Pharmaceutical solid dispersions

• US 20040013734A1
• Filed: 06/10/2003
• Published: 01/22/2004
• Est. Priority Date: 02/10/1999
• Status: Active Grant

• Current Assignee: Bend Research Inc. (Lonza Group AG)
• Original Assignee: Pfizer Inc.
• Inventors: Friesen, Dwayne T., Shanker, Ravi M., Nightingale, James A. S., Babcock, Walter C.
• Granted Patent: US 8,481,081 B2
• Time in Patent Office: Days
• US Class Current: 424/488
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

A composition comprises a solid dispersion comprising a low-solubility drug and at least one polymer. At least a major portion of the drug in the dispersion is amorphous. The polymer has a glass transition temperature of at least 100° C. measured at a relative humidity of fifty percent. Another aspect of the invention comprises the same composition except that the dispersion has a glass transition temperature of at least 50° C. at a relative humidity of fifty percent. In another aspect of the invention, a composition comprises a solid dispersion comprising a low-solubility drug and a stabilizing polymer. At least a major portion of the drug in the dispersion is amorphous. The composition also includes a concentration-enhancing polymer that increases the concentration of the drug in a use environment. The stabilizing polymer has a glass transition temperature that is greater than the glass transition temperature of the concentration-enhancing polymer at a relative humidity of 50%.

Claims

1. A composition comprising a solid dispersion comprising a low-solubility drug and at least one polymer, at least a major portion of said drug once dispersed in said dispersion being amorphous, said polymer having a glass transition temperature of at least 100°

C. measured at 50% relative humidity, and said dispersion being formed by solvent processing.

2. The composition of claim 1 wherein said polymer has a glass transition temperature of at least 105°

C. measured at 50% relative humidity.

3. The composition of claim 1 wherein said polymer has a glass transition temperature of at least 110°

C. measured at 50% relative humidity.

4. The composition of claim 1 wherein said dispersion has a glass transition temperature of at least 30°

C. measured at 50% relative humidity.

5. The composition of claim 1 wherein said dispersion has a glass transition temperature of at least 50°

C. measured at 50% relative humidity.

6. The composition of claim 1 wherein said polymer is cellulosic.

7. The composition of claim 6 wherein said polymer has at least one of an ester-linked aromatic substituent and an ether-linked aromatic substituent.

8. The composition of claim 7 wherein said at least one of said ester-linked aromatic substituent is an ester-linked carboxylic acid-functional aromatic substituent and said ether-linked aromatic substituent is an ether-linked carboxylic acid-functional aromatic substituent.

9. The composition of claim 8 wherein said polymer has a degree of substitution of at least 0.2, for said ester-linked carboxyl acid-functional aromatic substituent and said ether-linked carboxylic acid-functional aromatic substituent.

10. The composition of claim 8 wherein said at least one of said ester-linked carboxylic acid-functional aromatic substituent is chosen from the group consisting of the various structural isomers of phthalate, trimellitate and pyridine dicarboxylic acid and alkyl substituted derivatives thereof and said ether-linked carboxylic acid-functional aromatic substituent is chosen from the group consisting of the various structural isomers of salicylic acid, ethoxybenzoic acid, propoxybenzoic acid, butoxybenzoic acid, ethoxyphthalic acid, propoxyphthalic acid, butoxyphthalic acid, ethoxynicotinic acid, propoxynicotinic acid, butoxynicotinic acid and alkyl-substituted derivatives thereof.

11. The composition of claim 10 wherein said polymer is chosen from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, ethyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate succinate, cellulose propionate phthalate, hydroxypropyl cellulose butyrate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate succinate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, cellulose acetate pyridinedicarboxylate, salicylic acid cellulose acetate, hydroxypropyl salicylic acid cellulose acetate, ethylbenzoic acid cellulose acetate, hydroxypropyl ethylbenzoic acid cellulose acetate, ethyl phthalic acid cellulose acetate, ethyl nicotinic acid cellulose acetate, and ethyl picolinic acid cellulose acetate.

12. The composition of claim 10 wherein said polymer is chosen from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, ethyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, cellulose propionate phthalate, hydroxypropyl cellulose butyrate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate succinate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, salicylic-acid cellulose acetate, and ethylbenzoic acid cellulose acetate.

13. The composition of claim 10 wherein said polymer is chosen from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimelaitate, cellulose acetate terephthalate, and cellulose acetate isophthalate.

