Oil-containing, orally administrable pharmaceutical composition for improved delivery of a therapeutic agent

• US 20030235595A1
• Filed: 03/25/2003
• Published: 12/25/2003
• Est. Priority Date: 06/30/1999
• Status: Abandoned Application

• Current Assignee: Lipocine Inc.
• Original Assignee: Lipocine Inc.
• Inventors: Chen, Feng-Jing, Patel, Mahesh V.
• Application Number:
  US10/397,969
• Publication Number:
  US 20030235595A1
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• 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 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention relates to oral pharmaceutical compositions and methods for improved delivery of therapeutic agents, e.g., lipid-regulating agents. Compositions of the present invention include a carrier, where the carrier contains a combination of a triglyceride and at least two surfactants, at least one of which is hydrophilic. Upon dilution with an aqueous medium, the composition forms a clear, aqueous dispersion. The invention also pertains to methods for treating lipid disorders such as hypercholesterolemia, hypertriglyceridemia, and mixed dyslipidemia by oral administration of the compositions provided.

Claims

1. A pharmaceutical composition for oral administration of a lipid-regulating agent, comprising:

(a) a carrier comprising a triglyceride and at least two surfactants, at least one of the surfactants being hydrophilic; and

(b) a therapeutically effective amount of a lipid-regulating agent,

wherein the triglyceride and surfactants are present in amounts that are pharmaceutically acceptable and are selected so that upon admixture of the composition with an aqueous medium in an aqueous medium to composition ratio of about 100;

1 by weight, a clear aqueous dispersion having an absorbance of less than about 0.3 at 400 nm is provided.

2. The composition of claim 1, wherein the lipid-regulating agent is capable of being solubilized in the triglyceride, the surfactants, or both the triglyceride and the surfactants.

3. The composition of claim 1, wherein the lipid-regulating agent is a fibric acid derivative.

4. The composition of claim 1, wherein the lipid-regulating agent is selected from bezafibrate, beclobrate, binifibrate, ciprofibrate, clinofibrate, clofibrate, etofibrate, fenofibrate, gemfibrozil, nicofibrate, pirifibrate, ronifibrate, simfibrate, and theofibrate.

5. The composition of claim 4, wherein the lipid-regulating agent is fenofibrate.

6. The composition of claim 1, wherein the lipid-regulating agent is a sterol absorption inhibitor.

7. The composition of claim 6, wherein the sterol absorption inhibitor is ezemitibe.

8. The composition of claim 1, wherein the lipid-regulating agent is an HMG CoA reductase inhibitor.

9. The composition of claim 8, wherein the lipid-regulating agent is selected from atorvastatin, cerivastatin, fluindostatin, fluvastatin, lovastatin, mevastatin, nystatin, pitivastatin, pravastatin, rosuvastatin, simvastatin, urinastatin, and velostatin.

10. The composition of claim 8, wherein the lipid-regulating agent is selected from atorvastatin, simvastatin, pravastatin, and lovastatin.

11. The composition of claim 1, wherein the lipid-regulating agent is selected from nicotinic acid, nicomol, and niceritrol.

12. The composition of claim 1, wherein the lipid-regulating agent is a bile acid sequestrant, probucol, a squalene synthesis inhibitor, or an LDL catabolism enhancer.

13. The composition of claim 1, further comprising a second therapeutic agent.

14. The composition of claim 13, wherein said second therapeutic agent is selected from the group consisting of an additional lipid-regulating agent, an anti-diabetic agent, an anti-coagulant, an antihypertensive agent, and mixtures thereof.

15. The composition of claim 14, wherein the additional lipid-regulating agent is selected from the group consisting of atorvastatin, cerivastatin, fluindostatin, fluvastatin, lovastatin, mevastatin, nystatin, pitivastatin, pravastatin, rosuvastatin, simvastatin, urinastatin, velostatin, nicotinic acid, nicomol, niceritrol, and mixtures thereof.

16. The composition of claim 14, wherein the anti-diabetic agent is selected from the group consisting of sulfonyl ureas, biguanides, thiazolidinediones, alpha glucosidase inhibitors, and meglitinides.

17. The composition of claim 14, wherein the anti-diabetic agent is selected from the group consisting of glyburide, metformin, glipizide, glimepiride, pioglitazone, rosiglitazone, miglitol, acarbose, repaglinide, nateglinide, and mixtures thereof.

