Topical Ophthalmic Compositions

Abstract

The topical ophthalmic composition includes a muscarinic receptor antagonist as an active pharmaceutical ingredient and a medium chain triglyceride (MCT) or light liquid paraffin oil as a liquid vehicle. The topical ophthalmic composition treats ophthalmic diseases.

Description

[Technical field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 145,091, filed February 3, 2021, which is incorporated by reference for all purposes as if fully set forth herein.

[0002] (Technical field) The present invention relates to topical ophthalmic compositions of muscarinic receptor antagonists dissolved in medium chain triglycerides (MCT) or light liquid paraffin oil as the liquid vehicle, and formulations of atropine are used to treat myopia. [Background technology]

[0003] Atropine is an antimuscarinic compound, a competitive antagonist of muscarinic receptors, with antiparasympathetic function, and is used for several indications, including anticholinergic intoxication and bradycardia. In the eye, atropine is traditionally used to dilate the pupil. Recently, it has been shown that low doses of atropine can inhibit the progression of myopia in young adults (Li 2019: Non-Patent Document 3). Atropine has only been approved for myopia in a few countries so far.

[0004] Myopia is a condition in which nearby objects are seen clearly, but distant objects appear blurry. Myopia occurs when the eyeball is too long or the cornea (the transparent front covering of the eyeball) is too curved to properly focus distant objects on the retina. Myopia is the most common eye disease in the world. Approximately 30 percent of the population in the United States is myopic. The etiology of myopia is unknown. Genetics is thought to play a role in myopia. The development of myopia can be influenced by how a person uses their eyes. Myopia can develop in school-age children and progress until around age 20. However, visual stress and health conditions such as diabetes can also cause myopia to develop in adults. Myopia can increase the risk of other eye diseases (Wu 2019: Non-Patent Document 5).

[0005] Atropine solution (aqueous) formulations have been tested in multiple clinical trials and have been shown to slow the progression of myopia (Cooper 2018: Non-Patent Document 2, Li 2019: Non-Patent Document 3, Yam 2020: Non-Patent Document 6). In aqueous formulations, atropine is prone to decomposition in neutral pH solutions when the container is open to air, so the shelf life of the product at neutral pH is often less than one year. To increase the stability of atropine in solution, the pH in the formulation has been lowered to 3-6 (Berton 2020: Non-Patent Document 1; Saito 2019: Non-Patent Document 4). However, it is also known that low pH can cause irritation and discomfort to the eyes. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Berton B, Chennell P, Yessaad M, BouattourY, Jouannet M, Wasiak M, Sautou V. Stability of Ophthalmic Atropine Solutions for Child Myopia Control.PharmaceutiCS.2020 Aug 17;12(8):E781. [Non-Patent Document 2] Cooper J,Tkatchenko AV.A Review of CurrentConcepts of the Etiology and Treatment of Myopia.Eye Contact Lens.2018 Jul;44(4):231-247. [Non-Patent Document 3] Li FF,Yam JC.Low-Concentration Atropine Eye Drops for Myopia Progression.Asia Pac J Ophthalmol(Phila).2019 Sep-Oct;8(5):360-365. [Non-Patent Document 4] Saito J, Imaizumi H, Yamatani A.Physical, chemical, and microbiological stability study of diluted atropine eye drops.J Pharm Health Care Sci.2019 Dec 5;5:25. [Non-Patent Document 5] Wu PC, Chuang MN, Choi J, Chen H, Wu G, Ohno-Matsui K, Jonas JB, Cheung CMG. Update in myopia and treatment strategy of atropine use in myopia control.Eye(Lond).2019 Jan;33(1):3-13. [Non-Patent Document 6] Yam JC,Li FF,Zhang Summary of the Invention [Problem to be solved by the invention]

[0007] In the present invention, an organic liquid carrier is used to create a more stable and less irritating atropine formulation for ophthalmic, particularly myopic, indications.

[0008] Additionally, atropine solutions have been used to produce cycloplegic refraction in a subject's eye, to produce pupil dilation in a subject's eye, to treat amblyopia or lazy eye in children, to reduce the symptoms of floaters, to treat or prevent painful ciliary muscle spasms, or to treat the progression of myopia in pediatric subjects. [Means for solving the problem]

[0009] (Summary of the invention) In one embodiment, the present invention provides a topical ophthalmic composition comprising a muscarinic receptor antagonist as an active pharmaceutical ingredient (API) and a liquid vehicle selected from the group consisting of medium chain triglycerides (MCT) and light liquid paraffin oil, the topical ophthalmic composition treating an ophthalmic disease.

