Room-temperature stable dronabinol formulations

• US 20060160888A1
• Filed: 12/09/2005
• Published: 07/20/2006
• Est. Priority Date: 12/09/2004
• Status: Active Grant

• Current Assignee: Benuvia Operations LLC
• Original Assignee: INSYS Therapeutics, Inc.
• Inventors: Zhu, Zhongyuan, Kottayil, S. George, Goskonda, Venkat R.
• Granted Patent: US 8,628,796 B2
• Time in Patent Office: Days
• US Class Current: 514/454
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 9/4875 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/4858
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents

Abstract

A room temperature stable cannabinoid formulation is disclosed. In preferred embodiments, the cannabinoid formulation is dronabinol in an oil-based carrier contained within a hard gelatin capsule.

Claims

1. A cannabinoid dosage form comprising;

an effective amount of a pharmaceutically acceptable cannabinoid dispersed in a pharmaceutically acceptable oil-based carrier; and

a hard gelatin capsule encapsulating the mixture of the cannabinoid and the oil-based carrier, said dosage form being stable at room temperature for at least one year.

2. The dosage form of claim 1, which contains at least about 80% w/w of the cannabinoid in undergraded form after exposure of the formulation to storage conditions selected from the group consisting of (i) elevated temperature and humidity conditions of 40°

C./75% relative humidity (RH) for 6 months;

(ii) elevated temperature conditions of 55°

C. for two weeks;

room temperature (25°

C.) for two years; and

any combination thereof.

3. The dosage form of claim 1, which contains at least about 90% w/w of undegraded cannabinoid upon exposure of the formulation to storage conditions selected from the group consisting of (i) elevated temperature and humidity conditions of 40°

C./75% relative humidity (RH) for 6 months;

(ii) elevated temperature conditions of 55°

C. for two weeks;

room temperature (25°

C.) for two years; and

any combination thereof.

4. The dosage form of claim 1, wherein said cannabinoid comprises dronabinol.

5. The dosage form of claim 1, wherein said oil-based carrier is a triglyceride selected from the group consisting of almond oil;

babassu oil;

borage oil;

blackcurrant seed oil;

canola oil;

castor oil;

coconut oil;

corn oil;

cottonseed oil;

evening primrose oil;

grapeseed oil;

groundnut oil;

mustard seed oil;

olive oil;

palm oil;

palm kernel oil;

peanut oil;

rapeseed oil;

safflower oil;

sesame oil;

shark liver oil;

soybean oil;

sunflower oil;

hydrogenated castor oil;

hydrogenated coconut oil;

hydrogenated palm oil;

hydrogenated soybean oil;

hydrogenated vegetable oil;

hydrogenated cottonseed and castor oil;

partially hydrogenated soybean oil;

soy oil;

glyceryl tricaproate;

glyceryl tricaprylate;

glyceryl tricaprate;

glyceryl triundecanoate;

glyceryl trilaurate;

glyceryl trioleate;

glyceryl trilinoleate;

glyceryl trilinolenate;

glyceryl tricaprylate/caprate;

glyceryl tricaprylate/caprate/laurate;

glyceryl tricaprylate/caprate/linoleate;

glyceryl tricaprylate/caprate/stearate;

saturated polyglycolized glycerides;

linoleic glycerides;

caprylic/capric glycerides;

modified triglycerides;

fractionated triglycerides; and

mixtures thereof.

6. The dosage form of claim 4, wherein said oil-based carrier comprises sesame oil.

7. The dosage form of claim 6, wherein said sesame oil is selected from a Food Grade sesame oil or a NF grade sesame oil.

8. The dosage form of claim 1, wherein said oil-based carrier is selected from the group consisting of soybean oil, olive oil, cotton seed oil, peanut oil, sesame oil, castor oil, and mixtures of any of the foregoing.