18. The composition of claim 1, wherein said triglyceride is a medium chain triglyceride.

19. The composition of claim 18, wherein said medium chain triglyceride is glyceryl tricaprylate/caprate.

20. The composition of claim 18, wherein said medium chain triglyceride is a triglyceride composition in which at least 50% of the fatty acids have a chain length of 6 to 12 carbon atoms.

21. The composition of claim 1, wherein the at least one hydrophilic surfactant is selected from the group consisting of polyoxyethylene sorbitan fatty acid esters, polyoxyethylene vegetable oil, polyoxyethylene hydrogenated vegetable oil and mixtures thereof.

22. The composition of claim 21, wherein the at least one hydrophilic surfactant is selected from polysorbate 80, PEG-35 castor oil, and PEG-40 castor oil.

23. The composition of claim 1, wherein the at least one hydrophilic surfactant is selected from the group consisting of hydrophilic transesterification products of oils and alcohols and mixtures thereof.

24. The composition of claim 23, wherein the oil is an oil-soluble vitamin

25. The composition of claim 23, wherein the at least one hydrophilic surfactant is tocopheryl PEG-1000 succinate.

26. The composition of claim 23, wherein the at least one hydrophilic surfactant is selected from the group consisting of PEG-8 caprylic/capric glycerides, lauroyl macrogol-32 glycerides, stearoyl macrogol glyceride, and mixtures thereof.

27. The composition of claim 1, wherein the carrier further comprises at least one hydrophobic surfactant.

28. The composition of claim 27, wherein the at least one hydrophobic surfactant is selected from hydrophobic transesterification products of oils and alcohols and mixtures thereof.

29. The composition of claim 28, wherein the at least one hydrophobic surfactant is selected from transesterification products of PEG-6 corn oil, PEG-6 apricot kernel oil, and mixtures thereof.

30. The composition of claim 27, wherein the at least one hydrophobic surfactant is a glycerol fatty acid ester selected from monoglycerides, diglycerides, and mixtures thereof.

31. The composition of claim 30, wherein the at least one hydrophobic surfactant is a glycerol fatty acid ester selected from glyceryl caprylate, glyceryl caprylate/caprate and mixtures thereof.

32. The composition of claim 30, wherein the at least one hydrophobic surfactant is selected from glyceryl linoleate, glyceryl monooleate, glyceryl dioleate and mixtures thereof.

33. The composition of claim 27, wherein the at least one hydrophobic surfactant is a propylene glycol fatty acid ester.

34. The composition of claim 33, wherein the propylene glycol fatty acid ester is selected from propylene glycol monocaprylate, propylene glycol dicaprylate/dicaprate, and mixtures thereof.

35. The composition of claim 1, further comprising a solubilizer.

36. The composition of claim 2, wherein the lipid-regulating agent is solubilized in the triglyceride, the surfactants, or both the triglyceride and the surfactants.

37. The composition of claim 36, further comprising an additional amount of the lipid-regulating agent that is not solubilized.

38. The composition of claim 1, further comprising an antioxidant.

39. The composition of claim 1, further comprising a viscomodulator.

40. The composition of claim 1, further comprising a suspending agent.

41. A dosage form comprising the composition of claim 1, wherein said dosage form is a capsule.

42. The dosage form of claim 41, wherein the capsule is a starch, hydroxypropyl methylcellulose, or gelatin capsule.

43. The dosage form of claim 42, wherein the capsule is a hard gelatin capsule or a soft gelatin capsule.

44. The composition of claim 1, wherein the absorbance of the clear aqueous dispersion formed is less than about 0.2 at 400 nm.

45. The composition of claim 44, wherein the absorbance of the clear aqueous dispersion formed is less than about 0.1 at 400 nm.

46. The composition of claim 1, comprising a preconcentrate in a liquid, semi-solid, or solid form, or an aqueous or organic diluted preconcentrate.

47. The composition of claim 1, wherein the composition is substantially free of water.

48. The composition of claim 1, wherein the triglyceride and surfactants are present in amounts such that upon admixture of the composition with an aqueous medium in an aqueous medium to composition ratio of about 10:

1 by weight, a clear aqueous dispersion having an absorbance of less than about 0.3 at 400 nm is provided.

