Controlled Release Compositions Comprising a Cephalosporin for the Treatment of a Bacterial Infection

• US 20080069870A1
• Filed: 04/12/2006
• Published: 03/20/2008
• Est. Priority Date: 04/12/2005
• Status: Abandoned Application

• Current Assignee: Elan Pharma International Limited (Perrigo Company PLC)
• Original Assignee: Elan Corporation PLC (Perrigo Company PLC)
• Inventors: Liversidge, Gary, Jenkins, Scott A.
• Application Number:
  US11/571,379
• Publication Number:
  US 20080069870A1
• Time in Patent Office: Days
• US Class Current: 424/456
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• 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: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 31/04 Antibacterial agents

Abstract

The invention relates to a controlled release composition comprising a cephalosporin that in operation delivers the drug in a pulsed or bimodal manner for the treatment of bacterial infection. The controlled release composition comprises an immediate release component and a modified release component; the immediate release component comprising a first population of cephalosporin-containing particles and the modified release component comprising a second population of cephalosporin-containing particles coated with a controlled release coating; wherein the combination of the immediate release and modified release components in operation deliver the active ingredient in a pulsed or bi-modal manner. Preferably, the cephalosporin is cefcapene pivoxil or a salt thereof which can be released from the dosage form in an erodable, diffusion and/or osmotic-controlled release profile.

Claims

1. A controlled release antibiotic composition comprising a first population of cephalosporin-containing particles and at least one subsequent population of cephalosporin-containing particles, wherein the cephalosporin contained in the first population is substantially uncoated, and the subsequent population of cephalosporin-containing particles further comprises a modified release coating or, alternatively or additionally, a modified release matrix material, such that the composition following oral delivery to a subject delivers the cephalosporin in the first and subsequent populations in a pulsatile manner.

2. The controlled release composition of claim 1, wherein said cephalosporin is cefcapene pivoxil or a salt thereof.

3. The composition according to claim 2, wherein the first population comprises immediate-release particles and the subsequent population comprises modified-release particles.

4. The composition according to claim 2, wherein the first population comprises immediate-release particles and the formulation comprising the subsequent population is an erodable formulation.

5. The composition according to claim 2, wherein the formulation comprising the subsequent population is a diffusion controlled formulation.

6. The composition according to claim 2, wherein the formulation comprising the subsequent population is an osmotic controlled formulation.

7. The composition according to claim 3, wherein the modified release particles have a modified-release coating.

8. The composition according to claim 3, wherein the modified release particles comprise a modified-release matrix material.

9. The compositions of claim 7 or 8 wherein said modified release particles are combined in formulation that releases said cefcapene pivoxil or salt thereof by erosion, diffusion or osmosis to the surrounding environment.

10. The composition according to claim 9, wherein at least one of the first and subsequent populations further comprises an enhancer.

11. The composition according to claim 10, wherein the amount of active ingredient contained in each of the first and subsequent populations is from about 0.1 mg to about 1 g.

12. The composition according to claim 11, wherein the first and subsequent populations have different in vitro dissolution profiles.

13. The composition according to claim 12, which in operation releases substantially all of the cefcapene pivoxil from the first population prior to release of the antibiotic from the subsequent population.

14. The dosage form according to claim 13 comprising a blend of the particles of each of the first and subsequent populations contained in a hard gelatin or soft gelatin capsule.

15. The dosage form according to claim 14, wherein the particles of each of the populations are in the form of mini-tablets and the capsule contains a mixture of the mini-tablets.

16. The dosage form according to claim 13, in the form of a multilayer tablet comprising a first layer of compressed cefapene pivoxil or salt thereof-containing particles of the first population and another layer of compressed antibiotic-containing particles of the subsequent population.

17. The dosage form according to claim 16, wherein the first and subsequent populations of cefcapene pivoxil or salt thereof-containing particles are provided in a rapidly dissolving dosage form.

18. The dosage form according to claim 17, comprising a fast-melt tablet.

19. A method for the treatment of bacterial infection comprising administering a therapeutically effective amount of a composition according to claim 2.

20. The composition according to claim 2, wherein the modified-release particles comprise a pH-dependent polymer coating which is effective in releasing a pulse of the active ingredient following a time delay.

21. The composition according to claim 20, wherein the polymer coating comprises methacrylate copolymers.

22. The composition according to claim 21, wherein the polymer coating comprises a mixture of methacrylate and ammonio methacrylate copolymers in a ratio sufficient to achieve a pulse of the active ingredient following a time delay.

23. The composition according to claim 22, wherein the ratio of methacrylate to ammonio methacrylate copolymers is 1:

1.