Long-acting non-aqueous injectable formulations and use thereof

1. A long-acting, non-aqueous injectable pharmaceutically acceptable composition, comprising:

a) a lipophilic active substance, wherein the lipophilic active substance is buprenorphine;

b) caprylic/capric triglyceride carrier at about 85.0 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 about 0.5 to 5.0% w/w; and

e) glycerol mono-, di- or tristearate at a concentration of about 0.1 to 2.5% w/w.

2. The composition of claim 1 , wherein the composition comprises:

i) buprenorphine at a concentration of about 0.5 to 1.0% w/w;

ii) caprylic/capric triglyceride at a concentration of about 90.0 to 92.0% w/w;

iii) benzyl alcohol at a concentration of about 0.5 to 2.5% w/w;

iv) cholesterol at a concentration of about 5.0 to 7.0% w/w; and

v) glycerol tristearate at a concentration of about 0.1 to 1.0% w/w.

3. The composition of claim 1 , wherein the composition comprises:

i) buprenorphine at a concentration of about 0.6-0.7% w/w;

ii) caprylic/capric triglyceride at a concentration of about 90.0-92.0% w/w;

iii) benzyl alcohol at a concentration of about 2.0% w/w;

iv) cholesterol at a concentration of about 6.5% w/w; and

v) glycerol tristearate at a concentration of about 0.5-0.6% w/w.

4. 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.

5. The composition of claim 1 , 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.

6. The composition of claim 1 , wherein the buprenorphine is present as the free base (unprotonated) form.

7. The composition of claim 1 , wherein the buprenorphine is present as a pharmaceutically acceptable salt.

8. The composition of claim 1 , wherein the composition is stable at room temperature for at least 6 months.

9. The composition of claim 8 , wherein the composition is stable at room temperature for at least 12 months.

10. 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.

11. The method of claim 10 , wherein the subject is a mammal.

12. The method of claim 11 , wherein the subject is a canine.

13. The method of claim 11 , wherein the subject is a feline.

14. The method of claim 10 , wherein the composition is administered by subcutaneous injection.

15. The method of claim 10 , wherein the composition is administered by intramuscular injection.

16. The method of claim 10 , 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.

17. The method of claim 16 , wherein the lipophilic active substance is buprenorphine.