[0010] In other embodiments, the muscarinic receptor antagonist is selected from the group consisting of atropine, pirenzepine, aclidinium bromide, benztropine, cyclopentolate, diphenhydramine, doxylamine, dimenhydrinate, dicyclomine, darifenacin, flavoxate, hydroxyzine, ipratropium, mebeverine, oxybutynin, procyclidine, scopolamine, solifenacin, tropicamide, tiotropium, trihexyphenidyl, and tolterodine.

[0011] In another embodiment, the muscarinic receptor antagonist is atropine.

[0012] In another embodiment, the atropine is in a free base or salt form.

[0013] In other embodiments, the concentration of the atropine in free base form is about 0.001% to about 0.1% (w / w).

[0014] In another embodiment, the atropine free base is incorporated into the MCT or is incorporated into the light liquid paraffin.

[0015] In another embodiment, The MCT is a triglyceride of fatty acids; The fatty acid is selected from the group consisting of hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid.

[0016] In another embodiment, the topical ophthalmic composition further comprises a partially fluorinated alkane compound having the formula RFRH or RFRHRF, where RF is a perfluorinated hydrocarbon having 1-15 carbon atoms and RH is a non-fluorinated hydrocarbon having 1-15 carbon atoms.

[0017] In another embodiment, the weight ratio of the MCT or the light liquid paraffin oil to the partially fluorinated alkane is 99-1.

[0018] In another embodiment, the partially fluorinated alkane is selected from the group consisting of perfluorobutylpentane (F4H5), perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyldecane (F6H10), preferably the partially fluorinated alkane is F6H8 (perfluorohexyloctane).

[0019] In other embodiments, the topical ophthalmic composition further comprises an organic co-solvent selected from the group consisting of phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, and polyethylene glycol, preferably, the organic co-solvent is phenethyl alcohol.

[0020] In another embodiment, the concentration of the phenethyl alcohol is from about 0.01% to about 1% (w / w).

[0021] In other embodiments, the topical ophthalmic composition is a non-aqueous solution, suspension, or emulsion.

[0022] In other embodiments, the atropine is chemically stable for at least 0.5 years, at least 1 year, or at least 2 years.

[0023] In other embodiments, the topical ophthalmic composition is adapted to be administered topically as eye drops to the patient's eye.

[0024] In another embodiment, the topical ophthalmic composition causes minimal irritation to the eye.

[0025] In another embodiment, the eye condition is myopia.

[0026] In another embodiment, the topical ophthalmic composition comprises: Slows the progression of myopia, Treating amblyopia in children Reduce the symptoms of floaters, or Treats or prevents painful ciliary muscle spasms.

[0027] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.

[0028] The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention. [Brief description of the drawings]

[0029] [Figure 1] The chromatogram of atropine (tR: 12.947) standard solution is shown. [Diagram 2] 1 shows the measured pupil size 7 days after administration in Example 5. [Diagram 3] 1 shows the measured pupil size on day 22 after administration in Example 5. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0030] Reference will now be made in detail to the embodiments of the present invention, examples of which are illustrated in the accompanying drawings.

[0031] Muscarinic receptor antagonist is an anticholinergic agent that inhibits the activity of muscarinic acetylcholine receptor.The muscarinic receptor antagonist is atropine, pirenzepine, aclidinium bromide, benztropine, cyclopentolate, diphenhydramine, doxylamine, dimenhydrinate, dicyclomine, darifenacin, flavoxate, hydroxyzine, ipratropium, mebeverine, oxybutynin, procyclidine, scopolamine, solifenacin, tropicamide, tiotropium, trihexyphenidyl, or tolterodine.Preferably, the muscarinic receptor antagonist is atropine or pirenzepine.More preferably, the muscarinic receptor antagonist is atropine.

