Azithromycin dosage forms with reduced side effects
View Patent ↗The present invention is related to an oral dosage form comprising an effective amount of an alkalizing agent and an azithromycin multiparticulate wherein said multiparticulate comprises azithromycin, a glyceride which comprises glyceryl monobehenate, glyceryl dibehenate, glyceryl tribehenate, or a mixture thereof and a poloxamer. Typically, the oral dosage form includes any suitable oral dosing means such as a powder for oral suspension, a unit dose packet or sachet, a tablet or a capsule.
1. An oral dosage form comprising:
(a) an effective amount of an alkalizing agent; and
(b) multiparticulates wherein said multiparticulates comprise (i) about 20% to about 75% azithromycin, and (ii) about 25% to about 80% of a glyceride which comprises glyceryl monobehenate, glyceryl dibehenate, glyceryl tribehenate or a mixture thereof; and (iii) a poloxamer.
2. An oral dosage form of claim 1 wherein the poloxamer comprises poloxamer 407.
3. An oral dosage form of claim 1 wherein the alkalizing agent comprises a bicarbonate, a phosphate, a metal hydroxide, a metal oxide or a combination thereof.
4. An oral dosage form of claim 3 wherein the alkalizing agent comprises tribasic sodium phosphate and magnesium hydroxide.
5. An oral dosage form of claim 3 further comprising about 250 mgA to about 7 gA of azithromycin.
6. An oral dosage form of claim 5 further comprising about 1.5 gA to about 4 gA of azithromycin.
7. An oral dosage form of claim 5 further comprising 1.8 to 2.2 gA of azithromycin.
8. An azithromycin oral dosage form, comprising:
(a) at least about 200 mg of tribasic sodium phosphate; and
(b) multiparticulates, wherein said multiparticulates comprise (i) azithromycin, (ii) a mixture of glyceryl monobehenate, glyceryl dibehenate and glyceryl tribehenate, and (iii) poloxamer 407, and wherein said dosage form contains about 1.5 gA to about 4 gA of azithromycin.
9. An oral dosage form of claim 8 , further comprising at least about 100 mg of magnesium oxide.
10. An oral dosage form of claim 8 , comprising:
(a) 300 mg to 400 mg of tribasic sodium phosphate;
(b) 200 mg to 300 mg of magnesium hydroxide; and
(c) multiparticulates, wherein said multiparticulates comprise (i) azithromycin, (ii) a mixture of glyceryl monobehenate, glyceryl dibehenate and glyceryl tribehenate, and (iii) poloxamer 407,
and wherein said dosage form contains about 1.5 gA to about 4 gA of azithromycin.
11. An oral dosage form of claim 8 further comprising 1.8 to 2.2 gA of azithromycin.
12. An oral dosage form of claim 11 wherein said azithromycin is azithromycin dihydrate.
13. An oral dosage form of claim 1 wherein said azithromycin is azithromycin dihydrate.
14. An oral dosage form of claim 3 wherein said azithromycin is at least 70 wt % crystalline.
15. An oral dosage form of claim 3 wherein said oral dosage form is a powder for oral suspension, a unit dose packet, an oral suspension, a tablet or a capsule.
16. A method for reducing the frequency of gastrointestinal side effects, associated with administering azithromycin to a mammal, comprising contiguously administering oral dosage form of claim 1 to said mammal wherein the frequency of gastrointestinal side effects is reduced as compared to the frequency experienced when administering an equal dose of azithromycin without said alkalizing agent.
17. A method of claim 16 wherein said mammal is a human.
18. A method of claim 17 further comprising administering between about 250 mgA and about 7 gA of azithromycin to said human.
19. A method of claim 18 wherein the azithromycin is administered in a single dose.
20. A method of claim 19 further comprising administering between about 1.5 and about 4 gA of azithromycin.
21. A method of claim 19 further comprising administering between about 1.5 and about 3 gA of azithromycin.
22. A method of claim 19 further comprising administering between 1.8 and 2.2 gA of azithromycin to said human in a single dose.
23. A method of claim 17 further comprising administering between 30 mgA/kg and 90 mgA/kg of azithromycin to a human, wherein said human is a child weighing 30 kg or less.
24. A method of claim 23 wherein the azithromycin is administered in a single dose.
25. A method of claim 24 further comprising administering between 45 mgA/kg and 75 mgA/kg of azithromycin to a child weighing 30 kg or less.
26. A method of claim 24 further comprising administering about 60 mgA/kg of azithromycin to a child weighing 30 kg or less.
27. A method of claim 16 wherein the alkalizing agent further comprises a bicarbonate, a phosphate, a metal hydroxide, a metal oxide, or a combination thereof.
28. A method of claim 27 wherein the alkalizing agent comprises tribasic sodium phosphate and magnesium hydroxide.
29. A method of claim 27 wherein said azithromycin comprises an immediate release form of azithromycin.
30. A method of claim 27 wherein said azithromycin comprises a sustained release form of azithromycin.
31. A method of claim 27 wherein said azithromycin comprises azithromycin multiparticulates.
32. A method of claim 31 wherein said azithromycin multiparticulates comprise:
(a) azithromycin; and
(b) a pharmaceutically acceptable carrier.
33. A method of treating a bacterial or protozoal infection in a mammal in need thereof comprising administering to said mammal a single dose of an oral dosage form of claim 1 .
34. A method of claim 33 wherein said mammal is a human.
35. A method of claim 34 further comprising administering between about 250 mgA and about 7 gA of azithromycin to said human.
36. A method of claim 35 wherein the azithromycin is administered in a single dose.
37. A method of claim 36 further comprising administering between about 1.5 and about 4 gA of azithromycin to said human.
38. A method of claim 36 further comprising administering between about 1.5 and about 3 gA of azithromycin to said human.
39. A method of claim 36 further comprising administering 1.8 gA to 2.2 gA of azithromycin to said human.
40. A method of claim 34 further comprising administering between 30 mgA/kg and 90 mgA/kg of azithromycin to said human, wherein said human is a child weighing 30 kg or less.
41. A method of claim 34 wherein the azithromycin is administered in a single dose.
42. A method of claim 41 further comprising administering between 45 mgA/kg and 75 mgA/kg of azithromycin to a child weighing 30 kg or less.
43. A method of claim 41 further comprising administering 60 mgA/kg of azithromycin to a child weighing 30 kg or less.
44. A method of claim 33 wherein the alkalizing agent comprises a bicarbonate, a phosphate, a metal hydroxide, a metal oxide, or a combination thereof.
45. A method of claim 44 wherein the alkalizing agent comprises tribasic sodium phosphate.
46. A method of claim 45 wherein the alkalizing agent further comprises magnesium hydroxide.
47. A method of claim 44 wherein said azithromycin comprises an immediate release form of azithromycin.
48. A method of claim 44 wherein said azithromycin comprises a sustained release form of azithromycin.