Oral cannabinoid formulations
Oral cannabinoid formulations, including an aqueous-based oral dronabinol solution, that are stable at room or refrigerated temperatures and may possess improved in vivo absorption profiles with faster onset and lower inter-subject variability.
1 . A method of administering dronabinol to a human subject, comprising orally administering to the human subject a stable pharmaceutical solution comprising:
(a) about 0.1% w/w to about 5% w/w dronabinol;
(b) 31.9% w/w or less water;
(c) about 15% w/w to about 90% w/w ethanol;
(d) about 17.5% w/w co-solvent consisting of propylene glycol and polyethylene glycol or a mixture thereof; and
(e) an antioxidant.
2 . The method according to claim 1 , wherein said stable pharmaceutical solution comprises ethanol at a concentration from about 40% w/w to about 90% w/w.
3 . The method according to claim 2 , wherein said stable pharmaceutical solution comprises ethanol at a concentration from about 15% w/w to about 65% w/w.
4 . The method according to claim 1 , wherein said stable pharmaceutical solution comprises about 5 mg dronabinol.
5 . The method according to claim 1 , wherein said antioxidant is selected from the group consisting of butylated hydroxyanisole (BHA), butylated hydroxytoulene (BHT), disodium ethylenediaminetetracetic acid (EDTA), a paraben, and combinations thereof.
6 . The method according to claim 1 , wherein said stable pharmaceutical solution comprises about 5% w/w dronabinol, about 12% w/w polyethylene glycol 400, about 5.5% w/w propylene glycol, 30-31.90% w/w water, and 50% w/w ethanol.
7 . The method according to claim 6 , wherein said stable pharmaceutical solution further comprises butylated hydroxyl anisole (BHA), sucralose, methyl paraben, and propyl paraben.
8 . The method according to claim 6 , wherein said stable pharmaceutical solution further comprises 0.01% w/w butylated hydroxyl anisole (BHA) or disodium ethylenediaminetetracetic acid (EDTA).
9 . The method according to claim 1 , wherein said stable pharmaceutical solution comprises about 0.54% w/w dronabinol and about 15% to about 65% w/w ethanol.
10 . A method of administering dronabinol to a human subject, comprising orally administering to the human subject a stable pharmaceutical solution consisting essentially of 0.1 to 5% w/w of dronabinol, 25-33% w/w water, 15-65% w/w solvent, a cosolvent consisting of 5.5% w/w propylene glycol and 12% w/w polyethylene glycol, and an excipient selected from the group consisting of butylated hydroxyanisole (BHA), butylated hydroxytoulene (BHT), disodium ethylenediaminetetracetic acid (EDTA), a paraben and combinations thereof, wherein said oral pharmaceutical solution is stable for at least eighteen months at room or refrigerated temperatures, has an in vivo absorption variability of less than 50%, and a 5 mg dose of dronabinol provides a pharmacokinetic profile of C max of 2.4+/−1.30 (ng/ml), AUC (0-t) of 4.23+/−1.97 (h*ng/mL) or a T max of 0.25-4.00 (h) following oral administration.
11 . The method according to claim 1 , wherein said stable oral solution is administered orally via the buccal or sublingual routes.
12 . The method according to claim 1 , wherein said stable oral solution is administered in combination with another cannabinoid.
13 . The method according to claim 1 , wherein the stable oral dronabinol solution is administered as a suspension, emulsion, suppository, spray, aerosol, gel, drop, syrup, or elixir.
14 . The method according to claim 1 , wherein said human has nausea or vomiting associated with chemotherapy.
15 . The method according to claim 1 , wherein said human has loss of appetite associated with an autoimmune deficiency syndrome (AIDS).
16 . The method according to claim 6 , wherein said human has nausea or vomiting associated with chemotherapy.
17 . The method according to claim 6 , wherein said human has loss of appetite associated with an autoimmune deficiency syndrome (AIDS).
18 . The method according to claim 10 , wherein said human has nausea or vomiting associated with chemotherapy.
19 . The method according to claim 10 , wherein said human has loss of appetite associated with an autoimmune deficiency syndrome (AIDS).