9. The dosage form of claim 1, which comprises from about 0.05 to about 90% cannabinoid, by weight.

10. The dosage form of claim 1, which comprises from about 0.1% to about 50% cannabinoid, by weight.

11. The dosage form of claim 1, which comprises from about 1.5 to about 6% cannabinoid, by weight.

12. The dosage form of claim 1, which comprises from about 2.5% to about 4.5% cannabinoid by weight.

13. The dosage form of claim 6, wherein said sesame oil contains an effective amount of an anti-oxidant selected from the group consisting of sesamin, sesamol, sesamolin, lecithin and any combination of the foregoing.

14. The dosage form of claim 1, which contains an effective amount of one or more anti-oxidants to promote stability of the cannabinoid against unacceptable degradation.

15. The dosage form of claim 14, which comprises from about 0.001% to about 10% anti-oxidant, by weight.

16. The dosage form of claim 2, wherein the cannabinoid is dronabinol and does not contain unacceptable levels of dronabinol degradants in the dosage form selected from the group consisting of greater than 2% delta-8 tetrahydrocannabinol (D8THC), greater than 2% cannabinol (CBN), greater than 2% cannabidiol (CBD), and any combination thereof.

17. The dosage form of claim 1, which contains an effective amount of one or more organic bases to promote stability of the cannabinoid against unacceptable degradation.

18. The dosage form of claim 17, which comprises from about 0.001% w/w to about 5% organic base, by weight.

19. The dosage form of claim 17, which comprises from about 0.007% w/w to about 2% organic base, by weight.

20. The dosage form of claim 17, wherein said organic base is selected from the group consisting of ethanolamine, methanolamine, meglumine, and any combination of the foregoing.

21. The dosage form of claim 1, wherein said hard gelatin capsule contains from about 85% to about 100% gelatin and from about 1% to about 15% water, by weight.

22. The dosage form of claim 14, wherein said anti-oxidant comprises lecithin, said dosage from comprising from about 0.1% to about 10% lecithin, by weight.

23. The dosage form of claim 22, wherein said lecithin is included in an amount from about 0.3% to about 8.25%, by weight.

24. The dosage form of claim 12, wherein said anti-oxidant is L-ascorbic acid-6-palmitate in an amount from about 0.001% to about 1%, by weight.

25. The dosage form of claim 24, wherein said L-ascorbic acid-6-palmitate is in an amount from about 0.01% to about 0.1%, by weight.

26. The dosage form of claim 1, wherein the anti-oxidant is selected from the group consisting of butyl hydroxyl anisole (BHA), butyl hydroxyl toluene (BHT), propyl gallate, lecithin, Vitamin E tocopherol, sesamin, sesamol, sesamolin, alpha tocopherol, ascorbic acid, ascorbyl palmitate, fumaric acid, malic acid, sodium ascorbate and sodium metabisulphite, disodium EDTA, and combinations of any of the foregoing.

27. The dosage form of claim 1, which further comprises one or more additional therapeutically active agents.

28. The dosage form of claim 27, wherein said additional therapeutically active agent is selected from a narcotic analgesic, a non-narcotic analgesic, an anti-emetic, a steroid, and mixtures of any of the foregoing.

29. The dosage form of claim 1, wherein the cannabinoid is dronabinol in an amount from about 0.05 mg to about 20 mg.

30. The dosage form of claim 1 which contains dronabinol as the active ingredient, the dosage form containing ingredients at a level selected from the following during its claimed shelf-life as follows:

(i) not less than 90% of the initial dronabinol content;

(ii) not greater than about 2% cannabinol;

(iii) not greater than about 2% cannabidiol;

(iv) not greater than about 2% delta-8-THC;

(v) not greater than about 0.5% exo-THC; and

(vi) any combination of the foregoing.

31. The dosage form of claim 30, wherein the oil-based carrier is sesame oil.

32. The dosage form of claim 1, wherein the oil-based carrier comprises a semi-solid lipophilic material selected from the group consisting of arachis oil (Groundnut 36);

castor oil (Cutina HR);

cottonseed oil (Sterotex);

palm oil (Softisan

     154);

soybean oil (Alkosol

     407).

