Claims
- 1. A pharmaceutical product comprising:
a) an extruded particle comprising an opioid antagonist dispersed in a first hydrophobic material; and b) a layer comprising a second hydrophobic material disposed about the extruded particle, the second hydrophobic material in an amount from about 5% to about 30% of the weight of the extruded particle.
- 2. A pharmaceutical product comprising:
a) a plurality of extruded particles comprising an opioid antagonist dispersed in a first hydrophobic material and a layer comprising a second hydrophobic material disposed about each of the extruded particles, the second hydrophobic material in an amount from about 5% to about 30% of the weight of the extruded particles; b) a plurality of particles comprising an opioid agonist dispersed in a third hydrophobic material; and c) a capsule containing the plurality of opioid agonist particles and the plurality of opioid antagonist extruded particles.
- 3. A pharmaceutical product comprising:
a plurality of extruded particles, each of the particles comprising an opioid antagonist dispersed in a matrix; and a layer disposed about the extruded particles; the matrix and the layer sequestering the opioid antagonist in an intact dosage form.
- 4. The pharmaceutical product of claim 2, wherein the opioid agonist particles are formed by extrusion.
- 5. The pharmaceutical product of claim 1, wherein the opioid antagonist particles are formed by
a) blending the opioid antagonist and the first hydrophobic material to form a blend; b) heating the blend to a temperature sufficient to at least soften the mixture; c) extruding the mixture to form a strand; and d) cutting the strand into particles.
- 6. The pharmaceutical product of claim 5, wherein the opioid antagonist particles have a mean diameter from about 0.1 to about 6.0 mm.
- 7. The pharmaceutical product of claim 4, wherein the opioid agonist particles are formed by
a) blending the opioid agonist and the third hydrophobic material to form a mixture; b) heating the mixture to a temperature sufficient to at least soften the mixture; c) extruding the mixture to form a strand; and d) cutting the strand into particles.
- 8. The pharmaceutical product of claim 3, wherein the matrix comprises a first hydrophobic material.
- 9. The pharmaceutical product of claim 8, wherein the layer comprises a second hydrophobic material.
- 10. The pharmaceutical product of claim 1, wherein the first hydrophobic material is selected from the group consisting of a cellulosic polymer, acrylic polymer and copolymer, methacrylic acid polymer and copolymers, shellac, zein, hydrogenated castor oil, hydrogenated vegetable oil, and mixtures of any of the foregoing.
- 11. The pharmaceutical product of claim 9, wherein the second hydrophobic material is selected from the group consisting of a cellulosic polymer, acrylic polymer and copolymer, methacrylic acid polymer and copolymers, shellac, zein, hydrogenated castor oil, hydrogenated vegetable oil, and mixtures of any of the foregoing.
- 12. The pharmaceutical product of claim 9, wherein the first hydrophobic material and the second hydrophobic material are the same.
- 13. The pharmaceutical product of claim 9, further comprising a second plurality of pharmaceutically acceptable particles, each of the second plurality of particles comprising an opioid agonist dispersed in a third hydrophobic material.
- 14. The pharmaceutical product of claim 13, wherein the third hydrophobic material is selected from the group consisting of a cellulosic polymer, acrylic polymer and copolymer, methacrylic acid polymer and copolymers, shellac, zein, hydrogenated castor oil, hydrogenated vegetable oil, and mixtures of any of the foregoing.
- 15. The pharmaceutical product of claim 13, wherein the first hydrophobic material, the second hydrophobic material and the third hydrophobic material are the same.
- 16. The pharmaceutical product of claim 13, wherein the first hydrophobic material and the third hydrophobic material are the same.
- 17. The pharmaceutical product of claim 13, wherein the second hydrophobic material and the third hydrophobic material are the same.
- 18. The pharmaceutical product of claim 2, wherein the amount of opioid antagonist released after ingestion of a tampered dosage form is effective to block the euphoric effect of the opioid agonist.
- 19. The pharmaceutical product of claim 13, wherein the amount of opioid antagonist released after ingestion of a tampered dosage form is effective to block the euphoric effect of the opioid agonist.
- 20. The pharmaceutical product of claim 1, wherein the plurality of particles have a mean diameter of about 0.1 to about 3 mm.
- 21. The pharmaceutical product of claim 2, wherein the opioid agonist is selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, etorphine, dihydroetorphine, fentanyl and derivatives, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, nalbuphene, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, sufentanil, tilidine, tramadol, pharmaceutically acceptable salts thereof, and mixtures of any of the foregoing.
