Pharmaceutical compositions having desirable bioavailability
View Patent ↗The present invention is directed to the provision of pharmaceutical compositions. The compositions include a therapeutic agent and a relatively low amount of surfactant for providing higher bioavailability of the therapeutic agent. The compositions are particularly desirable as ophthalmic compositions in which the therapeutic agent is a prostaglandin such as travoprost and the surfactant is a vegetable oil such as castor oil.
1. A pharmaceutical composition, comprising:
an ophthalmic pharmaceutical vehicle suitable for topical application to an eye of a human;
an amount of prostaglandin suitable for reducing intraocular pressure of the eye; and
surfactant at a relatively low concentration, the concentration being sufficient for providing a high degree of bioavailability of the therapeutic agent, wherein:
i. the amount of surfactant is below 0.4 w/v % of the composition;
ii. the surfactant is entirely ethoxylated and/or hydrogenated vegetable oil; and
iii. the ethoxylated and/or hydrogenated vegetable oil is the only surfactant in the composition;
iv. the composition is substantially free of any benzalkonium chloride; and
v. the pharmaceutical vehicle includes water.
2. A composition as in claim 1 further comprising a carbonic anhydrase inhibitor wherein the surfactant acts a wetting agent for the carbonic anhydrase inhibitor.
3. A composition as in claim 1 wherein an area under a concentration/time curve when determined for the pharmaceutical composition of the present invention as applied to a biological target is at least 200% relative to a area under a concentration/time curve when determined for a control composition as applied to the biological target, the control composition being substantially identical to the pharmaceutical composition with the exception that the concentration of surfactant is at least doubled and wherein the biological target is eyes of rabbits and concentrations for the concentration/time curve are based upon measurements of prostaglandin in the aqueous humor of the eye of the rabbits.
4. A composition as in claim 1 wherein the prostaglandin is travoprost.
5. A composition as in claim 1 wherein the surfactant is a castor oil.
6. A composition as in claim 1 wherein the surfactant is Polyoxyl 40 Hydrogenated castor oil.
7. A composition as in claim 1 wherein the surfactant is less than 0.3 w/v % of the composition.
8. A composition as in claim 1 wherein the composition satisfies Ph. Eur. A, Ph. Eur. B or both.
9. A composition as in claim 1 wherein the composition is free of any chlorine containing preservation agents.
10. A composition as in claim 1 wherein the prostaglandin is dissolved in aqueous solution with the assistance of the surfactant.
11. A pharmaceutical composition, comprising:
an ophthalmic pharmaceutical vehicle suitable for topical application to an eye of a human;
an amount of prostaglandin suitable for reducing intraocular pressure of the eye; and
surfactant at a relatively low concentration, the concentration being sufficient for providing a high degree of bioavailability of the therapeutic agent, wherein:
i. the amount of surfactant is below 0.3 w/v % of the composition;
ii. the surfactant is entirely ethoxylated and/or hydrogenated vegetable oil;
iii. the ethoxylated and/or hydrogenated vegetable oil is the only surfactant in the composition;
iv. the prostaglandin is travoprost;
v. the pharmaceutical vehicle includes water; and
vi. the composition is substantially free of any benzalkonium chloride.
12. A composition as in claim 11 wherein the surfactant is Polyoxyl 40 Hydrogenated castor oil.
13. A composition as in claim 11 wherein the surfactant is less than 0.3 w/v % of the composition.
14. A composition as in claim 12 wherein the surfactant is less than 0.3 w/v % of the composition.
15. A composition as in claim 11 wherein the composition satisfies Ph. Eur. A, Ph. Eur. B or both.
16. A composition as in claim 1 wherein the ophthalmic pharmaceutical vehicle includes a preservative system comprised of a borate, a polyol or both.
17. A composition as in claim 11 wherein the ophthalmic pharmaceutical vehicle includes a preservative system comprised of a borate, a polyol or both.