Tamper-resistant dosage form containing one or more particles

• US 10,154,966 B2
• Filed: 05/27/2014
• Issued: 12/18/2018
• Est. Priority Date: 05/29/2013
• Status: Expired due to Fees

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Barnscheid, Lutz, Geiβler, Anja, Wening, Klaus, Patz, Jana
• Primary Examiner(s): Shomer, Isaac
• Application Number:
  US14/287,512
• Publication Number:
  US 20140356426A1
• Time in Patent Office: 1,666 Days
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• 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: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/36 Opioid-abuse

Abstract

The invention relates to a tamper-resistant pharmaceutical dosage form comprising one or more particles, wherein each of said one or more particles

• • comprises a pharmacologically active ingredient and a physiologically acceptable polymer;
  • has a breaking strength of at least 300 N;
  • has a weight of at least 2 mg; and
  • optionally, comprises a film-coating;
    wherein the total weight of the pharmaceutical dosage form is greater than the total weight of said one or more particles.

Claims

1. A tamper-resistant pharmaceutical dosage form for oral administration, said pharmaceutical dosage form being a capsule comprising:

(a) one or more prolonged release particles, wherein each of said one or more particles;

(i) comprises a pharmacologically active ingredient selected from the group consisting of stimulants;

(ii) comprises a physiologically acceptable polymer selected from the group consisting of acrylic polymers and polyalkylene oxides, wherein the physiologically acceptable polymer has a weight average molecular weight of at least 200,000 g/mol, wherein the physiologically acceptable polymer is present in a content of at least 30 wt.-% relative to a total weight of the one or more particles, and wherein the pharmacologically active ingredient is embedded in a matrix comprising the physiologically acceptable polymer;

(iii) has a breaking strength of at least 300 N;

(iv) has a weight of at least 100 mg; and

(v) optionally comprises a film-coating; and

(b) one or more additional particles having a weight of less than 2 mg;

wherein the pharmaceutical dosage form has a total weight greater than a combined weight of the particles (a) and (b);

wherein the pharmaceutical dosage form contains no aversive agent and contains no antagonist; and

wherein the pharmaceutical composition can be chewed without significantly deteriorating tamper-resistance and without significantly altering drug release.

2. The pharmaceutical dosage form according to claim 1, wherein the total volume of the pharmaceutical dosage form is greater than the total volume of the one or more particles.

3. The pharmaceutical dosage form according to claim 1, wherein the breaking strength of the pharmaceutical dosage form is below the breaking strength of the one or more particles.

4. The pharmaceutical dosage form according to claim 1, wherein the content of the pharmacologically active ingredient is at least 1.0 wt.-%, based on the total weight of one of the one or more particles.

5. The pharmaceutical dosage form according to claim 1, which has released at most 50% of the pharmacologically active ingredient after 60 min measured under in vitro conditions and in accordance with Ph. Eur.

6. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is embedded in a matrix material comprising the physiologically acceptable polymer.

7. The pharmaceutical dosage form according to claim 1, wherein the total amount of the pharmacologically active ingredient that is contained in the pharmaceutical dosage form is contained in the one or more particles.

8. The pharmaceutical dosage form according to claim 1, wherein the physiologically acceptable polymer is selected from the group consisting of polyalkylene oxides, non-ionic acrylates, anionic acrylates and cationic acrylates.

9. The pharmaceutical dosage form according to claim 1, wherein the content of the physiologically acceptable polymer is at least 25 wt.-%, based on the total weight of one of the one or more particles.

10. The pharmaceutical dosage form according to claim 1, which contains at least two particles that are identical or differ from one another.

11. The pharmaceutical dosage form according to claim 1, wherein the one or more particles are of cylindrical shape.

12. The pharmaceutical dosage form according to claim 1, wherein the one or more particles are melt-extruded.

13. The pharmaceutical dosage form according to claim 1, wherein each of said one or more particles has a weight of at least 260 mg.

14. The pharmaceutical dosage form according to claim 1, wherein each of said one or more particles has a weight of at least 300 mg.