14. The composition of claim 1 wherein said drug and said polymer are soluble in a common non-aqueous solvent.

15. The composition of claim 14 wherein said dispersion is formed by spray-drying.

16. The composition of claim 1 further comprising a concentration-enhancing polymer, said concentration-enhancing polymer increasing the maximum drug concentration in an environment of use relative to a control composition comprising an equivalent quantity of undispersed drug.

17. The composition of claim 16 wherein said concentration-enhancing polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose phthalate, hydroxypropylmethyl cellulose;

hydroxypropylcellulose, methyl cellulose, hydroxyethyl cellulose, hydroxy ethyl methyl cellulose, hydroxy ethyl cellulose acetate, hydroxyethyl ethyl cellulose, hydroxy ethyl methyl cellulose acetate succinate, hydroxyethyl methyl cellulose acetate phthalate, carboxymethyl cellulose, carboxyethyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyvinyl acetate copolymers, polyethylene glycol, polyethylene glycol polypropylene glycol copolymers, polyvinyl pyrrolidone, polyethylene polyvinyl alcohol copolymers, carboxylic acid-functionalized polymethacrylates, amine-functionalized polymethacrylates, chitosan, and chitin.

18. The composition of claim 16 wherein said concentration-enhancing polymer is codispersed with the other polymer.

19. The composition of claim 16 wherein said concentration-enhancing polymer is mixed with said dispersion subsequent to formation of said dispersion.

20. The composition of claim 1 wherein said composition provides a maximum concentration of said drug in a use environment that is at least 1.5-fold that of a control comprising an equivalent quantity of undispersed drug.

21. The composition of claim 1 wherein said dispersion is substantially homogeneous.

22. The composition of claim 1 wherein said drug is substantially amorphous.

23. The composition of claim 1 wherein said drug is almost completely amorphous.

24. The composition of claim 1 wherein said glass transition temperature of said polymer measured at 0% relative humidity is at least 140°

C.

25. The composition of claim 24 wherein said polymer absorbs less than 10% by weight of water at 50% relative humidity.

134. A method for treating a disorder, comprising administering to a patient, a therapeutically .effective amount of a composition as defined in claim 1.

26. A composition comprising a solid dispersion comprising a low-solubility drug and at least one polymer, at least a major portion of said drug once dispersed in said dispersion being amorphous, and said dispersion having a glass transition temperature of at least 30°

C. measured at 50% relative humidity.

27. The composition of claim 26 wherein said dispersion has a glass transition temperature of 50°

C. measured at 50% relative humidity.

28. The composition of claim 26 wherein said low-solubility drug comprises at least 15 wt % of said solid dispersion.

29. The composition of claim 26 wherein said polymer has a glass transition temperature of at least. 100°

C. measured at 50% relative humidity.

30. The composition of claim 26 wherein said polymer is cellulosic.

31. The composition of claim 30 wherein said polymer has at least one of an ester-linked aromatic substituent and an ether-linked aromatic substituent.

32. The composition of claim 31 wherein said at least one of said ester-linked aromatic substituent is an ester-linked carboxylic acid-functional aromatic substituent and said ether-linked aromatic substituent is an ether-linked carboxylic acid-functional aromatic substituent.

33. The composition of claim 32 wherein said polymer has a degree of substitution of at least 0.2 for said substituents.

34. The composition of claim 33 wherein said at least one of said ester-linked carboxylic acid-functional aromatic substituent is chosen from the group consisting of the various structural isomers of phthalate, trimellitate and pyridine dicarboxylic acid and alkyl substituted derivatives thereof and said ether-linked carboxylic acid-functional aromatic subatituent is chosen from the group consisting of the various structural isomers of salicylic acid, ethoxybenzoic acid, propoxybenzoic acid, butoxybenzoic acid, ethoxyphthalic acid, propoxyphthalic acid, butoxyphthalic acid, ethoxynicotinic acid, propoxynicotinic acid, butoxynicotinic acid and alkyl-substituted derivatives thereof.

35. The composition of claim 34 wherein said polymer is chosen from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, ethyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate succinate, cellulose propionate phthalate, hydroxypropyl cellulose butyrate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate succinate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, cellulose acetate pyridinedicarboxylate, salicylic acid cellulose acetate, hydroxypropyl salicylic acid cellulose acetate, ethylbenzoic acid cellulose acetate, hydroxypropyl ethylbenzoic acid cellulose acetate, ethyl phthalic acid cellulose acetate, ethyl nicotinic acid cellulose acetate, and ethyl picolinic acid cellulose acetate.