[0032] Medium chain triglycerides (MCTs) are triglycerides of fatty acids. The fatty acids have fatty chains of 6 to 12 carbon atoms, and may be, for example, hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid. MCTs may be a single triglyceride or a mixture of multiple triglycerides. A representative chemical structure of MCTs is shown below. [ka]

[0033] Light liquid paraffin oil (Paraffinum liquidum) is a refined mineral oil used in cosmetics and pharmaceuticals. Light liquid paraffin oil contains a mixture of liquid saturated hydrocarbons.

[0034] Partially fluorinated alkanes are amphiphilic liquids that are formed by covalently bonding two immiscible segments (hydrocarbon segments and perfluorinated segments). Examples of partially fluorinated alkanes include perfluorobutylpentane (F4H5), perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyldecane (F6H10), and preferably include perfluorobutylpentane (F4H5), perfluorohexylhexane (F6H6), and perfluorohexyloctane (F6H8).

[0035] The structure of F6H8 is shown below. [ka]

[0036] Atropine solution (aqueous) formulations have already proven effective in treating myopia, particularly in slowing the progression of myopia. This solution formulation has two drawbacks. The first drawback is that the shelf life of the product at neutral pH is often less than one year, because atropine at neutral pH in solution is susceptible to degradation when the container is open to air. Furthermore, this instability of atropine in this solution requires that the formulation be used within about one month. The second drawback is that a low pH, such as pH 3.5-6.0, used to reduce the degradation of atropine to enhance the shelf life of the product, can cause irritation or discomfort to the human eye, as reported by patients in adverse events. The term "about" means a range of +20% to -20% of the value, +10% to -10% of the value, or +5% to -5% of the value.

[0037] In order to overcome the above two drawbacks of solution formulations, the present disclosure provides a composition that uses MCT or light liquid paraffin oil as a liquid vehicle to dissolve atropine. As shown in the examples, the present disclosure demonstrates that these vehicles can dissolve atropine in a concentration range sufficient to be effective in treating myopia.

[0038] In some embodiments, the present disclosure is based on the studies described in the Examples which show that atropine can be dissolved in MCT or light liquid paraffin oil at concentrations sufficient to have biological effectiveness.

[0039] In some embodiments, a co-solvent and / or a partially fluorinated alkane is added to the formulation. The co-solvent may be, for example, phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, or polyethylene glycol. The co-solvent and the partially fluorinated alkane improve the solubility of atropine and the stability of the formulation over time. EXAMPLES

[0040] Example 1: Dissolution of atropine in MCT or light liquid paraffin oil

[0041] Methods: The formulation of atropine free base was investigated using the following procedure.

[0042] 1. Dissolution of atropine Atropine powder, 4 mg or more, is added to 4 mL of study solvent and the formulation is stirred for 2 days.

[0043] 2. HPLC Sample Preparation The above formulations were centrifuged and the supernatants were filtered through a 0.45 micron filter without further dilution. One sample was prepared from each solvent for HPLC analysis.

[0044] 3. HPLC Sample Analysis The samples were analyzed by RP-HPLC using an Agilent Eclipse Plus C18 HPLC column (150 mm x 2.1 mm ID) connected to a guard column (12.5 mm x 2.1 mm ID) with a gradient elution from 100% water to 100% acetonitrile at a flow rate of 0.2 ml / min. The chromatogram was monitored with UV at 220 nm. The atropine peak is at retention time 12.947 as shown in the chromatogram in Figure 1.

[0045] result The solubility of atropine free base in MCT or light liquid paraffin oil is shown in Table 1.

[0046] [Table 1]

[0047] Atropine free base was determined to be soluble in light liquid paraffin oil at 75 μg / ml (0.0075% w / w). Addition of 0.1% ethanol to the light liquid paraffin oil increased the solubility to 82 μg / ml, and addition of 0.25% phenethyl alcohol to the light liquid paraffin oil increased the solubility to over 100 μg / ml. Atropine free base was determined to be soluble in MCT at 3100 μg / ml (0.31% w / w). This particular study used the free base form of atropine, but the monosulfate salt is already used in solution formulations approved for myopia. The molecular weight (MW) of the free base corresponds to 83% of the monosulfate form of atropine solution formulations. A 0.01% atropine monosulfate solution has already been shown to be effective in the clinic for the treatment of myopia and is approved in several countries. This 0.01% atropine salt concentration was equivalent to a free base concentration of 0.0083%. The solubility we observed in MCT well exceeds that required for efficacy, and the concentration in light liquid paraffin is within the effective range. In the present application, the concentration of atropine in its free base form may be about 0.001% to about 0.5% (w / w), or about 0.001% to about 0.1% (w / w), e.g., about 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, or any range thereof.