- 22. The pharmaceutical product of claim 2, wherein the opioid agonist is selected from the group consisting of hydrocodone, morphine, hydromorphone, oxycodone, codeine, levorphanol, meperidine, methadone, oxymorphone, buprenorphine, fentanyl and derivatives thereof, dipipanone, heroin, tramadol, etorphine, dihydroetorphine, butorphanol, levorphanol, pharmaceutically acceptable salts thereof, mixtures of any of the foregoing.
- 23. The pharmaceutical product of claim 1, wherein the opioid antagonist is selected from the group consisting of naltrexone, naloxone, nalmefene, cyclazacine, levallorphan, pharmaceutically acceptable salt thereof, and mixtures of any of the foregoing.
- 24. The pharmaceutical product of claim 1, wherein the opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof.
- 25. The pharmaceutical product of claim 3 wherein the matrix is capable of sequestering the antagonist without the layer, and the layer enhances the sequestration.
- 26. The pharmaceutical product of claim 3 wherein the layer is capable of sequestering the antagonist without the matrix, and the matrix enhances the sequestration.
- 27. The pharmaceutical product of claim 3 wherein the matrix is incapable of sequestering the antagonist without the layer, the layer is incapable of sequestering the antagonist without the matrix and the matrix and the layer together are capable of sequestering the antagonist.
- 28. A pharmaceutical product comprising a plurality of extruded particles, each of the particles comprising an opioid antagonist dispersed in a matrix; and a layer disposed about the particles; the matrix and the layer sequestering the opioid antagonist in the dosage form such that the ratio of the amount of antagonist released from the dosage form after tampering to the amount of the antagonist released from the intact dosage form based on the dissolution at 1 hour of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. is about 20:1 or greater; about 50:1 or greater; about 100:1 or greater; about 150:1 or greater; or about 1000:1 or greater.
- 29. The pharmaceutical product of claim 28 wherein the ratio of the amount of antagonist released from the dosage form after tampering to the amount of the antagonist released from the intact dosage form based on the dissolution at 2 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 1 hour, is about 20:1 or greater; about 50:1 or greater; about 100:1 or greater; about 150:1 or greater; or about 1000:1 or greater.
- 30. The pharmaceutical product of claim 28 wherein the ratio of the amount of antagonist released from the dosage form after tampering to the amount of the antagonist released from the intact dosage form based on the dissolution at 4 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 1 hour, is about 20:1 or greater; about 50:1 or greater; about 100:1 or greater; about 150:1 or greater; or about 1000:1 or greater.
- 31. The pharmaceutical product of claim 28 wherein the ratio of the amount of antagonist released from the dosage form after tampering to the amount of the antagonist released from the intact dosage form based on the dissolution at 12 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 1 hour, is about 20:1 or greater; about 50:1 or greater; about 100:1 or greater; about 150:1 or greater; or about 1000:1 or greater.
- 32. The pharmaceutical product of claim 28 wherein the ratio of the amount of antagonist released from the dosage form after tampering to the amount of the antagonist released from the intact dosage form based on the dissolution at 24 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 1 hour, is about 20:1 or greater; about 50:1 or greater; about 100:1 or greater; about 150:1 or greater; or about 1000:1 or greater.
- 33. The pharmaceutical product of claim 28 wherein the ratio of the amount of antagonist released from the dosage form after tampering to the amount of the antagonist released from the intact dosage form based on the dissolution at 36 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 1 hour, is about 20:1 or greater; about 50:1 or greater; about 100:1 or greater; about 150:1 or greater; or about 1000:1 or greater.
- 34. A pharmaceutical product comprising: a plurality of extruded particles, each of the particles comprising an opioid antagonist dispersed in a matrix; and a layer disposed about the particles; the matrix and the layer sequestering the opioid antagonist in the dosage form such that the weight percent of antagonist released from the intact dosage form based on the dissolution at 1 hour of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. is less than 1.0% by weight; less than 0.5% by weight; less than 0.2% by weight; or less than 0.1% by weight.
- 35. The pharmaceutical product of claim 34 wherein the weight percent of antagonist released from the intact dosage form based on the dissolution at 2 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 1 hour, is less than 2.0% by weight; less than 1.0% by weight; less than 0.5% by weight; or less than 0.25% by weight.
- 36. The pharmaceutical product of claim 34 wherein the weight percent of antagonist released from the intact dosage form based on the dissolution at 4 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 1 hour, is less than 2.2% by weight; less than 1.5% by weight; less than 1.0% by weight; or less than 0.75% by weight.