36. The composition of claim 34 wherein said polymer is chosen from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, ethyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, cellulose propionate phthalate, hydroxypropyl cellulose butyrate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate succinate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, salicylic acid cellulose acetate, and ethylbenzoic acid cellulose acetate.

37. The composition of claim 34 wherein said polymer is chosen from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, cellulose acetate terephthalate, and cellulose acetate isophthalate.

38. The composition of claim 26 wherein said drug and said polymer are soluble in a common non-aqueous solvent.

39. The composition of claim 38 wherein said dispersion is formed by removing said solvent from said drug and said polymer.

40. The composition of claim 39 wherein said dispersion is formed by spray-drying.

41. The composition of claim 26 further comprising a concentration-enhancing polymer, said concentration-enhancing polymer increasing the measured concentration of said drug in an environment of use relative to a control comprising an equivalent quantity of undispersed drug.

42. The composition of claim 41 wherein said concentration-enhancing polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose phthalate, hydroxypropylmethyl cellulose, hydroxypropylcellulose, methyl cellulose, hydroxyethyl cellulose, hydroxy ethyl methyl cellulose, hydroxy ethyl cellulose-acetate, hydroxyethyl ethyl cellulose, hydroxy ethyl methyl cellulose acetate succinate, hydroxyethyl methyl cellulose acetate phthalate, carboxymethyl cellulose, carboxyethyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyvinyl acetate copolymers, polyethylene glycol, polyethylene glycol polypropylene glycol copolymers, polyvinyl pyrrolidone, polyethylene polyvinyl alcohol copolymers, carboxylic acid-functionalized polymethacrylates, amine-functionalized polymethacrylates, chitosan, and chitin.

43. The composition of claim 41 wherein said concentration-enhancing polymer is codispersed with the other polymer.

44. The composition of claim 41 wherein said concentration-enhancing polymer is mixed with said dispersion subsequent to formation of said dispersion.

45. The composition of claim 26 wherein said composition provides a maximum concentration of said drug in a use environment that is at least 1.5-fold that of a control comprising an equivalent quantity of undispersed drug.

46. The composition of claim 26 wherein said dispersion is substantially homogeneous.

47. The composition of claim 26 wherein said drug is substantially amorphous.

48. The composition of claim 26 wherein said drug is almost completely amorphous.

49. The composition of claim 26 wherein said glass transition temperature of said polymer at 0% relative humidity is at least 140°

C.

50. The composition of claim 49 wherein said polymer absorbs less than 10% by weight of water at 50% relative humidity.

135. A method for treating a disorder, comprising administering to a patient, a therapeutically effective amount of a composition as defined in claim 26.

51. A composition, comprising:

(a) a solid dispersion comprising a low-solubility drug and a stabilizing polymer, at least a major portion of said drug being amorphous; and

,

(b) a concentration-enhancing polymer that increases the maximum drug concentration in a use environment relative to a control composition comprising an equivalent quantity of undispersed drug, said stabilizing polymer and said concentration-enhancing polymer each having a respective glass transition temperature measured at a relative humidity of 50%, said glass transition temperature of said stabilizing polymer being greater than said glass transition temperature of said concentration-enhancing polymer.

52. The composition of claim 51 wherein said glass tansition temperature of said stabilizing polymer is at least 10°

C. greater than said glass transition temperature of said concentration-enhancing polymer at 50% relative humidity.

53. The composition of claim 51 wherein said glass transition temperature of said stabilizing polymer is at least 20°

C. greater than said glass transition temperature of said concentration-enhancing polymer measured at 50% relative humidity.

54. The composition of claim 51 wherein said stabilizing polymer is cellulosic.

55. The composition of claim 54 wherein said stabilizing polymer is selected from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, ethyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate succinate, cellulose propionate phthalate, hydroxypropyl cellulose butyrate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate succinate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, cellulose acetate pyridinedicarboxylate, salicylic acid cellulose acetate, hydroxypropyl salicylic acid cellulose acetate, ethylbenzoic acid cellulose acetate, hydroxypropyl ethylbenzoic acid cellulose acetate, ethyl phthalic acid cellulose acetate, ethyl nicotinic acid cellulose acetate, ethyl picolinic acid cellulose acetate, hydroxypropyl methyl cellulose acetate succindte, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose succinate, hydroxypropylmethyl cellulose phthalate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxy ethyl methyl cellulose, hydroxy ethyl cellulose acetate, hydroxyethyl ethyl cellulose, hydroxy ethyl methyl cellulose acetate succinate, hydroxyethyl methyl cellulose acetate phthalate, carboxymethyl cellulose, and carboxyethyl cellulose.

