Compositions and dosage forms for enhanced absorption of 3-amino-n-butyl-phosphinic acid

• US 20050163841A1
• Filed: 10/29/2004
• Published: 07/28/2005
• Est. Priority Date: 10/31/2003
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Lam, Andrew, Hwang, Stephen, Wong, Patrick S.L., Yan, Dong, Guittard, George V.
• Application Number:
  US10/978,138
• Publication Number:
  US 20050163841A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/295 Iron group metal compounds
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/662 Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
• CPC Class Codes: A61K 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 47/541 Organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent
• CPC Class Codes: A61K 47/585 Ion exchange resins, e.g. polystyrene sulfonic acid resin
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 : Antianaemics

Abstract

Disclosed are substances, compositions, dosage forms and methods relating to drugs including 3-aminopropyl-n-butyl-phosphinic acid; structural homologs thereof; 3-aminopropyl-n-butyl-phosphinic acid complexes; complexes that comprise structural homologs of 3-aminopropyl-n-butyl-phosphinic acid; pharmaceutically acceptable salts of 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof; and mixtures of the above.

Claims

1. A dosage form comprising:

(i) a controlled delivery dosing structure comprising structure that controllably delivers a drug;

(ii) the drug being selected from the group consisting of 3-aminopropyl-n-butyl-phosphinic acid;

structural homologs thereof;

complexes that comprise 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof;

pharmaceutically acceptable salts of 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof; and

mixtures of the above;

wherein at least a portion of the drug is contained by the controlled delivery dosing structure; and

wherein the controlled delivery dosing structure is adapted to controllably deliver the portion of the drug contained by the controlled delivery dosing structure at a rate that is effective to, after a single administration of the dosage form to a patient;

a. provide a Cmax ranging from about 0.01 to about 700 μ

mol/L,

b. provide an AUC from about 30 to about 1500 h·

μ

mol/L, and

c. maintain a plasma drug concentration that is at least about fifteen percent of the Cmax throughout a window of at least about ten hours duration.

2. The dosage form of claim 1, wherein the window has a duration of at least about twelve hours.

3. The dosage form of claim 1, wherein the window has a duration of at least about sixteen hours.

4. The dosage form of claim 1, wherein the window has a duration of at least about eighteen hours.

5. The dosage form of claim 1, wherein the window has a duration of at least about twenty hours.

6. The dosage form of claim 1, wherein the Cmax ranges from about 10 to about 500 μ

mol/L.

7. The dosage form of claim 6, wherein the Cmax ranges from about 30 to about 300 μ

mol/L.

8. The dosage form of claim 1, wherein the AUC ranges from about 50 to about 1200 h·

μ

mol/L.

9. The dosage form of claim 8, wherein the AUC ranges from about 10 to about 1000 h·

μ

mol/L.

10. The dosage form of claim 1, wherein the complexes comprise a transport moiety that comprises alkyl sulfate salts.

11. The dosage form of claim 10, wherein the transport moiety comprises sodium lauryl sulfate.

12. The dosage form of claim 1, wherein the dosage form is a multiple unit dosage form.

13. A method comprising:

administering to a patient in need thereof a dosage form comprising a controlled delivery dosing structure comprising structure adapted to controllably deliver a drug, wherein the drug is selected from the group consisting of 3-aminopropyl-n-butyl-phosphinic acid, structural homologs thereof, complexes that comprise 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof, pharmaceutically acceptable salts of 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof, and mixtures of the above; and

wherein at least a portion of the drug is contained by the controlled delivery dosing structure; and

controllably delivering the portion of the drug contained by the controlled delivery dosing structure at a rate that is effective to, after a single administration of the dosage form to a patient;

a. provide a Cmax ranging from about 0.01 to about 700 μ

mol/L,

b. provide an AUC (zero to infinity) from about 30 to about 1500 h·

μ

mol/L, and

c. maintain a plasma drug concentration that is at least about fifteen percent of the Cmax throughout a window of at least about ten hours duration.

14. The method of claim 13, wherein the window has a duration of at least about twelve hours.

15. The method of claim 13, wherein the window has a duration of at least about sixteen hours.

16. The method of claim 13, wherein the window has a duration of at least about eighteen hours.

17. The method of claim 13, wherein the window has a duration of at least about twenty hours.

18. The method of claim 13, wherein the Cmax ranges from about 10 to about 500 μ

mol/L.

19. The method of claim 18, wherein the Cmax ranges from about 30 to about 300 μ

mol/L.

20. The method of claim 13, wherein the AUC ranges from about 50 to about 1200 h·

μ

mol/L.

