Compressed composition comprising magnesium salt

• US 20050220865A1
• Filed: 04/02/2004
• Published: 10/06/2005
• Est. Priority Date: 04/02/2004
• Status: Abandoned Application

• Current Assignee: Blaine Pharmaceuticals
• Original Assignee: Blaine Pharmaceuticals
• Inventors: Crowley, Michael M., Koleng, John J.
• Application Number:
  US10/816,771
• Publication Number:
  US 20050220865A1
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/08 Oxides; Hydroxides
• CPC Class Codes: A61K 33/10 Carbonates; Bicarbonates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• 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

An oral solid compress composition comprising a magnesium salt is provided. The composition provides a rapid dissolution of the magnesium salt, wherein not less than 75% of the magnesium salt dissolves within 45 minutes after placement in hydrochloric acid (0.1 N, 900 mL) as per USP Method <711>. In a particular embodiment, the magnesium salt is an inorganic salt such as MgO, Mg(OH)₂, MgCl₂, and others. The composition can be prepared by dry granulation, direct compression or another suitable process. The composition provides a substantially stable dissolution profile for the magnesium salt so that the dissolution profile changes only minimally even after an extended period of storage under pharmaceutically acceptable conditions when packaged in a sealed container-enclosure system. The solid composition may also exclude a cellulose-based composition. The compressed composition can be prepared and stored under anhydrous conditions.

Claims

1. A rapidly dissolving solid oral compressed composition comprising:

a. one or more magnesium salts;

b. one or more hydrophilic polymers;

c. one or more disintegrants;

d. optionally one or more surfactants;

e. optionally one or more glidants;

f. optionally one or more fillers; and

g. optionally one or more lubricants;

h. wherein the composition provides a substantially stable dissolution profile when evaluated in vitro according to USP <

711>

for the one or more magnesium salts when the composition is stored for at least two months at 40°

C. and 75% relative humidity in a sealed container-enclosure system.

2. The composition of claim 1, wherein the magnesium salt is MgO, Mg Carbonate, MgF₂, or Mg(OH)₂.

3. The composition of claim 1, wherein the one or more hydrophilic polymers is a combination of polymers.

4. The composition of claim 3, wherein the one or more hydrophilic polymers is selected from the group consisting of polyethylene glycol, poloxamer, povidone, and co-povidone.

5. The composition of claim 1, wherein the disintegrant is selected from the group consisting of:

crospovidone, low substituted hydroxypropylcellulose, croscarmellose sodium, and sodium starch glycolate.

6. The composition of claim 1 further comprising a coating surrounding the compressed composition.

7. The composition of claim 1, wherein the composition is included in a tablet or capsule dosage form

8. The composition of claim 1, wherein the composition is prepared by dry granulation.

9. The composition of claim 1, wherein the composition is prepared by direct compression.

10. The composition of claim 1, wherein the magnesium salt is a sparingly soluble, slightly soluble, very slightly soluble, practically insoluble or insoluble salt.

11. The composition of claim 1, wherein the magnesium salt is the only component present in a therapeutically effective amount.

12. The composition of claim 1 further comprising a capsule shell within which the compressed composition is enclosed.

13. The composition of claim 1, wherein the compressed composition is tablet or pill.

14. The composition of claim 13, wherein the tablet or pill exhibits a hardness of about 4 kp to about 50 kp.

15. The composition of claim 1, wherein the dissolution medium for evaluation is dilute hydrochloric acid.

16. The composition of claim 1, wherein the solid oral compressed composition is in a sealed container-enclosure system during storage.

17. The composition of claim 16, wherein

a. the container comprises a material selected from the group consisting of glass, metal, or polymers;

b. the enclosure comprises a material selected from the group consisting of metal or polymers; and

c. the container-enclosure system is sealed by mechanical tightening and induction sealing of a taper evident liner onto the orifice of the container.

18. The composition of claim 17, wherein

a. the container comprises high density polyethylene;

b. the enclosure comprises CRC or non-CRC polypropylene; and

c. the container-enclosure system is sealed using an appropriate torque and an induction sealed aluminum tamper evident liner.

19. The composition of claim 18, wherein the compressed composition is prepared by direct compression.

20. The composition of claim 1, where in the compressed composition contains less than 7.5% water.

21. The composition of claim 20, wherein the compressed composition contains less than 5.5% water.

22. The composition of claim 21, wherein the compressed composition contains less than 4% water.

23. A solid oral dosage form comprising:

a. a compressed composition comprising;

i. one or more magnesium salts;

ii. one or more hydrophilic polymers;

iii. one or more disintegrants;

iv. optionally one or more surfactants;

v. optionally one or more glidants;

vi. optionally one or more fillers; and

vii. optionally one or more lubricants;

wherein

viii. the composition provides a substantially stable dissolution profile when evaluated in vitro according to USP <

711>

for the one or more magnesium salts when the composition is stored for at least two months at 40°

C. and 75% relative humidity in a sealed container-enclosure system.

24. The dosage form of claim 23, wherein the magnesium salt is the only component present in a therapeutically effective amount.

25. The dosage form of claim 23, wherein the magnesium salt is a sparingly soluble, slightly soluble, very slightly soluble, practically insoluble or insoluble salt.

26. The dosage form of claim 25, wherein the magnesium salt is selected from the group consisting of MgO, Mg(OH)₂, MgF₂, and Mg Carbonate.