33. The dosage form of claim 32, which further comprises an effective amount of a viscosity modifier to provide a pharmaceutically acceptable viscosity to the cannabinoid dispersed in the oil-based carrier, said viscosity modifier selected from the group consisting of Aerosil (silicon dioxide);

cetostearyl alcohol;

cetyl alcohol;

stearyl alcohol;

Gelucire 33/01;

Gelucire 39/01;

Gelucire 43/01;

glyceryl behenate (Compritol 888 ATO);

glyceryl palmitostearate (Precirol AT05);

Softisan 100;

Softisan 142;

Softisan 378;

Softisan 649; and

mixtures thereof.

34. The dosage form of claim 1, which further comprises an effective amount of a solubilizer for said cannabinoid.

35. The dosage form of claim 1, which further comprises an emulsifier.

36. The dosage form of claim 1, which further comprises an absorption enhancer.

37. The dosage form of claim 1, which further comprises a surfactant.

38. The dosage form of claim 1, which further includes a stabilizer which stabilizes the cannabinoid against unacceptable degradation.

39. The dosage form of claim 6, wherein the sesame oil is an NF grade sesame oil.

40. The formulation of claim 6, wherein the sesame oil contains an anti-oxidant selected from the group consisting of sesamin, sesamol, sesamolin, lecithin and any combination of the foregoing.

41. The dosage form of claim 6, wherein the sesame oil is a refined grade to which a sufficient amount of anti-oxidant has been added to promote stability of the cannabinoid in the dosage form.

42. The dosage form of claim 4, wherein the dronabinol is from a source selected from the group consisting of a natural source, a synthetic source, a semi-synthetic source, and a mixture of any of the foregoing.

43. The dosage form of claim 1, wherein the cannabinoid is in a form selected from the group consisting of its free form, a salt, an ester, a prodrug, a complex, and a mixture of any of the foregoing.

44. The dosage form of claim 14, which contains an effective amount of one or more organic bases to promote stability of the cannabinoid against unacceptable degradation.

45. The dosage form of claim 1, wherein said formulation is homogeneous and thermodynamically stable.

46. The dosage form of claim 1, in which the formulation contains at least about 90% w/w of the cannabinoid in undegraded form after exposure of the formulation to storage conditions selected from the group consisting of (i) elevated temperature and humidity conditions of 40°

C./75% relative humidity (RH) for 6 months;

(ii) elevated temperature conditions of 55°

C. for two weeks;

room temperature (25°

C.) for two years; and

any combination thereof.

117. The dosage form of claim 1, wherein the oil-based carrier is lecithin.

118. The dosage form of claim 1, further comprising an effective amount of a stabilizer to promote the stability of the cannabinoid in the formulation, the stabilizer being selected from the group consisting of one or more anti-oxidants, one or more organic bases, and combinations thereof.

47. A room-temperature stable formulation of a cannabinoid, comprising a therapeutically effective amount of a cannabinoid dispersed in an oil-based carrier contained in a unit dose enclosure, said unit dose enclosure composed of one or more materials which do not react with the cannabinoid or allow substantial permeation of oxygen and which effectively seals the cannabinoid from moisture, such that the cannabinoid in the formulation is protected against unacceptable degradation and at least about 80% w/w of the cannabinoid is maintained in undegraded form after exposure of the formulation to storage conditions selected from the group consisting of (i) controlled temperature and humidity conditions of 25°

C./60% relative humidity (RH), (ii) controlled temperature and humidity conditions of 30°

C./60% relative humidity (iii) elevated temperature and humidity conditions of 40°

C./75% relative humidity (RH) for 6 months;

(iv) elevated temperature conditions of 55°

C. for two weeks;

room temperature (25°

C.) for two years; and

any combination thereof.