49. The composition of claim 48, wherein the absorbance of the clear aqueous dispersion is less than about 0.2 at 400 nm.

50. The composition of claim 49, wherein the absorbance of the clear aqueous dispersion is less than about 0.1 at 400 nm.

51. The composition of claim 1, wherein the therapeutically effective amount is in a unit dosage.

52. The composition of claim 1, wherein following oral administration, the composition provides an increase in the rate of absorption of the lipid-regulating agent relative to the rate of absorption for a corresponding composition, administered under an identical dosage regimen, containing (a) the lipid-regulating agent, (b) at least one hydrophilic surfactant, and (c) at least one lipophilic component selected from a triglyceride, a hydrophobic surfactant, and mixtures thereof, but which results in an aqueous dispersion having an absorbance of greater than 0.5 at 400 nm upon admixture with an aqueous medium in an aqueous medium to composition ratio of about 100:

1 by weight, after dose normalization.

53. The composition of claim 52, wherein the increase in the rate of absorption is such that the time to reach maximum plasma concentration of the lipid-regulating agent or an active metabolite thereof is reduced by at least about 10%.

54. The composition of claim 53, wherein the time to reach maximum plasma concentration of the lipid-regulating agent or an active metabolite thereof is reduced by at least about 20%.

55. The composition of claim 54, wherein the time to reach maximum plasma concentration of the lipid-regulating agent or an active metabolite thereof is reduced by at least about 50%.

56. The composition of claim 5, wherein following oral administration, the composition provides an increase in the rate of absorption of fenofibrate relative to the rate of absorption for a corresponding composition, administered under an identical dosage regimen, containing (a) fenofibrate, (b) at least one hydrophilic surfactant, and (c) at least one lipophilic component selected from a triglyceride, a hydrophobic surfactant, and mixtures thereof, but which results in an aqueous dispersion having an absorbance of greater than 0.5 at 400 nm upon admixture with an aqueous medium in an aqueous medium to composition ratio of about 100:

1 by weight, after dose normalization.

57. The composition of claim 56, wherein the increase in the rate of absorption is such that the time to reach maximum plasma concentration of fenofibric acid is reduced by at least 10%.

58. The composition of claim 57, wherein the increase in the rate of absorption is such that the time to reach maximum plasma concentration of fenofibric acid is reduced by at least 20%.

59. The composition of claim 58, wherein the increase in the rate of absorption is such that the time to reach maximum plasma concentration of fenofibric acid is reduced by at least 50%.

60. The composition of claim 1, wherein following oral administration, the composition provides an increase in the extent of absorption of the lipid-regulating agent relative to the extent of absorption for a corresponding composition, administered under an identical dosage regimen, containing (a) the lipid-regulating agent, (b) at least one hydrophilic surfactant, and (c) at least one lipophilic component selected from a triglyceride, a hydrophobic surfactant, and mixtures thereof, but which results in an aqueous dispersion having an absorbance of greater than 0.5 at 400 nm upon admixture with an aqueous medium in an aqueous medium to composition ratio of about 100:

1 by weight, after dose normalization.

61. The composition of claim 60, wherein the increase in the extent of absorption is such that the area under the curve (AUC) of the plasma concentration of the lipid-regulating agent or an active metabolite thereof is increased by at least about 10%.

62. The composition of claim 61, wherein the increase in the extent of absorption is such that the area under the curve (AUC) of the plasma concentration of the lipid-regulating agent or an active metabolite thereof is increased by at least about 20%.

63. The composition of claim 62, wherein the increase in the extent of absorption is such that the area under the curve (AUC) of the plasma concentration of the lipid-regulating agent or an active metabolite thereof is increased by at least about 50%.

64. The composition of claim 5, wherein following oral administration, after dose normalization, the composition provides an increase in the extent of absorption of fenofibrate relative to the extent of absorption for a corresponding composition, administered under an identical dosage regimen, containing (a) fenofibrate, (b) at least one hydrophilic surfactant, and (c) at least one lipophilic component selected from a triglyceride, a hydrophobic surfactant, and mixtures thereof, but which results in an aqueous dispersion having an absorbance of greater than 0.5 at 400 nm upon admixture with an aqueous medium in an aqueous medium to composition ratio of about 100:

1 by weight.