56. The composition of claim 54 wherein said stabilizing polymer is selected from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, ethyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, cellulose propionate phthalate, hydroxypropyl cellulose butyrate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, salicylic acid cellulose acetate, ethylbenzoic acid cellulose acetate, hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, and hydroxypropyl methyl cellulose.

57. The composition of claim 54 wherein said stabilizing polymer is selected from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, and hydroxypropyl methyl cellulose.

58. The composition of claim 51 wherein said drug and said stabilizing polymer are soluble in a common solvent.

59. The composition of claim 58 wherein said dispersion is formed by removing said solvent from said drug and said stabilizing polymer.

60. The composition of claim 59 wherein said dispersion is formed by spray-drying.

61. The composition of claim 51 wherein said concentration-enhancing polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose phthalate, hydroxypropylmethyl cellulose, hydroxypropylcellulose, methyl cellulose, hydroxyethyl cellulose, hydroxy ethyl methyl cellulose, hydroxy ethyl cellulose acetate, hydroxyethyl ethyl cellulose, hydroxy ethyl methyl cellulose acetate succinate, hydroxyethyl methyl cellulose acetate phthalate, carboxymethyl cellulose, carboxyethyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyvinyl acetate copolymers, polyethylene glycol, polyethylene glycol polypropylene glycol copolymers, polyvinyl pyrrolidone, polyethylene polyvinyl alcohol copolymers, carboxylic acid-functionalized polymethacrylates, amine-functionalized polymethacrylates, chitosan, and chitin.

62. The composition of claim 51 wherein said concentration-enhancing polymer is codispersed with said stabilizing polymer.

63. The composition of claim 51 wherein said concentration-enhancing polymer is mixed with said dispersion subsequent to formation of said dispersion.

64. The composition of claim 51 wherein said composition provides a maximum concentration of said drug in a use environment that is at least 1.5-fold that of a control comprising an equivalent quantity of undispersed drug.

65. The composition of claim 51 wherein said dispersion is substantially homogeneous.

66. The composition of claim 51 wherein said concentration-enhancing polymer provides a maximum concentration of said drug in said use environment least 1.5-fold that of a control comprising an equivalent quantity of drug dispersed in an equivalent quantity of said stabilizing polymer and in the absence of said concentration-enhancing polymer.

67. The composition of claim 51 wherein said drug, once dispersed in said dispersion, is substantially amorphous.

68. The composition of claim 51 wherein said drug, once dispersed in said dispersion, is almost completely amorphous.

136. A method for treating a disorder, comprising administering to a patient, a therapeutically effective amount of a composition as defined in claim 51.

137. A method for treating a disorder, comprising administering to a patient, a therapeutically effective amount of a composition as defined in claim 68.

69. A composition comprising:

(a) a solid dispersion comprising a low-solubility drug and at least one polymer, at least a major portion of said drug once dispersed in said dispersion being amorphous, said polymer having a glass transition temperature of at least 100°

C. measured at 50% relative humidity; and

(b) wherein said polymer is cellulosic and has at least one of an ester-linked carboxylic acid-functional aromatic substituent and an ether-linked carboxylic acid-functional aromatic substituent, said ester-linked carboxylic acid-functional aromatic substituent being chosen from the group consisting of the various structural isomers of trimellitate and pyridine dicarboxylic acid and alkyl substituted derivatives thereof and said ether-linked carboxylic acid-functional aromatic substituent being chosen from the group consisting of the various structural isomers of salicylic acid, ethoxybenzoic acid, propoxybenzoic acid, butoxybenzoic acid, ethoxyphthalic acid, propoxyphthalic acid, butoxyphthalic acid, ethoxynicotinic acid, propoxynicotinic acid, butoxynicotinic acid and alkyl-substituted derivatives thereof.

