High-concentration lidocaine compositions and methods for their preparation
View Patent ↗A composition comprising lidocaine-containing liposomes wherein the weight concentration of lidocaine in said composition is greater than 10%. The composition is prepared by mixing water with an oil phase comprising lidocaine, a C 14 -C 20 alcohol, an alkyl ester of a fatty acid, propylene glycol, and a polyalkyl stearate. The non-aqueous phase may also include a phospholipid such as phosphatidyl choline.
1. A method for preparing a composition comprising topical anesthetic containing liposomes wherein the weight concentration of the topical anesthetic in said composition is greater than 10%, said method comprising:
providing a non-aqueous composition, said non-aqueous composition comprising:
a topical anesthetic,
a C 14 -C 20 alcohol,
an alkyl ester of a fatty acid,
propylene glycol,
a polyalkyl stearate;
providing an aqueous composition comprising water; and
mixing said aqueous composition and said non-aqueous composition so as to form a liposomal structure wherein said liposomes are disposed in said aqueous composition and wherein the concentration of said topical anesthetic in said composition is greater than 10%.
2. The method of claim 1 , wherein said topical anesthetic is lidocaine.
3. The method of claim 1 , wherein said non-aqueous composition further includes a phospholipid.
4. The method of claim 3 , wherein said phospholipid is phosphatidyl choline.
5. The method of claim 1 , wherein said non-aqueous composition further includes benzyl alcohol.
6. The method of claim 1 , wherein said non-aqueous composition further includes one or more of: a polysorbate, vitamin E, cholesterol, and an emulsifier.
7. The method of claim 1 , wherein said C 14 -C 20 alcohol comprises a C 16 -C 18 alcohol.
8. The method of claim 1 , wherein said C 14 -C 20 alcohol comprises cetostearyl alcohol.
9. The method of claim 1 , wherein said alkyl ester of a fatty acid comprises a C 1 -C 4 ester of a C 8 -C 18 fatty acid.
10. The method of claim 8 , wherein said alkyl ester of a fatty acid comprises isopropyl myristate.
11. The method of claim 1 , wherein said polyalkyl stearate comprises a polyoxyethylene derivative of stearic acid.
12. The method of claim 2 , wherein said lidocaine comprises, on a weight basis, 20-30% of said non-aqueous phase.
13. The method of claim 1 , wherein said C 14 -C 20 alcohol comprises, on a weight basis, 10-30% of said non-aqueous phase.
14. The method of claim 1 , wherein said alkyl ester of a fatty acid comprises, on a weight basis, 5-15% of said non-aqueous phase.
15. The method of claim 1 , wherein said propylene glycol comprises, on a weight basis, 10-30% of said non-aqueous phase.
16. The method of claim 1 , wherein said polyalkyl stearate comprises, on a weight basis, 0.5-5% of said non-aqueous composition.
17. The method of claim 3 , wherein said phospholipid comprises, on a weight basis, 10-20% of said non-aqueous phase.
18. The method of claim 1 , wherein said step of mixing said non-aqueous composition and said aqueous composition comprises mixing equal weight amounts of said aqueous composition and said non-aqueous composition.
19. A composition made according to the method of claim 2 .
20. A method of making a composition comprising lidocaine-containing liposomes wherein the weight concentration of lidocaine in said composition is greater than 10%, said method comprising the steps of:
preparing a non-aqueous composition, said non-aqueous composition comprising, on a weight basis, 4% benzyl alcohol, 11.5% isopropyl myristate, 0.6% cholesterol, 2.0% polyoxyethylene stearate, 20% cetostearyl alcohol, 20% propylene glycol, 0.6% vitamin E acetate, 3.0% polysorbate, 14.64% phosphatidyl choline, and 25% lidocaine;
providing an aqueous composition comprising water; and
mixing approximately equal weight amounts of said non-aqueous composition and said water, and stirring said composition so as to form said liposomes.