65. The composition of claim 64, wherein the increase in the extent of absorption is such that the area under the curve (AUC) of the plasma concentration of fenofibric acid is increased by at least about 10%.

66. The composition of claim 65, wherein the increase in the extent of absorption is such that the area under the curve (AUC) of the plasma concentration of fenofibric acid is increased by at least about 20%.

67. The composition of claim 66, wherein the increase in the rate of absorption is such that the time to reach maximum plasma concentration of fenofibric acid is reduced by at least 50%.

68. The composition of claim 5, wherein the composition provides an AUC_0-inf of the plasma concentration of fenofibric acid, per milligram of dosed fenofibrate, of at least 1.25 μ

g·

hr/ml, following oral administration of the composition to a human patient.

90. A method of treating a lipid disorder, comprising administering the composition of claim 1 to a patient in need of such treatment.

91. The method of claim 90, wherein the patient is diabetic.

94. The method of any one of claims 90, 91, 92, or 93, wherein the lipid disorder is hypercholesterolemia, hypertriglyceridemia, or mixed dyslipidemia.

95. The method of any one of claims 90, 91, 92, or 93, wherein the lipid disorder is a metabolic disorder.

96. The method of any one of claims 90, 91, 92, or 93, wherein the lipid disorder is associated with a metabolic syndrome.

97. A method for reducing the dependency of absorption on lipolysis of an orally administered lipid-regulating agent, comprising administering the lipid-regulating agent in a composition that comprises the composition of claim 1.

98. A method for reducing the dependency of absorption on endogenous bile, bile-related patient disease states, or meal fat contents of an orally administered lipid-regulating agent, comprising administering the lipid-regulating agent in a composition that comprises the composition of claim 1.

99. A method of treating a lipid disorder, comprising administering the composition of claim 5 to a patient in need of such treatment.

100. The method of claim 99, wherein the patient is diabetic.

101. A method of treating a lipid disorder, comprising administering the composition of claim 5 to a patient in need of such treatment.

103. The method of any one of claims 99, 100, 101, or 102, wherein the lipid disorder is hypercholesterolemia, hypertriglyceridemia, or mixed dyslipidemia.

104. The method of any one of claims 99, 100, 101, or 102, wherein the lipid disorder is a metabolic disorder.

105. The method of claim 104, wherein the lipid disorder is associated with a metabolic syndrome.

106. A method for reducing the dependency of absorption on lipolysis of orally administered fenofibrate, comprising administering the fenofibrate in a composition that comprises the composition of claim 5.

107. A method for reducing the dependency of absorption on endogenous bile, bile-related patient disease states, or meal fat contents of orally administered fenofibrate, comprising administering the fenofibrate in a composition that comprises the composition of claim 5.

108. A method for reducing the dependency of absorption on lipolysis of orally administered fenofibrate, comprising administering the fenofibrate in a composition that comprises the composition of claim 5.

109. A method for reducing the dependency of absorption on endogenous bile, bile-related patient disease states, or meal fat contents of orally administered fenofibrate, comprising administering the fenofibrate in a composition that comprises the composition of claim 5.

69. A pharmaceutical composition comprising:

(a) a carrier comprising a triglyceride and at least two surfactants, at least one of the surfactants being hydrophilic; and

(b) a therapeutically effective amount of a lipid-regulating agent,

wherein the triglyceride and the surfactants are present in amounts that are pharmaceutically acceptable and selected so that upon admixture of the composition with an aqueous medium in an aqueous medium to composition ratio of about 10;

1 by weight, a clear aqueous dispersion is provided.

70. A pharmaceutical composition for oral administration, comprising:

(a) a carrier comprising a medium chain triglyceride and at least two surfactants, at least one of the surfactants being a hydrophilic surfactant selected from polyoxyethylene sorbitan fatty acid esters, polyoxyethylene vegetable oil, polyoxyethylene hydrogenated vegetable oil, and hydrophilic transesterification products of oils and alcohol and mixtures thereof; and

(b) a therapeutically effective amount of a lipid-regulating agent selected from bezafibrate, beclobrate, binifibrate, ciprofibrate, clinofibrate, clofibrate, etofibrate, fenofibrate, gemfibrozil, nicofibrate, pirifibrate, ronifibrate, simfibrate, theofibrate, and the acid forms thereof,

wherein the triglyceride and surfactants are present in amounts that are pharmaceutically acceptable and are selected so that upon admixture of the composition with an aqueous medium in an aqueous medium to composition ratio of about 100;

1 by weight, a clear aqueous dispersion having an absorbance of less than about 0.3 at 400 nm is provided.