[0048] Example 2: Miscibility of partially fluorinated alkanes in MCT or light liquid paraffin oil

[0049] The miscibility of F6H8, a partially fluorinated alkane, with MCT was tested at ratios of F6H8:MCT ranging from 1:99 to 99:1. As a result, F6H8 was miscible with MCT at all ratios. The miscibility of F6H8, a partially fluorinated alkane, with light liquid paraffin oil was tested at ratios of F6H8:light liquid paraffin oil ranging from 1:99 to 99:1. As a result, F6H8 was miscible with light liquid paraffin oil at all ratios.

[0050] Example 3: Atropine solubility in MCT and F6H8 formulations with and without co-solvent

[0051] The solubility of atropine in formulations of MCT and F6H8 with and without the co-solvent phenethyl alcohol was determined using formulation preparation and sample analysis methods similar to those described in Example 1. The results are summarized in Table 2.

[0052] [Table 2]

[0053] The data showed that atropine was well soluble in mixtures of MCT and F6H8 at various ratios ranging from 10% MCT:90% F6H8 to 70% MCT:30% F6H8. The solubility of atropine in mixtures of MCT and F6H8 was further improved by adding the co-solvent phenethyl alcohol. Compared to the solubility of atropine in 100% F6H8, the solubility of atropine was significantly improved with the addition of MCT or with the co-solvent phenethyl alcohol.

[0054] Example 4: Stability of Atropine in Formulations of MCT and F6H8 with and without Co-Solvents

[0055] Using formulation preparation and sample analysis methods similar to those described in Example 1, the stability of atropine at room temperature in formulations of MCT and F6H8 with and without the co-solvent phenethyl alcohol was monitored at baseline, 1 month, 2 months, and 3 months. The results are summarized in Tables 3-7.

[0056] [Table 3]

[0057] [Table 4] [Table 5]

[0058] [Table 6]

[0059] [Table 7]

[0060] Data showed that atropine at doses of 0.01%, 0.025%, and 0.05% was stable at room temperature for at least 3 months in formulations containing MCT, F6H8, and / or phenethyl alcohol.

[0061] Example 5: In vivo pharmacological and ocular toxicity studies in a rabbit model

[0062] The purpose of this study was to determine the pharmacological effects and potential ocular toxicity of atropine formulations in 0.25% phenylethyl alcohol, 10% MCT, and 89.75% F6H8. Test substances were administered by topical eye drops to New Zealand White rabbits twice daily for 28 days. Pharmacological effects were measured as pupil dilation in normal naive rabbits. Three concentrations of atropine in the formulations (0.01%, 0.025%, 0.05%) were compared to that of an aqueous formulation containing 0.03% atropine sulfate, a salt known to have good pupil dilation effects. The formulation without atropine served as the vehicle control for the study.

[0063] Test Design

[0064] The study design is shown in Table 8. Forty-eight rabbits (24 per sex) were randomly assigned into five groups to determine the toxicity of atropine when administered twice daily for 28 days via topical eye drops. The control group received vehicle. Animals were randomly assigned to each group based on weight. The control and high dose groups had six animals per sex per group, and the low, mid, and comparison groups had four animals per sex per group. The last surviving animals from the control and high dose groups were assigned for evaluation of recovery.

[0065] [Table 8]

[0066] Atropine in vehicle or control or comparative substance alone was administered to the left eye of the animals by topical eye drop twice a day, approximately 12 hours apart, for 28 days. The right eye was left untreated as a control eye. The left eye of the animals was administered 40 μL / eye by topical eye drop.

[0067] The study included various in-life measurements including survival rate, clinical findings, body weight, food consumption, ophthalmologic examination, intraocular pressure, electroretinography, as well as pharmacological evaluation of pupil size measurements. In addition, necropsy macroscopic examination, gross observations, organ weight measurements, and histopathology were performed at the end of the study. The study followed Good Laboratory Practice (GLP).

