is about 5.1. In some embodiments, the initial pD of the composition is about 5.In some embodiments, the initial pD of the composition is about 4.9. In some embodiments, the initial pD of the composition is about 4.8. In some embodiments, the initial pD of the composition is about 4.7. In some embodiments, the initial pD of the composition is about 4.6. In some embodiments, the initial pD of the composition is about 4.5. In some embodiments, the initial pD of the composition is about 4.4. In some embodiments, the initial pD of the composition is about 4.3. In some embodiments, the initial pD of the composition is about 4.2. In some embodiments, the initial pD of the composition is about 4.1. In some embodiments, the initial pD of the composition is about 4.

[0146] In some embodiments, the pH of the compositions described herein is related to the stability of the composition. In some examples, stable compositions include pH values ​​between about 4 and about 8, about 4.2 and about 7.9, about 4.5 and about 7.8, about 5 and about 7.5, or about 5.5 and about 7. In some embodiments, stable compositions include a pH of about 8.0. In some embodiments, stable compositions include a pH of about 7.9. In some embodiments, stable compositions include a pH of about 7.8. In some embodiments, stable compositions include a pH of about 7.7. In some embodiments, stable compositions include a pH of about 7.6. In some embodiments, stable compositions include a pH of less than about 7.5. In some embodiments, stable compositions include a pH of less than about 7.4. In some embodiments, stable compositions include a pH of less than about 7.3. In some embodiments, stable compositions include a pH of less than about 7.2. In some embodiments, stable compositions include a pH of less than about 7.1. In some embodiments, stable compositions include a pH of less than about 7. In some embodiments, stable compositions include a pH of less than 6.9. In some embodiments, the stable composition contains a pH of less than about 6.8. In some embodiments, the stable composition contains a pH of less than about 6.7. In some embodiments, the stable composition contains a pH of less than about 6.6. In some embodiments, the stable composition contains a pH of less than about 6.5. In some embodiments, the stable composition contains a pH of less than about 6.4. In some embodiments, the stable composition contains a pH of less than about 6.3. In some embodiments, the stable composition contains a pH of less than about 6.2. In some embodiments, the stable composition contains a pH of less than about 6.1. In some embodiments, the stable composition contains a pH of less than about 6. In some embodiments, the stable composition contains a pH of less than about 5.9. In some embodiments, the stable composition contains a pH of less than about 5.8. In some embodiments, the stable composition contains a pH of less than about 5.7. In some embodiments, the stable composition contains a pH of less than about 5.6. In some embodiments, the stable composition contains a pH of less than about 5.5.In some embodiments, the stable composition contains a pH of less than about 5.4. In some embodiments, the stable composition contains a pH of less than about 5.3. In some embodiments, the stable composition contains a pH of less than about 5.2. In some embodiments, the stable composition contains a pH of less than about 5.1. In some embodiments, the stable composition contains a pH of less than about 5. In some embodiments, the stable composition contains a pH of less than about 4.9. In some embodiments, the stable composition contains a pH of less than about 4.8. In some embodiments, the stable composition contains a pH of less than about 4.7. In some embodiments, the stable composition contains a pH of less than about 4.6. In some embodiments, the stable composition contains a pH of less than about 4.5. In some embodiments, the stable composition contains a pH of less than about 4.4. In some embodiments, the stable composition contains a pH of less than about 4.3. In some embodiments, the stable composition contains a pH of less than about 4.2. In some embodiments, the stable composition contains a pH of less than about 4.1. In some embodiments, the stable composition contains a pH of less than about 4.