71. The composition of claim 70, wherein the carrier contains a hydrophilic surfactant.

72. The composition of claim 71, wherein the hydrophilic surfactant is a hydrophilic transesterification product of an oil and an alcohol.

73. The composition of claim 72, wherein the oil is an oil-soluble vitamin.

74. The composition of claim 70, wherein the carrier further includes at least one hydrophobic surfactant selected from (a) hydrophobic transesterification products of an oil and an alcohol;

and (b) glycerol fatty acid esters selected from monoglycerides, diglycerides, and mixtures thereof.

75. The composition of claim 70, wherein the lipid-regulating agent is fenofibrate and the therapeutically effective amount is a unit dosage.

92. A method of treating a lipid disorder, comprising administering the composition of claim 75 to a patient in need of such treatment.

76. A pharmaceutical composition comprising:

(a) a carrier comprising glyceryl tricaprylate/caprate, at least one hydrophilic surfactant selected from the group consisting of tocopheryl PEG-1000 succinate, polysorbate 80, PEG-35 castor oil, PEG-40 hydrogenated castor oil, PEG-8 caprylic/capric glycerides, lauroyl macrogol-32 glycerides, stearoyl macrogol glyceride, and mixtures thereof; and

at least one hydrophobic surfactant selected from the group consisting of glyceryl caprylate, glyceryl caprylate/caprate and mixtures thereof; and

(b) a therapeutically effective amount of fenofibrate,

wherein the triglyceride and surfactants are present in amounts that are pharmaceutically acceptable and selected so that upon admixture of the composition with an aqueous solution in an aqueous solution to composition ratio of about 100;

1 by weight, a clear aqueous dispersion having an absorbance of less than about 0.3 at 400 nm is provided.

77. The composition of claim 76, wherein the at least one hydrophilic surfactant is selected from the group consisting of tocopheryl PEG-1000 succinate, polysorbate 80, and mixtures thereof.

78. The composition of claim 76, wherein following oral administration, the composition provides an increase in the rate of absorption of fenofibrate relative to the rate of absorption for a corresponding composition in the form of a hard gelatin capsule containing fenofibrate in a dry powder form, wherein said fenofibrate is co-micronized with sodium lauryl sulfate, after dose normalization.

79. The composition of claim 78, wherein the increase in the rate of absorption is such that the time to reach maximum plasma concentration of fenofibric acid is reduced by at least 25%.

80. The composition of claim 79, wherein the increase in the rate of absorption is such that the time to reach maximum plasma concentration of fenofibric acid is reduced by at least 50%.

81. The composition of claim 80, wherein the increase in the rate of absorption is such that the time to reach maximum plasma concentration of fenofibric acid is reduced by at least 75%.

82. The composition of claim 76, wherein following oral administration, the composition provides an increase in the extent of absorption of the lipid-regulating agent relative to the extent of absorption for a corresponding composition in the form in the form of a hard gelatin capsule containing fenofibrate in a dry powder form, wherein said fenofibrate is co-micronized with sodium lauryl sulfate, after dose normalization.

83. The composition of claim 82, wherein the increase in the extent of absorption is such that the area under the curve (AUC) of the plasma concentration of fenofibric acid is increased by at least about 25%.

84. The composition of claim 83, wherein the increase in the extent of absorption is such that the area under the curve (AUC) of the plasma concentration of fenofibric acid thereof is increased by at least about 50%.

85. The composition of claim 84, wherein the increase in the extent of absorption is such that the area under the curve (AUC) of the plasma concentration of fenofibric acid is increased by at least about 75%.