70. The composition of claim 69 wherein said polymer has a glass transition temperature of at least 105°

C. measured at 50% relative humidity.

71. The composition of claim 69 wherein said polymer has a glass transition temperature of at least 110°

C. measured at 50% relative humidity.

72. The composition of claim 69 wherein said dispersion has a glass transition temperature of at least 30°

C. measured at 50% relative humidity.

73. The composition of claim 69 wherein said dispersion has a glass transition temperature of at least 50°

C. measured at 50% relative humidity.

74. The composition of claim 69 wherein said polymer has a degree of substitution of at least 0.2 for said substituents.

75. The composition of claim 69 wherein said polymer is chosen from the group consisting of cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate succinate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, cellulose acetate pyridinedicarboxylate, salicylic acid cellulose acetate, hydroxypropyl salicylic acid cellulose acetate, ethylbenzoic acid cellulose acetate, hydroxypropyl ethylbenzoic acid cellulose acetate, ethyl phthalic acid cellulose acetate, ethyl nicotinic acid cellulose acetate, and ethyl picolinic acid cellulose acetate.

76. The composition of claim 69 wherein said polymer is chosen from the group consisting of cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate succinate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, salicylic acid cellulose acetate, and ethylbenzoic acid cellulose acetate.

77. The composition of claim 69 wherein said polymer is chosen from the group consisting of cellulose acetate trimellitate, methyl cellulose acetate trimellitate, cellulose acetate terephthalate, and cellulose acetate isophthalate.

78. The composition of claim 69 wherein said drug and said polymer are soluble in a common non-aqueous solvent.

79. The composition of claim 78 wherein said dispersion is formed by spray-drying.

80. The composition of claim 69 further comprising a concentration-enhancing polymer, said concentration-enhancing polymer increasing the maximum measured concentration of said drug in an environment of use relative to a control composition comprising an equivalent quantity of undispersed drug.

81. The composition of claim 80 wherein said concentration-enhancing polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose phthalate, hydroxypropylmethyl cellulose, hydroxypropylcellulose, methyl cellulose, hydroxyethyl cellulose, hydroxy ethyl methyl cellulose, hydroxy ethyl cellulose acetate, hydroxyethyl ethyl cellulose, hydroxy ethyl methyl cellulose acetate succinate, hydroxyethyl methyl cellulose acetate phthalate, carboxymethyl cellulose, carboxyethyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyvinyl acetate copolymers, polyethylene glycol, polyethylene glycol polypropylene glycol copolymers, polyvinyl pyrrolidone, polyethylene polyvinyl alcohol copolymers, carboxylic acid-functionalized polymethacrylates, amine-functionalized polymethacrylates, chitosan, and chitin.

82. The composition of claim 81 wherein said concentration-enhancing polymer is codispersed with the other polymer.

83. The composition of claim 81 wherein said concentration-enhancing polymer is mixed with said dispersion subsequent to formation of said dispersion.

84. The composition of claim 69 wherein said composition provides a maximum concentration of said drug in a use environment that is at least 1.5-fold that of a control comprising an equivalent quantity of undispersed drug.

85. The composition of claim 69 wherein said dispersion is substantially homogeneous.

86. The composition of claim 69 wherein said drug is substantially amorphous.

87. The composition of claim 69 wherein said drug is almost completely amorphous.

88. The composition of claim 69 wherein said glass transition temperature of said polymer measured at 0% relative humidity is at least 140°

C.

89. The composition of claim 88 wherein said polymer absorbs less than 10% by weight of water at 50% relative humidity.

90. A composition comprising:

(a) a solid dispersion comprising a low-solubility drug and at least one polymer, at least a major portion of said drug once dispersed in said dispersion being amorphous, said polymer having a glass transition temperature of at least 100°

C. measured at 50% relative humidity; and

(b) said polymer is chosen from the group consisting of methyl cellulose acetate phthalate, ethyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate succinate, cellulose propionate phthalate, and hydrdxypropyl cellulose butyrate phthalate.

91. The composition of claim 90 wherein said polymer has a glass transition temperature of at least 105°

C. measured at 50% relative humidity.

92. The composition of claim 90 wherein said polymer has a glass transition temperature of at least 110°

C. measured at 50% relative humidity.

93. The composition of claim 90 wherein said dispersion has a glass transition temperature of at least 30°

C. measured at 50% relative humidity.

94. The composition of claim 90 wherein said dispersion has a glass transition temperature of at least 50°

C. measured at 50% relative humidity.

95. The composition of claim 90 wherein said polymer has a degree of substitution of at least 0.2 for the phthalate substituent.