- 37. The pharmaceutical product of claim 34 wherein the weight percent of antagonist released from the intact dosage form based on the dissolution at 12 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 12 hours, is less than 3.0% by weight; less than 1.8% by weight; less than 1.25% by weight; or less than 0.3% by weight.
- 38. The pharmaceutical product of claim 34 wherein the weight percent of antagonist released from the intact dosage form based on the dissolution at 24 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 1 hour, is less than 4.8% by weight; less than 2.5% by weight; less than 1.8% by weight; or less than 0.4% by weight.
- 39. The pharmaceutical product of claim 34 wherein the weight percent of antagonist released from the intact dosage form based on the dissolution at 36 hours of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. with a switch to 900 ml of SIF at 1 hour, is less than 7.0% by weight; less than 6.5% by weight; less than 3.0% by weight; or less than 1.5% by weight.
- 40. A pharmaceutical product comprising: a plurality of extruded particles, each of the particles comprising an opioid antagonist dispersed in a matrix; and a layer disposed about the particles; the matrix and the layer sequestering the opioid antagonist in the dosage form such that the intact dosage form releases 1.0% or less antagonist at 1 hour, 2.0% or less antagonist at 2 hours, 2.2% or less antagonist at 4 hours, 3.0% or less antagonist at 12 hours, 4.8% or less antagonist at 24 hours, and 7.0% or less antagonist at 36 hours, based on dissolution of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. for the first hour, followed by a switch to 900 ml of SIF thereafter.
- 41. The pharmaceutical product of claim 40 wherein the intact dosage form releases 0.5% or less antagonist at 1 hour, 1.0% or less antagonist at 2 hours, 1.5% or less antagonist at 4 hours, 1.8% or less antagonist at 12 hours, 2.5% or less antagonist at 24 hours and 6.5% or less antagonist at 36 hours based on dissolution of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. for the first hour, followed by a switch to 900 ml of SIF thereafter.
- 42. The pharmaceutical product of claim 40 wherein the intact dosage form releases 0.2% or less antagonist at 1 hour, 0.5% or less antagonist at 2 hours, 1.0% or less antagonist at 4 hours, 1.25% or less antagonist at 12 hours, and 1.8% or less antagonist at 24 hours, and 3.0% or less antagonist at 36 hours based on dissolution of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. for the first hour, followed by a switch to 900 ml of SIF thereafter.
- 43. The pharmaceutical product of claim 40, wherein the intact dosage form releases 0.1% or less antagonist at 1 hour, 0.25% or less antagonist at 2 hours, 0.75% or less antagonist at 4 hours, 0.3% or less antagonist at 12 hours, 0.4% or less antagonist at 24 hours, and 1.5% or less antagonist at 36 hours based on dissolution of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. for the first hour, followed by a switch to 900 ml of SIF thereafter.
- 44. The pharmaceutical product of claim of claim 2, wherein the weight percent of the agonist released from the dosage form after tampering based on the dissolution at 1 hour of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. is less than 50% by weight; less than 40% by weight; or less than 35% by weight.
- 45. The pharmaceutical product of claim of claim 13, wherein the weight percent of the agonist released from the dosage form after tampering based on the dissolution at 1 hour of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. is less than 50% by weight; less than 40% by weight; or less than 35% by weight.
- 46. The pharmaceutical product of claim of claim 22, wherein the weight percent of the agonist released from the dosage form after tampering based on the dissolution at 1 hour of the dosage form in 700 ml of SGF using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C. is less than 50% by weight; less than 40% by weight; or less than 35% by weight.
- 47. The pharmaceutical product of claim 7, wherein the opioid antagonist particles have a mean diameter from about 0.1 to about 6.0 mm.
- 48. The pharmaceutical product of claim 28, wherein the opioid antagonist particles are formed by
a) blending the opioid antagonist and a first hydrophobic material to form a mixture; b) heating the mixture to a temperature sufficient to at least soften the mixture; c) extruding the mixture to form a strand; and d) cutting the strand into particles.
- 49. The pharmaceutical product of claim 48, wherein the opioid antagonist particles have a mean diameter from about 0.1 to about 6.0 mm.
- 50. A pharmaceutical product comprising a plurality of particles comprising an opioid agonist and a layer disposed about the opioid agonist particles; and a plurality of opioid antagonist particles and a layer disposed about the opioid antagonist particles, wherein the agonist particles and the antagonist particles are similar in a property selected from the group consisting of appearance, texture, smell, taste, hardness, shape, size or a combination thereof.