27. The dosage form of claim 25, wherein the one or more hydrophilic polymers is a combination of polymers.

28. The dosage form of claim 23, wherein the one or more hydrophilic polymers is a combination of polymers.

29. The dosage form of claim 23, wherein the composition is prepared by dry granulation.

30. The dosage form of claim 23, wherein the composition is prepared by direct compression.

31. The dosage form of claim 23, wherein the composition contains less than 7.5% water.

32. The dosage form of claim 31, wherein the composition is prepared by dry granulation.

33. The dosage form of claim 31, wherein the composition is prepared by direct compression.

34. The dosage form of claim 23 further comprising a coating surrounding the compressed composition.

35. The dosage form of claim 23 further comprising a capsule shell within which the compressed composition is enclosed.

36. A compressed composition adapted for oral administration to a subject comprising:

a. one or more magnesium salts;

b. one or more hydrophilic polymers;

c. one or more disintegrants;

d. optionally one or more surfactants;

e. optionally one or more glidants;

f. optionally one or more fillers; and

g. optionally one or more lubricants;

wherein

h. the magnesium salt is the only component present in a therapeutically effective amount;

i. the composition provides a substantially stable dissolution profile when evaluated in vitro according to USP <

711>

for the one or more magnesium salts when the composition is stored for at least two months at 40°

C. and 75% relative humidity in a sealed container-enclosure system; and

j. the composition contains less than 7.5% water.

37. The composition of claim 36, wherein the magnesium salt is a sparingly soluble, slightly soluble, very slightly soluble, practically insoluble or insoluble salt.

38. The composition of claim 37, wherein the magnesium salt is selected from the group consisting of MgO, Mg(OH)₂, MgF₂, and Mg Carbonate.

39. The composition of claim 37, wherein the composition is prepared by direct compression or dry granulation.

40. The composition of claim 36, wherein the composition is prepared by direct compression or dry granulation.

41. The composition of claim 36, wherein the composition is prepared by a process that does not include the addition of water.

42. The composition of claim 36, wherein

a. the container comprises a material selected from the group consisting of glass, metal, or polymers;

b. the enclosure comprises a material selected from the group consisting of metal or polymers; and

c. the container-enclosure system is sealed by mechanical tightening and induction sealing of a taper evident liner onto the orifice of the container.

43. The composition of claim 36, wherein the composition excludes microcrystalline cellulose.

44. A rapidly dissolving solid oral compressed composition comprising:

a. one or more magnesium salts;

b. one or more hydrophilic polymers;

c. one or more disintegrants; and

d. at least one or more of the following;

surfactant, glidant, filler, and lubricant;

wherein

e. the composition provides a substantially stable dissolution profile when evaluated in vitro according to USP <

711>

for the one or more magnesium salts when the composition is stored for at least two months at 40°

C. and 75% relative humidity in a sealed container-enclosure system;

f. the composition is prepared by a substantially anhydrous process; and

g. the magnesium salt is a sparingly soluble, slightly soluble, very slightly soluble, practically insoluble or insoluble salt.

45. The composition of claim 44, wherein the magnesium salt is selected from the group consisting of MgO, Mg(OH)₂, MgF₂, and Mg Carbonate.

46. The composition of claim 44, wherein the composition is prepared by direct compression or dry granulation.

47. The composition of claim 44, wherein the composition contains less than 7.5% water.

48. The dosage form of claim 44, wherein the one or more hydrophilic polymers is a combination of polymers.

49. The composition of claim 44, wherein the magnesium salt is the only component present in a therapeutically effective amount.

50. The composition of claim 44, wherein the one or more hydrophilic polymers is selected from the group consisting of polyethylene glycol, poloxamer, povidone, and co-povidone.

51. The composition of claim 44, wherein the disintegrant is selected from the group consisting of:

crospovidone, low substituted hydroxypropylcellulose, croscarmellose sodium, and sodium starch glycolate.

52. A rapidly dissolving solid oral compressed composition comprising:

a. one or more magnesium salts selected from the group consisting of MgO, Mg(OH)₂, MgF₂, and Mg Carbonate;

b. one or more hydrophilic polymers;

c. one or more disintegrants; and

d. at least one or more of the following;

surfactant, glidant, filler, and lubricant;

wherein

e. the composition provides a substantially stable dissolution profile when evaluated in vitro according to USP <

711>

for the one or more magnesium salts when the composition is stored for at least two months at 40°

C. and 75% relative humidity in a sealed container-enclosure system;

f. the composition is prepared by a substantially anhydrous process;

g. the magnesium salt is a sparingly soluble, slightly soluble, very slightly soluble, practically insoluble or insoluble salt; and

h. the magnesium salt is the only component present in a therapeutically effective amount.

53. The composition of claim 52, wherein the composition is prepared by direct compression or dry granulation.

54. The composition of claim 52, wherein the composition contains less than 7.5% water.

55. The dosage form of claim 52, wherein the one or more hydrophilic polymers is a combination of polymers.

56. The composition of claim 55, wherein the one or more hydrophilic polymers is selected from the group consisting of polyethylene glycol, poloxamer, povidone, and co-povidone.

57. The composition of claim 52, wherein the disintegrant is selected from the group consisting of:

crospovidone, low substituted hydroxypropylcellulose, croscarmellose sodium, and sodium starch glycolate.

58. The composition of claim 52, wherein the composition excludes microcrystalline cellulose.