[0147] In some embodiments, the pD of the compositions described herein is related to the stability of the composition. In some examples, stable compositions include pDs between about 4 and about 8, about 4.2 and about 7.9, about 4.5 and about 7.8, about 5 and about 7.5, or about 5.5 and about 7. In some embodiments, stable compositions include a pD of about 8.0. In some embodiments, stable compositions include a pD of about 7.9. In some embodiments, stable compositions include a pD of about 7.8. In some embodiments, stable compositions include a pD of about 7.7. In some embodiments, stable compositions include a pD of about 7.6. In some embodiments, stable compositions include a pD of less than about 7.5. In some embodiments, stable compositions include a pD of less than about 7.4. In some embodiments, stable compositions include a pD of less than about 7.3. In some embodiments, stable compositions include a pD of less than about 7.2. In some embodiments, stable compositions include a pD of less than about 7.1. In some embodiments, stable compositions include a pD of less than about 7. In some embodiments, the stable composition contains a pD of less than about 6.9. In some embodiments, the stable composition contains a pD of less than about 6.8. In some embodiments, the stable composition contains a pD of less than about 6.7. In some embodiments, the stable composition contains a pD of less than about 6.6. In some embodiments, the stable composition contains a pD of less than about 6.5. In some embodiments, the stable composition contains a pD of less than about 6.4. In some embodiments, the stable composition contains a pD of less than about 6.3. In some embodiments, the stable composition contains a pD of less than about 6.2. In some embodiments, the stable composition contains a pD of less than about 6.1. In some embodiments, the stable composition contains a pD of less than about 6.9. In some embodiments, the stable composition contains a pD of less than about 5.8. In some embodiments, the stable composition contains a pD of less than about 5.7. In some embodiments, the stable composition contains a pD of less than about 5.6. In some embodiments, the stable composition contains a pD of less than about 5.5.In some embodiments, the stable composition contains a pD of less than about 5.4. In some embodiments, the stable composition contains a pD of less than about 5.3. In some embodiments, the stable composition contains a pD of less than about 5.2. In some embodiments, the stable composition contains a pD of less than about 5.1. In some embodiments, the stable composition contains a pD of less than about 5. In some embodiments, the stable composition contains a pD of less than about 4.9. In some embodiments, the stable composition contains a pD of less than about 4.8. In some embodiments, the stable composition contains a pD of less than about 4.7. In some embodiments, the stable composition contains a pD of less than about 4.6. In some embodiments, the stable composition contains a pD of less than about 4.5. In some embodiments, the stable composition contains a pD of less than about 4.4. In some embodiments, the stable composition contains a pD of less than about 4.3. In some embodiments, the stable composition contains a pD of less than about 4.2. In some embodiments, the stable composition contains a pD of less than about 4.1. In some embodiments, the stable composition contains a pD of less than about 4.

[0148] As described elsewhere in this specification, in some examples, the D2O / aqueous system stabilizes a muscarinic antagonist (e.g., atropine). In some embodiments, this stabilization is due to the lower concentration of the reactive species (e.g., -OD) in the D2O / aqueous system than the lower concentration of the reactive species (e.g., -OH) in the equivalent pure aqueous system. In some examples, the concentration of the reactive species (e.g., -OD) in the D2O / aqueous system is less than about one-third of the concentration of the reactive species (e.g., -OH) in the equivalent pure aqueous system. In some cases, this concentration is due to the lower or smaller dissociation constant of D2O than of H2O. For example, K a (H2O) is 1 × 10 -14 However, K a (D2O) is 1 × 10 -15Therefore, D2O is a weaker acid than H2O. In some cases, base-catalyzed hydrolysis leads to the presence of tropine degradation products from atropine. In some cases, at lower concentrations of the reactive species that cause tropine degradation product formation, the atropine solution is more stable in a D2O / aqueous system than in an equivalent pure aqueous system. In some embodiments, ophthalmic compositions formulated with deuterated water allow for more stable ophthalmic compositions compared to ophthalmic compositions formulated with H2O.

[0149] In some embodiments, the presence of deuterated water alters the pKa of the buffer. In some embodiments, the presence of deuterated water allows the ophthalmic composition to simulate lower pH stability. In some examples, the buffer capacity of the ophthalmic composition is reduced, thereby enabling a faster pH transition. In some examples, the reduced buffering capacity of the ophthalmic composition upon administration to the eye allows the ophthalmic composition to reach physiological pH at a faster rate compared to ophthalmic compositions formulated in H2O. In some examples, ophthalmic compositions formulated with deuterated water allow for reduced tear production or a decrease in the tear reflex in the eye compared to ophthalmic compositions formulated with H2O.

[0150] In some examples, the compositions described herein further include a disinfectant. In some embodiments, the disinfectant may be a high molecular weight biguanide, a high molecular weight quaternary ammonium compound, a chlorite, a bis-biguanide, a chlorite compound (e.g., potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite, or a mixture thereof), or a combination thereof.