86. A pharmaceutical composition for oral administration of a lipid-regulating agent, comprising:

(a) a carrier comprising a triglyceride and at least two surfactants, at least one of the surfactants being hydrophilic; and

(b) a therapeutically effective amount of a lipid-regulating agent selected from bezafibrate, beclobrate, binifibrate, ciprofibrate, clinofibrate, clofibrate, etofibrate, fenofibrate, gemfibrozil, nicofibrate, pirifibrate, ronifibrate, simfibrate, and theofibrate,

wherein the triglyceride and surfactants are present in amounts selected so that upon admixture of the composition with an aqueous medium in an aqueous medium to composition ratio of about 100;

1 by weight, a clear aqueous dispersion is provided, and further wherein following oral administration, the composition provides for absorption of the lipid-regulating agent or an active metabolite thereof that is less dependent upon lipolysis relative to a corresponding composition, administered under an identical dosage regimen, containing (a) the lipid-regulating agent, (b) at least one hydrophilic surfactant, and (c) at least one lipophilic component selected from a triglyceride, a hydrophobic surfactant, and mixtures thereof, but which results in an aqueous dispersion having an absorbance of greater than 0.5 at 400 nm upon admixture with an aqueous medium in an aqueous medium to composition ratio of about 100;

1 by weight, after dose normalization.

87. The composition of claim 86, wherein the lipid-regulating agent is fenofibrate.

88. A pharmaceutical composition for oral administration of a lipid-regulating agent, comprising:

(a) a carrier comprising a triglyceride and at least two surfactants, at least one of the surfactants being hydrophilic; and

(b) a therapeutically effective amount of a lipid-regulating agent is selected from bezafibrate, beclobrate, binifibrate, ciprofibrate, clinofibrate, clofibrate, etofibrate, fenofibrate, gemfibrozil, nicofibrate, pirifibrate, ronifibrate, simfibrate, and theofibrate,

wherein the triglyceride and surfactants are present in amounts selected so that upon admixture of the composition with an aqueous medium in an aqueous medium to composition ratio of about 100;

1 by weight, a clear aqueous dispersion is provided, and further wherein following oral administration, the composition provides for absorption of the lipid-regulating agent or an active metabolite thereof that is less dependent upon endogenous bile, bile-related patient disease states, or meal fat contents lipolysis relative to a corresponding composition, administered under an identical dosage regimen, containing (a) the lipid-regulating agent, (b) at least one hydrophilic surfactant, and (c) at least one lipophilic component selected from a triglyceride, a hydrophobic surfactant, and mixtures thereof, but which results in an aqueous dispersion having an absorbance of greater than 0.5 at 400 nm upon admixture with an aqueous medium in an aqueous medium to composition ratio of about 100;

1 by weight, after dose normalization.

89. The composition of claim 88, wherein the lipid-regulating agent is fenofibrate.

93. A method of treating a lipid disorder, comprising orally administering to a patient in need of such treatment:

(a) a dosage form of a carrier comprising (i) a triglyceride and (ii) at least two surfactants, at least one of the surfactants being hydrophilic, wherein the triglyceride and surfactants are present in amounts that are pharmaceutically acceptable and selected so that upon mixing with an aqueous solution in an aqueous solution to carrier ratio of about 100;

1 by weight, the carrier forms a clear aqueous dispersion having an absorbance of less than about 0.3 at 400 nm; and

(b) a therapeutically effective unit dosage of a lipid-regulating agent.

102. A method of treating a lipid disorder, comprising orally administering to a patient in need of such treatment:

(a) a dosage form of a carrier comprising (i) a triglyceride and (ii) at least two surfactants, at least one of the surfactants being hydrophilic, wherein the triglyceride and surfactants are present in amounts that are pharmaceutically acceptable and selected so that upon mixing with an aqueous solution in an aqueous solution to carrier ratio of about 100;

1 by weight, the carrier forms a clear aqueous dispersion having an absorbance of less than about 0.3 at 400 nm; and

(b) a therapeutically effective unit dosage of fenofibrate.

110. A pharmaceutical composition for oral administration, comprising:

(a) a carrier comprising a medium chain triglyceride and at least two surfactants, at least one of the surfactants being a hydrophilic surfactant selected from polyoxyethylene sorbitan fatty acid esters, polyoxyethylene vegetable oil, polyoxyethylene hydrogenated vegetable oil, and hydrophilic transesterification products of oils and alcohol and mixtures thereof; and

(b) a therapeutically effective amount of a therapeutic agent,

wherein the triglyceride and surfactants are present in amounts that are pharmaceutically acceptable and are selected so that upon admixture of the composition with an aqueous medium in an aqueous medium to composition ratio of about 100;

1 by weight, a clear aqueous dispersion having an absorbance of less than about 0.3 at 400 nm is provided.