Tamper-resistant tablet providing immediate drug release

• US 10,695,297 B2
• Filed: 05/20/2019
• Issued: 06/30/2020
• Est. Priority Date: 07/29/2011
• Status: Active Grant

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Schwier, Sebastian, Haupts, Marcel, Ruttgers, Udo, Barnscheid, Lutz, Denker, Jana
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Singh, Randeeop
• Application Number:
  US16/416,532
• Publication Number:
  US 20190269621A1
• Time in Patent Office: 407 Days
• Field of Search: None
• 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 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/36 Opioid-abuse

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 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 polyalkylene oxide; and form a discontinuous phase within the matrix material;
  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. % of a total weight of the tablet;

and

(ii) a plurality of particulates in an amount of not more than 60 wt. % of the total weight of the tablet;

wherein said particulates comprise (a) a pharmacologically active compound selected from the group consisting of hydrocodone, hydromorphone, oxycodone, oxymorphone, morphine, tapentadol, tramadol, and the phyiologically acceptable salts thereof and (b) a polyalkylene oxide having a weight average molecular weight of at least 200,000 g/mol;

the polyalkylene oxide being present in the particulates in an amount of at least 25 wt. % based on a total weight of the particulates;

wherein said particulates do not comprise a disintegrant;

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

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

wherein the tablet releases after 30 minutes at least 90% of the pharmacologically active compound when measured in vitro with a paddle apparatus equipped without a sinker, at 50 rpm, at 37±

5°

C., in 900 ml simulated intestinal fluid at pH 6.8.

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 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 pharmacologically active compound is dispersed in the polyalkylene oxide.

5. 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.

6. The tablet according to claim 1, wherein the particulates are hot melt-extruded.

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

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

9. The tablet according to claim 1, wherein the matrix material is dry granulated or compacted.

10. The tablet according to claim 1, wherein the matrix material comprises one or more materials selected from the group consisting of a binder, a filler, a disintegrant, and a lubricant.

11. The tablet according to claim 10, wherein the disintegrant is crosslinked.

12. A method of treating a condition 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.

13. The method according to claim 12, wherein the condition is pain.