[0151] In some examples, the compositions described herein further include preservatives. Where applicable, preservatives are added to the compositions described herein at certain concentrations to prevent the growth of microorganisms introduced into the composition or to destroy the microorganisms. In some examples, microorganisms represent bacteria (e.g., Proteus mirabilis, Serratia marcesens), viruses (e.g., herpes simplex virus, herpes zoster virus), fungi (e.g., fungi of the genus Fusarium), yeasts (e.g., Candida albicans), parasites (e.g., Plasmodium spp., Gnathostoma spp.), protozoa (e.g., Giardia lamblia), nematodes (e.g., Onchocercus volvulus), insects (e.g., Dirofilaria immitis), and / or amoebas (e.g., Acanthamoeba).

[0152] In some examples, the concentration of preservatives is between approximately 0.0001% and 1%, approximately 0.001% and 0.8%, approximately 0.004% and 0.5%, approximately 0.008% and 0.1%, and approximately 0.01% and 0.08%. Depending on the case, the concentration of preservatives may be approximately 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.008%, 0.009%, 0.009%, 0.01%, 0.015%, 0.02%, 0.025%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1.0%.

[0153] In some embodiments, the preservative is selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia(Alcon), polyquaternium-1, chlorobutanol, disodium edetate, and polyhexamethylene biguanide.

[0154] In some embodiments, the ophthalmic compositions described herein are substantially free of preservatives. In some examples, the ophthalmic compositions are substantially free of benzalkonium chloride preservatives. In some examples, the compositions do not contain detectable amounts of benzalkonium chloride preservatives. In some examples, the compositions do not contain detectable amounts of benzalkonium chloride. In some examples, the compositions are substantially free of preservatives selected from cetrimonium, sodium perborate, stabilized oxychloro complexes, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof. In some examples, the compositions do not contain detectable amounts of preservatives. In some examples, the compositions are substantially free of any preservatives.

[0155] In some embodiments, the compositions described herein are stored in plastic containers. In some embodiments, the material of the plastic container includes high-density polyethylene (HDPE), low-density polyethylene (LDPE), polyethylene terephthalate (PET), polyvinyl chloride (PVC), polypropylene (PP), polystyrene (PS), fluorinated HDPE, post-consumer resin (PCR), K-resin (SBC), or bioplastics. In some embodiments, the material of the plastic container includes LDPE.

[0156] In some embodiments, the compositions described herein are stored in plastic containers. In some embodiments, the pH of the composition stored in the plastic container is between about 4 and about 8, about 4.2 and about 7.9, about 4.5 and about 7.9, or about 4.9 and about 7.5. In some embodiments, the pH of the composition stored in the plastic container is about 7.9. In some embodiments, the pH of the composition stored in the plastic container is about 7.8. In some embodiments, the pH of the composition stored in the plastic container is about 7.7. In some embodiments, the pH of the composition stored in the plastic container is about 7.6. In some embodiments, the pH of the composition stored in the plastic container is less than about 7.5. In some embodiments, the pH of the composition stored in the plastic container is less than about 7.4. In some embodiments, the pH of the composition stored in the plastic container is less than about 7.3. In some embodiments, the pH of the composition stored in the plastic container is less than about 7.2. In some embodiments, the pH of the composition stored in the plastic container is less than about 7.1. In some embodiments, the pH of the composition stored in the plastic container is less than about 7. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.9. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.8. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.7. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.6. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.5. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.4. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.3. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.2. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.1. In some embodiments, the pH of the composition stored in the plastic container is less than about 6.In some embodiments, the pH of the composition stored in the plastic container is less than about 5.9. In some embodiments, the pH of the composition stored in the plastic container is less than about 5.8. In some embodiments, the pH of the composition stored in the plastic container is less than about 5.7. In some embodiments, the pH of the composition stored in the plastic container is less than about 5.6. In some embodiments, the pH of the composition stored in the plastic container is less than about 5.5. In some embodiments, the pH of the composition stored in the plastic container is less than about 5.4. In some embodiments, the pH of the composition stored in the plastic container is less than about 5.3. In some embodiments, the pH of the composition stored in the plastic container is less than about 5.2. In some embodiments, the pH of the composition stored in the plastic container is less than about 5.1. In some embodiments, the pH of the composition stored in the plastic container is less than about 5. In some embodiments, the pH of the composition stored in the plastic container is less than about 5. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.9. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.8. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.7. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.6. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.5. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.4. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.3. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.2. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.1. In some embodiments, the pH of the composition stored in the plastic container is less than about 4.