48. The formulation of claim 47, wherein the cannabinoid is dronabinol derived from a source selected from the group consisting of a natural source, a synthetic source, a semi-synthetic source, and a mixture of any of the foregoing.

49. The formulation of claim 48, wherein the oil-based carrier is sesame oil.

50. The formulation of claim 49, wherein the sesame oil contains an anti-oxidant selected from the group consisting of sesamin, sesamol, sesamolin, lecithin and any combination of the foregoing.

51. The formulation of claim 49, wherein the sesame oil is a refined grade to which a sufficient amount of anti-oxidant has been added to promote stability of the cannabinoid in the dosage form.

52. The formulation of claim 47, wherein the the oil-based carrier comprises a semi-solid lipophilic material selected from the group consisting of arachis oil (Groundnut 36);

castor oil (Cutina HR);

cottonseed oil (Sterotex);

palm oil (Softisan

     154);

soybean oil (Alkosol

     407).

53. The formulation of claim 52, which further comprises an effective amount of a viscosity modifier to provide a pharmaceutically acceptable viscosity to the cannabinoid dispersed in the oil-based carrier, said viscosity modifier selected from the group consisting of Aerosil (silicon dioxide);

cetostearyl alcohol;

cetyl alcohol;

stearyl alcohol;

Gelucire 33/01;

Gelucire 39/01;

Gelucire 43/01;

glyceryl behenate (Compritol 888 ATO);

glyceryl palmitostearate (Precirol AT05);

Softisan 100;

Softisan 142;

Softisan 378;

Softisan 649; and

mixtures thereof.

54. The formulation of claim 47;

further comprising a pharmaceutical excipient selected from the group consisting of viscosity modifiers;

solubilizers;

stabilizers;

surfactants;

emulsifiers, absorption enhancers, and mixtures thereof.

55. The formulation of claim 47, wherein the oil-based carrier is a lipophilic liquid is selected from the group consisting of arachis oil;

castor oil;

cottonseed oil;

maize (corn) oil;

olive oil;

sesame oil;

soybean oil;

sunflower oil;

Alkomed E and Alkomed R;

Captex 355;

Labrafac CC and Labrafac PG;

Lauroglycol FCC;

Miglyol 810;

Miglyol 812;

Miglyol 829;

Miglyol 840;

Softisan 645; and

mixtures thereof.

56. The formulation of claim 48, wherein the cannabinoid is dronabinol in an amount from about 2.5 mg to about 20 mg.

57. The formulation of claim 47, wherein the unit dose enclosure is a capsule having a coating on its surface selected from the group consisting of an enteric coating, a seal coating, or both.

58. The formulation of claim 47, wherein the unit dose enclosure is selected from the group consisting of a starch capsule;

a cellulosic capsule;

a hydrocolloid film-forming composition comprising a mixture of iota carrageenan, a bulking agent and kappa carrageenan; and

a hard gelatin capsule.

59. The formulation of claim 50, wherein the unit dose enclosure is a sealed hard gelatin capsule.

119. The dosage form of claim 47, wherein the oil-based carrier is lecithin.

120. The dosage form of claim 47, further comprising an effective amount of a stabilizer to promote the stability of the cannabinoid in the formulation, the stabilizer being selected from the group consisting of one or more anti-oxidants, one or more organic bases, and combinations thereof.

60. A formulation of a therapeutically effective amount of an encapsulated cannabinoid and means for stabilizing the cannabinoid, such that the formulation contains at least about 80% w/w of the cannabinoid in undegraded form after exposure of the formulation to storage conditions selected from the group consisting of (i) elevated temperature and humidity conditions of 40°

C./75% relative humidity (RH) for 6 months;

(ii) elevated temperature conditions of 55°

C. for two weeks;

room temperature (25°

C.) for at least one year; and

any combination thereof.