- 51. A pharmaceutical product comprising a plurality of particles comprising an opioid agonist and a layer disposed about the opioid agonist particles; and a plurality of opioid antagonist particles and a layer disposed about the opioid antagonist particles, wherein the agonist particles and the antagonist particles are virtually indistinguishable in a property selected from the group consisting of appearance, texture, smell, taste, hardness, shape, size or a combination thereof.
- 52. A method of preparing a pharmaceutical product comprising preparing a plurality of particles comprising an opioid agonist;
preparing a plurality of particles comprising an opioid antagonist; applying a layer to the opioid agonist particles and the opioid antagonist particles such that the opioid agonist particles and the opioid antagonist particles are similar in appearance.
- 53. A method of preparing a pharmaceutical product comprising
preparing a plurality of particles comprising an opioid agonist; preparing a plurality of particles comprising an opioid antagonist; applying a layer to the opioid agonist particles and the opioid antagonist particles such that the opioid agonist particles and the opioid antagonist particles are virtually indistinguishable in appearance.
- 54. A method of preparing a pharmaceutical product comprising
a) dispersing an opioid antagonist in a first hydrophobic material by extrusion to form a particle; and b) disposing a layer comprising a second hydrophobic material about the particle, the second hydrophobic material in an amount from about 5% to about 30% of the weight of the particle.
- 55. A method of preparing a pharmaceutical product comprising:
a) dispersing an opioid antagonist in a first hydrophobic material by extrusion to form a plurality of particles and disposing a layer comprising a second hydrophobic material about each of the particles, the second hydrophobic material in an amount from about 5% to about 30% of the weight of the particles; b) dispersing an opioid agonist in a third hydrophobic material to form a plurality of particles; and c) containing the plurality of opioid agonist particles and the plurality of opioid antagonist particles in a capsule.
- 56. A method of preparing a pharmaceutical product comprising:
dispersing an opioid antagonist in a matrix by extrusion to form a plurality of pharmaceutically acceptable particles and disposing a layer over each of the particles such that the matrix and the layer sequester the opioid antagonist in an intact dosage form.
- 57. A pharmaceutical product comprising: a plurality of extruded particles, each of the particles comprising an opioid antagonist dispersed in a matrix; and a layer disposed about the particles; the matrix sequestering the opioid antagonist in an intact dosage form.
- 58. The pharmaceutical product of claim 1, wherein the ratio of the mean Cmax of antagonist provided after single dose administration of a tampered dosage form to a patient population, to the mean Cmax of the antagonist provided after single dose administration of an intact dosage form to a patient population is about 20:1 or greater.
- 59. The pharmaceutical product of claim 58, wherein the ratio of the mean Cmax of antagonist provided after single dose administration of a tampered dosage form to a patient population, to the mean Cmax of the antagonist provided after single dose administration of an intact dosage form to a patient population is about 100:1 or greater.
- 60. The pharmaceutical product of claim 58, wherein the ratio of the mean Cmax of antagonist provided after single dose administration of a tampered dosage form to a patient population, to the mean Cmax of the antagonist provided after single dose administration of an intact dosage form to a patient population is about 125:1 or greater.
- 61. The pharmaceutical product of claim 58, wherein the ratio of the mean Cmax of antagonist provided after single dose administration of a tampered dosage form to a patient population, to the mean Cmax of the antagonist provided after single dose administration of an intact dosage form to a patient population is about 150:1 or greater.
- 62. The pharmaceutical product of claim 28, wherein said tampering is by crushing to a powder.
- 63. The pharmaceutical product of claim 62, wherein said crushing is with a mortar and pestel.
- 64. A pharmaceutical product comprising: a plurality of extruded particles comprising about 2 mg naltrexone or a pharmaceutically acceptable salt dispersed in a matrix; and a layer disposed about the particles; the matrix and the layer sequestering the naltrexone or salt thereof in the dosage form such that the intact dosage form releases 0.065 mg or less antagonist at 36 hours, based on dissolution of the dosage form in 700 ml of SGF for one hour then 900 ml of SIF thereafter using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C.
- 65. The pharmaceutical product of claim 64, wherein the intact dosage form releases 0.04 mg or less antagonist at 36 hours, based on dissolution of the dosage form in 700 ml of SGF for one hour then 900 ml of SIF thereafter using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C.