[0157] In some embodiments, the compositions described herein are stored in plastic containers. In some embodiments, the pD of the compositions stored in plastic containers is between about 4 and about 8, about 4.2 and about 7.9, about 4.5 and about 7.9, or about 4.9 and about 7.5. In some embodiments, the pD of the compositions stored in plastic containers is about 7.9. In some embodiments, the pD of the compositions stored in plastic containers is about 7.8. In some embodiments, the pD of the compositions stored in plastic containers is about 7.7. In some embodiments, the pD of the compositions stored in plastic containers is about 7.6. In some embodiments, the pD of the compositions stored in plastic containers is less than about 7.5. In some embodiments, the pD of the compositions stored in plastic containers is less than about 7.4. In some embodiments, the pD of the compositions stored in plastic containers is less than about 7.3. In some embodiments, the pD of the compositions stored in plastic containers is less than about 7.2. In some embodiments, the pD of the composition stored in the plastic container is less than about 7.1. In some embodiments, the pD of the composition stored in the plastic container is less than about 7. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.9. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.8. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.7. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.6. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.5. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.4. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.3. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.2. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.1. In some embodiments, the pD of the composition stored in the plastic container is less than about 6.In some embodiments, the pD of the composition stored in the plastic container is less than about 5.9. In some embodiments, the pD of the composition stored in the plastic container is less than about 5.8. In some embodiments, the pD of the composition stored in the plastic container is less than about 5.7. In some embodiments, the pD of the composition stored in the plastic container is less than about 5.6. In some embodiments, the pD of the composition stored in the plastic container is less than about 5.5. In some embodiments, the pD of the composition stored in the plastic container is less than about 5.4. In some embodiments, the pD of the composition stored in the plastic container is less than about 5.3. In some embodiments, the pD of the composition stored in the plastic container is less than about 5.2. In some embodiments, the pD of the composition stored in the plastic container is less than about 5.1. In some embodiments, the pD of the composition stored in the plastic container is less than about 5. In some embodiments, the pD of the composition stored in the plastic container is less than about 5. In some embodiments, the pD of the composition stored in the plastic container is less than about 4.8. In some embodiments, the pD of the composition stored in the plastic container is less than about 4.7. In some embodiments, the pD of the composition stored in the plastic container is less than about 4.6. In some embodiments, the pD of the composition stored in the plastic container is less than about 4.5. In some embodiments, the pD of the composition stored in the plastic container is less than about 4.4. In some embodiments, the pD of the composition stored in the plastic container is less than about 4.3. In some embodiments, the pD of the composition stored in the plastic container is less than about 4.2. In some embodiments, the pD of the composition stored in the plastic container is less than about 4.1. In some embodiments, the pD of the composition stored in the plastic container is less than about 4.

[0158] In some embodiments, the efficacy of the composition stored in a plastic container is at least about 80% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition stored in a plastic container is at least about 85% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition stored in a plastic container is at least about 90% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition stored in a plastic container is at least about 93% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition stored in a plastic container is at least about 95% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition stored in a plastic container is at least about 97% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition stored in a plastic container is at least about 98% after a long period of time under storage conditions. In some embodiments, the efficacy of the composition stored in a plastic container is at least about 99% after a long period of time under storage conditions. In some examples, the storage conditions include temperatures of about 25°C, about 40°C, or about 60°C. For some purposes, a long period of time is at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months.

[0159] In some embodiments, the efficacy of the composition stored in the plastic container is at least 80% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition stored in the plastic container is at least 85% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition stored in the plastic container is at least 90% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition stored in the plastic container is at least 93% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition stored in the plastic container is at least 95% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition stored in the plastic container is at least 97% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition stored in the plastic container is at least 98% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the efficacy of the composition stored in the plastic container is at least 99% at temperatures of about 0°C, about 2°C, about 5°C, about 10°C, about 15°C, about 25°C, about 40°C, or about 60°C. In some embodiments, the potency of the composition stored in the plastic container is at least 80%, at least 85%, at least 90%, at least 93%, at least 95%, at least 97%, at least 98%, or at least 99% at temperatures of about 0°C to about 30°C, 2°C to about 10°C, or about 16°C to about 26°C.

[0160] In some ways, the potency of a composition stored in a plastic container is at least 80% for at least one week, at least two weeks, at least three weeks, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least eight months, at least ten months, at least twelve months, at least eighteen months, or at least twenty-four months. In some ways, the potency of a composition stored in a plastic container is at least 85% for at least one week, at least two weeks, at least three weeks, at least o...

