Rapidly dissolving robust dosage form

• US 6,024,981 A
• Filed: 04/09/1998
• Issued: 02/15/2000
• Est. Priority Date: 04/16/1997
• Status: Expired due to Term

• Current Assignee: Cima Labs Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cima Labs Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Khankari, Rajendra K., Hontz, John, Katzner, Leo, Chastain, Sara J.
• Primary Examiner(s): Spear, James M.
• Application Number:
  US09/057,884
• Time in Patent Office: 677 Days
• Field of Search: 424/464, 424/465, 424/468, 424/469, 424/470, 424/484, 424/488, 424/489, 424/490, 424/441, 424/435
• US Class Current: 424/464
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence
• 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 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates

Abstract

The invention is directed to a hard tablet that can be stored, packaged and processed in bulk. Yet the tablet dissolves rapidly in the mouth of the patient with a minimum of grit. The tablet is created from an active ingredient mixed into a matrix of a non-direct compression filler and a relatively high lubricant content.

Claims

1. A hard, compresed, rapidly dissolvable dosage form adapted for direct oral dosing comprising:

an active ingredient and a matrix including a non-direct compression filter and a lubricant, said dosage form being adapted to rapidly dissolve in the mouth of a patient and thereby liberate said active ingredient, and having a friability of about 2% or less when tested according to the U.S.P., said dosage form having a hardness of at least about 15 Newtons.

2. The dosage form as claimed in claim 1 wherein said friability is less than or equal to about 1%.

4. The dosage form as claimed in claim 1 wherein said hardness ranges from between about 20 Newtons and about 50 Newtons.

5. The dosage form as claimed in claim 4 wherein said hardness is about 35 Newtons.

6. The dosage form as claimed in claim 1 wherein said dosage form will dissolve in about 90 seconds or less.

7. The dosage form as claimed in claim 6 wherein said dosage form will dissolve in about 60 seconds or less.

8. The dosage form as claimed in claim 7 wherein said dosage form will dissolve in about 45 seconds or less.

9. The dosage form as claimed in claim 1 further comprising at least one particle, said particle including said active ingredient and a protective material.

10. The dosage form as claimed in claim 9 wherein said protective material is selected from the group consisting of an adsorbate, microgranule, a matrix or a coating.

11. The dosage form as claimed in claim 10 wherein said protective material is a coating.

12. The dosage form as claimed in claim 11 wherein said coating constitutes at least about 5% of the particle by weight.

13. The dosage form as claimed in claim 11 wherein said coating constitutes between about 5% and about 75% of the particle by weight.

14. The dosage form as claimed in claim 1 wherein said non-direct compression filler is present in an amount of between about 25 and about 95% by weight.

15. The dosage form as claimed in claim 14 wherein said non-direct compression filler is present in an amount of between about 50 and about 95% by weight.

16. The dosage form as claimed in claim 15 wherein said non-direct compression filler is present in an amount of between about 60 and about 95% by weight.

17. The dosage form as claimed in claim 1 wherein said non-direct compression filler is a non-direct compression sugar or non-direct compression sugar alcohol.

18. The dosage form as claimed in claim 1 wherein said active ingredient is selected from the group consisting of systematically distributable pharmaceutical ingredients, vitamins, minerals and dietary supplements, as well as non-systematically distributable pharmaceutical ingredients.

19. The dosage form as claimed in claim 18 wherein said pharmaceutical ingredients include antacids, analgesics, anti-inflammatories, antipyretics antibiotics, antimicrobials, laxatives, anorexics, antihistamines, antiasthmatics, antidiuretics, antiflatuents, antimigraine agents, antispasmodics, sedatives, antihyperactives, antihypertensives, tranquilizers, decongestants, beta blockers and combinations thereof.

20. The dosage form as claimed in claim 1 wherein said active ingredient is provided in an amount between about greater than zero and about 80% by weight of the finished dosage form.

21. The dosage form as claimed in claim 20 wherein said active ingredient is provided in an amount between about greater than zero and about 60% by weight of the finished dosage form.

