Pharmaceutical compositions for the treatment of ophthalmic conditions
The invention provides emulsion compositions comprising at least one cannabinoid compound, and methods for making the same. The emulsion compositions are stable, well tolerated and are capable of delivering therapeutically effective amounts of cannabiniods to target sites, including sites on the surface of and/or within an eye. Also provided are methods of using the compositions to provide ocular neuroprotection and/or to treat ophthalmic conditions such as glaucoma.
1. An emulsion composition, comprising:
about 0.005% (w/w) to about 0.5% (w/w) of (−)-trans-Δ 9 -tetrahydrocannabinol, or a pharmaceutically acceptable salt thereof;
about 1.5% (w/w) to about 2.0% (w/w) of sesame oil;
about 0.5% (w/w) to about 2% (w/w) of polyoxyethylene sorbitan monooleate;
about 2.5% (w/w) glycerin;
about 0.03% (w/w) butylated hydroxytoluene (BHT) and/or 0.03% (w/w) beta hydroxy acid (BHA); and
water,
wherein the ratio (w/w) of oil to water in the composition is in the range of about 1:20 to about 1:100, the emulsion comprises an oil phase component comprising a plurality of oil droplets dispersed with an aqueous phase component, wherein at least 90% of the oil droplets in the emulsion are less than about 200 nm in diameter, wherein the emulsion remains stable after being stored at a condition selected from the group consisting of: at least two years at about −18° C.; at least three months at about 4° C.; and at least one month at about 23° C., such that there is an absence of visible phase separation between the oil phase component and the aqueous phase component after such storage condition, the (−)-trans-Δ 9 -tetrahydrocannabinol remains chemically stabile in the composition such that at least about 90% (w/w) of the initial (−)-trans-Δ 9 -tetrahydrocannabinol content in the emulsion is present after exposure of the emulsion to the storage condition.
2. A method of treating an ophthalmic condition in a subject in need thereof, the method comprising administering to the eye of the subject a therapeutically effective amount of the emulsion composition of claim 1 , wherein said method provides ocular neuroprotection to the subject.
3. The method of claim 2 , wherein the subject is suffering from or is at substantial risk of developing a neuropathic condition.
4. The method of claim 3 , wherein the neuropathic condition is a blinding eye disease or neuropathic pain.
5. The method of claim 3 , wherein the neuropathic condition is a disease selected from the group consisting of macular degeneration, retinitis pigmentosa, and glaucoma.
6. A method of preparing the emulsion composition of claim 1 , comprising:
combining (−)-trans-Δ 9 -tetrahydrocannabinol or a pharmaceutically acceptable salt thereof, sesame oil, polyoxyethylene sorbitan monooleate, and a first portion of water to form a premix;
homogenizing the premix to form a homogenized premix;
adding a second portion of water after the homogenization step to form a bulk sample;
filtering the bulk sample over a membrane to afford the emulsion composition.
7. A method of preparing the emulsion composition of claim 1 , comprising:
combining (−)-trans-Δ 9 -tetrahydrocannabinol or a pharmaceutically acceptable salt thereof, sesame oil, polyoxyethylene sorbitan monooleate, and a first portion of water to form a premix;
homogenizing the premix at a speed of about 3000 rpm to about 5000 rpm for a time period of about 2 minutes to about 20 minutes to form a homogenized premix;
adjusting the pH of the homogenized premix solution to about 6.5 to about 7.5 to form a neutralized premix;
adding a second portion of water to the neutralized premix to form a bulk sample;
filtering the bulk sample over a membrane having a maximum pore size of about 200 nm to afford the emulsion composition.
8. An emulsion composition, comprising:
about 0.05% (w/w) to about 0.5% (w/w) of (−)-trans-Δ9-tetrahydrocannabinol, or a pharmaceutically acceptable salt thereof;
about 1.5% (w/w) of sesame oil;
about 2% (w/w) of (polyoxyethylene sorbitan monooleate);
about 2.5% (w/w) glycerin;
about 0.03% (w/w) butylated hydroxytoluene (BHT) and/or 0.03% (w/w) beta hydroxy acid (BHA); and
water,
wherein the emulsion comprises an oil phase component comprising a plurality of oil droplets, dispersed with an aqueous phase component, wherein the emulsion remains stable after being stored at a condition selected from the group consisting of: at least two years at about −18° C.; at least three months at about 4° C.; and at least one month at about 23° C., such that about 90% (w/w) of the initial (−)-trans-Δ 9 -tetrahydrocannabinol content in the emulsion is present after exposure of the emulsion to the storage condition.
9. The emulsion composition of claim 8 , wherein the composition is a topical formulation suitable for administration to the eye.
10. The emulsion composition of claim 8 , wherein the ratio (w/w) of oil to water in the composition is in the range of about 1:20 to about 1:100.
11. The emulsion composition of claim 8 , wherein the osmolarity of the emulsion is substantially similar to human tear fluid osmolarity.
12. The emulsion composition of claim 11 , having an osmolarity of about 300 mOsm/L to about 340 mOsm/L.
13. A method of treating an ophthalmic condition in a subject in need thereof, the method comprising administering to the eye of the subject a therapeutically effective amount of the emulsion composition of claim 8 , wherein said method provides ocular neuroprotection to the subject.
14. The method of claim 13 , wherein the subject is suffering from or is at substantial risk of developing a neuropathic condition.
15. The method of claim 14 , wherein the neuropathic condition is a blinding eye disease or neuropathic pain.
16. The method of claim 14 , wherein the neuropathic condition is a disease selected from the group consisting of macular degeneration, retinitis pigmentosa, and glaucoma.
17. A method of treating an ophthalmic condition in a subject identified in need of such treatment, the method comprising administering to the eye of the subject a therapeutically effective amount of the emulsion composition of claim 8 .
18. The method of claim 17 , wherein the ophthalmic condition is selected from the group consisting of glaucoma, age-related macular degeneration (AMD), ophthalmitis, and conjunctivitis dry eye disease, posterior uveitis, retinitis, uveoretinitis, proliferative vitreoretinopathy, anterior uveitis, episcleritis, scleritis, ocular neuropathic pain and ocular inflammation caused by a non-infectious condition.
19. A method of preparing the emulsion composition of claim 8 , comprising:
combining (−)-trans-Δ 9 -tetrahydrocannabinol or a pharmaceutically acceptable salt thereof, sesame oil, polyoxyethylene sorbitan monooleate, and a first portion of water to form a premix;
homogenizing the premix to form a homogenized premix;
adding a second portion of water after the homogenization step to form a bulk sample;
filtering the bulk sample over a membrane to afford the emulsion composition.
20. A method of preparing the emulsion composition of claim 8 , comprising:
combining (−)-trans-Δ 9 -tetrahydrocannabinol or a pharmaceutically acceptable salt thereof, sesame oil, polyoxyethylene sorbitan monooleate, and a first portion of water to form a premix;
homogenizing the premix at a speed of about 3000 rpm to about 5000 rpm for a time period of about 2 minutes to about 20 minutes to form a homogenized premix;
adjusting the pH of the homogenized premix solution to about 6.5 to about 7.5 to form a neutralized premix;
adding a second portion of water to the neutralized premix to form a bulk sample;
filtering the bulk sample over a membrane having a maximum pore size of about 200 nm to afford the emulsion composition.