21. The method of claim 20, wherein the AUC ranges from about 10 to about 1000 h·

μ

mol/L.

22. The method of claim 13, wherein the complexes comprise a transport moiety that comprises an alkyl sulfate salt.

23. The method of claim 22, wherein the transport moiety comprises sodium lauryl sulfate.

24. The method of claim 13, wherein the dosage form is a multiple unit dosage form.

25. A method comprising:

orally delivering a drug to a patient in need thereof at a substantially zero order delivery rate during a window;

wherein the drug is selected from the group consisting of structural homologs of 3-aminopropyl-n-butyl-phosphinic acid;

complexes that comprise 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof;

pharmaceutically acceptable salts of structural homologs of 3-aminopropyl-n-butyl-phosphinic acid; and

mixtures of the above; and

wherein the window has a duration of at least about ten hours.

26. The method of claim 25, wherein the drug is selected from the group consisting of complexes that comprise 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof.

27. The method of claim 26, wherein the window has a duration of at least about twelve hours.

28. The method of claim 26, wherein the window has a duration of at least about sixteen hours.

29. The method of claim 25, wherein the window has a duration of at least about eighteen hours.

30. The method of claim 25, wherein the window has a duration of at least about twenty hours.

31. A dosage form comprising:

an oral controlled delivery dosing structure that is adapted to controllably deliver orally a drug at a substantially zero order delivery rate a during a window;

wherein the drug is selected from the group consisting of structural homologs of 3-aminopropyl-n-butyl-phosphinic acid;

complexes that comprise 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof;

pharmaceutically acceptable salts of structural homologs of 3-aminopropyl-n-butyl-phosphinic acid; and

mixtures of the above; and

wherein the window has a duration of at least about ten hours.

32. The dosage form of claim 31, wherein the drug is selected from the group consisting of complexes that comprise 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof.

33. The dosage form of claim 31, wherein the window has a duration of at least about twelve hours following oral delivery.

34. The dosage form of claim 33, wherein the window has a duration of at least about sixteen hours following oral delivery.

35. The dosage form of claim 34, wherein the window has a duration of at least about eighteen hours following oral delivery.

36. The dosage form of claim 35, wherein the window has a duration of at least about twenty hours following oral delivery.

37. The dosage form of claim 31, wherein the dosage form is a multiple unit dosage form.

38. A dosage form comprising

(i) a controlled delivery dosing structure comprising structure that controllably delivers a drug;

(ii) the drug being selected from the group consisting of structural homologs of 3-aminopropyl-n-butyl-phosphinic acid;

complexes that comprise 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof;

pharmaceutically acceptable salts of structural homologs of 3-aminopropyl-n-butyl-phosphinic acid; and

mixtures of the above;

wherein at least a portion of the drug is contained by the controlled delivery dosing structure; and

wherein the controlled delivery dosing structure is adapted to controllably deliver the portion of the drug contained by the controlled delivery dosing structure in a delivery dose pattern of from about 0 wt % to about 20 wt % in about 0 to about 4 hrs, about 20 wt % to about 50 wt % in about 0 to about 8 hrs, about 55 wt % to about 85 wt % in about 0 to about 14 hrs, and about 80 wt % to about 100 wt % in about 0 to about 24 hrs.

39. A method of administering to a patient in need thereof a dose of a drug comprising:

administering the drug to a patient in a delivery dose pattern of from about 0 wt % to about 20 wt % in about 0 to about 4 hrs, about 20 wt % to about 50 wt % in about 0 to about 8 hrs, about 55 wt % to about 85 wt % in about 0 to about 14 hrs, and about 80 wt % to about 100 wt % in about 0 to about 24 hrs; and

wherein the drug is selected from the group consisting of structural homologs of 3-aminopropyl-n-butyl-phosphinic acid;

complexes that comprise 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof;

pharmaceutically acceptable salts of structural homologs of 3-aminopropyl-n-butyl-phosphinic acid; and

mixtures of the above.

40. A substance comprising:

a complex that comprises 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof; and

a transport moiety.

41. A composition comprising:

the substance of claim 40 and a pharmaceutically acceptable carrier or excipient.

42. The composition of claim 41, wherein the pharmaceutically acceptable carrier or excipient comprises an osmagent, a binder, or a lubricant.