[0068] result

[0069] Pharmacology Evaluation: During acclimation prior to the start of dosing, pupil size was measured in both eyes of all animals on three separate days to establish baseline and acclimation of the animals to the procedure. Results are shown in Figure 2 (pupillary size measurements on day 7 post-dose) and Figure 3 (pupillary size measurements on day 22 post-dose). Pupil size was measured in both eyes of all animals at baseline (30 minutes prior to dosing) and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the first dose on days 7 and 22. CBT-009 stands for atropine. Data showed that pupil dilation was observed in all three groups receiving 0.01%, 0.025%, and 0.05% CBT-009 (atropine), as well as a comparison group receiving an aqueous formulation of 0.03% atropine sulfate, but no change in pupil size was observed in the vehicle-treated group. In addition, a dose response of pupil dilation was observed for atropine from 0.01% to 0.05% on both days 7 and 22. The magnitude of change in pupil size was comparable between F6H8-based atropine formulations and aqueous atropine sulfate at comparable doses.

[0070] Ocular Toxicity: Male and female New Zealand White rabbits were administered F6H8f-based formulations containing 0.01%, 0.025%, and 0.05% atropine, control vehicle, or a 0.03% aqueous atropine sulfate comparator by topical instillation twice daily. The right eye was untreated. Following the end of the dosing period, terminal animals were euthanized and recovery animals were maintained for a 14-day recovery period and then euthanized. All animals were maintained for a 14-day recovery period and then euthanized. All terminal and recovery animals survived until scheduled euthanasia. There were no atropine-related macroscopic (gross necropsy) or microscopic findings in ocular or non-ocular tissues at any time. A small number of microscopic findings in various ocular and nonocular tissues in males and females in the control, atropine-treated, and / or comparison groups during both periods were considered incidental and unrelated to atropine. Treatment was well tolerated in all study groups, and no animal deaths were observed during the study.

[0071] Example 6: In vivo ocular tolerability testing in a rabbit model

[0072] Test Design

[0073] Three female Dutch Belted rabbits were administered 40 μL of 100% MCT containing 0.012% atropine free base to the right eye and 40 μL of 100% light liquid paraffin (LLP) containing 0.012% atropine free base to the left eye, one drop per eye, twice a day, 12 hours apart, for 14 consecutive days. Eye discomfort observations and eye irritation observations were performed on all animals before administration (twice on different days) and daily during the administration phase after administration of the last dose of the day. Corneal examinations were performed on all animals once before administration and once after administration of the last dose of the day on days 1 and 14. The first administration day was designated D1, and the last administration day was designated D14.

[0074] The eye irritation results are shown in Tables 9 and 10.

[0075] [Table 9]

[0076] [Table 10]

[0077] The atropine formulation was well tolerated in all rabbits. No significant eye irritation or ophthalmic findings were observed in any of the animals. There were no test article related effects on body weight and food consumption during the study. There were no other test article related ophthalmic findings at scheduled examinations of all animals. No or only mild (+1) conjunctival swelling or hyperemia was observed during the study. This example demonstrates the safety of the claimed novel formulation of ophthalmic atropine.

[0078] Example 7: In vivo ocular tolerability testing in a dog model

[0079] Test Design

[0080] Three male beagle dogs were administered 40 μL of 100% MCT containing 0.012% atropine free base to the right eye and 40 μL of 100% LLP containing 0.012% atropine free base to the left eye, one drop per eye, twice a day, 12 hours apart, for 14 consecutive days. Eye discomfort observations and eye irritation observations were performed on all animals before dosing (twice on different days) and daily during the dosing phase after the last dose of the day. Corneal examinations were performed on all animals once before dosing and once after the last dose of the day on days 1 and 14. The first dosing day was designated D1, and the last dosing day was designated D14.

[0081] The eye irritation results are shown in Tables 11 and 12.

[0082] [Table 11]

[0083] [Table 12]

[0084] The atropine formulation was well tolerated in all dogs. No significant eye irritation or ophthalmic findings were observed in any animal. There were no test article related effects on body weight and food consumption during the study. There were no other test article related ophthalmic findings at scheduled examinations of all animals. No or only mild (+1) conjunctival swelling or hyperemia was observed during the study. This example demonstrates the safety of the claimed novel formulation of ophthalmic atropine.

