Modified release coated drug preparation

• US 6,958,161 B2
• Filed: 04/12/2002
• Issued: 10/25/2005
• Est. Priority Date: 04/12/2002
• Status: Expired due to Term

• Current Assignee: Mayne Pharma International Pty Limited (Mayne Pharma)
• Original Assignee: F H Faulding & Co Limited (Mayne Pharma)
• Inventors: Lukas, Stefan, Quinn, Eugene, LoPore, Angelo, Hayes, David
• Primary Examiner(s): Spear, James M.
• Application Number:
  US10/120,376
• Publication Number:
  US 20030199480A1
• Time in Patent Office: 1,292 Days
• Field of Search: 424/458, 424/459, 424/461, 424/462, 424/463, 424/474, 424/470, 424/468, 424/469, 424/480, 424/482, 424/490, 424/494, 424/497, 424/475
• US Class Current: 424/475
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 31/665 having oxygen as a ring hetero atom, e.g. fosfomycin
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5042 Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings

Abstract

A modified release preparation having one or more coated core elements, each core element including an active ingredient and having a modified release coating, wherein a stabilising coat is provided between each core element and its modified release coating so that, upon in vitro dissolution testing, the amount of active ingredient released at any time on a post-storage dissolution profile is within 40 percentage points of the amount of active ingredient released at any time on a pre-storage dissolution profile.

Claims

1. A modified release preparation having one or more coated core elements, each core element comprising an active ingredient selected from the group consisting of the acid salts of doxycycline, tetracycline, oxytetracycline, minocycline, chlortetracycline or demeclocycline and having a modified release coating, wherein a stabilising coat is provided between each core element and its modified release coating so that, upon in vitro dissolution testing, the amount of active ingredient released at any time on a post-storage dissolution profile is within 40 percentage points of the amount of active ingredient released at any time on a pre-storage dissolution profile.

2. The preparation according to claim 1, wherein the amount of active ingredient released at the majority of time points on the post-storage dissolution profile is within 30 percentage points of the amount of active ingredient released at the same time on the pre-storage dissolution profile.

3. The preparation according to claim 1, wherein the amount of active ingredient released at the majority of time points on the post-storage dissolution profile is within 20 percentage points of the amount of active ingredient released at the same time on the pre-storage dissolution profile.

4. The preparation according to claim 1, wherein the amount of active ingredient released at the majority of time points on the post-storage dissolution profile is within 10 percentage points of the amount of active ingredient released at the same time on the pre-storage dissolution profile.

5. The preparation according to claim 1, wherein the modified release coating is a delayed release coating.

6. The preparation according to claim 1, wherein the modified release coating is a delayed release coating suitable to release, in a pre-storage in vitro dissolution, 20% or less of the active ingredient in a pH of about 1.2 by 20 minutes and at least 80% of the active ingredient in a pH of at least 5 by 60 minutes.

7. The preparation according to claim 1, wherein the modified release coating is a delayed release coating suitable to release, in a pre-storage in vitro dissolution, 10% or less of the active ingredient in a pH of about 1.2 by 20 minutes and at least 90% of the active ingredient in a pH of at least 5 by 60 minutes.

8. The preparation according to claim 1, wherein the modified release coating is an enteric coating, a semi-enteric coating, a delayed release coating, a pulsed release coating, a mixture of enteric polymers, or a mixture of an enteric polymer with a water permeable, water swellable or water soluble material.

9. The preparation according to claim 8, wherein the water soluble or water permeable materials are one or a mixture of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone and polyethylene glycol.

10. The preparation according to claim 1, wherein the modified release coating comprises one or more of hydroxypropylmethyl cellulose phthalate, a pH dependent anionic methacrylate based polymer, or hydroxypropylmethyl cellulose acetate succinate.

11. The preparation according to claim 1, wherein the stabilising coat is at least semi-permeable in aqueous media.

12. The preparation according to claim 1, wherein the stabilising coat is one or a mixture of a water-soluble, water swellable or water permeable polymeric or monomeric material.

13. The preparation according to claim 1, wherein the stabilising coat is one or a mixture of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyethylene glycol, a pH dependent anionic methacrylate based polymer.

14. A method of administering an active ingredient that, upon administration in an immediate release form, normally causes nausea and gastric irritation, the method comprising administering a modified release preparation in accordance with claim 1.

15. The preparation according to claim 1, the preparation being provided as a plurality of coated core elements in a capsule.

16. The preparation according to claim 1, the preparation being provided as a plurality of coated core elements compressed to form a tablet.

17. The preparation according to claim 16, wherein the percentage of coated core elements in each tablet is in the range of 20 to 40 by weight of the total dosage weight.

18. The preparation according to claim 16, wherein the percentage of coated core elements in each tablet is in the range of 25 to 35% by weight of the total dosage weight.

19. The preparation according to claim 16, wherein the percentage of coated core elements in each tablet is about 30% by weight of the total dosage weight.

20. The preparation according to claim 1, wherein the modified release coating is a delayed release coating, the active ingredient is an acid salt of doxycycline, and the preparation is provided as a plurality of coated core elements compressed to form a tablet.

24. The method according to claim 14, wherein the modified release coating is a delayed release coating, and the active ingredient is an acid salt of doxycycline.

21. A tablet for oral administration, the tablet being a modified release preparation having one or more coated core elements, each core element comprising an active ingredient comprising an acid salt of doxycycline and having a modified release coating, wherein a stabilising coat is provided between each core element and its modified release coating so that, upon in vitro dissolution testing, the amount of active ingredient released at any time on a post-storage dissolution profile is within 40 percentage points of the amount of active ingredient released at any time on a pre-storage dissolution profile.

22. The tablet according to claim 21, wherein the modified release coating is a delayed release coating.

23. A pellet for use in a dosage form for oral administration, the pellet being a modified release preparation having one or more coated core elements, each core element comprising an active ingredient comprising an acid salt of doxycycline and having a modified release coating, wherein a stabilising coat is provided between each core element and its modified release coating so that, upon in vitro dissolution testing, the amount of active ingredient released at any time on a post-storage dissolution profile is within 40 percentage points of the amount of active ingredient released at any time on a pre-storage dissolution profile.