Long-acting injectable formulations and use thereof
Provided herein are long-acting, non-aqueous pharmaceutically acceptable compositions of active ingredients for subcutaneous injection.
1. A non-aqueous, extended release, injectable pharmaceutically acceptable composition, comprising:
a) a pharmaceutically active agent present at about 1.0 to 25% w/w;
b) glycerol monooleate present at about 5.0 to 40.0% w/w;
c) a C8 triglyceride, a C10 triglyceride, or a combination thereof present at about 5.0 to 80.0% w/w;
d) ethanol and benzyl alcohol present at about 1 to 25% w/w in combination; and
e) a surfactant present in an amount of about 0.5 to 5.0% w/w,
wherein the composition forms a water-insoluble depot upon injection wherein the pharmaceutically acceptable active agent is selected from a fluroquinolone and florfenicol, and wherein upon subcutaneous injection, at least 90% of the pharmaceutically active agent is released by about 150 hours.
2. The composition of claim 1 , comprising:
the glycerol monooleate present at about 20% w/w;
C8 triglyceride, a C10 triglyceride, or a combination thereof present at about 60% w/w; and
the ethanol and benzyl alcohol present at about 10% w/w in combination.
3. The composition of claim 1 , wherein the fluoroquinolone is benofloxacin, binfloxacin, cinoxacin, ciprofloxacin, danofloxacin, difloxacin, enoxacin, enrofloxacin, fleroxacin, ibafloxacin, levofloxacin, lomefloxacin, marbofloxacin, moxifloxacin, norfloxacin, ofloxacin, orbifloxacin, pefloxacin, pipemidic acid, temafloxacin, tosufloxacin, sarafloxacin, sparfloxacin, or combination thereof.
4. The composition of claim 1 , further comprising an excipient.
5. The composition of claim 1 , further comprising polyoxyl castor oil.
6. The composition of claim 1 , further comprising hydrogenated phosphatidylcholine from soybean lecithin.
7. The composition of claim 1 , further comprising an anti-oxidant.
8. The composition of claim 1 , further comprising cholesterol.
9. The composition of claim 1 , wherein the C8 triglyceride is caprylic acid, and the C10 triglyceride is capric acid.
10. The composition of claim 1 , wherein at least about 100, 500, 1,000, 2,000, 3,000, 4,000, 5,000, 10,000, 15,000 or 20,000 ng/ml of the pharmaceutically active agent is present in the blood stream of a subject for at least about 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 hours or greater upon administration to a mammal.
11. A method of treating a disease or disorder in a subject, comprising administering to the subject an effective amount of the composition of claim 1 .
12. The method of claim 11 , wherein the subject is a mammal.
13. The method of claim 12 , wherein the subject is a canine.
14. The method of claim 11 , wherein the subject is a feline.
15. The method of claim 11 , wherein the disease or disorder is an infection.
16. The method of claim 11 , wherein at least about 100, 500, 1,000, 2,000, 3,000, 4,000, 5,000, 10,000, 15,000 or 20,000 ng/ml of the pharmaceutically active agent is present in the blood stream of the subject for at least about 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 hours or greater upon administration to a mammal.
17. An extended release, injectable pharmaceutically acceptable composition comprising:
a) a pharmaceutically active agent that is marbofloxacin present at about 15 to 25% w/w;
b) glycerol monooleate present at about 15 to 40% w/w;
c) a C8 triglyceride, a C10 triglyceride, or a combination thereof present at about 40 to 55% w/w;
d) ethanol present at about 1 to 10% w/w; and
e) benzyl alcohol present at about 1 to 10% w/w;
wherein the composition forms a water-insoluble depot upon injection,
wherein the composition is suitable for either subcutaneous or intramuscular injection and wherein upon subcutaneous injection, at least 90% of the pharmaceutically active agent is released by about 150 hours.