EMULSIONS FOR LOCAL ANESTHETICS
An emulsion and use of an emulsion for pain relief comprising a local anesthetic, lecithin, oil and an aqueous phase, wherein the local anesthetic is non-covalent bound to the emulsion oil droplets and the emulsion is physically and chemically stable and the emulsion provides better safety, extended release pharmacokinetics and a prolonged duration of action of the local anesthetic.
1 . An emulsion composition comprising:
(a) an amide local anesthetic at a concentration up to 4% by weight of the emulsion,
(b) an oil phase, comprising lecithin and a vegetable oil at a weight ratio between 2:1 to 5:4, at a concentration between about 20% and 99.8% by weight of the emulsion, and
(c) an aqueous phase,
wherein the emulsion contains particles or droplets with an average diameter between about 100 and 2500 nanometers.
2 . The composition of claim 1 , wherein the amide local anesthetic is a member selected from the group consisting of lidocaine, bupivacaine, prilocaine, levobupivacaine, ropivacaine, mepivacaine, etidocaine, articaine, dibucaine, and pharmaceutically acceptable salts thereof.
3 . The composition of claim 1 , wherein the amide local anesthetic is ropivacaine freebase, a pharmaceutically acceptable ropivacaine salt or a mixture thereof.
4 . The composition 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.
5 . The composition of claim 4 , wherein the vegetable oil is sesame oil.
6 . The composition of claim 1 , wherein the lecithin is a member selected from the group consisting of LIPOID S75, LIPOID S 100, LIPOID E80, Phospholipon 90 G and a combination thereof.
7 . The composition of claim 1 , wherein the lecithin contains no less than 75% by weight phosphatidylcholine.
8 . The composition of claim 1 , wherein the emulsion further comprises a water-miscible organic solvent selected from a group consisting of ethanol, propylene glycol, glycerol and liquid polyethylene glycol.
9 . The composition of claim 1 , wherein the emulsion is of the water-in-oil type, oil-in-water type or a mixture thereof.
10 . The composition of claim 1 , wherein the emulsion contains both ionized and nonionized forms of a local anesthetic.
11 . The composition of claim 1 , wherein the emulsion contains a base in a quantity sufficient to convert 5 to 25% mole percent (% mol) of a ropivacaine salt to the nonionized ropivacaine form.
12 . The composition of claim 1 , wherein the emulsion contains an acid in a sufficient quantity to convert 75 to 95% mole percent (% mol) of a ropivacaine freebase to the ionized ropivacaine form.
13 . The composition of claim 11 , wherein the base is a member selected from the group consisting of sodium hydroxide, potassium hydroxide, arginine, lysine and a combination thereof.
14 . The composition of claim 12 , wherein the acid is a member selected from the group consisting of hydrochloric acid, acetic acid, citric acid, methanesulfonic acid and sulfuric acid and a combination thereof.
15 . The composition of claim 1 , wherein the emulsion has a viscosity between about 2 and 600 centipoise.
16 . The composition of claim 1 , wherein the emulsion has a pH of between about 4 and about 7.
17 . The composition of claim 1 , wherein the composition is a translucent or white opaque liquid and is filterable through a 0.2-micron filter.
18 . The composition of claim 1 , wherein more than 90% by weight of the amide local anesthetic is non-covalently bound to the emulsion oil droplets.
19 . The composition of claim 1 , wherein the emulsion oil droplets are non-liposomal and substantially free of the liposomal bilayer membrane structure.
20 . The composition of claim 1 , wherein the emulsion is diluted with normal saline at 2:1 or greater volume ratio (normal saline:emulsion) or diluted with water at 4:1 or greater volume ratio (water:emulsion) before administration.