Controlled release oxycodone compositions

• US 5,266,331 A
• Filed: 11/27/1991
• Issued: 11/30/1993
• Est. Priority Date: 11/27/1991
• Status: Expired due to Term

• Current Assignee: Purdue Pharmaceuticals L.P. (Purdue Pharma L.P.), Purdue Pharma L.P., The PF Laboratories, Inc. (Purdue Pharma L.P.)
• Original Assignee: Euroceltique SA
• Inventors: Oshlack, Benjamin, Chasin, Mark, Minogue, John J.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Spear, James M.
• Application Number:
  US07/800,549
• Time in Patent Office: 734 Days
• Field of Search: 424/464, 424/465, 424/468, 424/469, 424/470, 424/486, 424/487, 424/488, 424/494, 424/496, 424/497, 424/498
• US Class Current: 424/468
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• 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 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

A solid controlled release, oral dosage form, the dosage form comprising a therapeutically effective amount of oxycodone or a salt thereof in a matrix wherein the dissolution rate in vitro of the dosage form, when measured by the USP Paddle Method of 100 rpm in 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37° C. is between 12.5% and 42.5% (by weight) oxycodone released after 1 hour, between 25% and 55% (by weight) oxycodone released after 2 hours, between 45% and 75% (by weight) oxycodone released after 4 hours and between 55% and 85% (by weight) oxycodone released after 6 hours, the in vitro release rate being independent of pH between pH 1.6 and 7.2 and chosen such that the peak plasma level of oxycodone obtained in vivo occurs between 2 and 4 hours after administration of the dosage form.

Claims

1. A solid, controlled release, oral dosage form, the dosage form comprising an analgesically effective amount of oxycodone or a salt thereof in a matrix wherein the dissolution rate in vitro of the dosage form, when measured by the USP Paddle Method at 100 rpm at 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37°

C. is between 12.5% and 42.5% (by wt) oxycodone released after 1 hour, between 25% and 55% (by wt) oxycodone released after 2 hours, between 45% and 75% (by wt) oxycodone released after 4 hours and between 55% and 85% (by wt) oxycodone released after 6 hours, the in vitro release rate being independent of pH between pH 1.6 and 7.2 and chosen such that the peak plasma level of oxycodone obtained in vivo occurs between 2 and 4 hours after administration of the dosage form.

2. A dosage form according to claim 1 wherein the in vitro dissolution rate is between 17.5% and 38% (by wt) oxycodone released after 1 hour, between 30% and 50% (by wt) oxycodone released after 2 hours, between 50% and 70% (by wt) oxycodone released after 4 hours and between 60% and 80% (by wt) oxycodone released after 6 hours.

3. A dosage form according to claim 2 wherein the in vitro dissolution rate is between 17.5% and 32.5% (by wt) oxycodone released after 1 hour, between 35% and 45% (by wt) oxycodone released after 2 hours, between 55% and 65% (by wt) oxycodone released after 4 hours and between 65% and 75% (by wt) oxycodone released after 6 hours.

4. A dosage form according to claim 1 wherein the peak plasma level of oxycodone occurs between 2.25 and 3.75 hours after administration of the dosage form.

5. A dosage form according to claim 1 wherein a therapeutically effective amount of an oxycodone salt comprises between 2 and 50 mg of oxycodone hydrochloride.

6. A dosage form according to claim 1 wherein a therapeutically effective amount of an oxycodone salt comprises between 2 and 40 mg of oxycodone hydrochloride.

7. A solid controlled release oral dosage form, comprising an analgesically

(a) effective amount of oxycodone or a salt thereof;

(b) an effective amount of a controlled release matrix selected from the group consisting of hydrophilic polymers, hydrophobic polymers, digestible substituted or unsubstituted hydrocarbons having from about 98 to about 50 carbon atoms, and polyalkylene glycols; and

(c) a suitable amount of a suitable pharmaceutical diluent, wherein said composition provides an in vitro dissolution rate of the dosage form when measured by the USP Paddle Method at 100 rpm at 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37°

C. is between 12.5% and 42.5% (by wt) oxycodone released after 1 hour, between 25% and 55% (by wt) oxycodone released after 2 hours, between 45% and 75% (by wt) oxycodone released after 4 hours and between 55% and 85% (by wt) oxycodone released after 6 hours, the in vitro release rate being independent of pH between pH 1.6 and 7.2 and chosen such that the peak plasma level of oxycodone obtained in vivo occurs between 2 and 4 hours after administration of the dosage form.

