Pharmaceutical Multiparticulate Composit Ion Comprising Mycophenolic Acid or Myco Phenolate Sodium and Combination Compositions with Rapamycin

• US 20080206322A1
• Filed: 08/29/2005
• Published: 08/28/2008
• Est. Priority Date: 08/31/2004
• Status: Abandoned Application

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Kerc, Janez, Beyer, Jutta, Kramer, Andrea, Becker, Dieter, Loggia, Nicoletta, Ogorka, Jorg, Luftensteiner, Chirstian-Peter
• Application Number:
  US11/573,647
• Publication Number:
  US 20080206322A1
• Time in Patent Office: Days
• US Class Current: 424/457
• 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 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

The present invention relates to a novel composition, e.g. of mycophenolic acid, a salt or a prodrug thereof, in a modified release form.

Claims

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

2. A composition according to claim 1 which is a tablet, a capsule or in the form of multiparticulates and comprises a modified release coating.

3. A composition according to claim 2 which is in the form of multiparticulates which are compressed into tablet or dispensed in a capsule or a sachet.

4. A composition according to claim 3 wherein the multiparticulates comprise a modified release coating.

5. A composition according to claim 3 wherein the tablet or capsule is able to disintegrate or dissolve in the mouth, stomach or small intestine to give modified release coated multiparticulates.

6. A composition according to claim 2 wherein the composition comprise a mixture of multiparticulates which provide different modified release profiles.

7. A composition according to claim 2 wherein the multiparticulates are microparticles, minitablets, pellets, granules, beads or drug particles.

8. A composition according to claim 2 wherein the modified release coating is a diffusion coating.

9. A composition according to claim 2 wherein the coating comprises cellulose derivative, acrylic copolymer, methacrylic copolymer or mixture thereof.

10. A composition according to claim 9 wherein the coating comprises ethylcellulose, acrylic or methacrylic copolymer containing quaternary ammonium groups or mixture thereof.

11. A composition according to claim 10 wherein the acrylic or methacrylic copolymer contains tri(C_1-4alkyl)-ammonium methylmethacrylate groups.

12. A composition according to claim 1 wherein the composition comprises one or more excipients selected from a plasticizer, an antisticking agent, a wetting agent, a thickening agent and a pore former, preferably a pH-dependent pore former.

13. A composition according to claim 2 wherein the coating comprises a pH-dependent pore former selected from the group consisting of hydroxypropylmethylcellulose-phthalate, hydroxypropylmethylcellulose-acetate-succinate, methylacrylic acid copolymer, ethylacylic acid copolymer, celluloseacetatephthalate, polyvinylacetatephthalate and mixture thereof.

14. A composition according to claim 2 wherein the coating comprises a pore former selected from the group consisting of polyethyleneglycol, polyvinylpyrrolidone, polyethyleneoxide, cellulose derivative, hydroxypropylmethylcellulose, hydroxypropylcellulose, water-soluble acrylate esters, water-soluble acrylate methacrylate esters, polyacrylic acid, PEG, triacetine, triethylcitrate, hydrophilic silicium dioxide and mixture thereof.

15. A composition according to claim 2 wherein an enteric coating is coated upon the modified release coating.

16. A composition according to claim 15 wherein the enteric coating comprises cellulose acetate phthalate, cellulose acetate trimellitate, methacrylic acid copolymers, hydroxypropyl methylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, polyvinylacetatephthalate cellulose acetate phthalate;

cellulose acetate trimellitate;

methacrylic acid copolymers, e.g. copolymers derived from methylacrylic acid and esters thereof, containing at least 40% methylacrylic acid;

hydroxypropyl methylcellulose phthalate;

hydroxypropylmethylcellulose acetate succinate or Polyvinylacetatephthalate, mixture thereof.

17. A composition according to claim 1 containing mycophenolic acid, mycophenolate mofetil or sodium mycophenolate.

18. A fixed combination comprising a) a composition according to claim 1 and b) rapamycin or a rapamycin derivative.

19. A composition according to claim 1 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 immune-mediated and/or inflammatory disease.

20. A method of immunosuppressing a subject which comprises administering a composition according to claim 1 to a subject in need thereof, optionally with the simultaneous, sequential or separate administration of another immunosuppressant.

21. A method for reducing inter- and intrapatient PK variability in a subject comprising administering a therapeutically effective amount of a composition according to claim 1.