Enhanced solubility drug-containing formulations
This invention describes compositions comprising at least 75 mg/mL of solubilized otherwise poorly soluble drug in an aqueous environment, wherein the composition further comprises a combination of 3 or more acids. Methods of providing analgesia, anti-pyretic effects or reducing pain in a subject presenting with a pain condition, and methods of reducing administration site irritation, inflammation or a combination thereof in a subject presenting with a pain condition, comprising the steps of administering such compositions and infusion pumps containing such compositions are also described.
1. A composition comprising an aqueous solution comprising drug selected from the group consisting of bupivacaine, ropivacaine, mepivacaine, levobupivacaine, procaine, chloroprocaine, etidocaine, prilocaine, and tetracaine, wherein a concentration of the drug in the aqueous solution is at least 75 mg/mL.
2. The composition of claim 1 , wherein the aqueous solution is prepared by adding to said drug in a free-base form a combination of 3 or more acids.
3. The composition of claim 2 , wherein each acid of said combination of 3 or more acids is selected from the group consisting of acetic, phosphoric, hydrochloric and sulfuric acids.
4. The composition of claim 2 , wherein each acid of said combination of 3 or more acids is selected from the group consisting of acetic, phosphoric, hydrochloric, sulfuric, and citric acids.
5. The composition of claim 2 , wherein said combination of 3 or more acids comprises a combination of four or more acids.
6. The composition of claim 5 , wherein said combination of 3 or more acids is a combination of four acids.
7. The composition of claim 1 , wherein said drug is an anesthetic.
8. The composition of claim 1 , wherein said drug is bupivacaine or ropivacaine.
9. The composition of claim 2 , wherein said drug is bupivacaine and said combination of acids consists essentially of sulfuric, acetic, phosphoric and hydrochloric acid at a 6:1:1:2 molar ratio.
10. The composition of claim 2 , wherein said drug is ropivacaine and said combination of acids consists essentially of sulfuric, acetic, phosphoric and hydrochloric acid at a 6:1:1:2 molar ratio.
11. The composition of claim 1 , wherein said solution has a pH of from about 5 to about 5.6.
12. The composition of claim 2 , wherein said combination of 3 or more acids includes 4 acids, at a 6:1:1:2 molar ratio of sulfuric:acetic:phosphoric:hydrochloric acid ratio.
13. The composition of claim 2 , wherein the combination of 3 or more acids is added to the drug at a molar ratio of the drug to the acids of between 1.5-1.
14. The composition of claim 2 , wherein said combination of 3 or more acids comprises a combination of at least one strong acid and at least one weak acid.
15. The composition of claim 14 , wherein the at least one weak acid has is a pKa value being at least 2 less than a pKa value of said drug.
16. The composition of claim 15 , wherein the at least one strong acid has a pKa value being at least 2 less than a pKa value of said at least one weak acid.
17. The composition of claim 16 , wherein the at least one strong acid is selected from the group consisting of hydrochloric, hydrobromic, nitric, sulfuric, methanesulfonic, ethanesulfonic, benzenesulfonic or toluenesulfonic acid.
18. The composition of claim 1 , wherein said composition is preservative-free, excipient free or a combination thereof.
19. The composition of claim 1 , wherein said solution is provided in a volume of 5-10 mL.
20. A method of providing analgesia, anti-pyretic effects or reducing pain in a subject presenting with a pain condition, comprising the steps of: administering the composition of claim 1 .
21. A method of reducing administration site irritation, inflammation or a combination thereof in a subject presenting with a pain condition, comprising the steps of: administering the composition of claim 1 .
22. The method of claim 20 , wherein said method makes use of a selectively activatable body-worn infusion-pump assembly.
23. The method of claim 22 , wherein said infusion-pump assembly comprises said composition formulated for single use delivery in a volume not to exceed 10 mL of the solution.
24. A drug infusion pump loaded with the composition of claim 1 .