Rapid-Melt Compositions and Methods of Making Same

• US 20100010101A1
• Filed: 07/13/2009
• Published: 01/14/2010
• Est. Priority Date: 07/05/2000
• Status: Abandoned Application

• Current Assignee: Capricorn Pharma Incorporated
• Original Assignee: Capricorn Pharma Incorporated
• Inventors: Cherukuri, S. Rao
• Application Number:
  US12/501,652
• Publication Number:
  US 20100010101A1
• Time in Patent Office: Days
• US Class Current: 514/770
• CPC Class Codes: A61K 31/09 having two or more such linkages
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/726 Glycosaminoglycans, i.e. mucopolysaccharides chondroitin sulfate, dermatan sulfate A61K31/737
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1664 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/1617
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2068 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/2013
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00

Abstract

The present invention provides a novel rapid-melt pharmaceutical composition comprising a binder, a super emulsifier, a diluent/bulking material; and an active ingredient. The present invention also provides a rapid-melt bead composition comprising a binder having a melting point from about 20 to about 90° C., an emulsifier; a diluent/bulking material; and an active ingredient. Further, the present invention provides a chew tablet composition comprising a binder; an emulsifier having a melting point of greater than about 40° C.; a diluent/bulking material; and an active ingredient. Methods of making the disclosed compositions are also described.

Claims

1. A rapid-melt pharmaceutical composition comprising:

a binder;

a super emulsifier;

a diluent/bulking material; and

an active ingredient.

2. The composition of claim 1, wherein the super emulsifier has a hydrophilic-lipophilic balance of greater than about 10.

3. The composition of claim 1, wherein the super emulsifier is selected from the group consisting of polyethoxylated fatty acids, polyethylene glycol (PEG) fatty acid diesters, PEG glycerol fatty acid esters, transesterification products of oils and alcohols, polyglycerized fatty acids, sterol and sterol derivatives, PEG sorbitan fatty acid esters, PEG alkyl ethers, Sugar esters, PEG alkyl phenols, poloxamers, ionic surfactants, polyoxyethylene fatty acid esters, polysorbates, and reaction products of a natural or hydrogenated castor oil and ethylene oxide.

4. The composition of claim 1, wherein the super emulsifier comprises polysorbate 80 and sodium lauryl sulfate.

5. The composition of claim 4, wherein the polysorbate 80 and sodium lauryl sulfate is in a weight ratio of about 2:

1 to about 3;

1.

6. The composition of claim 1, wherein the binder is in an amount from about 0.01% to about 70% by weight.

7. The composition of claim 1, wherein the super emulsifier is in an amount from about 0.05% to about 15% by weight.

8. The composition of claim 1, wherein the diluent/bulking material is in an amount from about 10% to about 90% by weight.

9. The composition of claim 1, wherein the binder is povidone.

10. The composition of claim 1, further comprising a lubricant.

11. The composition of claim 10, wherein the lubricant is magnesium stearate, silicon dioxide, talc, or combinations thereof.

12. The composition of claim 1, wherein the emulsifier is adsorbed on a disintegrant.

13. The composition of claim 12, wherein the emulsifier is polysorbate 80 and the binder is crospovidone.

14. The composition of claim 1, wherein the diluent/bulking material is silicon dioxide, sugars, starches, lactose, sucrose, sorbitol, fructose, talc, stearic acid, magnesium stearate, dicalcium phosphate, erythitol, xylitol, mannitol, maltitol, isomalt, dextrose, maltose, lactose, microcrystalline celluloses, or mixtures thereof.

15. The composition of claim 1, wherein the composition dissolves in a mouth in less than about 45 seconds.

16. The composition of claim 1, wherein the composition is a flashbead or a compressed tablet.

17. A method for making rapid-melt compressed solid pharmaceutical composition, said method comprising the steps of

a. blending a binder and a super emulsifier to form a first mixture;

b. blending a diluent/bulking material and an active ingredient to form a second mixture;

c. blending the first and second mixtures; and

d. compressing the third mixture to form a tablet.

18. The method of claim 17, further comprising the step of compressing the mixture into a tablet using a compression force at about 18 to 32 KN.

19. The method of claim 17, wherein step c. further comprising the blending to lubricants with the first and second mixtures.

20. The method of claim 17, wherein the super emulsifier wherein the super emulsifier has a hydrophilic-lipophilic balance of greater than about 10.