61. The formulation of claim 60, wherein said means for stabilizing the cannabinoid comprises a hard gelatin capsule.

62. The formulation of claim 60, wherein said means for stabilizing the cannabinoid comprises an effective amount of an anti-oxidant.

63. The formulation of claim 60, wherein said means for stabilizing the cannabinoid comprises an effective amount of an organic base.

64. The formulation of claim 60, wherein said means for stabilizing the cannabinoid comprises an effective amount of at least one anti-oxidant together with an effective amount of an organic base.

65. The formulation of claim 60, wherein said means for stabilizing the cannabinoid comprises a starch capsule.

66. The formulation of claim 65, wherein said means for stabilizing the cannabinoid further comprises an effective amount of at least one anti-oxidant, an effective amount of an organic base, or both.

67. The formulation of claim 60, wherein said means for stabilizing the cannabinoid comprises a cellulosic capsule.

68. The formulation of claim 67, wherein said means for stabilizing the cannabinoid further comprises an effective amount of at least one anti-oxidant, an effective amount of an organic base, or both.

69. The formulation of claim 60, wherein said means for stabilizing the cannabinoid comprises a non-animal based hydrocolloid film-forming composition for use in the manufacture of encapsulated dosage forms.

70. The formulation of claim 69, wherein said means for stabilizing the cannabinoid further comprises an effective amount of at least one anti-oxidant, an effective amount of an organic base, or both.

71. The formulation of claim 69, wherein said hydrocolloid film-forming composition comprises a mixture of iota carrageenan, a bulking agent and kappa carrageenan.

72. The formulation of claim 60, wherein said means for stabilizing the cannabinoid comprises an oil-based carrier containing an effective amount of at least one anti-oxidant.

73. The formulation of claim 72, wherein said means for stabilizing the cannabinoid further comprises an encapsulation composed of one or more materials which do not react with the cannabinoid or allow substantial permeation of oxygen and which effectively seals the cannabinoid from moisture.

74. The formulation of claim 60, wherein said cannabinoid is dronabinol, and wherein after two years of storage at room temperature the dosage form contains (i) not less than 90% of the initial dronabinol content;

(ii) not greater than about 2% cannabinol;

(iii) not greater than about 2% cannabidiol;

(iv) not greater than about 2% delta-8-THC; and

(v) any combination of the foregoing.

75. The formulation of claim 73, wherein the cannabinoid is dronabinol.

76. The formulation of claim 60, where the dosage form contains dronabinol as the active ingredient, the dosage form containing ingredients at a level selected from the following during its claimed shelf-life:

(i) not less than 90% of the initial dronabinol content;

(ii) not greater than about 2% cannabinol;

(iii) not greater than about 2% delta-8-THC;

(iv) not greater than about 0.5% exo-THC; and

any combination of the foregoing.

77. The formulation of claim 76, wherein the cannabinoid is dronabinol in an amount from about 2.5 mg to about 20 mg.

78. A room-temperature stable cannabinoid formulation comprising a sealed hard gelatin capsule containing a therapeutically effective amount of a pharmaceutically acceptable cannabinoid in an oil-based carrier.

79. The formulation of claim 78, wherein the cannabinoid is dronabinol derived from a source selected from the group consisting of a natural source, a synthetic source, a semi-synthetic source, and a mixture of any of the foregoing.

80. The formulation of claim 79, wherein the oil-based carrier is sesame oil.

81. The formulation of claim 80, wherein the sesame oil contains an anti-oxidant selected from the group consisting of sesamin, sesamol, sesamolin, lecithin and any combination of the foregoing.

82. The formulation of claim 78, wherein the oil-based carrier further comprises an organic base is selected from the group consisting of ethanolamine, methanolamine, meglumine, and any combination of the foregoing.

83. The formulation of claim 78, wherein the cannabinoid is dronabinol and does not contain unacceptable levels of dronabinol degradants in the dosage form selected from the group consisting of greater than 2% delta-8 tetrahydrocannabinol (D8THC), greater than 2% cannabinol (CBN), greater than 2% cannabidiol (CBD), and any combination thereof, when the dosage form is stored at room temperature for two years.

