Room-temperature stable dronabinol formulations

• US 8,628,796 B2
• Filed: 12/09/2005
• Issued: 01/14/2014
• Est. Priority Date: 12/09/2004
• Status: Active Grant

• Current Assignee: Benuvia Operations LLC
• Original Assignee: INSYS Therapeutics, Inc.
• Inventors: Kottayil, S. George, Zhu, Zhongyuan, Goskonda, Venkat R.
• Primary Examiner(s): CLAYTOR, DEIRDRE RENEE
• Application Number:
  US11/299,183
• Publication Number:
  US 20060160888A1
• Time in Patent Office: 2,958 Days
• Field of Search: 424/456, 514/454
• US Class Current: 424/456
• 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 consisting essentially of:

synthetic dronabinol in an amount of 0.05 to 20 mg per dose and L-ascorbic acid-6-palmitate in an amount of 0.01% to 1% by weight, both dispersed in sesame oil; and

a gelatin capsule encapsulating said synthetic dronabinol, said L-ascorbic acid-6-palmitate, and said sesame oil, said dosage form being stable at room temperature for at least one year.

2. The dosage form of claim 1, which contains not less than 90% of the initial dronabinol content 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) room temperature (25°

C.) for two years; and

(iii) any combination thereof.

3. The dosage form of claim 1, wherein the dronabinol does not contain more than 5% dronabinol degradants in the dosage form, the degradants selected from the group consisting of no more than 2% delta-8 tetrahydrocannabinol (D8THC), no more than 2% cannabinol (CBN), no more than 0.2% cannabidiol (CBD), and any combination thereof.

4. 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.

5. The dosage form of claim 4, which comprises from 0.001% to 5% organic base, by weight.

6. The dosage form of claim 4, which comprises from 0.005% to 2% organic base, by weight.

7. The dosage form of claim 4, wherein said organic base is selected from the group consisting of ethanolamine, methanolamine, meglumine, and any combination of the foregoing.

8. The dosage form of claim 1, wherein said gelatin capsule is soft or hard.

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

10. The dosage form of claim 9, 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.

11. 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 2% cannabinol;

(iii) not greater than 2% cannabidiol;

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

(v) any combination of the foregoing.

12. The dosage form of claim 1, further comprising a pharmaceutical excipient selected from the group consisting of solubilizers;

stabilizers;

surfactants;

emulsifiers, absorption enhancers, and mixtures thereof.

13. The dosage form of claim 1, wherein the gelatin capsule is a capsule having a coating on its surface selected from the group consisting of an enteric coating, a seal coating, or both.

14. The dosage form of claim 13, wherein the gelatin capsule 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 gelatin capsule.

15. A cannabinoid dosage form consisting essentially of:

synthetic dronabinol in an amount of 0.05 mg to 20 mg per unit dose and L-ascorbic acid-6-palmitate in an amount of 0.001% to 1% by weight, both dispersed in sesame oil; and

a gelatin capsule encapsulating said dronabinol, said L-ascorbic acid-6-palmitate, and said sesame oil, said dosage form contains at least about 90% w/w of the synthetic dronabinol in undegraded form after storage at room temperature for at least one year.