Rapidly dissoluble medicinal dosage unit and method of manufacture

• US 4,855,326 A
• Filed: 03/18/1988
• Issued: 08/08/1989
• Est. Priority Date: 04/20/1987
• Status: Expired due to Term

• Current Assignee: Biovail Laboratories International Srl (Bausch Health Cos., Inc.)
• Original Assignee: Fuisz Pharmaceutical Limited
• Inventors: Fuisz, Richard C.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): Nutter, Nathan M.
• Application Number:
  US07/169,838
• Time in Patent Office: 508 Days
• Field of Search: 514/772, 514/777, 514/781, 424/400, 424/439, 424/440, 424/445, 425/9, 426/658, 426/660, 426/517, 206/569
• US Class Current: 514/777
• CPC Class Codes: A23L 13/43 Addition of vegetable fats or oils; Addition of non-meat animal fats or oils; Addition of fatty acids
• CPC Class Codes: A23L 33/20 Reducing nutritive value; Dietetic products with reduced nutritive value
• CPC Class Codes: A23P 10/25 Agglomeration or granulation by extrusion or by pressing, e.g. through small holes, through sieves or between surfaces
• CPC Class Codes: A23P 10/28 Tabletting; Making food bars by compression of a dry powdered mixture
• CPC Class Codes: A61K 8/02 characterised by special physical form
• CPC Class Codes: A61K 8/027 Fibers; Fibrils
• CPC Class Codes: A61K 8/445 aromatic, i.e. the carboxylic acid directly linked to the aromatic ring
• CPC Class Codes: A61K 8/60 Sugars; Derivatives thereof
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61Q 17/04 Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: A61Q 5/12 Preparations containing hair conditioners

Abstract

A melt spinnable carrier agent such as sugar is combined with a medicament then converted into fiber form by melt spinning with "cotton candy" fabricating equipment. The as-spun product is converted to compacted individual dosage units. For certain medicaments a binding agent is added to the carrier agent. Examples are presented for oral administration, topical application, systemic and non-systemic, intravenous and intra-muscular infusion via multicameral containers. All applications utilize the extraordinarily rapid entry into solution upon contact with a solvent.

Claims

1. A spun fibrous pharmaceutical composition comprising a mass of spun fibers of a material capable of being spun into fibers that are readily water-soluble and a medicament distributed on or incorporated in said fibrous mass.

2. A spun fibrous pharmaceutical composition according to claim 1, wherein said material is a sugar or a cellulosic material.

3. A spun fibrous pharmaceutical composition according to claim 2, wherein said material is a sugar.

4. A spun fibrous pharmaceutical composition according to claim 3, wherein said medicament is an analgesic.

5. A spun fibrous pharmaceutical composition according to claim 3, wherein said medicament is an antihistaminic labyrinthine function depressant.

6. A spun fibrous pharmaceutical composition according to claim 3, wherein said medicament is a decongestant.

7. A spun fibrous pharmaceutical composition according to claim 1, wherein said medicament is acetaminophen.

8. A spun fibrous pharmaceutical composition according to claim 1, wherein said medicament is diethylcarbamazine citrate.

9. A spun fibrous pharmaceutical composition according to claim 1, wherein said composition further comprises an adhesion promoter for promoting adhesion between said material and said medicament.

10. A spun fibrous pharmaceutical composition according to claim 9, wherein said adhesion promoter comprises polyvinylpyrrolidone.

11. A spun fibrous pharmaceutical composition according to claim 10, wherein said medicament comprises diethylcarbamazine citrate.

12. A spun fibrous pharmaceutical composition according to claim 3, wherein said sugar is selected from the group consisting of maltose, fructose, sorbitol, dextrose, mannitol, sucrose, lactose, and combinations thereof.

13. A spun fibrous pharmaceutical composition according to claim 12, wherein said mass of spun fibers is in the form of a compacted unit-dose body of said fibers where the fibers have retained their fibrous identity.

14. A spun fibrous pharmaceutical composition according to claim 1, wherein said mass of spun fibers is in the form of a compacted unit-dose body of said fibers where the fibers have retained their fibrous identity.

15. A spun fibrous pharmaceutical composition according to claim 3, wherein said sugar comprises at least 10% lactose and the remainder sucrose.

16. A spun fibrous pharmaceutical composition according to claim 12, wherein said medicament is of the type that is rapidly assimilated when in contact with the tissues of the oral cavity.

17. A pharmaceutical dosage unit comprising compacted spun fibers of a spinnable, readily water soluble material and an effective amount of a medicament.

18. A system for topical delivery of a medicament comprising a wafer containing a mass of fibers, and means for securing said wafer in contact with a dermal area to be treated, said mass of fibers, comprising a soluble fiber forming ingredient and a medicament where at least said fiber forming ingredient has been spun into fibers, and in said fiber form said ingredient has a solubility characteristic corresponding to that of spun sugar fibers in water.

19. A system according to claim 18, wherein said ingredient in fiber form is hydrophilic.

20. A system according to claim 19, wherein said ingredient is essentially lactose.

21. A system according to claim 18, wherein said medicament is a dermatotropic agent.

22. A system according to claim 18, wherein said medicament includes an antibiotic agent.

23. A system according to claim 18, wherein said medicament includes a corticosteroid.

24. A system according to claim 18, wherein said medicament is characterized by transdermal systemic activity.

25. A multicameral container for intravenous or intra muscular administration comprising a first compartment containing a pharmaceutically acceptable solvent, and a second compartment containing a spun fibrous pharmaceutical composition comprising a mass of spun fibers of a material capable of being spun into fibers that are readily water-soluble and a medicament distributed on or incorporated in said fibrous mass.

