Once daily formulations of tetracyclines

• US 20090011006A1
• Filed: 06/06/2008
• Published: 01/08/2009
• Est. Priority Date: 04/07/2003
• Status: Active Grant

• Current Assignee: TCD Royalty Sub LLC
• Original Assignee: Supernus Pharmaceuticals Incorporated
• Inventors: Chang, Rong-Kun, Shah, Niraj, Raoufinia, Arash
• Granted Patent: US 8,206,740 B2
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• 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 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/08 Antiseborrheics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/18 : of the parathyroid hormones

Abstract

Disclosed are once-daily formulations containing tetracyclines, especially doxycycline. Such formulations are useful, for instance, for the treatment of collagenase destructive enzyme-dependent diseases, such as periodontal disease and acne, and acute and chronic inflammatory disease states, such as rosacea and arthritis.

Claims

1-25. -25. (canceled)

47. A process for preparing a once-daily oral pharmaceutical composition containing a tetracycline, which will give steady state blood levels of the tetracycline of a minimum of about 0.1 μ

g/ml and a maximum of about 1.0 μ

g/ml, comprising combining between 50 mg and 25 mg doxycycline with orally pharmaceutically acceptable excipients.

49. An oral pharmaceutical composition for the treatment of a disease or a condition without exerting an antibacterial effect comprising a combination of an immediate release (IR) formulation of doxycycline and a delayed release (DR) formulation of doxycycline, wherein the portion of IR formulation is from about 100 percent to about 70 percent wherein said composition at a once-daily dosage will give steady state blood levels of doxycycline of a minimum of about 0.1 μ

g/ml and a maximum of about 1.0 μ

g/ml.

50. The oral pharmaceutical composition of claim 49 in the form of pellets, wherein a portion of the pellets is of an IR formulation and the remaining pellets are of a DR formulation coated with at least one enteric polymer, and wherein the portion of the pellets of the IR formulation is from about 99 percent to about 70 percent of the total pellets.

51. The oral pharmaceutical composition of claim 50, wherein the portion of the pellets of the IR formulation is from about 80 percent to about 70 percent of the total pellets.

52. The oral pharmaceutical composition of claim 51, wherein the portion of the pellets of the IR formulation is about 75 percent of the total pellets.

53. The composition of claim 49, wherein the amount of doxycycline is less than 50 mg.

54. The composition of claim 52 wherein said composition is contained in a capsule.

55. An oral pharmaceutical composition of doxycycline, which at once-daily dosage will give steady state blood levels of the doxycycline of a minimum of about 0.1 μ

g/ml and a maximum of about 1.0 μ

g/ml, which is a layered pellet, wherein a delayed release (DR) portion having at least one enteric polymer comprises the core of the pellet, and the immediate release portion (IR) surrounds the core.

56. An oral pharmaceutical composition containing less than about 50 mg of doxycycline, which with once-daily dosing provides a blood level of the doxycycline between a minimum of about 0.1 μ

g/ml and a maximum of about 1.0 μ

g/ml wherein the composition does not exert an antibacterial effect and is effective for the treatment of a collagenase-dependent disease or condition.

57. The composition of claim 56, which with once-daily dosing provides the blood level of the doxycycline between of about 0.3 μ

g/ml and of about 0.8 μ

g/ml for the entire course of the treatment.

58. The composition of claim 56, comprising an immediate release formulation of doxycycline wherein said immediate release formulation releases substantially all of the doxycycline on administration with no enhanced, delayed or extended release effect.

59. The composition of claim 58, additionally comprising a delayed release formulation.

60. The composition of claim 56 in a form of a capsule, a tablet, a pellet, a particle or a gel.

61. An oral pharmaceutical composition containing a submicrobial amount of a tetracycline, wherein the composition does not exert an antibacterial effect and is effective for the treatment of a collagenase-dependent disease or condition.

62. The composition of claim 61, wherein said composition is a combination of an immediate release formulation and a delayed release formulation.

63. The composition of claim 62 in a form of a layered pellet, wherein a delayed release (DR) formulation comprising at least one enteric polymer forms the core of the pellet, and the immediate release formulation (IR) surrounds the core.

64. The composition of claim 62 in the form of pellets, wherein a portion of the pellets is of an IR formulation and the remaining pellets are of a DR formulation coated with at least one enteric polymer, and wherein the portion of the pellets of the IR formulation is from about 99 percent to about 70 percent of the total pellets.