Pharmaceutical multiparticulate composition comprising mycophenolic acid or mycophenolate sodium and combination with rapamycin

• US 20070036857A1
• Filed: 10/01/2004
• Published: 02/15/2007
• Est. Priority Date: 10/03/2003
• Status: Abandoned Application

• Current Assignee: Andrea Kramer, Carsten Burger, Christian-Peter Luftensteiner, Dieter Becker, Gilles Feutren, Harald Ottinger, Jorg Ogorka, Nicoletta Loggia, Patrice Guitard
• Original Assignee: Andrea Kramer, Carsten Burger, Christian-Peter Luftensteiner, Dieter Becker, Gilles Feutren, Harald Ottinger, Jorg Ogorka, Nicoletta Loggia, Patrice Guitard
• Inventors: Feutren, Gilles, Guitard, Patrice, Kramer, Andrea, Becker, Dieter, Loggia, Nicoletta, Burger, Carsten, Ottinger, Harald, Luftensteiner, Christian-Peter, Ogorka, Jorg
• Application Number:
  US10/570,752
• Publication Number:
  US 20070036857A1
• Time in Patent Office: Days
• US Class Current: 424/470
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention relates to a novel composition of mycophenolic acid, a salt or a prodrug thereof and to a fixed combination of mycophenolic acid, a salt or a prodrug thereof and rapamycin or a rapamycin derivative.

Claims

1. A composition comprising mycophenolic acid, a salt or a prodrug thereof in multiparticulate form.

3. A composition according to claim 1 wherein the multiparticulate form or the multiparticles are microparticles, minitablets, pellets, granules or beads.

4. A composition according to claim 3 in the form of minitablets, wherein the mean total weight of the minitablets is 3 to 10 mg.

5. A composition according to claim 3 in the form of microparticles having an average size of less than 1000 μ

m.

6. A composition according to claim 3 in the form of granules, pellets or beads having a diameter of from 0.2 to 2 mm.

7. A composition according to claim 1, wherein the multiparticles are enteric coated.

8. A composition according to claim 1, comprising one or more excipients selected from a binder, a filler, a disintegrant and a lubricant.

9. A composition according to claim 1, wherein the enteric coating comprises 15 to 50% of the total weight of the multiparticles.

10. A composition according to claim 1, further comprising a subcoating.

11. A composition according to claim 10 wherein the subcoating comprises hydroxypropylmethylcellulose or ethylcellulose.

12. A composition according to claims 1 comprising mycophenolate mofetil or sodium mycophenolate.

15. A combination comprising a) mycophenolic acid, a salt thereof or a prodrug thereof and b) rapamycin or a rapamycin derivative, wherein the subunits or administration units comprising mycophenolic acid, a salt thereof or a prodrug thereof are in the form of a composition according to claim 1.

16. A combination according to claim 15 wherein the mycophenolic acid, a salt thereof or a prodrug thereof is formulated into minitablets, or the rapamycin or rapamycin derivative is formulated into a tablet or into minitablets.

17. A composition or a combination according to any preceding claim for use in the treatment or prevention of native or transgenic organ, tissue or cellular allograft or xenograft transplant rejection, or treatment or prevention of autoimmune diseases.

2. A composition comprising mycophenolic acid, a salt or a prodrug thereof, adapted to disintegrate or dissolve in the mouth, stomach or small intestine to give multiparticles.

13. A fixed combination comprising a) mycophenolic acid, a salt thereof or a prodrug thereof and b) rapamycin or a rapamycin derivative.

14. A combination according to claim 13 wherein the active substances a) and b) are formulated

separately in subunits which are then combined in a single administration unit;

or

in a common administration unit.

18. A method for reducing inter- and intrapatient variability in a subject comprising administering a therapeutically effective amount of a composition comprising as active ingredient mycophenolic acid, a salt thereof or a prodrug thereof, wherein the composition is in a particulate form.