26. A multicameral container according to claim 25, wherein said material is a sugar selected from the group consisting of maltose, fructose, sorbitol, dextrose, mannitol, sucrose, lactose, and combinations thereof.

27. A multicameral container according to claim 26, wherein said mass of spun fibers is in the form of a compacted body of said fibers where the fibers have retained their fibrous identity.

28. A multicameral container according to claim 27, wherein said sugar comprises about 10% lactose and the remainder sucrose.

29. A spun fibrous pharmaceutical composition according to claim 29, wherein said material is methyl cellulose.

30. A spun fibrous pharmaceutical composition according to claim 29, wherein said medicament comprises dimenhydrinate.

31. A method for preparing a pharmaceutical dosage unit for delivering a medicament, comprising producing a mass of medicament bearing spun fibers by melt spinning a composition containing said medicament.

32. A method according to claim 31, wherein said medicament is combined with a melt spinnable compatible water soluble carrier agent to provide an intermediate product, and said intermediate product is converted to a mass of spun fibers by melt spinning product.

33. A method according to claim 32, wherein said carrier agent comprises a mixture of sucrose and lactose.

34. A method according to claim 33, wherein said lactose is combined with said sucrose in the ratio of about 1:

9 by weight.

35. A method according to claim 32, wherein said medicament has a higher melting point than said carrier agent, and said melt spinning is carried out at a temperature lying between the melting points of said medicament and said carrier agent but less than the melting point of said medicament.

36. A method for preparing a rapidly dissoluble medicinal dosage unit for administering medication comprising in combination the steps of combining a medicament with a melt spinnable compatible carrier agent to provide an intermediate product, and producing a mass of medicament bearing fibers by melt spinning said intermediate product.

37. A method according to claim 36, wherein said carrier agent is a sugar having a spinning temperature below the degradation temperature of said medicament.

38. A method according to claim 37, wherein said intermediate product is produced by coating granules of said sugar with a slurry of said medicament where the vehicle for said slurry is not a solvent for said sugar.

39. A method according to claim 38, wherein said vehicle is isopropyl alcohol.

40. A method according to claim 39, wherein said granules of sugar are added to said slurry and the slurry coated granules are thereafter dried then spun to produce said fibers.

41. A method according to claim 40, wherein said slurry is produced by admixing acetaminophen with isopropyl alcohol to produce a 60-70% w/v solution of said medicament in said vehicle.

42. A method according to claim 40, wherein said slurry is produced by adding 2-3% by weight of polyvinylpyrrolidone to isopropyl alcohol and admixing the resulting solution with diethylcarbamazine citrate to obtain a slurry containing about 60% w/v of said medicament in said vehicle.

43. A method according to claim 36, wherein the spun fiber product resulting from said melt spinning of said intermediate product is compacted to produce a body whose enclosed volume is substantially less than the as-spun enclosed volume, and the compacted product is thereafter subdivided into dosage units.

44. A method according to claim 43, wherein said compaction step is performed to produce said body with an enclosed volume at least 30% less than said as-spun enclosed volume, said compaction step being limited to less than that compaction which would result in noticeable fracturing of said fibers.

45. A rapidly dissoluble spun fibrous medicinal dosage unit for administering medication orally, sublingually, or buccally, consisting essentially of a compacted mass of spun fibers of a carrier agent capable of being spun into fibers that are readily water-soluble which dissolve in the saliva of the mouth, said mass having an enclosed volume that is at least 30% less than the as-spun enclosed volume, said carrier agent being selected from the group consisting of sugars, sugar alcohols and mixtures thereof, and an effective amount of an orally, sublingually, or buccally effective medicament distributed within or coated on said spun carrier agent fibers.

46. A rapidly dissoluble medicinal dosage unit according to claim 45, wherein said medicament is acetaminophen.

47. A rapidly dissoluble medicinal dosage unit according to claim 45, wherein said medicament is diethylcarbamazine citrate.

48. A rapidly dissoluble medicinal dosage unit according to claim 45, wherein said fibers consist essentially of a compound containing said carrier agent and said medicament.

49. A rapidly dissoluble medicinal dosage unit according to claim 48, wherein said fibers are the product resulting from melt spinning of said compound.

50. A rapidly dissoluble medicinal dosage unit according to claim 49, wherein said medicament is acetaminophen.

51. A rapidly dissoluble medicinal dosage unit according to claim 49, wherein said medicament is diethylcarbamazine citrate.

52. A rapidly dissoluble medicinal dosage unit according to claim 48, wherein said compound consists essentially of said carrier agent, said medicament, and adducts selected from the group consisting of coloring agents, flavoring agents, and promoters of adhesion between said carrier agent and the other constituents.

53. A rapidly dissoluble medicinal dosage unit according to claim 52, wherein said adhesion promoter comprises polyvinylpyrrolidine.

54. A rapidly dissoluble medicinal dosage unit according to claim 53, wherein said medicament comprises diethylcarbamazine citrate.

55. A rapidly dissoluble medicinal dosage unit according to claim 45, wherein said mass of spun fibers is in the form of a tablet of compacted spun fibers where the fibers have retained their fibrous identity.

56. A rapidly dissoluble medicinal dosage unit according to claim 55, wherein said fibers consist essentially of a compound containing said carrier agent and said medicament.

57. A rapidly dissoluble medicinal dosage unit according to claim 56, wherein said fibers are the product resulting from melt spinning of said compound.

58. A rapidly dissoluble medicinal dosage unit according to claim 57, wherein said medicament is acetaminophen.

59. A rapidly dissoluble medicinal dosage unit according to claim 57, wherein said medicament is diethylcarbamazine citrate.