THIN FILM WITH HIGH LOAD OF ACTIVE INGREDIENT

• US 20140333003A1
• Filed: 05/09/2013
• Published: 11/13/2014
• Est. Priority Date: 05/09/2013
• Status: Active Grant

• Current Assignee: CURE Pharmaceutical Incorporated
• Original Assignee: CURE Pharmaceutical Holding Corp.
• Inventors: Allen, Eric, Davidson, Robert Steven, Bernardo, Jose
• Granted Patent: US 10,413,516 B2
• Time in Patent Office: Days
• US Class Current: 264/211
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence

Abstract

A method of preparing a thin film, the method comprising: (a) mixing a lipid, emulsifier, and solvent to provide a uniform first mixture; (b) contacting an active ingredient with the uniform first mixture to provide a thickened second mixture; (c) contacting a binder with the thickened second mixture to provide a slurry; and (d) hot extruding, casting, and condensing the slurry to provide the thin film; or cooling, shearing, mixing, casting, and condensing the slurry to provide the thin film.

Claims

1. A method of preparing a thin film, the method comprising:

(a) mixing a lipid, emulsifier, and solvent to provide a uniform first mixture;

(b) contacting an active ingredient with the uniform first mixture to provide a thickened second mixture;

(c) contacting a binder with the thickened second mixture to provide a slurry; and

(d) hot extruding, casting, and condensing the slurry to provide the thin film;

or cooling, shearing, mixing, casting, and condensing the slurry to provide the thin film.

2. The method of claim 1, wherein the mixing comprises blending, carried out at a temperature of about 130-140°

F. (54.4-60°

C.).

3. The method of claim 1, wherein the contacting of the active ingredient with the uniform first mixture comprises initially contacting a non-sticky binder with the uniform first mixture, and subsequently contacting a sticky binder with the uniform first mixture.

4. The method of claim 1, wherein the contacting of the active ingredient with the uniform first mixture comprises initially contacting microcrystalline cellulose with the uniform first mixture, and subsequently contacting pectin with the uniform first mixture.

5. The method of claim 1, wherein the condensing comprises heating at a temperature of at least about 50°

F. (10°

C.).

6. The method of claim 1, further comprising contacting a powder coating with two opposing external sides of the thin film.

7. The method of claim 6, wherein the powder coating comprises at least one of talc and microcrystalline cellulose.

8. The method of claim 1, wherein the solvent comprises at least one of water and ethanol.

9. The method of claim 1, wherein the solvent is present in about 2-24 wt. %.

10. The method of claim 1, wherein the binder comprises at least one of pectin, microcrystalline cellulose, xanthan gum, locust bean gum, guar gum, gum arabic, gum tragacanth, gum karaya, beta glucan, glucomannan, tapioca starch, carrageenan, xanthan gum, gellan gum, alginic acid or sodium alginate, konjac gum, tara gum, chitosan, agar, maltodextrin, polyvinyl alcohol, pullulan, polycarbophil, povidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl starch, and polyethylene glycol.

11. The method of claim 1, wherein the binder is present in about 4-50 wt. %.

12. The method of claim 1, wherein the lipid comprises at least one of almond oil, argan oil, avocado oil, canola oil, cashew oil, castor oil, cocoa butter, coconut oil, colza oil, corn oil, cottonseed oil, grape seed oil, hazelnut oil, hemp oil, hydroxylated lecithin, lecithin, linseed oil, macadamia oil, mango butter, marula oil, mongongo nut oil, olive oil, palm kernel oil, palm oil, peanut oil, pecan oil, perilla oil, pine nut oil, pistachio oil, poppy seed oil, pumpkin seed oil, rice bran oil, safflower oil, sesame oil, Shea butter, soybean oil, sunflower oil, walnut oil, and watermelon seed oil.

13. The method of claim 1, wherein the lipid is present in about 4-22 wt. %.

14. The method of claim 1, wherein the emulsifier comprises at least one of glycerin, propylene glycol, and polyethylene glycol.

