Controlled release preparations comprising tramadol and topiramate

• US 20060147527A1
• Filed: 12/12/2003
• Published: 07/06/2006
• Est. Priority Date: 12/13/2002
• Status: Abandoned Application

• Current Assignee: Cilag AG (Johnson & Johnson)
• Original Assignee: Cilag AG (Johnson & Johnson)
• Inventors: Braun, Christian, Eivaskhani, Reza, Bachmann, Dieter, Strong, Brian, Spycher, Rene
• Application Number:
  US10/538,946
• Publication Number:
  US 20060147527A1
• Time in Patent Office: Days
• US Class Current: 424/468
• 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 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• 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 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

This invention relates to an oral pharmaceutical preparation, suitable for dosing every 24 hours, comprising a substrate, which substrate comprises a pharmaceutically effective amount of tramadol or a salt thereof and a pharmaceutically effective amount of topiramate and wherein said substrate may be coated with a controlled release coating; said preparation having a specific dissolution rate in vitro.

Claims

1. A controlled release oral pharmaceutical preparation suitable for dosing every 24 hours comprising a substrate comprising a pharmaceutically effective amount of tramadol or a salt thereof and a pharmaceutically effective amount of topiramate;

said preparation having a dissolution rate in vitro when measured using the Ph. Eur. Paddle Method at 75 rpm in 900 ml 0.05 M phosphate buffer at 37°

C. and using HPLC;

between 15 and 35% tramadol released after 1 hour;

between 28 and 48% tramadol released after 2 hours;

between 47 and 67% tramadol released after 4 hours;

between 68 and 88% tramadol released after 8 hours;

between 79 and 99% tramadol released after 12 hours;

between 86 and 105% tramadol released after 18 hours;

about 100% tramadol released after 24 hours;

by weight,

said preparation providing a therapeutic effect for about 24 hours after oral administration.

2. An oral pharmaceutical preparation as in claim 1, said preparation having a dissolution rate as follows:

between 20 and 30% tramadol released after 1 hour;

between 33 and 43% tramadol released after 2 hours;

between 52 and 62% tramadol released after 4 hours;

between 73 and 83% tramadol released after 8 hours;

between 84 and 94% tramadol released after 12 hours;

between 91 and 100% tramadol released after 18 hours;

about 100% tramadol released after 24 hours;

by weight.

3. An oral pharmaceutical preparation as in claim 1, said preparation having a dissolution rate as follows:

25% tramadol released after 1 hour;

38% tramadol released after 2 hours;

57% tramadol released after 4 hours;

78% tramadol released after 8 hours;

89% tramadol released after 12 hours;

95,5% tramadol released after 18 hours;

about 100% tramadol released after 24 hours;

by weight.

4. An oral pharmaceutical preparation according to claims 1 wherein the tramadol salt is tramadol hydrochloride.

5. An oral pharmaceutical preparation according to claim 1, wherein said substrate is a suitable matrix material in which tramadol or its salt form is incorporated.

6. An oral pharmaceutical preparation according to claim 5 wherein thematrix material is xanthan gum.

7. An oral pharmaceutical preparation according to claim 1, wherein the preparation comprises two or more phases.

8. An oral pharmaceutical preparation according to claim 7 wherein the major part of the tramadol or its salt form and of the topiramate are in different phases of the said pharmaceutical preparation.

9. An oral pharmaceutical preparation according to claim 7 wherein the tramadol or its salt form and the topiramate are in different phases of the said pharmaceutical preparation.

10. An oral pharmaceutical preparation according to claim 9 wherein at least one phase contains the major part of tramadol or a salt thereof and at least another phase contains the major part of topiramate.

11. An oral pharmaceutical preparation according to claims 7 wherein the phases take the form of layers and at least one layer contains tramadol or a salt thereof and at least another layer contains topiramate.

12. An oral pharmaceutical preparation according to claims 1, which has two layers, one layer containing topiramate and another layer containing tramadol or a salt thereof.

13. An oral pharmaceutical preparation according to claims 1 which has three layers, one layer containing topiramate, another layer containing tramadol or a salt thereof, and a third isolator layer in between the tramadol and the topiramate layers.

14. An oral pharmaceutical preparation according to claims 7 wherein at least one of the phases take the form of pellets.

15. An oral pharmaceutical preparation according to claim 14 wherein all phases take the form of pellets.

16. An oral pharmaceutical preparation according to claims 14 wherein the pellets contain either tramadol or a salt thereof or topiramate.

17. (canceled)