Crush-resistant oxycodone tablets intended for preventing accidental misuse and unlawful diversion

• US 8,501,160 B2
• Filed: 03/01/2007
• Issued: 08/06/2013
• Est. Priority Date: 03/01/2006
• Status: Active Grant

• Current Assignee: Ethypharm SA
• Original Assignee: Ethypharm SA
• Inventors: Bacon, Johnatan, Oury, Pascal, Cailly-Dufestel, Vincent, Herry, Catherine
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): PERREIRA, MELISSA JEAN
• Application Number:
  US12/224,385
• Publication Number:
  US 20090011016A1
• Time in Patent Office: 2,350 Days
• US Class Current: 424/10.2
• 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 31/485 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 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/36 Opioid-abuse

Abstract

Water-insoluble matrix tablets based on oxycodone or one of its pharmaceutically acceptable salts and capable of prolonged release of oxycodone to the body, exhibiting a crush resistance of at least 4 MPa.

Claims

1. Water-insoluble, matrix tablets comprising oxycodone or one of its pharmaceutically acceptable salts, capable of releasing oxycodone into the body over an extended time period and comprising oxycodone within a compression matrix, said matrix comprising

a mixture of microcrystalline cellulose and polyvinyl acetate/polyvinylpyrrolidone (80:

20) to the proportion of (1;

1),

magnesium stearate as an anti-adherent agent,

a cellulose derivative as a binder, and

one or more of the following substances (a) to (f) or a mixture thereof;

(a) a substance which irritates the nasal and/or pharyngeal tracts,

(b) a viscosity-increasing agent, leading to formation of a gel when the tablet is dissolved in a minimum amount of water,

(c) an emetic substance,

(d) an aversive coloring agent,

(e) a bittering-substance,

(f) an antagonist of the active ingredient (s) which may be the subject of drug abuse wherein said matrix represents 50-98% in weight of the total weight of the tablets, and wherein said matrix tablets have a cured outercoating.

2. Matrix tablets according to claim 1, wherein neither the mixture to be compressed, nor the compression tooling are subjected to a heating step either before or during the actual compression step.

3. Matrix tablets according to claim 1, wherein said compression matrix represents 85 to 95% weight % of the total weight of said tablet.

4. Matrix tablets according to claim 1, wherein said compression matrix also comprises at least one pharmaceutically acceptable excipient selected from the group consisting of anti-adherent agents, agents able to improve tablet cohesion on compressing, fillers, lubricants, plasticizers, bulking agents, sweeteners and colouring agents.

5. Matrix tablets according to claim 1, wherein the antagonist agent of the said active ingredient(s) which may be the subject of drug abuse is naloxone or naltrexone or one of their pharmaceutically acceptable salts.

6. Matrix tablets according to claim 1, wherein said outer coating comprises at least one sustained-release polymer advantageously chosen from the group comprising ethylcellulose derivatives and methacrylic polymers.

7. Matrix tablets according to claim 1, wherein the outer coating consists of ethylcellulose.

8. Matrix tablets according to claim 1, wherein said tablets are capable of releasing oxycodone over a period of more than 12 hours.

9. Matrix tablets according to claim 1, wherein said tablets are capable of releasing oxycodone over a period of more than 20 hours.

10. Matrix tablets according to claim 1, wherein said tablets have a plasma profile after once-a-day administration in man, such that the ratio of the Cmax observed after administration of said tablets to the Cmax value observed after administration of oxycodone extended release tablets containing the same dose, does not exceed 0.7.

11. Matrix tablets containing oxycodone according to claim 1, wherein a plasma profile after once-a-day administration in man is such that the ratio of AUC∞

observed for said tablets to the AUC ∞

value observed with oxycodone extended release tablets with the same dose, lies in the interval of 80 to 125%.

12. Tablets according to claim 1, wherein said tablets can be administered once a day.

13. Matrix tablets according to claim 1, wherein the two polymers microcrystalline cellulose and polyvinyl acetate/polyvinylpyrrolidone (80:

20) each represent a weight proportion in the order of 40% of the total weight of said compression matrix.