15. The method of claim 1, wherein the emulsifier is present in about 3-22 wt. %.

16. The method of claim 1, wherein the active ingredient is present in at least about 30 wt. %.

17. The method of claim 1, wherein the active ingredient is at least partially encapsulated by the lipid.

18. The thin film of any one of the above claims, wherein the active ingredient is present in about 25-40 wt. %.

19. A method of preparing a thin film, the method comprising:

(a) blending at a temperature of about 130-140°

F. (54.4-60°

C.) a lipid, emulsifier, and solvent to provide a uniform first mixture;

wherein the solvent comprises at least one of water and ethanol;

wherein the lipid comprises at least one of almond oil, argan oil, avocado oil, canola oil, cashew oil, castor oil, cocoa butter, coconut oil, colza oil, corn oil, cottonseed oil, grape seed oil, hazelnut oil, hemp oil, hydroxylated lecithin, lecithin, linseed oil, macadamia oil, mango butter, marula oil, mongongo nut oil, olive oil, palm kernel oil, palm oil, peanut oil, pecan oil, perilla oil, pine nut oil, pistachio oil, poppy seed oil, pumpkin seed oil, rice bran oil, safflower oil, sesame oil, shea butter, soybean oil, sunflower oil, walnut oil, and watermelon seed oil;

wherein the emulsifier comprises at least one of glycerin, propylene glycol, and polyethylene glycol;

(b) contacting an active ingredient with the uniform first mixture to provide a thickened second mixture;

wherein the active ingredient is at least partially encapsulated by the lipid;

(c) contacting a binder with the thickened second mixture to provide a slurry;

wherein the binder comprises at least one of pectin, microcrystalline cellulose, xanthan gum, locust bean gum, guar gum, gum arabic, gum tragacanth, gum karaya, beta glucan, glucomannan, tapioca starch, carrageenan, xanthan gum, gellan gum, alginic acid or sodium alginate, konjac gum, tara gum, chitosan, agar, maltodextrin, polyvinyl alcohol, pullulan, polycarbophil, povidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl starch, and polyethylene glycol;

(d) hot extruding, casting, and condensing the slurry to provide the thin film;

or cooling, shearing, mixing, casting, and condensing the slurry to provide the thin film; and

(e) contacting a powder coating with two opposing external sides of the thin film;

wherein the powder coating comprises at least one of talc and microcrystalline cellulose.

20. A method of preparing a thin film, the method comprising:

(a) blending at a temperature of about 130-140°

F. (54.4-60°

C.) a lipid, emulsifier, and solvent to provide a uniform first mixture;

wherein the solvent comprises at least one of water and ethanol;

wherein the lipid comprises at least one of almond oil, argan oil, avocado oil, canola oil, cashew oil, castor oil, cocoa butter, coconut oil, colza oil, corn oil, cottonseed oil, grape seed oil, hazelnut oil, hemp oil, hydroxylated lecithin, lecithin, linseed oil, macadamia oil, mango butter, marula oil, mongongo nut oil, olive oil, palm kernel oil, palm oil, peanut oil, pecan oil, perilla oil, pine nut oil, pistachio oil, poppy seed oil, pumpkin seed oil, rice bran oil, safflower oil, sesame oil, shea butter, soybean oil, sunflower oil, walnut oil, and watermelon seed oil;

wherein the emulsifier comprises at least one of glycerin, propylene glycol, and polyethylene glycol;

(b) contacting an active ingredient with the uniform first mixture to provide a thickened second mixture;

wherein the active ingredient is at least partially encapsulated by the lipid by the formation of at least one of micelles and liposomes;

(c) contacting a binder with the thickened second mixture to provide a slurry;

wherein the binder comprises at least one of pectin, microcrystalline cellulose, xanthan gum, locust bean gum, guar gum, gum arabic, gum tragacanth, gum karaya, beta glucan, glucomannan, tapioca starch, carrageenan, xanthan gum, gellan gum, alginic acid or sodium alginate, konjac gum, tara gum, chitosan, agar, maltodextrin, polyvinyl alcohol, pullulan, polycarbophil, povidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl starch, and polyethylene glycol;

(d) hot extruding, casting, and condensing the slurry to provide the thin film;

or cooling, shearing, mixing, casting, and condensing the slurry to provide the thin film; and

(e) contacting a powder coating with two opposing external sides of the thin film;

wherein the powder coating comprises at least one of talc and microcrystalline cellulose.