Claims

1. An ophthalmic composition having a pH of approximately 4.2 to 7.9, comprising approximately 0.001 wt% to approximately 0.5 wt% of a muscarinic antagonist and deuterated water, and substantially free of benzalkonium chloride preservative.

2. The ophthalmic composition according to claim 1, substantially free of preservatives selected from cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or combinations thereof.

3. An ophthalmic composition according to either claim 1 or 2, which does not contain a detectable amount of benzalkonium chloride preservative.

4. An ophthalmic composition according to any one of claims 1 to 3, which does not contain a detectable amount of benzalkonium chloride.

5. An ophthalmic composition according to any one of claims 1 to 4, which does not contain a detectable amount of preservative.

6. The ophthalmic composition according to any one of claims 1 to 5, wherein the muscarinic antagonist comprises atropine, atropine sulfate, noatropine, atropine-n-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof.

7. The ophthalmic composition according to claim 1, wherein the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine.

8. The aforementioned muscarinic antagonist is present in amounts of approximately 0.001 wt% to approximately 0.40 wt%, approximately 0.001 wt% to approximately 0.30 wt%, approximately 0.001 wt% to approximately 0.20 wt%, approximately 0.001 wt% to approximately 0.10 wt%, approximately 0.001 wt% to approximately 0.09 wt%, approximately 0.001 wt% to approximately 0.08 wt%, approximately 0.001 wt% to approximately 0.07 wt%, approximately 0.001 wt% to approximately 0.06 wt%, and approximately 0.001 wt% to approximately 0.0 The ophthalmic composition according to claim 1, wherein the ophthalmic composition is present in one of the following concentrations: 5 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%.

9. The ophthalmic composition according to claim 1, wherein the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.001 wt% to about 0.10 wt%.

10. An ophthalmic composition according to any one of claims 1 to 8, further comprising 0.004 wt% to about 0.20 wt% citrate.

11. An ophthalmic composition according to any one of claims 1 to 8, further comprising a molar osmotic pressure concentration adjusting agent.

12. The ophthalmic composition according to claim 11, wherein the molar osmotic pressure concentration adjusting agent is sodium chloride.

13. The ophthalmic composition according to claim 12, wherein the sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%.

14. An ophthalmic composition according to any one of claims 1 to 13, further comprising a buffering agent.

15. The ophthalmic composition according to claim 14, wherein the buffering agent is selected from boroate, boroate-polyol complex, phosphate buffering agent, citrate buffering agent, acetate buffering agent, carbonate buffering agent, organic buffering agent, amino acid buffering agent, or a combination thereof.

16. An ophthalmic composition according to any one of claims 1 to 15, which essentially does not contain procaine and benactidine, or pharmaceutically acceptable salts thereof.

17. An ophthalmic composition according to any one of claims 1 to 16, further comprising a pH adjuster.

18. The pH adjusting agent is DCl, HCl, NaOH, NaOD, CD ３ COOD, C ６ D ８ O ７ ,CH ３ COOH, C ６ H ８ O ７ The ophthalmic composition according to claim 17, comprising, or a combination thereof.

19. The ophthalmic composition according to claim 1, comprising less than 10% of the degradation product of the muscarinic antagonist resulting from the degradation of the muscarinic antagonist.

20. An ophthalmic composition having a pH of about 4.2 to about 7.9, comprising about 0.001 wt% to about 0.5 wt% of a muscarinic antagonist, deuterated water, and one or more sodium phosphate buffers, wherein at least one of the sodium phosphate buffers is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%.

21. The ophthalmic composition according to claim 20, wherein the muscarinic antagonist comprises atropine, atropine sulfate, noatropine, atropine-n-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof.

22. The ophthalmic composition according to claim 20, wherein the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine.

23. The ophthalmic composition according to claim 20, wherein the first sodium phosphate buffer of the one or more sodium phosphate buffers is anhydrous monosodium phosphate.

24. The ophthalmic composition according to claim 23, wherein the anhydrous monosodium phosphate is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%.

25. The ophthalmic composition according to claim 23, wherein the second sodium phosphate buffer of the one or more sodium phosphate buffers is anhydrous disodium phosphate.

26. The ophthalmic composition according to claim 25, wherein the anhydrous disodium phosphate is present in the ophthalmic composition at a concentration of about 0.050 wt% to about 2.0 wt%.