- 66. A pharmaceutical product comprising: a plurality of extruded particles comprising about 8 mg naltrexone or a pharmaceutically acceptable salt dispersed in a matrix; and a layer disposed about the particles; the matrix and the layer sequestering the naltrexone or salt thereof in the dosage form such that the intact dosage form releases 0.08 mg or less antagonist at 36 hours, based on dissolution of the dosage form in 700 ml of SGF for one hour then 900 ml of SIF thereafter using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C.
- 67. The pharmaceutical product of claim 64, wherein the intact dosage form releases 0.12 mg or less antagonist at 36 hours, based on dissolution of the dosage form in 700 ml of SGF for one hour then 900 ml of SIF thereafter using a USP Type II (paddle) apparatus at 50 rpm at 37 degrees C.
- 68. A pharmaceutical product comprising:
a) an extruded particle comprising naltrexone hydrocloride dispersed in a first hydrophobic material selected from the group consisting of an acrylic resin, stearyl alcohol, stearic acid and a mixture thereof; and b) a layer comprising a second hydrophobic material disposed about the particle, the second hydrophobic material selected from the group consisting of an alkylcellulose, an acrylic resin, and a mixture thereof.
- 69. A pharmaceutical product comprising:
a) a plurality of extruded particles comprising naltrexone hydrochloride dispersed in a first hydrophobic material selected from the group consisting of an acrylic resin, stearyl alcohol, stearic acid and a mixture thereof and a layer comprising a second hydrophobic material selected from the group consisting of an alkylcellulose, an acrylic resin, and a mixture thereof disposed about each of the particles; b) a plurality of particles comprising an opioid agonist selected from the group consisting of oxycodone, hydrocodone, hydromorphone and pharmaceutically acceptable salts thereof dispersed in a third hydrophobic material selected from the group consisting of an acrylic resin, stearyl alcohol, stearic acid and a mixture thereof; and c) a capsule containing the plurality of opioid agonist particles and the plurality of naltrexone hydrochloride particles.
- 70. A pharmaceutical product comprising: a plurality of extruded particles, each of the particles comprising naltrexone hydrochloride dispersed in a matrix comprising a hydrophobic material selected from the group consisting of an acrylic resin, stearyl alcohol, stearic acid and a mixture thereof; and a layer comprising a material selected from the group consisting of an alkylcellulose, an acrylic resin, and a mixture thereof disposed about the particles; the matrix and the layer sequestering the naltrexone hydrochloride in an intact dosage form.
- 71. The pharmaceutical product of claim 68, wherein the naltrexone hydrochloride is in an amount of from about 2 mg to about 12 mg.
- 72. The pharmaceutical product of claim 71, wherein the naltrexone hydrochloride is in an amount of from about 2 mg to about 8 mg.
- 73. The pharmaceutical product of claim 68, wherein the naltrexone hydrochloride particles comprise greater than 90% hydrophobic material.
- 74. The pharmaceutical product of claim 73, wherein the naltrexone hydrochloride particles comprise greater than 95% hydrophobic material.
- 75. The pharmaceutical product of claim 68, wherein the layer is in an amount of from about 5% to about 30% of the weight of the naltrexone hydrochloride particles.
- 76. A pharmaceutical product comprising: a plurality of extruded particles, each of the particles comprising an opioid antagonist dispersed in a matrix; and a layer disposed about the particles; the matrix and the layer sequestering the opioid antagonist in an intact dosage form, wherein the layer comprises an acrylic polymer and a cellulosic polymer in bilaminar arraignment.
- 77. The pharmaceutical product of claim 76, wherein the acrylic polymer is disposed about the antagonist particles and the cellulosic polymer is disposed about the acrylic polymer layered antagonist particles.
- 78. The pharmaceutical product of claim 1, wherein the second hydrophobic material is in an amount from about 16% to about 30% of the weight of the particles
- 79. The pharmaceutical product of claim 1, wherein the second hydrophobic material is in an amount from about 20% to about 29% of the weight of the particles
- 80. The pharmaceutical product of claim 1, wherein the second hydrophobic material is in an amount from about 22% to about 28% of the weight of the particles
- 81. The pharmaceutical product of claim 1, wherein the layer is substantially devoid of antagonist.
- 82. The pharmaceutical product of claim 1, wherein the dosage form is devoid of immediate release antagonist.
- 83. The pharmaceutical product of claim 63, wherein said crushing is with 24 strokes of a mortar and pestel.
