Compositions having improved bioavailability of therapeutics
The present specification discloses pharmaceutical composition disclosed herein comprises one or more therapeutic compounds, one or more glycerolipids, and one or more digestion enhancers. The disclosed glycerolipids comprise one or more hard fats and one or more liquid fats. The disclosed digestion enhancers comprise one or more bile acids, one or more phospholipids, one or more free C 14-24 fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof. The present specification also discloses methods and procedures to formulate the disclosed one or more therapeutic compounds into the disclosed pharmaceutical compositions.
1 . A pharmaceutical composition comprising:
a) one or more pharmaceutically active agents selected from the group consisting of an abiraterone, an amlexanox, an aprepitant, an auranofin, a cannabidiol, a diclofenac, an eliglustat, an ezetimibe, a fenofibrate, an ibuprofen, an icatibant, a mebendazole, a mefenamic acid, a midostaurin, a naproxen, a niflumic acid, a nintedanib, an olaparib, a pirfenidone, a pitolisant, a telmisartan, tetrahydrocannabinol, and combinations thereof; and
b) about 45% to about 95% by weight of the pharmaceutical composition of one or more glycerolipids, the one or more glycerolipids being one or more saturated C 10 -C 22 triglycerides and a mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides; and
c) about 1.0% to about 8.0% by weight of the pharmaceutical composition of one or more free C 14-24 fatty acid surfactants, about 15% to about 40% by weight of the pharmaceutical composition of one or more free C 14-24 fatty acids, or both the one or more free C 14-24 fatty acid surfactants and the one or more free C 14-24 fatty acids; and
wherein the pharmaceutical composition is an anhydrous formulation; and
wherein the pharmaceutical composition is not an emulsion.
2 . The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically active agents are in an amount of about 0.1% to about 25% by weight of the pharmaceutical composition.
3 . The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically active agents are in an amount of about 25 mg/mL to about 600 mg/mL.
4 . The pharmaceutical composition of claim 1 , wherein the one or more glycerolipids are present in an amount of about 45% to about 75% by weight of the pharmaceutical composition.
5 . The pharmaceutical composition of claim 1 , wherein the one or more saturated C 10 -C 22 triglycerides are present in an amount of about 10% to about 35% by weight of the pharmaceutical composition.
6 . The pharmaceutical composition of claim 5 , wherein the one or more saturated C 10 -C 22 triglycerides are a mixture of saturated C 10 -C 18 triglycerides.
7 . The pharmaceutical composition of claim 5 , wherein the one or more saturated C 10 -C 22 triglycerides are present in an amount of about 15% to about 30% by weight of the pharmaceutical composition.
8 . The pharmaceutical composition of claim 5 , wherein the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 20% to about 75% by weight of the pharmaceutical composition.
9 . The pharmaceutical composition of claim 8 , wherein the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are a mixture of unsaturated C 16 -C 20 monoglycerides, C 16 -C 20 diglycerides, and C 16 -C 20 triglycerides.
10 . The pharmaceutical composition of claim 8 , wherein the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 20% to about 50% by weight of the pharmaceutical composition.
11 . The pharmaceutical composition of claim 8 , wherein the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 50% to about 75% by weight of the pharmaceutical composition.
12 . The pharmaceutical composition of claim 5 , wherein the one or more saturated C 10 -C 22 triglycerides and the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are in a triglyceride to mixture weight ratio of about 1:1 to about 1:5.
13 . The pharmaceutical composition of claim 1 , wherein the one or more free C 14-24 fatty acid surfactants are present in an amount of about 2.0% to about 7.0% by weight of the pharmaceutical composition.
14 . The pharmaceutical composition of claim 1 , wherein the one or more free C 14-24 fatty acid surfactants are an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
15 . The pharmaceutical composition of claim 1 , wherein the one or more free C 14-24 fatty acid surfactants are a sodium oleate, a sodium stearate, a sodium linoleate, or any combination thereof.
16 . The pharmaceutical composition of claim 1 , wherein the one or more free C 14-24 fatty acids are present in an amount of about 20% to about 35% by weight of the pharmaceutical composition.
17 . The pharmaceutical composition of claim 14 , wherein the one or more free C 14-24 fatty acids are an oleic acid, a stearic acid, a linoleic acid, or any combination thereof.
18 . The pharmaceutical composition of claim 1 , wherein the one or more saturated C 10 -C 22 triglycerides are present in an amount of about 10% to about 25% by weight of the pharmaceutical composition, the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 50% to about 75% by weight of the pharmaceutical composition, and the one or more free C 14-24 fatty acid surfactants are present in an amount of about 3.0% to about 7.0% by weight of the pharmaceutical composition.
19 . The pharmaceutical composition of claim 1 , wherein the one or more saturated C 10 -C 22 triglycerides are present in an amount of about 15% to about 35% by weight of the pharmaceutical composition, the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 20% to about 45% by weight of the pharmaceutical composition, and the one or more free C 14-24 fatty acids are present in an amount of about 20% to about 35% by weight of the pharmaceutical composition.
20 . The pharmaceutical composition of claim 1 , wherein the one or more glycerolipids are present in an amount of about 70% to about 95% by weight of the pharmaceutical composition.
21 . The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically active agents is an abiraterone, an amlexanox, an aprepitant, an auranofin, a diclofenac, an eliglustat, an ezetimibe, a fenofibrate, an ibuprofen, an icatibant, a mebendazole, a mefenamic acid, a midostaurin, a naproxen, a niflumic acid, a nintedanib, an olaparib, a pirfenidone, a pitolisant, a telmisartan, or a combination thereof.