96. The composition of claim 90 wherein said drug and said polymer are soluble in a common non-aqueous solvent.

97. The composition of claim 96 wherein said composition is formed by solvent processing.

98. The composition of claim 97 wherein said dispersion is formed by spray-drying.

99. The composition of claim 90 further comprising a concentration-enhancing polymer, said concentration-enhancing polymer increasing the maximum measured concentration of said drug in an environment of use.

100. The composition of claim 99 wherein said concentration-enhancing polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose phthalate, hydroxypropylmethyl cellulose, hydroxypropylcellulose, methyl cellulose, hydroxyethyl cellulose, hydroxy ethyl methyl cellulose, hydroxy ethyl cellulose acetate, hydroxyethyl ethyl cellulose, hydroxy ethyl methyl cellulose acetate succinate, hydroxyethyl methyl cellulose acetate phthalate, carboxymethyl cellulose, carboxyethyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyvinyl acetate copolymers, polyethylene glycol, polyethylene glycol polypropylene glycol copolymers, polyvinyl pyrrolidone, polyethylene polyvinyl alcohol copolymers, carboxylic acid-functionalized polymethacrylates, amine-functionalized polymethacrylates, chitosan, and chitin.

101. The composition of claim 99 wherein said concentration-enhancing polymer is codispersed with the other polymer.

102. The composition of claim 99 wherein said concentration-enhancing polymer is mixed with said dispersion subsequent to formation of said dispersion.

103. The composition of claim 99 wherein said composition provides a maximum concentration of said drug in a use environment that is at least 1.5-fold that of a control comprising an equivalent quantity of undispersed drug.

104. The composition of claim 90 wherein said dispersion is substantially homogeneous.

105. The composition of claim 90 wherein said drug is substantially amorphous.

106. The composition of claim 90 wherein said drug is almost completely amorphous.

107. The composition of claim 90 wherein said glass transition temperature of said polymer measured at 0% relative humidity is at least 140°

C.

108. The composition of claim 107 wherein said polymer absorbs less than 10% by weight of water at 50% relative humidity.

138. A method for treating a disorder, comprising administering to a patient, a therapeutically effective amount of a composition as defined in claim 90.

109. A composition comprising a solid dispersion comprising a low-solubility drug and at least one polymer, at least a major portion of said drug once dispersed in said dispersion being amorphous, said polymer having a glass transition temperature of at least 100°

C. measured at 50% relative humidity, and said dispersion is substantially homogeneous.

110. The composition of claim 109 wherein said polymer has a glass transition temperature of at least 105°

C. measured at 50% relative humidity.

111. The composition of claim 109 wherein said polymer has a glass transition temperature of at least 110°

C. measured at 50% relative humidity.

112. The composition of claim 109 wherein said dispersion has a glass transition temperature of at least 30°

C. measured at 50% relative humidity.

113. The composition of claim 109 wherein said dispersion has a glass transition temperature of at least 50°

C. measured at 50% relative humidity.

114. The composition of claim 109 wherein said polymer is cellulosic.

115. The composition of claim 114 wherein said polymer has at least one of an ester-linked aromatic substituent and an ether-linked aromatic substituent.

116. The composition of claim 115 wherein said at least one of said ester-linked aromatic substituent is an ester-linked carboxylic acid-functional aromatic substituent and said ether-linked aromatic substituent is an ether-linked carboxylic acid-functional aromatic substituent.

117. The composition of claim 116 wherein said polymer has a degree of substitution of at least 0.2, for said ester-linked carboxyl acid-functional aromatic substituent and said ether-linked carboxylic acid-functional aromatic substituent.

118. The composition of claim 116 wherein said at least one of said ester-linked carboxylic acid-functional aromatic substituent is chosen from the group consisting of the various structural isomers of phthalate, trimellitate and pyridine dicarboxylic acid and alkyl substituted derivatives thereof and said ether-linked carboxylic acid-functional aromatic substituent is chosen from the group consisting of the various structural isomers of salicylic acid, ethoxybenzoic acid, propoxybenzoic acid, butoxybenzoic acid, ethoxyphthalic acid, propoxyphthalic acid, butoxyphthalic acid, ethoxynicotinic acid, propoxynicotinic acid, butoxynicotinic acid and alkyl-substituted derivatives thereof.