84. The formulation of claim 79, which comprises from about 1.5 to about 6% dronabinol, by weight.

85. The formulation of claim 79, wherein the dronabinol is in a form selected from the group consisting of its free form, a salt, an ester, a prodrug, a complex, and a mixture of any of the foregoing.

86. A stabilized oral dosage form of a cannabinoid, comprising a mixture of a therapeutically effective amount of a cannabinoid dispersed in an oil-based carrier contained in unit dosage form selected from a hard gelatin capsule, a cellulosic capsule, a starch capsule, and a non-animal based hydrocolloid film-forming composition.

87. The stabilized oral dosage form of claim 86, wherein said oil-based carrier further comprises a stabilizer for the cannabinoid.

88. A stabilized cannabinoid dosage form prepared by utilizing liquid filled hard gelatin technology to obtain a dosage form in which the cannabinoid remains within about 90% to about 110% percent of its initial amount incorporated in the dosage form for at least about 2 years after manufacture.

89. A stabilized oral dosage form of a cannabinoid, comprising a therapeutically effective amount of a cannabinoid dispersed in an oil-based carrier and encapsulated within a soft gelatin capsule, said oil-based carrier containing an effective amount of a stabilizer for the cannabinoid to provide a room-temperature stable formulation for at least one year, such that the cannabinoid remains within about 90% to about 110% percent of its initial amount incorporated in the dosage form for at least 1 year after manufacture.

90. A method for stabilizing an oral dosage form containing a cannabinoid;

comprising incorporating a therapeutically effective amount of a cannabinoid dispersed in an oil-based carrier into a unit dosage form suitable for oral administration, said unit dosage form consisting of a material selected from a hard gelatin capsule, a cellulosic capsule, a starch capsule, and a non-animal based hydrocolloid film-forming composition.

91. A method for stabilizing a dosage form containing a cannabinoid as the active pharmaceutical ingredient, comprising encapsulating a therapeutically effective amount of the cannabinoid in a liquid filled hard gelatin capsule.

92. The method of claim 91, wherein said liquid is a pharmaceutically acceptable oil-based carrier which includes a stabilizer to promote the stability of the cannabinoid selected from the group consisting of an effective amount of one or more anti-oxidants, one or more organic bases, and combinations thereof.

93. The method of claim 92, wherein the oil-based carrier is lecithin.

94. A method for stabilizing a dosage form containing a cannabinoid as the active pharmaceutical ingredient, comprising encapsulating a therapeutically effective amount of the cannabinoid in a pharmaceutically acceptable oil-based carrier containing an effective amount of one or more anti-oxidants.

95. The method of claim 94, wherein the anti-oxidant is selected from the group consisting of sesamin, sesamol, sesamolin, lecithin and any combination of the foregoing.

96. The method of claim 94, further comprising adding an effective amount of one or more organic bases to said oil-based carrier.

97. The formulation of claim 96, wherein the organic base is selected from the group consisting of ethanolamine, methanolamine, meglumine, and any combination of the foregoing.

98. A method for stabilizing a dosage form containing a cannabinoid as the active pharmaceutical ingredient, comprising encapsulating a therapeutically effective amount of the cannabinoid in a pharmaceutically acceptable oil-based carrier containing an amount of one or more organic bases that is effective to stabilize the cannabinoid.

99. A method for preparing a stabilized dosage form containing a cannabinoid as the active pharmaceutical ingredient, comprising

mixing a solution of a cannabinoid with an oil-based carrier to obtain a flowable mixture;

filling an appropriately-sized hard gelatin capsule with a quantity of said mixture that contains a desired therapeutically effective amount of said cannabinoid; and

sealing the hard gelatin capsule.