[0085] References 1.Berton B, Chennell P, Yessaad M, BouattourY, Jouannet M, Wasiak M, Sautou V. Stability of Ophthalmic Atropine Solutions for Child Myopia Control.PharmaceutiCS.2020 Aug 17;12(8):E781. 2.Cooper J,Tkatchenko AV.A Review of CurrentConcepts of the Etiology and Treatment of Myopia.Eye Contact Lens.2018 Jul;44(4):231-247. 3.Li FF,Yam JC.Low-Concentration Atropine Eye Drops for Myopia Progression.Asia Pac J Ophthalmol(Phila).2019 Sep-Oct;8(5):360-365. 4.Saito J, Imaizumi H, Yamatani A.Physical, chemical, and microbiological stability study of diluted atropine eye drops.J Pharm Health Care Sci.2019 Dec 5;5:25. 5.Wu PC,Chuang MN,Choi J,Chen H,Wu G,Ohno-Matsui K,Jonas JB, Cheung CMG. Update in myopia and treatment strategy of atropine use in myopia control.Eye(Lond).2019 Jan;33(1):3-13. 6.Yam JC,Li FF,Zhang X,Tang SM,Yip BHK,Kam KW,Ko ST,Young AL,Tham CC, Chen LJ,Pang CP.Two-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression(LAMP)Study:Phase 2 Report.Ophthalmology.2020 Jul;127(7):910-919.

Claims

1. 1. A topical ophthalmic composition comprising: about 0.001% to about 0.1% (w / w) of atropine as an active pharmaceutical ingredient (API); A medium chain triglyceride (MCT) liquid vehicle; a partially fluorinated alkane compound selected from the group consisting of perfluorobutylpentane (F4H5), perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyldecane (F6H10); A topical ophthalmic composition that is non-aqueous.

2. The MCT is present in a concentration of about 10% to about 70% (w / w); 2. The topical ophthalmic composition of claim 1, wherein the partially fluorinated alkane compound is present in a concentration of about 30% to about 90% (w / w).

3. The topical ophthalmic composition of claim 1, wherein the atropine is present at a concentration of about 0.002% to 0.04% (w / w).

4. The topical ophthalmic composition of claim 3, wherein the atropine is in free base form.

5. The topical ophthalmic composition of claim 1, wherein the MCT is a triglyceride of a fatty acid selected from the group consisting of hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid.

6. The MCT is present in a concentration of about 10% (w / w), 2. The topical ophthalmic composition of claim 1, wherein the partially fluorinated alkane compound is present in a concentration of about 90% (w / w).

7. The topical ophthalmic composition of claim 1, wherein the partially fluorinated alkane is perfluorohexyl octane (F6H8).

8. The topical ophthalmic composition of claim 1, wherein the MCT comprises octanoic acid, decanoic acid, or a combination thereof.

9. 10. The topical ophthalmic composition of claim 1, wherein the atropine in the topical ophthalmic composition is chemically stable for at least one year.

10. 1. A topical ophthalmic composition comprising: about 0.001% to about 0.1% (w / w) of atropine in free base form as an active pharmaceutical ingredient (API); about 10% to about 50% (w / w) of a medium chain triglyceride (MCT) liquid vehicle; from about 50% to about 90% (w / w) of a partially fluorinated alkane compound selected from the group consisting of perfluorobutylpentane (F4H5), perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyldecane (F6H10); A topical ophthalmic composition that is non-aqueous.

11. The method of claim 10, wherein the MCT is present in a concentration of about 10% (w / w); 11. The topical ophthalmic composition of claim 10, wherein the partially fluorinated alkane compound is present in a concentration of about 90% (w / w).

12. The topical ophthalmic composition of claim 11, wherein the atropine is present at a concentration of about 0.002% to 0.04%, and the atropine is in free base form.

13. 10. A topical ophthalmic composition according to claim 1 for slowing the progression of myopia in a subject or for reducing the symptoms of floaters in a subject, comprising: A topical ophthalmic composition that is administered to the eye of a subject.

14. A topical ophthalmic composition as described in claim 10 for slowing the progression of myopia in a subject or for reducing the symptoms of floaters in a subject, comprising: A topical ophthalmic composition that is administered to the eye of a subject.

15. The method of claim 1, wherein the MCT is present in a concentration of about 10% to about 20% (w / w); The topical ophthalmic composition of claim 10, wherein the partially fluorinated alkane compound is present in a concentration of about 80% to about 90% (w / w).

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