8. The controlled release composition of claim 7, wherein said controlled release matrix comprises an acrylic resin.

9. The controlled release composition of claim 8 which contains from about 2 to about 50 mg of oxycodone hydrochloride.

10. A solid controlled release oral dosage form, comprising

(a) an analgesically effective amount of spheroids comprising oxycodone or a salt thereof and either a spheronising agent or an acrylic polymer or copolymer;

(b) a film coating which controls the release of the oxycodone or oxycodone salt at a controlled rate in an aqueous medium, wherein said composition provides an in vitro dissolution rate of the dosage form; and

(c) a suitable amount of a suitable pharmaceutical diluent, wherein said composition provides an in vitro dissolution rate of the dosage form when measured by the USP Paddle Method at 100 rpm at 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37°

C. between 12.5% and 42.5% (by wt) oxycodone released after 1 hour, between 25% and 55% (by wt) oxycodone released after 2 hours, between 45% and 75% (by wt) oxycodone released after 4 hours and between 55% and 85% (by wt) oxycodone released after 6 hours, the in vitro release rate being independent of pH between pH 1.6 and 7.2 and chosen such that the peak plasma level of oxycodone obtained in vivo occurs between 2 and 4 hours after administration of the dosage form.

11. The controlled release composition of claim 10, wherein said film coating comprises a water insoluble material selected from the group consisting of shellac or zein, a water insoluble cellulose, or a polymethacrylate.

12. The controlled release composition of claim 11, which contains from about 2 to about 50 mg of oxycodone hydrochloride.

13. A controlled release tablet for oral administration comprising an analgesically effective amount of oxycodone or an oxycodone salt dispersed in a controlled release matrix, comprising

from about 5% to about 25% of an acrylic resin and from about 8% to about 40% of at least one aliphatic alcohol of 12-36 carbon atoms, by weight, wherein the dissolution rate in vitro of the dosage form, when measured by the USP Paddle Method at 100 rpm at 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37°

C. is between 12.5% and 42.5% (by wt) oxycodone released after 1 hour, between 25% and 55% (by wt) oxycodone released after 2 hours, between 45% and 75% (by wt) oxycodone released after 4 hours and between 55% and 85% (by wt) oxycodone released after 6 hours, the in vitro release rate being independent of pH between pH 1.6 and 7.2 and chosen such that the peak plasma level of oxycodone obtained in vivo occurs between 2 and 4 hours after administration of the dosage form.

14. A process for the preparation of a solid, controlled release, oral dosage form comprising

incorporating an analgesically effective amount of oxycodone or a salt thereof in a controlled release matrix comprising from about 5% to about 25% of an acrylic resin and from about 8% to about 40% of at least one aliphatic alcohol of 12-36 carbon atoms, by weight,

wherein the dissolution rate in vitro of the dosage form, when measured by the USP Paddle Method of 100 rpm in 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37°

C. is between 25% and 60% (by weight) oxycodone release after 1 hour, between 45% and 80% (by weight) oxycodone released after 2 hours, between 60% and 90% (by weight) oxycodone released after 3 hours, and between 70% and 100% (by weight) oxycodone released after 4 hours, the in vitro release rate being independent of pH between 1.6 and 7.2 and chosen such that the peak plasma level of oxycodone obtained in vivo occurs between 2 and 4 hours after administration of the dosage form.

15. The process of claim 14, further comprising

wet granulating said oxycodone or a salt thereof with said acrylic resin in alcohol to form a granulate thereof;

adding said at least one aliphatic alcohol in a substantially liquid state to said granulate to obtain coated granules; and

compressing and shaping the granules.

16. The process of claim 14, further comprising

wet granulating said oxycodone or a salt thereof with said acrylic resin in water to form a granulate thereof;

adding said at least one aliphatic alcohol in a substantially liquid state to said granulate to obtain coated granules; and

compressing and shaping the granules.

17. The process of claim 16, wherein a portion of said acrylic resin is dispersed in a suitable solvent and sprayed onto said granulate prior to adding said at least one aliphatic alcohol.