LONG-ACTING INJECTABLE FORMULATIONS AND USE THEREOF
Provided herein are long-acting, non-aqueous pharmaceutically acceptable compositions of active ingredients for subcutaneous injection.
1 . An injectable pharmaceutically acceptable composition, comprising:
a) an antimicrobial agent selected from cabotegravir or dolutegravir;
b) a monoglyceride;
c) a triglyceride; and
d) ethanol, benzyl alcohol, or a combination thereof,
wherein the composition forms a water-insoluble depot upon subcutaneous injection, and
wherein no water source other than hydrate molecules are present.
2 . The composition of claim 1 , further comprising polyoxyl castor oil.
3 . The composition of claim 1 , further comprising hydrogenated phosphatidylcholine from soybean lecithin.
4 . The composition of claim 1 , further comprising an anti-oxidant.
5 . The composition of claim 1 , further comprising cholesterol.
6 . The composition of claim 1 , wherein the triglyceride is a medium chain triglyceride.
7 . The composition of claim 6 , wherein the medium chain triglyceride is caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, or a combination thereof.
8 . The composition of claim 7 , wherein the medium chain triglyceride is a caprylic/capric fatty acid mixture.
9 . The composition of claim 1 , wherein the triglyceride is present at 30 to 80.0% w/w.
10 . The composition of claim 1 , wherein the monoglyceride is selected from the group consisting of glycerol monooleate, glycerol monostearate, glycerol monolinoleate, glycerol monocaprylate, glycerol monocaprate, glycerol monolaurate, glycerol monomyristic, glycerol monopalmitic, glycerol monomyristoleic, glycerol monopalmitoleic, glycerol monosapienic and any combination thereof.
11 . The composition of claim 10 , wherein the monoglyceride is glycerol monooleate, glycerol monostearate, or a combination thereof.
12 . The composition of claim 1 , wherein the monoglyceride is present at 5.0 to 40.0% w/w.
13 . The composition of claim 2 wherein the polyoxyl castor oil is present in an amount of 0.01 to 10%.
14 . The composition of claim 1 , wherein the ethanol, benzyl alcohol, or a combination thereof is present at 5 to 20%.
15 . The composition of claim 14 , wherein the ethanol, benzyl alcohol, or combination thereof is a combination of ethanol and benzyl alcohol present at 5 to 20%.
16 . The composition of claim 1 , wherein the antimicrobial agent is present at 0.01 to 500 mg/ml.
17 . The composition of claim 1 , wherein at least 100 ng/ml of the antimicrobial agent is present in the blood stream of a subject for at least 48 hours or greater upon administration to a mammal.
18 . The composition of claim 17 , wherein at least 500 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
19 . The composition of claim 17 , wherein at least 1,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
20 . The composition of claim 17 , wherein at least 2,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
21 . The composition of claim 17 , wherein at least 3,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
22 . The composition of claim 17 , wherein at least 4,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
23 . The composition of claim 17 , wherein at least 5,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
24 . A method of treating a disease or disorder in a subject, wherein the disease or disorder is an infection, pain or inflammation, comprising administering a composition of claim 1 to the subject, thereby treating the disease or disorder.
25 . The method of claim 24 , wherein the subject is a mammal.
26 . The method of claim 25 , wherein the subject is a canine.
27 . The method of claim 25 , wherein the subject is a feline.
28 . The method of claim 25 , wherein at least 100 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
29 . The method of claim 28 , wherein at least 500 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
30 . The method of claim 28 , wherein at least 1,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
31 . The method of claim 28 , wherein at least 2,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
32 . The method of claim 28 , wherein at least 3,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
33 . The method of claim 28 , wherein at least 4,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.
34 . The method of claim 28 , wherein at least 5,000 ng/ml of the antimicrobial agent is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal.