Pharmaceuticals for oral delivery
View Patent ↗The present invention provides pharmaceutical compositions suitable for oral delivery and methods of treating subjects in need thereof. The pharmaceutical compositions of the present invention enhance bioavailability of at least one compound classified as BCS Class II, BCS Class III or BCS Class IV.
1. A solid oral dosage form comprising:
a mixture comprising:
a therapeutically effective amount of at least one active pharmaceutical compound classified as BCS Class III, wherein the compound does not include a peptide bond in the molecular structure of the compound;
an absorption enhancer; and
from 100 mg to 500 mg of coated citric acid particles, wherein the citric acid particles are coated with a water soluble coat that separates the citric acid from the active pharmaceutical compound, wherein, if the dosage form was added to ten milliliters of 0.1 M aqueous sodium bicarbonate solution, the pH of the solution would be acidified to a pH no higher than 5.5;
an enteric coating; and
a water soluble barrier positioned between the mixture and the enteric coating, thereby separating the mixture from the enteric coating,
wherein oral administration results in a synergistic increase in systemic bioavailability of the active pharmaceutical compound when compared to the systemic bioavailability provided by administration of a solid dosage form containing an equal dose of the active pharmaceutical compound without the absorption enhancer and the citric acid.
2. The solid oral dosage form of claim 1 , wherein the absorption enhancer is a combination of two or more absorption enhancers.
3. The solid oral dosage form of claim 1 , wherein the absorption enhancer comprises a surface acting agent.
4. The solid oral dosage form of claim 3 , wherein the surface acting agent is an acid soluble bile acid.
5. The solid oral dosage form of claim 1 , wherein the absorption enhancer comprises an acylcarnitine.
6. The solid oral dosage form of claim 1 , wherein the absorption enhancer comprises lauroyl carnitine.
7. The solid oral dosage form of claim 1 , wherein the at least one active pharmaceutical compound classified as BCS Class III is an antibiotic or an antiviral compound.
8. The solid oral dosage form of claim 1 , wherein the at least one active pharmaceutical compound classified as BCS Class III is an aminoglycoside.
9. The solid oral dosage form of claim 1 , wherein the at least one active pharmaceutical compound is selected from the group consisting of tigecycline, zanamivir, kanamycin, and tobramycin.
10. A method of treating a bacterial infection in a subject in need thereof comprising orally administering a solid oral dosage form comprising:
a mixture comprising:
at least one active pharmaceutical, antibacterial, or antiviral compound classified as BCS Class III, wherein the compound does not include a peptide bond in the compound's molecular structure
an absorption enhancer; and
from 100 mg to 500 mg of coated citric acid particles, wherein the citric acid particles are coated with a water soluble coat that separates the citric acid from the at least one active compound, wherein, if the dosage form was added to ten milliliters of 0.1 M aqueous sodium bicarbonate solution, the pH of the solution would be lowered to no higher than 5.5;
an enteric coating; and
a water soluble barrier positioned between the mixture and the enteric coating, thereby separating the mixture from the enteric coating,
wherein oral administration results in a synergistic increase in systemic bioavailability of the active compound when compared to the systemic bioavailability provided by administration of a solid dosage form containing an equal dose of the active compound without the absorption enhancer and the citric acid.
11. The method of claim 10 , wherein the infection is a gram-negative infection.
12. The method of claim 10 , wherein the infection is a gram-positive infection.
13. The method of claim 10 , wherein the at least one active compound is an antibiotic or an antiviral compound.
14. The method of claim 10 , wherein the at least one active compound is an aminoglycoside.
15. The method of claim 10 , wherein the at least one active compound is selected from the group consisting of tigecycline, zanamivir, kanamycin, and tobramycin.
16. The method of claim 10 , wherein the absorption enhancer is a combination of two or more absorption enhancers.
17. The method of claim 10 , wherein the absorption enhancer comprises an acylcarnitine.
18. The method of claim 10 , wherein the absorption enhancer comprises lauroyl carnitine.