PHARMACEUTICAL COMPOSITIONS HAVING DESIRABLE BIOAVAILABILITY

• US 20090234004A1
• Filed: 03/13/2009
• Published: 09/17/2009
• Est. Priority Date: 03/17/2008
• Status: Abandoned Application

• Current Assignee: Alcon Research Limited (Nestle SA)
• Original Assignee: Alcon Research Limited (Nestle SA)
• Inventors: Martinez, Carmen, Jimenez, Nuria, Cuchi, Monica, Galan, Francisco Javier, Puig, Elena Gonzalez, Carreras, Nuria, Mridvika, Kabra, Bhagwati P.
• Application Number:
  US12/403,543
• Publication Number:
  US 20090234004A1
• Time in Patent Office: Days
• US Class Current: 514/530
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61K 31/542 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

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.

Claims

1. A pharmaceutical composition, comprising:

an ophthalmic pharmaceutical vehicle suitable for topical application to an eye of a human;

a combination of a first therapeutic agent and a second therapeutic agent wherein the first therapeutic agents is a carbonic anhydrase inhibitor;

a surfactant that acts a wetting agent for the carbonic anhydrase inhibitor and is at a sufficiently low level to promote the bioavailability of the second therapeutic agent wherein the surfactant is at a concentration below 0.4 w/v %.

2. A composition as in claim 1 wherein the composition is an aqueous suspension and the second therapeutic agent is at least 90% solubilized within the composition and the first therapeutic agent is suspended within the composition.

3. A composition as in claim 1 wherein the surfactant is the single and only surfactant in the composition.

4. A composition as in claim 1 wherein an effectively low amount of surfactant is provided such that 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 having at least double the amount of surfactant relative to the pharmaceutical composition.

5. A composition as in claim 1 wherein:

i. the surfactant includes ethoxylated and/or hydrogenated vegetable oil;

ii. the second therapeutic agent is a prostaglandin; and

iii. the pharmaceutical vehicle includes water.

6. A composition as in claim 5 wherein the second therapeutic agent is travoprost.

7. A composition as in claim 1 wherein the surfactant is ethoxylated and/or hydrogenated vegetable oil.

8. A composition as in claim 1 wherein the surfactant is a castor oil.

9. A composition as in claim 1 wherein the surfactant is Polyoxyl 40 Hydrogenated castor oil.

10. A composition as in claim 1 wherein the surfactant is less than 0.3 w/v % of the composition.

11. A composition as in claim 1 wherein the composition satisfies Ph. Eur. A, Ph. Eur. B or both.

12. A composition as in claim 1 wherein the composition is free of any chlorine containing agents.

13. A composition as in claim 1 wherein the composition is free of any benzalkonium chloride.

14. A composition as in claim 1 wherein the second therapeutic agent is less than about 0.01 w/v % of the composition.

15. A composition as in claim 1 wherein the second therapeutic agent is non-ionic and relatively insoluble in aqueous solution.

16. A composition as in claim 15 wherein the therapeutic agent is dissolved in aqueous solution with the assistance of the surfactant.

17. A pharmaceutical composition, comprising:

a pharmaceutical vehicle suitable for topical application to a biological target;

a combination of a first therapeutic agent and a second therapeutic agent wherein the first therapeutic agents is a carbonic anhydrase inhibitor;

a surfactant that acts a wetting agent for the carbonic anhydrase inhibitor and is at a sufficiently low level to promote the bioavailability of the second therapeutic agent wherein the surfactant is at a concentration below 0.4 w/v % and wherein the surfactant is the single and only surfactant in the composition and wherein;

i. the surfactant includes ethoxylated and/or hydrogenated vegetable oil;

ii. the second therapeutic agent is a prostaglandin;

iii. the pharmaceutical vehicle includes water; and

iv. wherein the composition is substantially free of any benzalkonium chloride.

18. A composition as in claim 17 wherein the surfactant is Polyoxyl 40 Hydrogenated castor oil.

19. A composition as in claim 17 wherein the surfactant is less than 0.3 w/v % of the composition.

20. A composition as in claim 19 wherein the composition satisfies Ph. Eur. A, Ph. Eur. B or both.