27. The aforementioned muscarinic antagonist is present in amounts of approximately 0.001 wt% to approximately 0.40 wt%, approximately 0.001 wt% to approximately 0.30 wt%, approximately 0.001 wt% to approximately 0.20 wt%, approximately 0.001 wt% to approximately 0.10 wt%, approximately 0.001 wt% to approximately 0.09 wt%, approximately 0.001 wt% to approximately 0.08 wt%, approximately 0.001 wt% to approximately 0.07 wt%, approximately 0.001 wt% to approximately 0.06 wt%, and approximately 0.001 wt% to approximately 0.0 The ophthalmic composition according to claim 20, wherein the ophthalmic composition contains one of the following concentrations: 5 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%.

28. The ophthalmic composition according to claim 20, wherein the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.001 wt% to about 0.10 wt%.

29. The ophthalmic composition according to claim 20, which is essentially free of citrate buffering agents and acetate buffering agents.

30. An ophthalmic composition according to any one of claims 20 to 29, further comprising a molar osmotic pressure concentration adjusting agent.

31. The ophthalmic composition according to claim 30, wherein the molar osmotic pressure concentration adjusting agent is sodium chloride.

32. The ophthalmic composition according to claim 31, wherein the sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%.

33. An ophthalmic composition according to any one of claims 20 to 32, which does not contain a preservative selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or a combination thereof.

34. The ophthalmic composition according to claim 33, which is substantially free of benzalkonium chloride preservatives.

35. An ophthalmic composition according to any one of claims 20 to 34, which is substantially free of any preservatives.

36. An ophthalmic composition according to any one of claims 20 to 35, further comprising a buffering agent.

37. The ophthalmic composition according to claim 36, wherein the buffering agent is selected from boroate, boroate-polyol complex, phosphate buffering agent, citrate buffering agent, acetate buffering agent, carbonate buffering agent, organic buffering agent, amino acid buffering agent, or a combination thereof.

38. An ophthalmic composition according to any one of claims 20 to 37, further comprising EDTA.

39. The ophthalmic composition according to claim 38, wherein the EDTA is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.50 wt%.

40. An ophthalmic composition according to any one of claims 20 to 39, which essentially does not contain procaine and benactidine or pharmaceutically acceptable salts thereof.

41. An ophthalmic composition according to any one of claims 20 to 40, further comprising a pH adjuster.

42. The pH adjuster is DCl, HCl, NaOH, NaOD, CD ３ COOD, C ６ D ８ O ７ , CH ３ COOH, C ６ H ８ O ７ The ophthalmic composition according to claim 41, comprising or a combination thereof.

43. An ophthalmic composition with a pH of approximately 4.2 to 7.9, comprising approximately 0.001 wt% to approximately 0.5 wt% of a muscarinic antagonist, deuterated water, and approximately 0.01 wt% to approximately 0.50 wt% of EDTA.

44. The ophthalmic composition according to claim 43, wherein the muscarinic antagonist comprises atropine, atropine sulfate, noatropine, atropine-n-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof.

45. The ophthalmic composition according to claim 43, wherein the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine.

46. The ophthalmic composition according to any one of claims 43 to 45, further comprising one or more sodium phosphate buffers.

47. The ophthalmic composition according to claim 46, wherein the first sodium phosphate buffer of the one or more sodium phosphate buffers is anhydrous monosodium phosphate.

48. The ophthalmic composition according to claim 47, wherein the anhydrous sodium phosphate is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%.

49. The ophthalmic composition according to claim 46, wherein the second sodium phosphate in the one or more sodium phosphate buffers is anhydrous disodium phosphate.

50. The ophthalmic composition according to claim 49, wherein the anhydrous disodium phosphate is present in the ophthalmic composition at a concentration of about 0.050 wt% to about 2.0 wt%.

51. The aforementioned muscarinic antagonist is present in amounts of approximately 0.001 wt% to approximately 0.40 wt%, approximately 0.001 wt% to approximately 0.30 wt%, approximately 0.001 wt% to approximately 0.20 wt%, approximately 0.001 wt% to approximately 0.10 wt%, approximately 0.001 wt% to approximately 0.09 wt%, approximately 0.001 wt% to approximately 0.08 wt%, approximately 0.001 wt% to approximately 0.07 wt%, approximately 0.001 wt% to approximately 0.06 wt%, and approximately 0.001 wt% to approximately 0.0 The ophthalmic composition according to claim 43, wherein the ophthalmic composition contains one of the following concentrations: 5 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%.

