Claims
- 1. A method for treating pain in humans for a time period of about 24 hours, comprising
- preparing a solid, controlled-release oral dosage form consisting of a plurality of inert pharmaceutical beads coated with an analgesically effective amount of an opioid analgesic or a mixture of opioid analgesics or a salt thereof, said inert pharmaceutical beads overcoated with a controlled release coating, wherein the dissolution rate in-vitro of the dosage form when measured by the USP Paddle Method of U.S. Pharmacopeia XXII(1990) at 100 rpm at 900 ml aqueous buffer at 1.6 and 7.2 pH and 37.degree. C. from about 16.8% to about 42.5% (by wt) opioid release after 1 hour, from about 25% to about 65% (by wt) opioid released after 2 hours, from about 45% to about 85% (by wt) opioid released after 4 hours, and greater than about 60% (by wt) opioid release after 8 hours, the in-vitro release rate being substantially independent of pH in that a difference, at any given time, between an amount of opioid released at one pH and an amount released at any other pH, when measured in-vitro using the USP Paddle Method of U.S. Pharmacopeia XXII (1990) at 100 rpm in 900 ml aqueous buffer, is no greater than 10%, the in-vitro release rate being chosen such that the peak plasma level of said opioid obtained in-vivo occurs from about 2 to about 8 hours after administration of the dosage form; said dosage form providing an extended duration of therapeutic effect of about 24 hours; and
- administering said dosage form to a human patient at a dosing interval of about 24 hours.
- 2. The method of claim 1, wherein said controlled release coating comprises a pharmaceutically acceptable hydrophobic polymer.
- 3. The method of claim 1, further comprising the step of placing a sufficient quantity of said dosage form into a capsule prior to said administering step.
- 4. The method of claim 1, wherein said opioid analgesic is selected from the group consisting of hydromorphone, oxycodone, dihydrocodeine, codeine, dihydromorphone, morphine, buprenorphine, salts of any of the foregoing, and mixtures of any of the foregoing.
- 5. The method of claim 1, wherein said dosage form provides a peak plasma of said opioid analgesic from about 4 to about 6 hours after administration.
- 6. The method of claim 2, where said hydrophobic polymer is selected from the group consisting of a plasticized acrylic polymer, a plasticized ethylcellulose and a mixture thereof.
- 7. The method of claim 2, wherein said hydrophobic polymer is applied to said beads as an aqueous dispersion.
- 8. The method of claim 1, wherein said controlled release coating comprises a copolymer of acrylic and methacrylic acid.
- 9. The method of claim 1, wherein said controlled release coating comprises a material selected from the group consisting of methyl methacrylate copolymer, ethoxyethyl methacrylate, cyanoethyl methacrylate, poly(acrylic acid), poly(methacrylic acid), methacrylic acid alkylamide copolymer, poly(methyl methacrylate), polymethacrylate, poly(methyl methacrylate) copolymer, polyacrylamide, aminoalkyl methacrylate copolymer, poly(methacrylic acid anhydride), and glycidyl methacrylate copolymer.
- 10. The method of claim 1, wherein said controlled release coating comprises an alkylcellulose.
- 11. The method of claim 1, wherein said controlled release coating comprises one or more ammonio methacrylate copolymers.
- 12. The method of claim 1, wherein the dissolution rate in-vitro of the dosage form, when measured by the USP Paddle Method of U.S. Pharmacopeia XXII (1990) at 100 rpm at 900 ml aqueous buffer at 1.6 and 7.2 pH at 37.degree. C. is about 31.1% (by wt) opioid released after 1 hour, about 37% (by wt) opioid released after 2 hours, about 51.5% (by wt) opioid released after 4 hours and greater than about 60% (by wt) opioid released after 8 hours.
- 13. The method of claim 1, wherein the dissolution rate in-vitro of the dosage form, when measured by the USP Paddle Method of U.S. Pharmacopeia XXII (1990) at 100 rpm at 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37.degree. C. is about 31.1% (by wt) opioid released after 1 hour, about 37% (by wt) opioid released after 2 hours, about 51.5% (by wt) opioid released after 4 hours and greater than about 60% (by wt) opioid released after 8 hours.
Parent Case Info
This application is a continuation of U.S. application Ser. No. 08/677,797, filed Jul. 10, 1996, which is a continuation of U.S. application Ser. No. 08/561,829, filed Nov. 27, 1995, which is a continuation of U.S. application Ser. No. 08/086,248, filed Jul. 1, 1993.
US Referenced Citations (92)
Foreign Referenced Citations (4)
Number |
Date |
Country |
9047732 |
Jul 1990 |
AUX |
9341654 |
Feb 1995 |
AUX |
2082573 |
Nov 1992 |
CAX |
2131350 |
Jan 1994 |
CAX |
Continuations (3)
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Number |
Date |
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Parent |
677797 |
Jul 1996 |
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Parent |
561829 |
Nov 1995 |
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Parent |
086248 |
Jul 1993 |
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