REDUCTION OF OPIOID BLOOD FLUCTUATIONS

• US 20120083506A1
• Filed: 06/14/2010
• Published: 04/05/2012
• Est. Priority Date: 06/12/2009
• Status: Abandoned Application

• Current Assignee: ETHYPHARM
• Original Assignee: ETHYPHARM
• Inventors: Oury, Pascal, Herry, Catherine, Boyer, Maryline, Vauzelle-Kervroedan, Francoise
• Application Number:
  US13/377,750
• Publication Number:
  US 20120083506A1
• Time in Patent Office: Days
• US Class Current: 514/282
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• 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 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• 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 25/24 Antidepressants

Abstract

The present invention relates to the use of a sustained release matrix containing at least one opioid for producing a solid oral formulation in table form suitable for reducing blood concentration fluctuations of said opioid.

Claims

1. Sustained-release matrix-type tablet releasing at least one opioid or one of its pharmaceutically acceptable salts, the compression matrix of said matrix-type tablet consisting of at least one excipient selected from the group comprising sustained-release pH-independent water-soluble polymers, mineral excipients and their mixtures, for its use as medicinal product administered in repeat twice-a-day form via oral route spaced apart by 8 to 14 hours and preferably 10 to 13 hours.

2. Matrix-type tablet according to claim 1, the sustained-release, pH-independent and water-insoluble polymers being chosen from the group comprising cellulose polymers, polymers from the class of methacrylic acids, polyvinylalcohol derivatives, polymers of lactic and glycolic acids (PLGA), starches, waxes, polyvinyl acetate derivatives, polyvinyl pyrrolidone derivatives and mixtures thereof.

3. Matrix-type tablet according to claim 1 or 2, the mineral excipients being chosen from the group comprising calcium phosphates, aluminum and silicon silicates and magnesium carbonates.

4. Matrix-type tablet according to claim 1, coated with a sustained-release polymer, preferably ethylcellulose.

5. Matrix-type tablet according to claim 1, maintaining the steady-state opioid plasma concentration obtained in vivo is with a reduced fluctuation at above 60% of the Css_max value, preferably above 75% of the Css_max value for at least 10 hours and preferably at least 12 hours.

6. Matrix-type tablet according to claim 1, characterized by a swing parameter of less than 50%, preferably less than 25%.

7. Matrix-type tablets according to claim 1, characterized by a fluctuation parameter of less than 50%, preferably less than 25%.

8. Matrix-type tablet according to claim 1, characterized by a reduction in plasma fluctuations and in peaks and troughs, by limitation of resurgent pain due to lowered concentrations, and by limitation of episodes of acute pain.

9. Matrix-type tablet according to claim 1, characterized by a reduction in some side effects such as nausea, drowsiness or other cognitive side effects.

10. Matrix-type tablets according to claim 1, characterized in that the opioid is chosen from the group comprising codeine, narceine, noscapine, morphine, pholcodine, nalorphine, dihydrocodeine, hydromorphone, buprenorphine, butorphanol, dextromethorphane, nalbufine, naltrexone, naloxone, nalmefene, hydrocodone, oxymorphone and oxycodone, fentanyl, tramadol, apomorphine and etorphine, or a pharmaceutically acceptable salt thereof.

11. Matrix-type tablet according to claim 10, characterized in that the opioid is oxycodone hydrochloride.

12. Matrix-type tablet according to claim 1, characterized in that the compression matrix consists of a mixture of microcrystalline cellulose and polyvinyl acetate/polyvinyl pyrrolidone (80:

20).

13. Matrix-type tablet according to claim 1, characterized in that the matrix-type tablet consists of a mixture of microcrystalline cellulose and poly(ethyl acrylate/methyl methacrylate/trimethylamonioethyl methacrylate chloride) (1:

2;

0.2).