52. The ophthalmic composition according to claim 43, wherein the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.001 wt% to about 0.10 wt%.

53. An ophthalmic composition according to any one of claims 43 to 52, further comprising 0.004 wt% to about 0.20 wt% of citrate.

54. An ophthalmic composition according to any one of claims 43 to 53, further comprising a molar osmotic pressure concentration adjusting agent.

55. The ophthalmic composition according to claim 54, wherein the molar osmotic pressure concentration adjusting agent is sodium chloride.

56. The ophthalmic composition according to claim 55, wherein the sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%.

57. An ophthalmic composition according to any one of claims 43 to 56, which does not contain a preservative selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or a combination thereof.

58. The ophthalmic composition according to claim 57, which is substantially free of benzalkonium chloride preservatives.

59. An ophthalmic composition according to any one of claims 43 to 58, which is substantially free of any preservatives.

60. An ophthalmic composition according to any one of claims 43 to 59, further comprising a buffering agent.

61. The ophthalmic composition according to claim 60, wherein the buffering agent is selected from boroate, boroate-polyol complex, phosphate buffering agent, citrate buffering agent, acetate buffering agent, carbonate buffering agent, organic buffering agent, amino acid buffering agent, or a combination thereof.

62. An ophthalmic composition according to any one of claims 43 to 61, which essentially does not contain procaine and benactidine or pharmaceutically acceptable salts thereof.

63. An ophthalmic composition according to any one of claims 43 to 62, further comprising a pH adjuster.

64. The pH adjusting agent is DCl, HCl, NaOH, NaOD, CD ３ COOD, C ６ D ８ O ７ ,CH ３ COOH, C ６ H ８ O ７ The ophthalmic composition according to claim 63, comprising, or a combination thereof.

65. An ophthalmic composition having a pH of approximately 4.2 to approximately 7.9, comprising approximately 0.001 wt% to approximately 0.5 wt% of a muscarinic antagonist, deuterated water, and water, wherein the ratio of water to deuterated water is in the range of 60:40 to approximately 99:

1.

66. The ophthalmic composition according to claim 65, wherein the muscarinic antagonist comprises atropine, atropine sulfate, noatropine, atropine-n-oxide, tropine, tropic acid, hyostine, scopolamine, tropicamide, cyclopentolate, pirenzepine, homatropin, or a combination thereof.

67. The ophthalmic composition according to claim 65, wherein the muscarinic antagonist is atropine or a pharmaceutically acceptable salt of atropine.

68. The aforementioned muscarinic antagonist is present in amounts of approximately 0.001 wt% to approximately 0.40 wt%, approximately 0.001 wt% to approximately 0.30 wt%, approximately 0.001 wt% to approximately 0.20 wt%, approximately 0.001 wt% to approximately 0.10 wt%, approximately 0.001 wt% to approximately 0.09 wt%, approximately 0.001 wt% to approximately 0.08 wt%, approximately 0.001 wt% to approximately 0.07 wt%, approximately 0.001 wt% to approximately 0.06 wt%, and approximately 0.001 wt% to approximately 0.0 The ophthalmic composition according to claim 65, wherein the ophthalmic composition contains one of the following concentrations: 5 wt%, approximately 0.001 wt% to approximately 0.04 wt%, approximately 0.001 wt% to approximately 0.03 wt%, approximately 0.001 wt% to approximately 0.025 wt%, approximately 0.001 wt% to approximately 0.02 wt%, approximately 0.001 wt% to approximately 0.01 wt%, approximately 0.001 wt% to approximately 0.008 wt%, or approximately 0.001 wt% to approximately 0.005 wt%.

69. The ophthalmic composition according to claim 65, wherein the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.001 wt% to about 0.10 wt%.

70. The ophthalmic composition according to claim 65, wherein the ratio of water to deuterated water is in the range of about 80:20 to about 60:

40.

71. The ophthalmic composition according to claim 65, wherein the ratio of water to deuterated water is approximately 65:

35.

72. The ophthalmic composition according to claim 65, wherein the ratio of water to deuterated water is approximately 90:

10.

73. The ophthalmic composition according to claim 65, wherein the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.05 wt%.