43. The substance of claim 41, wherein the transport moiety comprises an alkyl sulfate salt.

44. The substance of claim 43, wherein the alkyl sulfate salt comprises a C6-C18 alkyl sulfate salt.

45. The substance of claim 44, wherein the C6-C18 alkyl sulfate salt comprises a C12 alkyl sulfate salt.

46. An oral dosage form comprising the composition of claim 41.

47. An oral dosage form, comprising a complex that comprises 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof, and a C12 alkyl sulfate salt, which complex is present in an amount effective to antagonize gamma-aminopropylbutyric acid B receptors in a patient for a window having a duration of at least about ten hours.

48. The dosage form of claim 47, wherein the window has a duration of at least about 12 hours.

49. The dosage form of claim 48, wherein the window has a duration of at least about 16 hours.

50. The dosage form of claim 49, wherein the window has a duration of at least about 20 hours.

51. The dosage form of claim 50, wherein the window has a duration of at least about 24 hours.

52. The dosage form of claim 47, wherein the dosage form comprises a weight equivalent of 3-aminopropyl-n-butyl phosphinic acid ranging from about 100 mg to about 1500 mg.

53. The dosage form of claim 52, wherein the dosage form comprises a weight equivalent of 3-aminopropyl-n-butyl phosphinic acid ranging from about 300 mg to about 1200 mg.

54. The dosage form of claim 53, wherein the dosage form comprises a weight equivalent of 3-aminopropyl-n-butyl phosphinic acid ranging from about 400 mg to about 900 mg.

55. A dosage form comprising:

(i) a controlled delivery dosing structure comprising structure that controllably delivers a drug;

(ii) the drug comprising a complex that comprises 3-aminopropyl-n-butyl-phosphinic acid or structural homologs thereof, and a C12 alkyl sulfate salt;

wherein at least a portion of the drug is contained by the controlled delivery dosing structure; and

wherein the controlled delivery dosing structure controllably delivers the portion of the drug contained by the controlled delivery dosing structure at a rate that is effective to, after a single administration of the dosage form to a patient;

a. provide a Cmax ranging from about 0.01 to about 700 μ

mol/L,

b. provide an AUC (zero to infinity) from about 30 to about 1500 h·

μ

mol/L, and

c. maintain a plasma drug concentration that is at least about fifteen percent of the Cmax throughout a window of at least about ten hours duration.

56. The dosage form of claim 55, wherein the window has a duration of at least about twelve hours.

57. The dosage form of claim 56, wherein the window has a duration of at least about sixteen hours.

58. The dosage form of claim 57, wherein the window has a duration of at least about eighteen hours.

59. The dosage form of claim 58, wherein the window has a duration of at least about twenty hours.

60. The dosage form of claim 55, wherein the dosage form comprises a weight equivalent of 3-aminopropyl-n-butyl phosphinic acid ranging from about 100 mg to about 1500 mg.

61. The dosage form of claim 60, wherein the dosage form comprises a weight equivalent of 3-aminopropyl-n-butyl phosphinic acid ranging from about 300 mg to about 1200 mg.

62. The dosage form of claim 61, wherein the dosage form comprises a weight equivalent of 3-aminopropyl-n-butyl phosphinic acid ranging from about 400 mg to about 900 mg.

63. The dosage form of claim 55, wherein the C12 alkyl sulfate salt comprises sodium lauryl sulfate.

64. The dosage form of claim 55, wherein the Cmax ranges from about 10 to about 500 μ

mol/L.

65. The dosage form of claim 64, wherein the Cmax ranges from about 30 to about 300 μ

mol/L.

66. The dosage form of claim 55, wherein the AUC ranges from about 50 to about 1200 h·

μ

mol/L.

67. The dosage form of claim 66, wherein the AUC ranges from about 10 to about 1000 h·

μ

mol/L.

68. The dosage form of claim 55, wherein the dosage form is a multiple unit dosage form.

69. A method of improving absorption of 3-aminopropyl-n-butyl-phosphinic acid comprising:

providing a complex of 3-aminopropyl-n-butyl-phosphinic acid and a transport moiety; and

administering the complex to a patient in need thereof.

70. The method of claim 69, wherein the transport moiety comprises an alkyl sulfate salt.

71. The method of claim 70, wherein the alkyl sulfate salt comprises a C6-C18 alkyl sulfate salt.

72. The method of claim 71, wherein the C6-C18 alkyl sulfate salt comprises a C12 alkyl sulfate salt.

73. The method of claim 69, wherein the complex is administered orally, and the improved absorption comprises improved oral absorption.

74. The method of claim 73, wherein the improved oral absorption comprises improved lower gastrointestinal tract absorption.

75. The method of claim 73, wherein the improved oral absorption comprises improved upper gastrointestinal tract absorption.