MANUFACTURING OF ACTIVE-FREE GRANULES AND TABLETS COMPRISING THE SAME

• US 20130165467A1
• Filed: 05/10/2011
• Published: 06/27/2013
• Est. Priority Date: 05/10/2010
• Status: Active Grant

• Current Assignee: Euroceltique SA
• Original Assignee: Euroceltique SA
• Inventors: Hayes, Geoffrey Gerard, Mohammad, Hassan, Walden, Malcolm, Tamber, Harjit
• Granted Patent: US 9,993,433 B2
• Time in Patent Office: Days
• US Class Current: 514/282
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• 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 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to prolonged release pharmaceutical dosage forms, the manufacture thereof as well as their use for administration to human beings.

Claims

1. A method of manufacturing an oral prolonged release pharmaceutical composition comprising:

a) producing granules comprising a prolonged release material, wherein the granules do not comprise a pharmaceutically active agent;

b) optionally selecting granules of step a) of substantially uniform size;

c) blending said granules of step a) or step b) with a pharmaceutically active agent;

d) compressing said blended granules of step c) to obtain an oral prolonged release pharmaceutical composition in the form of a tablet.

2. The method according to claim 1, further comprising the step of:

e) curing said tablet of step d).

3. The method according to claim 1, wherein granules of step a) are milled prior to step b).

4. The method according to claim 1, wherein granules of a mean size in the range of about 100 μ

m to about 2.0 mm are selected in step b).

5. The method according to claim 1, wherein the pharmaceutically active agent is substantially pure.

6. The method according to claim 1, wherein step d) takes place directly after step c) with no further intermediate steps.

7. The method according to claim 2, wherein curing takes place at a temperature in the range of about 40°

C. to about 100°

C. and for a time in the range of about 10 min to about 3 hours.

8. The method according to claim 1, wherein the prolonged release material is selected from the group consisting of hydrophobic or hydrophilic polymers, protein-derived material, gums, waxes, oils, fatty acids, fatty alcohols, and any combination thereof.

9. The method according to claim 8, wherein the polymers are selected from the group consisting of cellulose ethers, (meth)acrylic acid (co)polymers, and any combination thereof.

10. The method according to claim 1, wherein the pharmaceutically active agent is selected from the group consisting of oxycodone, hydromorphone, hydrocodone, tramadol, oxymorphone, naltrexone, naloxone, and pharmaceutically acceptable salts, hydrates and solvates of any of the foregoing.

11. The method according to claim 1, wherein at least two pharmaceutically active agents are blended with granules of step a) or step b).

12. The method according to claim 11, wherein the first pharmaceutically active agent is selected from the group consisting of oxycodone, hydromorphone, hydrocodone, tramadol, oxymorphone, and pharmaceutically acceptable salts, hydrates and solvates of any of the foregoing and wherein the second pharmaceutically active ingredient is selected from the group consisting of naloxone, naltrexone, nalmephene, and pharmaceutically acceptable salts, hydrates and solvates of any of the foregoing.

13. The method according to claim 1, wherein the oral prolonged release pharmaceutical composition releases the pharmaceutically active agent(s) with the following in vitro release when measured using the Ph. Eur. paddle method in 500 or 1000 ml of Simulated Gastric Fluid at 100 rpm at 37°

C.;

at 0.5 h;

10 to 60% by weight of the pharmaceutically active agent(s),

at 1 h;

30 to 80% by weight of the pharmaceutically active agent(s),

at 2 h;

35 to 85% by weight of the pharmaceutically active agent(s),

at 3 h;

40 to 95% by weight of the pharmaceutically active agent(s),

at 4 h;

50 to 100% by weight of the pharmaceutically active agent(s),

at 5 h;

60 to 100% by weight of the pharmaceutically active agent(s),

at 6 h;

70 to 100% by weight of the pharmaceutically active agent(s),

at 8 h;

80 to 100% by weight of the pharmaceutically active agent(s),

at 12 h;

85 to 100% by weight of the pharmaceutically active agent(s).

14. The method according to claim 1, wherein the ratio of the amount of the pharmaceutically active agent released after 0.5, 1 or 2 hours of in vitro dissolution of the dosage form in 500 or 1000 ml of Simulated Gastric Fluid pH 1.2 with up to 40% ethanol using the Ph. Eur. paddle method at 100 rpm at 37°

C. compared to the amount of the pharmaceutically active agent released after 0.5, 1 or 2 hours of in vitro dissolution of the dosage form in 500 or 1000 ml of Simulated Gastric Fluid pH 1.2 with 0% ethanol using the Ph. Eur. paddle method at 100 rpm at 37 C is about 2;

1 or less, about 1.5;

1 or less, about 1;

1 or less, about 1;

1.2 or less, about 1;

1.4 or less, about 1;

1.6 or less, about 1;

1.8 or less, about 1;

2 or less, about 1;

2.5 or less about 1;

3 or less or about 1;

5 or less.

15. An oral prolonged release pharmaceutical composition obtainable by the method of claim 1.

16. A method of manufacturing granules comprising the steps of:

a) producing granules comprising a prolonged release material, wherein the granules do not comprise a pharmaceutically active agent;

b) optionally selecting granules of step a) of substantially uniform size.

17. The method according to claim 16 wherein the prolonged release material is selected from the group consisting of hydrophobic or hydrophilic polymers, protein-derived material, gums, waxes, oils, fatty acids, fatty alcohols, and any combination thereof.

18. Granules obtainable by the method according claim 16.

19. (canceled)