22. The dosage form as claimed in claim 9 wherein said particles are provided in an amount between about greater than zero and about 75% by weight of the finished dosage form.

23. The dosage form as claimed in claim 22 wherein said particles are provided in an amount between about greater than zero and about 60% by weight of the finished dosage form.

24. The dosage form as claimed in claim 9 wherein said particles are rapid release particles.

25. The dosage form as claimed in claim 9 wherein said particles are sustained release particles.

26. The dosage form as claimed in claim 1 wherein said lubricant is a hydrophobic lubricant.

27. The dosage form as claimed in claim 26 wherein said hydrophobic lubricant is provided in an amount of between about 1 and about 5% by weight.

28. The dosage form as claimed in claim 27 wherein said hydrophobic lubricant is provided in an amount of between about 1 and about 2.5% by weight.

29. The dosage form as claimed in claim 28 wherein said hydrophobic lubricant is provided in an amount of between about 1.5 and about 2% by weight.

30. The dosage form as claimed in claim 1 further comprising a wicking agent.

31. The dosage form as claimed in claim 30 wherein said wicking agent is provided in an amount of less than about 5% by weight.

3. An openable and recloseable package containing a plurality of hard, compressed, rapidly dissolving tablets adapted for direct oral dosing comprising:

particles including an active ingredient and a protective material, said particles being provided in an amount of between about 0.01 and about 75% by weight based on the weight of said tablets; and

a tablet matrix including a non-direct compression filler and a hydrophobic lubricant;

said tablet matrix comprising at least about 60% rapidly water soluble ingredients based on the total weight of the matrix material;

said tablet having a hardness of between about 15 and about 50 Newtons, a friability of less than 2% when measured by U.S.P. and being adapted to both dissolve spontaneously in the mouth of a patient in less than about 60 seconds and thereby liberate said particles.

32. A hard, compressed, rapidly dissolving tablet adapted for direct oral dosing comprising:

particles including an active ingredient and a protective material, said particles being provided in an amount of between about 0.01 and about 75% by weight based on the weight of the tablet; and

a matrix including a non-direct compression filler, a wicking agent, and a hydrophobic lubricant;

said tablet matrix comprising at least about 60% rapidly water soluble ingredients based on the total weight of the matrix material;

said tablet having a hardness of between about 15 and about 50 Newtons, a friability of less than 2% when measured by U.S.P. and being adapted to dissolve spontaneously in the mouth of a patient in less than about 60 seconds and thereby liberate said particles and be capable of being stored in bulk.

33. The tablet of claim 32 wherein said non-direct compression filler has an average particle size of 90 microns or less, said filler being provided in an amount of between greater than about 25 and about 95% by weight of the tablet;

said wicking agent being provided in an amount of between about 2 and about 5% by weight based on the weight of the tablet; and

said lubricant being provided in an amount of between about 1.0 and about 2.5% by weight based on the weight of the tablet.

34. A tablet as claimed in claim 32 wherein said friability is less than or equal to about 1%.

35. A tablet as claimed in claim 32 wherein said hardness is about 35 Newtons.

36. A tablet as claimed in claim 32 wherein said tablet dissolves in less than about 45 seconds.

37. A method of making a packaged, orally disintegrable dosage form, comprising the steps of:

(a) forming a mixture including an active ingredient and a matrix including a non-direct compression filler and a lubricant;

(b) compressing said mixture to form a plurality of hard, compressed, rapidly disintegrable dosage forms having said active ingredient distributed in said orally dissolvable matrix, said dosage forms being adapted for direct oral dosing, said dosage forms having a hardness of at least about 15 Newtons and being adapted to dissolve spontaneously in the mouth of a patient in less than about 60 seconds and thereby liberate said active ingredient; and

(c) storing said tablets in bulk prior to packaging said tablets.

38. The method of claim 37 further comprising the step of packaging said tablets in a lumen of a package such that there is at least one tablet per package.

39. The method of claim 38 wherein a plurality of said compressed tablets are packaged in a single lumen of a single package.

40. The method of claim 37 wherein said compressing step is conducted using direct compression.