Oral pharmaceutical composition

1. A method of treating graft-versus-host disease (GvHD), the method comprising orally administering a composition to a subject, wherein the composition comprises an oral composition comprising minicapsules wherein the minicapsules comprise an immunosuppressant in a liquid, semi-solid, or solid core, the minicapsules having release profiles to release the immunosuppressant in an active form in the colon and the minicapsules comprising a gelling agent encapsulating the active immunosuppressant selected from solubilised active immunosuppressant and dispersed active immunosuppressant, and combinations thereof, and the minicapsules being coated to target release to at least the colon.

2. The method of claim 1 , wherein the immunosuppressant is solubilised and is also released in the ileum.

3. The method of claim 1 , wherein the immunosuppressant is solubilised or readily soluble, and the composition is a controlled release composition that permits release in the small intestine, ileum and colon.

4. The method of claim 1 , wherein the immunosuppressant is in a solubilised or readily soluble liquid, semi-liquid or solid form.

5. The method of claim 1 , wherein the immunosuppressant is in a solubilised form.

6. The method of claim 1 , wherein the immunosuppressant is cyclosporin A, tacrolimus or sirolimus, or a combination thereof.

7. The method of claim 1 , wherein the immunosuppressant is cyclosporin A.

8. The method of claim 1 , wherein the immunosuppressant is tacrolimus.

9. The method of claim 1 , wherein the immunosuppressant is cyclosporin or tacrolimus.

10. The method of claim 1 , wherein the gelling agent is gelatin.

11. The method of claim 1 , wherein the minicapsules comprise an emulsion comprising the gelling agent which emulsion is in extruded, gelled and dried form.

12. The method of claim 11 wherein the immunosuppressant is solubilised in a hydrophobic solution and the minicapsules comprise gelatin as the gelling agent.

13. The method of claim 1 wherein the immunosuppressant is as a solubilised formulation encapsulated with gelling agent and the minicapsules have the characteristics of minicapsules obtained by a process utilising surface tension of different solutions and comprising ejecting through a nozzle having a single orifice a hydrophobic solution or suspension and a solution comprising the gelling agent, to form into a spherical form and fall into a cooling air flow or into a cooling or hardening solution whereby the gelling agent is gelled and encapsulates the hydrophobic suspension or solution.

14. The method of claim 1 , wherein the minicapsules have a coating that uses ethylcellulose as the release rate controlling polymer.

15. The method of claim 1 , wherein the minicapsules are coated with any of acrylic-based polymers, methacrylic-based polymers or ethylcellulose-based polymers in combination with a natural polysaccharide.

16. The method of claim 15 , wherein the natural polysaccharide is selected from: amylose, pectin, alginate, amylopectin, chitosan, galactomannan, guar gum and derivatives thereof.

17. The method of claim 1 wherein the composition comprises immunosuppressant that is as a hydrophobic solution.

18. The method of claim 1 , wherein the composition is a single-unit formulation.

19. The method of claim 17 , wherein the single unit formulation is a hard gelatin capsule.

20. The method of claim 1 , wherein the minicapsules are seamless.

21. The method of claim 1 , wherein the immunosuppressant is protected from absorption and/or the environment of the upper gastrointestinal tract (GIT).

22. The method of claim 17 , wherein the composition allows abrupt and/or sustained release of the immunosuppressant into the proximal colon.

23. A method of treating graft-versus-host disease (GvHD), the method comprising orally administering a composition to a subject, wherein the composition comprises an oral composition comprising minicapsules wherein the minicapsules comprise an immunosuppressant in a liquid, semi-solid, or solid core, and the minicapsules have release profiles to release the immunosuppressant in an active form in the colon, the minicapsules comprising a gelling agent encapsulating the active immunosuppressant selected from solubilised active immunosuppressant and dispersed active immunosuppressant, and combinations thereof, and the minicapsules being coated to target release to at least the colon, further wherein the composition having has a dissolution profile, when tested in a U.S.P. Type II apparatus paddles at 37° C. and 50 rpm, in pH 6.8 buffer for the test as follows: 1 hour: less than or equal to about 20% drug released.

24. The method of claim 23 which has a dissolution profile, when tested in a U.S.P. Type II apparatus paddles at 37° C. and 50 rpm, in pH 6.8 buffer as follows: 24 hours: from about 75% to about 100% cyclosporin released.

25. The method of claim 23 which has a dissolution profile, when tested in a U.S.P. Type II apparatus paddles at 37° C. and 50 rpm, in pH 6.8 buffer as follows: 16 hours: about 75% cyclosporin released.

26. The method of claim 23 , wherein the immunosuppressant is in a solubilised or readily soluble liquid, semi-liquid or solid form.

27. The method of claim 23 , wherein the immunosuppressant is in a solubilised form.

28. The method of claim 23 , wherein the immunosuppressant is cyclosporin A, tacrolimus or sirolimus, or a combination thereof.

29. The method of claim 23 , wherein the immunosuppressant is cyclosporin A.

30. The method of claim 23 , wherein the immunosuppressant is tacrolimus.

31. The method of claim 23 , wherein the immunosuppressant is cyclosporin or tacrolimus.

32. The method of claim 23 , wherein the gelling agent is gelatin.

33. The composition of claim 23 , wherein the minicapsules comprise an emulsion comprising the gelling agent which emulsion is in extruded, gelled and dried form.

