Quetiapine formulations

• US 20050158383A1
• Filed: 10/21/2004
• Published: 07/21/2005
• Est. Priority Date: 10/21/2003
• Status: Abandoned Application

• Current Assignee: Actavis Group (Abbvie Incorporated)
• Original Assignee: Actavis Group (Abbvie Incorporated)
• Inventors: Boehm, Garth, Dundon, Josephine
• Application Number:
  US10/970,850
• Publication Number:
  US 20050158383A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention provides novel dosage forms of quetiapine and its salts, particularly quetiapine hemifumarate including wax dosage forms, press-coat dosage forms, and sprinkle dosage forms, and other novel dosage forms. The invention also provides sustained release and pulsed release dosage forms of quetiapine and its salts. Methods of making novel quetiapine dosage forms are given. Methods of treating schizophenia and other neuropsychiatric disorders by administering an effective amount of the dosage forms disclosed herein, either alone or in combination with one or more other medicaments, are also provided by the invention

Claims

1. A solid dosage formulation comprising a matrix wherein the matrix comprises:

a therapeutically effective amount of quetiapine or a pharmaceutically acceptable salt thereof; and

a wax material.

2. The solid dosage form of claim 1 wherein the matrix comprises a therapeutically effective amount of quetiapine hemifumarate.

3. The solid dosage form of claim 1, wherein the wax material includes carnauba wax, glyceryl behenate, castor wax, or any combination thereof.

4. The solid dosage form of claim 1 wherein the dosage is formulated as a sustained release dosage formulation.

5. The solid dosage form of claim 1, wherein the matrix is coated with a coating composition.

11. The solid dosage form of claim 1, wherein the matrix further comprises a processing aid.

6-10. -10. (canceled)

12-17. -17. (canceled)

18. A press-coat dosage form comprising

a core composition comprising an active agent, which active agent is quetiapine or a pharmaceutically acceptable salt thereof, a wax material;

and

a coating composition comprising a hydrophilic polymer, wherein the coating composition is press-coated onto the core composition.

19. The press-coat dosage form of claim 18 wherein the active agent is quetiapine hemifumarate.

23. The press-coat dosage form of claim 18, wherein the ratio of quetiapine in the core composition to quetiapine in the coating composition is greater than about 5:

3.

20-22. -22. (canceled)

24-44. -44. (canceled)

45. A controlled release dosage form comprising a pharmaceutically effective amount of quetiapine or a pharmaceutically acceptable salt thereof and at least one excipient,

exhibiting a dissolution profile such that

at 4 hours after combining the dosage form with a dissolution media 50 to 95% of the quetiapine or the pharmaceutically acceptable salt thereof is released.

46. The controlled release dosage form of claim 45 exhibiting a dissolution profile such that

at 1 hour after combining the dosage form with a dissolution media 30 to 80% of the quetiapine or the pharmaceutically acceptable salt thereof is released,

at 2 hours after combining the dosage form with a dissolution media 40 to 85% of the quetiapine or pharmaceutically acceptable salt thereof is released,

at 3 hours after combining the dosage form with a dissolution media 45 to 90% of the quetiapine or pharmaceutically acceptable salt thereof is released, and

at 4 hours after combining the dosage form with a dissolution media 50 to 95% of the quetiapine or pharmaceutically acceptable salt thereof is released.

47-57. -57. (canceled)

58. An oral dosage form comprising quetiapine or a pharmaceutically acceptable salt thereof in controlled release form which provides a maximum quetiapine plasma concentration (C_max) and an quetiapine plasma concentration at about 24 hours after administration (C₂₄), wherein the ratio of C_max to C₂₄ is less than about 4:

1.

59. The oral dosage form of claim 58 comprising quetiapine hemifumarate.

76. A sustained release oral dosage form according to claim 58 comprising a first subunit and a second subunit,

wherein the first subunit comprises quetiapine or a pharmaceutically acceptable salt thereof, and a first release-retarding material and

the second subunit comprises quetiapine or a pharmaceutically acceptable salt thereof and a second release-retarding material,

wherein the first and second release-retarding material can be the same or different.

77. The controlled release dosage form of claim 59 which provides an AUC between 0 and 24 hours after administration that is more than 80 percent and less than 120 percent of the AUC provided between 0 and 24 hours after administration by the same strength dosage form of quetiapine hemifumarate,

wherein the same strength dosage form of quetiapine hemifumarate comprises

povidone in a weight:

weight ratio of about 0.072;

1 to quetiapine hemifumarate,

dibasic dicalcium phosphate dihydrate in a weight;

weight ratio of about 0.087;

1 to quetiapine hemifumarate,

microcrystalline cellulose in a weight;

weight ratio of about 0.286;

1 to quetiapine hemifumarate,

sodium starch glycolate in a weight;

weight ratio of about 0.072;

1 to quetiapine hemifumarate,

lactose monohydrate in a weight;

weight ratio of about 0.194;

1 to quetiapine hemifumarate,

magnesium stearate in a weight;

weight ratio of about 0.026;

1 to quetiapine hemifumarate,

hydroxypropyl methyl cellulose in a weight;

weight ratio of about 0.043;

1 to quetiapine hemifumarate,

polyethyleneglycol in a weight;

weight ratio of about 0.009;

1 to quetiapine hemifumarate, and

titanium dioxide in a weight;

weight ratio of about 0.016;

1 to quetiapine hemifumarate.

99. The controlled release dosage form of any claim 58 wherein the controlled release dosage form does not contain a gelling agent.

60-65. -65. (canceled)

66. An oral dosage form comprising quetiapine or a pharmaceutically acceptable salt thereof in sustained release form, which, at steady-state, provides a first maximum quetiapine plasma concentration (C_max1) between 0 hours and about 12 hours after administration, and a second maximum quetiapine plasma concentration (C_max2) between about 12 hours and about 24 hours after administration.

67. The oral dosage form of claim 66 comprising quetiapine hemifumarate.

68-75. -75. (canceled)

78. (canceled)

79. An oral dosage form comprising quetiapine or a pharmaceutically acceptable salt thereof in sustained release form, which, at steady-state, provides a first AUC (AUC₁) between 0 and about 12 hours and a second AUC (AUC₂) between about 12 hours and about 24 hours, wherein difference between AUC₂ and AUC₁ is less than about 50%.

80-98. -98. (canceled)

100. (canceled)