- 84. A pharmaceutical product comprising:
a) an extruded particle comprising an adverse agent or antagonist dispersed in a first hydrophobic material; and b) a layer comprising a second hydrophobic material disposed about the particle, the second hydrophobic material in an amount from about 5% to about 30% of the weight of the extruded particle.
- 85. A pharmaceutical product comprising:
a) a plurality of extruded particles comprising an adverse agent or antagonist dispersed in a first hydrophobic material and a layer comprising a second hydrophobic material disposed about each of the particles, the second hydrophobic material in an amount from about 5% to about 30% of the weight of the particles; b) a plurality of particles comprising an active agent dispersed in a third hydrophobic material; and c) a capsule containing the plurality of active agent particles and the plurality of adverse agent or antagonist particles.
- 86. A pharmaceutical product comprising: a plurality of extruded particles, each of the particles comprising an adverse agent or antagonist dispersed in a matrix; and a layer disposed about the particles; the matrix and the layer sequestering the adverse agent or antagonist in an intact dosage form.
- 87. The pharmaceutical product of claim 6, wherein the opioid antagonist particles have a mean length from about 0.1 to about 6.0 mm.
- 88. The pharmaceutical product of claim 47, wherein the opioid antagonist particles have a mean length from about 0.1 to about 6.0 mm.
- 89. The pharmaceutical product of claim 49, wherein the opioid antagonist particles have a mean length from about 0.1 to about 6.0 mm.
- 90. The pharmaceutical product of claim 1 any of claims 1, wherein the ratio of the mean AUC of antagonist provided after single dose administration of a tampered dosage form to a patient population, to the mean AUC of the antagonist provided after single dose administration of an intact dosage form to a patient population is about 5:1 or greater.
- 91. The pharmaceutical product of claim 90, wherein the ratio of the mean AUC of antagonist provided after single dose administration of a tampered dosage form to a patient population, to the mean AUC of the antagonist provided after single dose administration of an intact dosage form to a patient population is about 25:1 or greater.
- 92. The pharmaceutical product of claim 90, wherein the ratio of the mean AUC of antagonist provided after single dose administration of a tampered dosage form to a patient population, to the mean AUC of the antagonist provided after single dose administration of an intact dosage form to a patient population is about 75:1 or greater.
- 93. The pharmaceutical product of claim 90, wherein the ratio of the mean AUC of antagonist provided after single dose administration of a tampered dosage form to a patient population, to the mean AUC of the antagonist provided after single dose administration of an intact dosage form to a patient population is about 200:1 or greater.
- 94. The pharmaceutical product of claim 2, wherein the opioid agonist is oxycodone or a pharmaceutically acceptable salt thereof.
- 95. The pharmaceutical product of claim 2, wherein the opioid agonist is hydromorphone or a pharmaceutically acceptable salt thereof.
- 96. The pharmaceutical product of claim 2, wherein the opioid agonist is hydrocodone or a pharmaceutically acceptable salt thereof.
- 97. The pharmaceutical product of claim 2, wherein the opioid agonist is oxymorphone or a pharmaceutically acceptable salt thereof.
- 98. The pharmaceutical product of claim 2, wherein the opioid agonist is morphine or a pharmaceutically acceptable salt thereof.
- 99. A method of treating pain comprising orally administering a pharmaceutical product of claim 2, to a patient in need thereof.
- 100. A method of administration comprising orally administering a pharmaceutically product of claim 2 to a patient.
- 101. A pharmaceutical product comprising:
a) a particle comprising an opioid antagonist dispersed in a first hydrophobic material; and b) a layer comprising a second hydrophobic material disposed about the particle, the ratio of the mean AUC of antagonist provided after single dose administration of a tampered dosage form comprising the product to a patient population, to the mean AUC of the antagonist provided after single dose administration of an intact dosage form comprising the product to a patient population is about 5:1 or greater.
- 102. A pharmaceutical product comprising:
a) a particle comprising an opioid antagonist dispersed in a first hydrophobic material; and b) a layer comprising a second hydrophobic material disposed about the particle, the ratio of the mean AUC of antagonist provided after single dose administration of a tampered dosage form comprising the product to a patient population, to the mean AUC of the antagonist provided after single dose administration of an intact dosage form comprising the product to a patient population is about 20:1 or greater.
Parent Case Info
[0001] This application claims priority to U.S. Provisional No. 60/464,323 filed Apr. 21, 2003, the disclosure of which is hereby incorporated by reference in its entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60464323 |
Apr 2003 |
US |