100. The method of claim 99, further comprising adding an effective amount of one or more stabilizers into the mixture prior to filling the hard gelatin capsule, the stabilizers promoting the stability of the cannabinoid against degradation over the claimed shelf life of the stabilized dosage form.

101. The method of claim 99, further comprising subjecting the stabilized formulation to stability testing selected from the group consisting of:

(i) elevated temperature and humidity conditions of 40°

C./75% relative humidity (RH) for 6 months;

(ii) elevated temperature conditions of 55°

C. for two weeks;

room temperature (25°

C.) for two years; and

any combination thereof.

102. The method of claim 101, further comprising adding an effective amount of one or more stabilizers into the mixture prior to filling the hard gelatin capsule, the stabilizers promoting the stability of the cannabinoid against degradation over the claimed shelf life of the stabilized dosage form.

103. The method of claim 100, wherein the at least one stabilizer is selected from the group consisting of an anti-oxidant, an organic base, and mixtures thereof.

104. The method of claim 99, wherein the cannabinoid is dronabinol, further comprising testing the stabilized formulation to ensure that two years of storage at room temperature the dosage form contains (i) not less than 90% of the initial dronabinol content;

(ii) not greater than about 2% cannabinol;

(iii) not greater than about 2% cannabidiol;

(iv) not greater than about 2% delta-8-THC; and

(v) any combination of the foregoing.

105. A method for preparing a stabilized dosage form containing a cannabinoid as the active pharmaceutical ingredient, comprising

mixing a solution of a cannabinoid with an oil-based carrier to obtain a flowable mixture;

encapsulating a quantity of the mixture containing a desired therapeutically effective amount of said cannabinoid within a non-glycerin based composition composed of one or more materials which do not react with the cannabinoid or allow substantial permeation of oxygen and which effectively seals the cannabinoid from moisture.

107. The stabilized oral dosage form of claim 105, wherein the stabilized dosage form contains at least about 90% w/w of undegraded dronabinol upon exposure of the formulation to storage conditions selected from the group consisting of (i) elevated temperature and humidity conditions of 40°

C./75% relative humidity (RH) for 6 months;

(ii) elevated temperature conditions of 55°

C. for two weeks;

room temperature (25°

C.) for two years; and

(iii) any combination thereof.

108. The stabilized oral dosage form of claim 107, wherein the sesame oil contains an effective amount of a stabilizer to promote the stability of the dronabinol.

109. The stabilized oral dosage form of claim 108, wherein the stabilizer is an anti-oxidant in an amount from about 0.001% to about 10%, by weight.

110. The stabilized oral dosage form of claim 109, wherein the anti-oxidant is selected from the group consisting of sesamin, sesamol, sesamolin, lecithin and any combination of the foregoing.

111. The stabilized oral dosage form of claim 110, wherein the anti-oxidant comprises lecithin in an amount from about 0.3% to about 8.25%, by weight.

112. The stabilized oral dosage form of claim 108, wherein the stabilizer comprises an organic base in an amount from about 0.001% w/w to about 5%, by weight.

113. The stabilized oral dosage form of claim 112, wherein the organic base is selected from the group consisting of ethanolamine, methanolamine, meglumine, and any combination of the foregoing.

106. A stabilized oral dosage form of dronabinol, comprising from about 0.05 mg to about 20 mg dronabinol dispersed in sesame oil, the concentration of dronabinol in the sesame oil being from about 1.5% to about 6% by weight, encapsulated in a sealed hard gelatin capsule.

114. The stabilized oral dosage form of claim 106, further comprising one or more additional therapeutically active agents.

115. The stabilized oral dosage form of claim 106, wherein the dronabinol is from a source selected from the group consisting of a natural source, a synthetic source, a semi-synthetic source, and a mixture of any of the foregoing.

116. The dosage form of claim 106, wherein the dronabinol is in a form selected from the group consisting of its free form, a salt, an ester, a prodrug, a complex, and a mixture of any of the foregoing.