74. The ophthalmic composition according to claim 65, wherein the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.03 wt%.

75. The ophthalmic composition according to claim 65, wherein the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.01 wt%.

76. The ophthalmic composition according to claim 65, wherein the muscarinic antagonist is present in the ophthalmic composition at a concentration of about 0.03 wt%.

77. An ophthalmic composition according to any one of claims 65 to 76, which is substantially free of benzalkonium chloride preservatives.

78. An ophthalmic composition according to any one of claims 65 to 76, which does not contain a detectable amount of benzalkonium chloride preservative.

79. An ophthalmic composition according to any one of claims 65 to 76, which does not contain a detectable amount of preservatives.

80. The ophthalmic composition according to claim 65, wherein the pH is approximately 5.1 to approximately 6.

0.

81. The ophthalmic composition according to claim 65, wherein the pH is approximately 5.54 to approximately 5.

59.

82. An ophthalmic composition according to any one of claims 65 to 81, further comprising 0.004 wt% to about 0.20 wt% of citrate.

83. An ophthalmic composition according to any one of claims 65 to 82, further comprising one or more sodium phosphate buffers.

84. The ophthalmic composition according to claim 83, wherein the first sodium phosphate buffer of the one or more sodium phosphate buffers is anhydrous monosodium phosphate.

85. The ophthalmic composition according to claim 84, wherein the anhydrous monosodium phosphate is present in the ophthalmic composition at a concentration of about 0.004 wt% to about 0.20 wt%.

86. The ophthalmic composition according to claim 85, wherein the second sodium phosphate of the one or more sodium phosphate buffers is anhydrous disodium phosphate.

87. The ophthalmic composition according to claim 86, wherein the anhydrous disodium phosphate is present in the ophthalmic composition at a concentration of about 0.050 wt% to about 2.0 wt%.

88. An ophthalmic composition according to any one of claims 65 to 87, further comprising a molar osmotic pressure concentration adjusting agent.

89. The ophthalmic composition according to any one of claims 65 to 88, wherein the molar osmotic pressure concentration adjusting agent is sodium chloride.

90. The ophthalmic composition according to claim 89, wherein the sodium chloride is present in the ophthalmic composition at one of the following concentrations: about 0.01 wt% to about 1.0 wt%, about 0.05 wt% to about 1.5 wt%, about 0.075 wt% to about 2.0 wt%, or about 0.1 wt% to about 3.0 wt%.

91. An ophthalmic composition according to any one of claims 65 to 90, which does not contain a preservative selected from benzalkonium chloride, cetrimonium, sodium perborate, stabilized oxychloro complex, SofZia, polyquaternium-1, chlorobutanol, disodium edetate, polyhexamethylene biguanide, or a combination thereof.

92. The ophthalmic composition according to claim 91, which is substantially free of benzalkonium chloride preservatives.

93. An ophthalmic composition according to any one of claims 65 to 92, which is substantially free of any preservatives.

94. An ophthalmic composition according to any one of claims 65 to 93, further comprising a buffering agent.

95. The ophthalmic composition according to claim 94, wherein the buffering agent is selected from boroate, boroate-polyol complex, phosphate buffering agent, citrate buffering agent, acetate buffering agent, carbonate buffering agent, organic buffering agent, amino acid buffering agent, or a combination thereof.

96. An ophthalmic composition according to any one of claims 65 to 95, further comprising EDTA.

97. The ophthalmic composition according to claim 96, wherein the EDTA is present in the ophthalmic composition at a concentration of about 0.01 wt% to about 0.50 wt%.

98. An ophthalmic composition according to any one of claims 65 to 97, which essentially does not contain procaine and benactidine or pharmaceutically acceptable salts thereof.

99. An ophthalmic composition according to any one of claims 65 to 98, further comprising a pH adjuster.

100. The pH adjusting agent is DCl, HCl, NaOH, NaOD, CD ３ COOD, C ６ D ８ O ７ ,CH ３ COOH, C ６ H ８ O ７ The ophthalmic composition according to claim 99, comprising, or a combination thereof.

101. The ophthalmic composition according to claim 65, comprising less than 10% of the degradation product of the muscarinic antagonist resulting from the degradation of the muscarinic antagonist.

102. An ophthalmic composition according to any one of claims 1 to 101, formulated as an ophthalmic solution for treating premyopia, myopia, the progression of myopia, or slowing the progression of myopia.

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