Tamper-resistant tablet providing immediate drug release

• US 10,201,502 B2
• Filed: 07/27/2012
• Issued: 02/12/2019
• Est. Priority Date: 07/29/2011
• Status: Expired due to Fees

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Schwier, Sebastian, Haupts, Marcel, Barnscheid, Lutz, Patz, Jana
• Primary Examiner(s): Blanchard, David J
• Assistant Examiner(s): Coughlin, Daniel F.
• Application Number:
  US13/559,644
• Publication Number:
  US 20130028970A1
• Time in Patent Office: 2,391 Days
• Field of Search: None
• 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 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The invention relates to a tamper-resistant tablet comprising

• (i) a matrix material in an amount of more than one third of the total weight of the tablet; and
• (ii) a plurality of coated particulates in an amount of less than two thirds of the total weight of the tablet; wherein said particulates comprise a pharmacologically active compound and a physiologically acceptable polymer, preferably a polyalkylene oxide; and form a discontinuous phase within the matrix material;
  which preferably provides under in vitro conditions immediate release of the pharmacologically active compound in accordance with Ph. Eur.;
  and method of using said tablet to treat pain and other conditions.

Claims

1. A tamper-resistant tablet comprising:

(i) a matrix material in an amount of at least 40 wt.-% based on a total weight of the tablet; and

(ii) a plurality of coated particulates in an amount of less than or equal to 60 wt.-% based the total weight of the tablet;

wherein said coated particulates comprise a pharmacologically active compound and a physiologically acceptable polymer;

wherein said pharmacologically active compound is selected from the group consisting of opioids;

wherein the physiologically acceptable polymer is a polyalkylene oxide having a weight average molecular weight of at least 500,000 g/mol;

wherein the physiologically acceptable polymer is present in said coated particulates in an amount of at least 25 wt.-% based on a total weight of coated particulates;

wherein the coated particulates comprise a coating comprising a coating material comprising a water-soluble polymer selected from the group consisting of cellulose esters, cellulose ethers, poly(meth)acrylates, vinyl polymers, and natural film formers;

wherein said coated particulates form a discontinuous phase within the matrix material;

wherein said coated particulates do not comprise a disintegrant; and

wherein said coated particulates have a breaking strength of at least 300 N;

said tablet providing under in vitro conditions immediate release of the pharmacologically active compound in accordance with European Pharmacopoeia (Ph. Eur.).

2. The tablet according to claim 1, which has under in vitro conditions a disintegration time measured in accordance with Ph. Eur. of at most 3 minutes.

3. The tablet according to claim 1, wherein the coated particulates have an average diameter of about 1000±

250 μ

m and/or an average length of about 750±

250 μ

m.

4. The tablet according to claim 1, wherein the content of the pharmacologically active compound is at least 25 wt.-%, based on the total weight of a particulate.

5. The tablet according to claim 1, which has a total weight of 500±

200 mg and contains

(i) 50±

10 wt.-% coated particulates having an average particle size of 800±

200 μ

m, wherein the coated particulates comprise

23±

10 wt.-% pharmacologically active compound,

22±

8 wt.-% physiologically acceptable polymer,

optionally, 4.0±

2.5 wt.-% plasticizer, and

optionally, 0.05±

0.03 wt.-% further excipients; and

(ii) 49±

9 wt.-% matrix material, wherein the matrix material comprises

43±

6 wt.-% filler and/or binder,

optionally, 5±

3 wt.-% disintegrant and

optionally, 0.15±

0.13 wt.-% lubricant;

all wt.-% being expressed relative to the total weight of the tablet.

6. The tablet according to claim 1, wherein the coated particulates are prepared by a process comprising hot melt-extrusion.

7. The tablet according to claim 1, wherein the matrix material is also present in particulate form.

8. The tablet according to claim 1, wherein the matrix material comprises binder, filler, disintegrant and/or lubricant.

9. A method of treating pain in a patient in need thereof by administering to a patient in need of such treating a tablet comprising an effective amount therefor of a pharmacologically active compound, wherein the tablet is a tablet according to claim 1.

10. The tablet according to claim 1, wherein the coated particulates are film coated.

11. The tablet according to claim 1, which, under physiological conditions, releases at least 86% of the pharmacologically active compound originally contained in the tablet within 30 minutes.

12. The tablet according to claim 1, which, under physiological conditions, releases at least 82% of the pharmacologically active compound originally contained in the tablet within 10 minutes.

13. The tablet according to claim 1, wherein the coated particulates comprise a water-soluble coating.

14. The tablet according to claim 1, wherein the coated particulates cannot be pulverized using a hammer or with the assistance of a mortar and pestle.

15. A tamper-resistant tablet comprising:

(i) a matrix material in an amount of at least 40 wt.-% based on a total weight of the tablet; and

(ii) a plurality of coated particulates in an amount of less than or equal to 60 wt.-% based the total weight of the tablet;

wherein said coated particulates comprise a pharmacologically active compound and a physiologically acceptable polymer;

wherein said pharmacologically active compound is selected from the group consisting of opioids;

wherein the physiologically acceptable polymer is a polyalkylene oxide having a weight average molecular weight of at least 500,000 g/mol;

wherein the physiologically acceptable polymer is present in said coated particulates in an amount of at least 25 wt.-% based on a total weight of coated particulates;

wherein the coated particulates comprise a coating comprising a coating material comprising a water-soluble polymer selected from the group consisting of cellulose esters, cellulose ethers, poly(meth)acrylates, vinyl polymers, and natural film formers;

wherein said coated particulates form a discontinuous phase within the matrix material;

wherein said coated particulates do not comprise a disintegrant; and

wherein said coated particulates have a breaking strength of at least 300 N;

said plurality of coated particulates releasing within 15 minutes at least 60% by weight of the plurality of coated particulates of pharmacologically active compound as monitored in 900 mL 0.1 HCL at 37°

C., using a paddle apparatus at 50 rpm; and

said tablet providing under in vitro conditions immediate release of the pharmacologically active compound in accordance with European Pharmacopoeia (Ph. Eur.).