119. The composition of claim 118 wherein said polymer is chosen from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, ethyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate succinate, cellulose propionate phthalate, hydroxypropyl cellulose butyrate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate succinate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthlalate, cellulose acetate isophthalate, cellulose acetate pyridinedicarboxylate, salicylic acid cellulose acetate, hydroxypropyl salicylic acid cellulose acetate, ethylbenzoic acid cellulose acetate, hydroxypropyl ethylbenzoic acid cellulose acetate, ethyl phthalic acid cellulose acetate, ethyl nicotinic acid cellulose acetate, and ethyl picolinic acid cellulose acetate.

120. The composition of claim 118 wherein said polymer is chosen from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, ethyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, cellulose propionate phthalate, hydroxypropyl cellulose butyrate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, ethyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, hydroxypropyl cellulose acetate trimellitate succinate, cellulose propionate trimellitate, cellulose butyrate trimellitate, cellulose acetate terephthalate, cellulose acetate isophthalate, salicylic acid cellulose acetate, and ethylbenzoic acid cellulose acetate.

121. The composition of claim 118 wherein said polymer is chosen from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, hydroxypropyl cellulose acetate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, cellulose acetate terephthalate, and cellulose acetate isophthalate.

122. The composition of claim 109 wherein said drug and said polymer are soluble in a common non-aqueous solvent.

123. The composition of claim 122 wherein said dispersion is formed by spray-drying.

124. The composition of claim 109 further comprising a concentration-enhancing polymer, said concentration-enhancing polymer increasing the maximum drug concentration in an environment of use relative to a control composition comprising an equivalent quantity of undispersed drug.

125. The composition of claim 124 wherein said concentration-enhancing polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose phthalate, hydroxypropylmethyl cellulose, hydroxypropylcellulose, methyl cellulose, hydroxyethyl cellulose, hydroxy ethyl methyl cellulose, hydroxy ethyl cellulose acetate, hydroxyethyl ethyl cellulose, hydroxy ethyl methyl cellulose acetate succinate, hydroxyethyl methyl cellulose acetate phthalate, carboxymethyl cellulose, carboxyethyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyvinyl acetate copolymers, polyethylene glycol, polyethylene glycol polypropylene glycol copolymers, polyvinyl pyrrolidone, polyethylene polyvinyl alcohol copolymers, carboxylic acid-functionalized polymethacrylates, amine-functionalized polymethacrylates, chitosan, and chitin.

126. The composition of claim 124 wherein said concentration-enhancing polymer is codispersed with the other polymer.

127. The composition of claim 124 wherein said concentration-enhancing polymer is mixed with said dispersion subsequent to formation of said dispersion.

128. The composition of claim 109 wherein said composition provides a maximum concentration of said drug in a use environment that is at least 1.5-fold that of a control comprising an equivalent quantity of undispersed drug.

129. The composition of claim 109 wherein said drug is substantially amorphous.

130. The composition of claim 109 wherein said drug is almost completely amorphous.

131. The composition of claim 109 wherein said glass transition temperature of said polymer measured at 0% relative humidity is at least 140°

C.

132. The composition of claim 131 wherein said polymer absorbs less than 10% by weight of water at 50% relative humidity.

133. The composition of claim 109 wherein said dispersion exhibits a single glass transition temperature.

139. A method for treating a disorder, comprising administering to a patient, a therapeutically effective amount of a composition as defined in claim 109.

140. A method of administering a drug comprising administering to a patient in need of said drug:

(a) a solid dispersion comprising a low-solubility drug and at least one stabilizing polymer, at least a major portion of said drug once dispersed in said dispersion being amorphous; and

(b) a concentration-enhancing polymer, said concentration-enhancing polymer increasing the measured concentration of said drug in an environment of use relative to a control comprising an equivalent quantity of undispersed drug;

wherein said stabilizing polymer has a glass transition temperature that is greater than the glass transition temperature of the concentration-enhancing polymer.

141. The method of claim 140 wherein said drug is administered separately from said concentration-enhancing polymer.

142. The method of claim 140 wherein said drug and said concentration-enhancing polymer are administered at essentially the same time.

143. The method of claim 140 wherein said drug is administered in a formulation also comprising said concentration-enhancing polymer.

144. The method of claim 140 wherein said dispersion has a glass transition temperature of at least 30°

C. measured at 50% relative humidity.

145. The method of claim 140 wherein said dispersion has a glass transition temperature of 50°

C. measured at 50% relative humidity.