15. The pharmaceutical dosage form according to claim 1, which under in vitro conditions in 600 mL 0.1 N HCl, using the basket method according to Ph. Eur. at 75 rpm, after 1 h, has released at most 60% of the pharmacologically active ingredient relative to the total amount of the pharmacologically active ingredients originally contained in the pharmaceutical dosage form.

16. The pharmaceutical dosage form according to claim 1, wherein the pharmaceutically acceptable active ingredient is selected from the group consisting of amphetamine, amphetaminil, lisdeamfetamine dimesylate, and metamphetamine, and the physiologically acceptable salts thereof, and combinations thereof.

17. The pharmaceutical dosage form according to claim 16, wherein the pharmaceutically acceptable active ingredient is selected from the group consisting of amphetamine and the physiologically acceptable salts thereof.

18. The pharmaceutical dosage form according to claim 1, wherein the pharmaceutically acceptable active ingredient is selected from the group consisting of methylphenidate and the physiologically acceptable salts thereof.

20. The pharmaceutical dosage form according to claim 18, which under in vitro conditions in 600 mL 0.1 N HCl, using the basket method according to Ph. Eur. at 75 rpm, after 1 h, has released at most 60% of the pharmacologically active ingredient relative to the total amount of the pharmacologically active ingredients originally contained in the pharmaceutical dosage form.

19. A tamper-resistant pharmaceutical dosage form for oral administration, said pharmaceutical dosage form being a capsule comprising:

(a) one or more prolonged release particles, wherein each of said one or more particles;

(i) comprises a first pharmacologically active ingredient selected from the group consisting of stimulants;

(ii) comprises a physiologically acceptable polymer selected from the group consisting of acrylic polymers and polyalkylene oxides, wherein the physiologically acceptable polymer has a weight average molecular weight of at least 200,000 g/mol, wherein the physiologically acceptable polymer is present in a content of at least 30 wt-% relative to a total weight of the one or more particles, and wherein the pharmacologically active ingredient is embedded in a matrix comprising the physiologically acceptable polymer;

(iii) has a breaking strength of at least 300 N;

(iv) has a weight of at least 100 mg; and

(v) optionally comprises a film-coating; and

(b) one or more additional particles having a weight of less than 2 mg;

wherein the pharmaceutical dosage form has a total weight greater than a combined weight of the particles (a) and (b); and

wherein the pharmaceutical dosage form does not contain a second pharmacologically active ingredient; and

wherein the pharmaceutical composition can be chewed without significantly deteriorating tamper-resistance and without significantly altering drug release.

21. A tamper-resistant pharmaceutical dosage form for oral administration, said pharmaceutical dosage form being a capsule comprising:

(a) one or more particles, wherein each of said one or more particles;

(i) comprises a prolonged release pharmacologically active ingredient selected from the group consisting of stimulants;

(ii) comprises a physiologically acceptable polymer selected from the group consisting of acrylic polymers and polyalkylene oxides, wherein the physiologically acceptable polymer has a weight average molecular weight of at least 200,000 g/mol, wherein the physiologically acceptable polymer is present in a content of at least 30 wt.-% relative to a total weight of the one or more particles, and wherein the pharmacologically active ingredient is embedded in a matrix comprising the physiologically acceptable polymer;

(iii) has a breaking strength of at least 300 N;

(iv) has a weight of at least 20 mg; and

(v) optionally comprises a film-coating; and

(b) one or more additional particles having a weight of less than 2 mg;

wherein the pharmaceutical dosage form has a total weight greater than a combined weight of the particles (a) and (b);

wherein the one or more particles number “

n,”

where n=1, 2, 3 or 4, and each of said n particles has a weight within the range of (250±

150)/n mg;

wherein the pharmaceutical dosage form contains no aversive agent and contains no antagonist; and

wherein the pharmaceutical composition can be chewed without significantly deteriorating tamper-resistance and without significantly altering drug release.

22. The pharmaceutical dosage form according to claim 21, which under in vitro conditions in 600 mL 0.1 N HCl, using the basket method according to Ph. Eur. at 75 rpm, after 1 h, has released at most 60% of the pharmacologically active ingredient relative to the total amount of the pharmacologically active ingredients originally contained in the pharmaceutical dosage form.