Long-acting non-aqueous injectable formulations and use thereof
Provided herein are long-acting, non-aqueous pharmaceutically acceptable compositions of active ingredients for subcutaneous injection, in particular analgesics such as buprenorphine.
1. A long-acting, non-aqueous injectable pharmaceutically acceptable composition, comprising:
a) a lipophilic active substance;
b) caprylic/capric triglyceride carrier at about 80.0 to 98.0% w/w of the composition;
c) cholesterol at about 1.0 to 10.0% w/w of the composition;
d) benzyl alcohol at a concentration of no more than about 5.0% w/w; and
e) glycerol mono-, di- or tristearate at a concentration of no more than about 2.5% w/w.
2. The composition of claim 1 , wherein the lipophilic active substance is buprenorphine.
3. The composition of claim 1 , wherein the mixture comprises about 40.0 to 85.0% caprylic acid and about 15.0 to 60.0% capric acid.
4. The composition of claim 3 , wherein the mixture comprises about 50.0 to 80.0% caprylic acid and about 20.0 to 50.0% capric acid.
5. The composition of claim 3 , wherein the mixture comprises about 65.0 to 80.0% caprylic acid and about 20.0 to 35.0% capric acid.
6. The composition of claim 3 , wherein the mixture comprises about 50.0 to 65.0% caprylic acid and about 30.0 to 45.0% capric acid.
7. The composition of claim 1 , wherein at least 1.0 ng/ml of active is present in the blood stream of the subject for at least about 48, 54, 60, 66, 72 hours or greater upon administration to a mammal.
8. The composition of claim 2 , wherein buprenorphine is present in a dose of about 0.1, 0.2, 0.3, 0.4, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5 or 7.0 mg/kg.
9. The composition of claim 1 , wherein the buprenorphine is present as the free base (unprotonated) form.
10. The composition of claim 1 , wherein the buprenorphine is present as a pharmaceutically acceptable salt.
11. The composition of claim 1 , wherein the composition is stable at room temperature for at least 6 months.
12. The composition of claim 11 , wherein the composition is stable at room temperature for at least 12 months.
13. A method of treating pain in a subject, comprising administering an effective amount of the composition of claim 1 to the subject to clinically resolve the pain.
14. The method of claim 13 , wherein the subject is a mammal.
15. The method of claim 14 , wherein the subject is a canine.
16. The method of claim 14 , wherein the subject is a feline.
17. The method of claim 13 , wherein the composition is administered by subcutaneous injection.
18. The method of claim 13 , wherein the composition is administered by intramuscular injection.
19. The method of claim 13 , wherein the blood concentration of the lipophilic active substance is greater than about 1 ng/ml for more than about 40, 50, 60, 70 or 80 hours following administration of the composition.
20. The method of claim 19 , wherein the lipophilic active substance is buprenorphine.