34. The method of claim 33 wherein the immunosuppressant is solubilised in a hydrophobic solution and the minicapsules comprise gelatin as the gelling agent.

35. The method of claim 23 wherein the immunosuppressant is as a solubilised formulation encapsulated with the gelling agent and the minicapsules have the characteristics of minicapsules obtained by a process utilising surface tension of different solutions and comprising ejecting through a nozzle having a single orifice a hydrophobic solution or suspension and a solution comprising the gelling agent, to form into a spherical form and fall into a cooling air flow or into a cooling or hardening solution whereby the gelling agent is gelled and encapsulates the hydrophobic suspension or solution.

36. The method of claim 23 , wherein the minicapsules have a coating that uses ethylcellulose as the release rate controlling polymer.

37. The method of claim 23 , wherein the minicapsules are coated with any of acrylic-based polymers, methacrylic-based polymers or ethylcellulose-based polymers in combination with a natural polysaccharide.

38. The method of claim 37 , wherein the natural polysaccharide is selected from: amylose, pectin, alginate, amylopectin, chitosan, galactomannan, guar gum and derivatives thereof.

39. The method of claim 23 , wherein the immunosuppressant is as a hydrophobic solution.

40. The method of claim 23 wherein the composition is a single-unit formulation.

41. The method of claim 40 , wherein the single unit formulation is a hard gelatine capsule.

42. The method of claim 1 , wherein the minicapsules are seamless.

43. The method of claim 23 , wherein the immunosuppressant is protected from absorption and/or the environment of the upper gastrointestinal tract (GIT).

44. The method of claim 43 , wherein the composition allows abrupt and/or sustained release of the immunosuppressant into the proximal colon.

45. A method of treating graft-versus-host disease (GvHD), the method comprising orally administering to a subject a composition comprising minicapsules that comprise an immunosuppressant in a solubilised, colon-targeted, oral drug delivery format, the minicapsules having release profiles to release the immunosuppressant in an active form in the colon, the minicapsules comprising a gelling agent encapsulating the immunosuppressant selected from solubilised immunosuppressant and dispersed immunosuppressant, and combinations thereof, and the minicapsules being coated to target release to at least the colon.

46. The method of claim 45 , wherein the drug delivery format is colon- and ileum-targeted.

47. The method of claim 45 , wherein the immunosuppressant is cyclosporin or tacrolimus.

48. The method of claim 45 , wherein the gelling agent is gelatin.

49. The method of claim 45 , wherein the minicapsules comprise an emulsion comprising the gelling agent which emulsion is in extruded, gelled and dried form.

50. The method of claim 49 , wherein the gelling agent is gelatin and the immunosuppressant is cyclosporin or tacrolimus.

51. The method of claim 45 , wherein the minicapsule format comprises seamless minicapsules have a coating comprising a controlled release polymer.

52. The method of claim 51 , wherein the controlled release polymer is ethylcellulose.

53. The method of claim 51 , wherein:

the immunosuppressant comprises an immunosuppressant in a solubilised form selected from cyclosporin A, tacrolimus or sirolimus, or a combination thereof, in a solubilised form;

the minicapsules comprise an emulsion comprising a gelling agent, the emulsion being in extruded, gelled and dried form and the gelling agent encapsulating immunosuppressant in a solubilised form.

54. The method of claim 45 , wherein:

the immunosuppressant comprises an immunosuppressant in a solubilised liquid form selected from cyclosporin A, tacrolimus or sirolimus, or a combination thereof, in a solubilised liquid form;

the minicapsule format comprises minicapsules that comprise an emulsion comprising a gelling agent, the emulsion being in extruded, gelled and dried form and the gelling agent encapsulating immunosuppressant in a solubilised liquid form; and

the minicapsules have a coating comprising a controlled release polymer.

55. The method of claim 54 , wherein the immunosuppressant in a solubilised liquid form is cyclosporin A in a solubilised liquid form.

56. The method of claim 54 , wherein the controlled release polymer is ethylcellulose.

57. The method of claim 55 , wherein the cyclosporin A in a solubilised liquid form is as a hydrophobic solution.

58. The method of claim 1 , wherein:

the immunosuppressant comprises an immunosuppressant in a solubilised form selected from cyclosporin A, tacrolimus or sirolimus, or a combination thereof, in a solubilised form;

the minicapsules comprise an emulsion comprising a gelling agent, the emulsion being in extruded, gelled and dried form and the gelling agent encapsulating immunosuppressant in a solubilised form.

59. The method of claim 1 , wherein:

the immunosuppressant comprises an immunosuppressant in a solubilised liquid form selected from cyclosporin A, tacrolimus or sirolimus, or a combination thereof, in a solubilised liquid form;

the minicapsule format comprises minicapsules that comprise an emulsion comprising a gelling agent, the emulsion being in extruded, gelled and dried form and the gelling agent encapsulating immunosuppressant in a solubilised liquid form; and

the minicapsules have a coating comprising a controlled release polymer.

60. The method of claim 59 , wherein the controlled release polymer is ethylcellulose and the immunosuppressant in a solubilised liquid form is cyclosporin A in a solubilised liquid form.