Emulsions for local anesthetics
Use of an emulsion for pain relief comprising a local anesthetic, lecithin, oil and an aqueous phase, wherein local anesthetic is non-covalent bound to the emulsion oil droplets and the emulsion is physically and chemically stable and said emulsion provides better safety, extended release pharmacokinetics and a prolonged duration of action of the local anesthetic.
1. A method for relief of a pain in a subject in need thereof, the method comprising:
administering to the subject an effective amount of a water-in-oil emulsion composition, comprising:
an amide local anesthetic, which is ropivacaine, a pharmaceutically acceptable salt thereof or a combination thereof, wherein the amide local anesthetic is no more than about 4% by weight of the emulsion;
an oil phase, the oil phase comprising lecithin and a vegetable oil at a weight ratio between 2:1 to 5:4; and
a water-miscible organic solvent between 6% and 10% of the emulsion weight;
an aqueous phase, where the water content is less than 5% of the emulsion weight, wherein small water droplets are dispersed in the oil phase and
the emulsion contains particles or water droplets with a diameter between about 30 nm and about 500 nm.
2. The method of claim 1 , wherein the vegetable oil is a member selected from the group consisting of sesame oil, soybean oil, olive oil and a combination thereof.
3. The method of claim 2 , wherein the vegetable oil which is sesame oil.
4. The method of claim 1 , wherein the lecithin is a member selected from the group consisting of LIPOID S75, LIPOID S 100, LIPOID E80, Phospholipond 90G and a combination thereof.
5. The method of claim 1 , wherein the lecithin contains no less than 75% by weight phosphatidylcholine.
6. The method of claim 1 , wherein the water-miscible organic solvent selected from a group consisting of ethanol, propylene glycol, glycerol and liquid polyethylene glycol.
7. The method of claim 1 , wherein the composition has a viscosity between about 2 and about 40,000 centipoises.
8. The method of claim 1 , wherein the composition is a translucent or white opaque liquid and is filterable through a 0.2-micron filter.
9. The method of claim 1 , wherein more than 90% by weight of the amide local anesthetic is non-covalently bound to the oil droplets.
10. The method of claim 1 , wherein the oil droplets or particles in the emulsion are non-liposomal and substantially free of liposomal bilayer membrane structure.
11. The method of claim 1 , wherein the composition is diluted with saline to a 2:1 ratio or greater, which represents volume of diluent-to-the volume of emulsion, or with water to a 4:1 ratio or greater before administration.
12. The method of claim 1 , wherein the composition is administered to the subject by a member selected from the group consisting of wound infiltration, instillation, and nerve block.
13. The method of claim 1 , wherein the composition is administered using a syringe, a syringe with a needle or a syringe with a catheter.
14. The method of claim 1 , wherein the composition is provided in a vial or a syringe, ready-to-inject or ready-to-administer.
15. The method of claim 1 , wherein administration of the composition provides a prolonged pharmacokinetic profile with a lower C max , longer T max and greater T 1/2 compared to the same local anesthetic in a solution formulation.
16. The method of claim 1 , wherein administering the ropivacaine composition by wound infiltration or instillation maintains a ropivacaine plasma level below its cardiotoxic level.
17. The method of claim 1 , wherein the administration of the composition does not cause any detectable local anesthetic systemic toxicity (LAST).
18. The method of claim 1 , wherein the pain is a member selected from the group consisting of somatogenic, neurogenic, and psychogenic pain.
19. The method of claim 1 , wherein the pain is post-operative pain or cancer pain.
20. The method of claim 1 , wherein administration of the composition provides pain relief for at least 24 hours in the subject.
21. The method of claim 1 , wherein the composition provides pain relief by reducing the pain intensity as measured by a pain intensity scale by no less than 10% for up to 72 hours.
22. The method of claim 1 , wherein administration of the composition provides a quick onset of relief within 60 minutes and lasts for about 48-72 hours after administration.
23. The method of claim 1 , wherein the composition provides a delay or reduction in opioid use by the subject.
24. The method of claim 1 , wherein the emulsion composition comprises about 30% to about 40% vegetable oil by weight of the emulsion.
25. The method of claim 1 , wherein the emulsion composition comprises about 50% to about 60% lecithin by weight of the emulsion.
26. The method of claim 1 , wherein the emulsion composition comprises:
about 2.55% w/w ropivacaine HCl monohydrate;
about 52% w/w soy lecithin;
about 0.02% w/w EDTA disodium dihydrate;
about 8% w/w ethanol;
about 36% w/w sesame oil; and
about 0.1% w/w L-cysteine.