Modified release dosage forms of skeletal muscle relaxants
View Patent ↗A unit dosage form, such as a capsule or the like, for delivering a skeletal muscle relaxant, such as cyclobenzaprine hydrochloride, into the body in an extended or sustained release fashion comprising one or more populations of drug-containing particles (beads, pellets, granules, etc.) is disclosed. At least one bead population exhibits a pre-designed sustained release profile. Such a drug delivery system is designed for once-daily oral administration to maintain an adequate plasma concentration—time profile, thereby providing relief of muscle spasm associated with painful musculoskeletal conditions over a 24 hour period.
1. A dosage form comprising a plurality of active-containing particles comprising cyclobenzaprine hydrochloride and a dissolution rate controlling polymer granulated together,
wherein the dissolution rate controlling polymer is selected from the group consisting of ethers of cellulose and esters of cellulose;
wherein the dosage form when dissolution tested using United States Pharmacopoeia Apparatus 2 (paddles @ 50 rpm) in 900 mL of 0.1N HCl at 37° C. exhibits a drug release profile substantially corresponding to the following pattern:
after 2 hours, no more than about 40% of the total active is released;
after 4 hours, from about 40-65% of the total active is released; and
after 8 hours, from about 60-85% of the total active is released; and
wherein the dosage form provides a therapeutically effective plasma concentration over a period of 24 hours to treat muscle spasm associated with painful musculoskeletal conditions.
2. The dosage form of claim 1 , wherein the particles are selected from the group consisting of pellets, beads, granules, and mini-tablets.
3. The dosage form of claim 1 , wherein the particles are pellets.
4. The dosage form of claim 1 , wherein the particles are beads.
5. The dosage form of claim 1 , wherein the particles are granules.
6. The dosage form of claim 1 , wherein the particles are mini-tablets.
7. The dosage form of claim 1 , wherein the pharmaceutical dosage form provides a maximum blood plasma concentration (C max ) within the range of about 80% to 125% of about 20 ng/mL of cyclobenzaprine hydrochloride following oral administration of a single 30 mg cyclobenzaprine dose.
8. The dosage form of claim 1 , wherein the pharmaceutical dosage form provides an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL following oral administration of a single 30 mg cyclobenzaprine dose.
9. The dosage form of claim 1 , wherein said pharmaceutical dosage form provides a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
10. The dosage form of claim 1 , wherein the pharmaceutical dosage form provides a maximum blood plasma concentration (C max ) within the range of about 80% to 125% of about 20 ng/mL of cyclobenzaprine hydrochloride, an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL, and a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
11. The dosage form of claim 6 , wherein the pharmaceutical dosage form provides a maximum blood plasma concentration (C max ) within the range of about 80% to 125% of about 20 ng/mL of cyclobenzaprine HCl, an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL, and a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
12. A capsule filled with the dosage form of claim 1 .
13. A capsule filled with the dosage form of claim 6 .
14. The dosage form of claim 1 , comprising 15 or 30 mg of cyclobenzaprine hydrochloride.
15. The dosage form of claim 6 , comprising 15 or 30 mg of cyclobenzaprine hydrochloride.
16. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 1 to the patient.
17. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 6 to the patient.
18. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 10 to said patient.
19. A dosage form comprising a plurality of active-containing particles comprising cyclobenzaprine hydrochloride and a dissolution rate controlling polymer, granulated together;
wherein the dissolution rate controlling polymer is selected from the group consisting of ethers of cellulose and esters of cellulose;
wherein said dosage form comprises 30 mg of cyclobenzaprine hydrochloride and provides a maximum blood plasma concentration (C max ) within the range of about 80% to 125% of about 20 ng/mL of cyclobenzaprine hydrochloride following oral administration of a single 30 mg cyclobenzaprine dose; and
wherein said dosage form provides a therapeutically effective plasma concentration over a period of 24 hours to treat muscle spasm associated with painful musculoskeletal conditions.
20. The dosage form of claim 19 , wherein the pharmaceutical dosage form provides an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL following oral administration of a single 30 mg cyclobenzaprine dose.
21. The dosage form of claim 20 , wherein said pharmaceutical dosage form provides a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
22. The dosage form of claim 19 , wherein the particles are selected from the group consisting of pellets, beads, granules, or mini-tablets.
23. The dosage form of claim 19 , wherein the particles are pellets.
24. The dosage form of claim 19 , wherein the particles are beads.
25. The dosage form of claim 19 , wherein the particles are granules.
26. The dosage form of claim 19 , wherein the particles are mini-tablets.
27. A capsule filled with the dosage form of claim 19 .
28. A capsule filled with the dosage form of claim 26 .
29. The dosage form of claim 26 , wherein the pharmaceutical dosage form provides an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL and a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
30. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 19 to the patient.
31. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 26 to the patient.
32. A dosage form comprising a plurality of active-containing particles comprising cyclobenzaprine hydrochloride and a dissolution rate controlling polymer surrounding the cyclobenzaprine hydrochloride,
wherein the dissolution rate controlling polymer is selected from the group consisting of ethers of cellulose and esters of cellulose;
wherein the dosage form when dissolution tested using United States Pharmacopoeia Apparatus 2 (paddles @ 50 rpm) in 900 mL of 0.1N HCl at 37° C. exhibits a drug release profile substantially corresponding to the following pattern:
after 2 hours, no more than about 40% of the total active is released;
after 4 hours, from about 40-65% of the total active is released; and
after 8 hours, from about 60-85% of the total active is released; and
wherein the dosage form provides a therapeutically effective plasma concentration over a period of 24 hours to treat muscle spasm associated with painful musculoskeletal conditions.