21. The composition of claim 17, wherein the super emulsifier is selected from the group consisting of polyethoxylated fatty acids, polyethylene glycol (PEG) fatty acid diesters, PEG glycerol fatty acid esters, transesterification products of oils and alcohols, polyglycerized fatty acids, sterol and sterol derivatives, PEG sorbitan fatty acid esters, PEG alkyl ethers, Sugar esters, PEG alkyl phenols, poloxamers, ionic surfactants, polyoxyethylene fatty acid esters, polysorbates, and reaction products of a natural or hydrogenated castor oil and ethylene oxide.

22. A rapid-melt bead composition comprising:

a binder having a melting point from about 20 to about 90°

C.;

an emulsifier;

a diluent/bulking material; and

an active ingredient.

23. The bead of claim 22, wherein the binder is cocoa butter.

24. The bead of claim 22, wherein the emulsifier is polysorbate 80, sodium lauryl sulfate, and/or PEG 3350.

25. The bead of claim 22, wherein the emulsifier is present at about 0.1-30% by weight of the composition.

26. A method for making a rapid-melt bead comprising the steps of

a. heating an emulsifier and a binder to a molten state to form a first mixture, wherein the emulsifier has a melting point from about 60 to about 40°

C.;

b. mixing the active ingredient and diluent/bulking material to form a second mixture;

c. adding and mixing the first and second mixtures to form a third mixture;

d. extruding and spheronizing the third mixture to form beads.

27. The method of claim 26, further comprising the steps of drying the beads.

28. The method of claim 26, wherein step a. comprises heating to greater than about 180°

F. and then maintaining the first mixture at about 115-140°

F.

29. The method of claim 26, wherein step c. takes place at about 115-140°

F.

30. The method of claim 26, wherein the wherein the binder is cocoa butter.

31. The method of claim 26, wherein the emulsifier is polysorbate 80, sodium lauryl sulfate, and/or PEG 3350.

32. A chew tablet composition comprising:

a binder;

an emulsifier having a melting point of greater than about 40°

C.;

a diluent/bulking material; and

an active ingredient.

33. The chew tablet of claim 32, wherein the binder is at least one glyceride.

34. The chew tablet of claim 32, wherein the binder is monoglyceride, diglyceride, lecithin, or combinations thereof.

35. The chew tablet of claim 32, further comprising a lubricant, flavor, sweetener, or combinations thereof.

36. The chew tablet of claim 35, wherein the lubricant is magnesium stearate, silicon dioxide, talc, or combinations thereof.

37. The chew tablet of claim 32, wherein the emulsifier also acts as a binder.

38. The chew tablet of claim 32, wherein the active ingredient is present at about 0.1% (w/w) to 90% of the total chew tablet.

39. The chew tablet of claim 32, wherein the emulsifier is present at about 0.1-25% by weight of the composition.

40. A method for making a chew tablet comprising the steps of

a. heating an emulsifier and a binder to a molten state to form a first mixture, wherein the binder has a melting point of greater than about 40°

C.;

b. mixing the active ingredient and diluent/bulking material to form a second mixture;

c. adding and mixing the first and second mixtures to form a third mixture and

d. compressing the third mixture to form a tablet.

41. The method of claim 40, wherein step a. comprises heating to greater than about 180°

F. and then maintaining the first mixture at about 115-140°

F.

42. The method of claim 40, wherein tableting occurs at a compression force at about 20 to about 25 KN.

43. The method of claim 40, wherein step b. also include the addition of lubricants, flavors, and sweeteners.

44. The method of claim 43, wherein the lubricant is magnesium stearate, silicon dioxide, talc, or combinations thereof.

45. The method of claim 40, wherein the wherein the binder is monoglyceride, diglyceride, lecithin, or combinations thereof.

46. The method of claim 40, wherein the emulsifier also acts as a binder.

47. The method of claim 40, wherein the active ingredient is present at greater than 40% (w/w) of the total chew tablet.

48. A composition comprising

first granules or beads having a binder having a melting point about 20-90°

C., an emulsifier, a diluent/bulking material; and

a second granules or beads having an active ingredient.

49. The composition of claim 48, wherein the emulsifier is cocoa butter.

50. The composition of claim 48, wherein the emulsifier is polysorbate 80, sodium lauryl sulfate, and/or PEG 3350.

51. The composition of claim 48, wherein the emulsifier is present at about 0.1-25% by weight of the composition.

52. The composition of claim 48, wherein the active ingredient is coated.