33. The dosage form of claim 32 , wherein the particles are selected from the group consisting of pellets, beads, granules, and mini-tablets.
34. The dosage form of claim 32 , wherein the particles are pellets.
35. The dosage form of claim 32 , wherein the particles are beads.
36. The dosage form of claim 32 , wherein the particles are granules.
37. The dosage form of claim 32 , wherein the particles are mini-tablets.
38. The dosage form of claim 32 , wherein the pharmaceutical dosage form provides a maximum blood plasma concentration (C max ) within the range of about 80% to 125% of about 20 ng/mL of cyclobenzaprine hydrochloride following oral administration of a single 30 mg cyclobenzaprine dose.
39. The dosage form of claim 32 , wherein the pharmaceutical dosage form provides an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL following oral administration of a single 30 mg cyclobenzaprine dose.
40. The dosage form of claim 32 , wherein said pharmaceutical dosage form provides a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
41. The dosage form of claim 32 , wherein the pharmaceutical dosage form provides a maximum blood plasma concentration (C max ) within the range of about 80% to 125% of about 20 ng/mL of cyclobenzaprine hydrochloride, an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL, and a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
42. The dosage form of claim 37 , wherein the pharmaceutical dosage form provides a maximum blood plasma concentration (C max ) within the range of about 80% to 125% of about 20 ng/mL of cyclobenzaprine HCl, an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL, and a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
43. A capsule filled with the dosage form of claim 32 .
44. A capsule filled with the dosage form of claim 37 .
45. The dosage form of claim 32 , comprising 15 or 30 mg of cyclobenzaprine hydrochloride.
46. The dosage form of claim 37 , comprising 15 or 30 mg of cyclobenzaprine hydrochloride.
47. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 32 to the patient.
48. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 37 to the patient.
49. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 41 to said patient.
50. A dosage form comprising a plurality of active-containing particles comprising cyclobenzaprine hydrochloride and a dissolution rate controlling polymer surrounding the cyclobenzaprine hydrochloride;
wherein the dissolution rate controlling polymer is selected from the group consisting of ethers of cellulose and esters of cellulose;
wherein said dosage form comprises 30 mg of cyclobenzaprine hydrochloride and provides a maximum blood plasma concentration (C max ) within the range of about 80% to 125% of about 20 ng/mL of cyclobenzaprine hydrochloride following oral administration of a single 30 mg cyclobenzaprine dose; and
wherein said dosage form provides a therapeutically effective plasma concentration over a period of 24 hours to treat muscle spasm associated with painful musculoskeletal conditions.
51. The dosage form of claim 50 , wherein the pharmaceutical dosage form provides an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL following oral administration of a single 30 mg cyclobenzaprine dose.
52. The dosage form of claim 50 , wherein said pharmaceutical dosage form provides a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
53. The dosage form of claim 50 , wherein the particles are selected from the group consisting of pellets, beads, granules, or mini-tablets.
54. The dosage form of claim 50 , wherein the particles are pellets.
55. The dosage form of claim 50 , wherein the particles are beads.
56. The dosage form of claim 50 , wherein the particles are granules.
57. The dosage form of claim 50 , wherein the particles are mini-tablets.
58. A capsule filled with the dosage form of claim 50 .
59. A capsule filled with the dosage form of claim 57 .
60. The dosage form of claim 57 , wherein the pharmaceutical dosage form provides an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL and a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose.
61. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 50 to the patient.
62. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 57 to the patient.
63. A dosage form comprising a plurality of active-containing particles comprising cyclobenzaprine hydrochloride and a dissolution rate controlling polymer, granulated together;
wherein the dissolution rate controlling polymer is selected from the group consisting of ethers of cellulose and esters of cellulose;
wherein said dosage form comprises 30 mg of cyclobenzaprine hydrochloride and provides a T max within the range of 80% to 125% of about 7 hours following oral administration of a single 30 mg cyclobenzaprine dose; and
wherein said dosage form provides a therapeutically effective plasma concentration over a period of 24 hours to treat muscle spasm associated with painful musculoskeletal conditions.
64. The dosage form of claim 63 , wherein the pharmaceutical dosage form provides an AUC 0-168 within the range of about 80% to 125% of about 740 ng·hr/mL following oral administration of a single 30 mg cyclobenzaprine dose.
65. The dosage form of claim 63 , wherein the particles are selected from the group consisting of pellets, beads, granules, or mini-tablets.
66. The dosage form of claim 63 , wherein the particles are pellets.
67. The dosage form of claim 63 , wherein the particles are beads.
68. The dosage form of claim 63 , wherein the particles are granules.
69. The dosage form of claim 63 , wherein the particles are mini-tablets.
70. A capsule filled with the dosage form of claim 63 .
71. A capsule filled with the dosage form of claim 69 .
72. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 63 to the patient.
73. A method of relieving muscle spasms in a patient in need thereof, comprising orally administering the dosage form of claim 69 to the patient.