Pharmaceuticals for Oral Delivery

Abstract

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 
 coated organic acid particles, wherein the organic acid particles are coated with a water soluble coat; 
   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 a 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 coated organic acid particles.   
     
     
         2 . The solid oral dosage form of  claim 1 , wherein the organic acid is a carboxylic acid selected from the group consisting of acetylsalicylic acid, acetic acid, ascorbic acid, citric acid, fumaric acid, glucuronic acid, glutaric acid, glyceric acid, glycocolic acid, glyoxic acid, isocitric acid, isovaleric acid, lactic acid, maleic acid, oxaloacetic acid, oxalosuccinic acid, propionic acid, pyruvic acid, succinic acid, tartaric acid, valeric acid and combinations thereof. 
     
     
         3 . The solid oral dosage form of  claim 2 , wherein the coated organic acid is present in a quantity which, 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, wherein the organic acid particles are coated with a water soluble coat that separates the organic acid from the active pharmaceutical compound. 
     
     
         4 . The solid oral dosage form of  claim 2 , wherein the water soluble coat separates the organic acid from the at least one active pharmaceutical compound. 
     
     
         5 . The solid oral dosage form of  claim 2 , comprising from 100 mg to 500 mg of coated organic acid particles. 
     
     
         6 . The solid oral dosage form of  claim 1 , wherein the absorption enhancer is a combination of two or more absorption enhancers. 
     
     
         7 . The solid oral dosage form of  claim 1 , wherein the absorption enhancer comprises a surface acting agent. 
     
     
         8 . The solid oral dosage form of  claim 7 , wherein the surface acting agent is an acid soluble bile acid. 
     
     
         9 . The solid oral dosage form of  claim 1 , wherein the absorption enhancer comprises an acylcarnitine. 
     
     
         10 . The solid oral dosage form of  claim 1 , wherein the absorption enhancer comprises lauroyl carnitine. 
     
     
         11 . 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. 
     
     
         12 . The solid oral dosage form of  claim 1 , wherein the at least one active pharmaceutical compound classified as BCS Class III is an aminoglycoside. 
     
     
         13 . 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. 
     
     
         14 . A solid oral dosage form comprising:
 a mixture comprising:
 a therapeutically effective amount of at least one active pharmaceutical compound classified as BCS Class II, BCS Class III or BCS Class IV, wherein the compound does not include a peptide bond in the molecular structure of the compound; 
 an absorption enhancer; and 
 coated organic acid particles, wherein the organic acid particles are coated with a water soluble coat; 
   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 a systemic bioavailability of the least one active pharmaceutical compound when compared to the systemic bioavailability provided by administration of a solid dosage form containing an equal dose of the least one active pharmaceutical compound without the absorption enhancer and the coated organic acid particles.   
     
     
         15 . A method of treating a bacterial infection or a viral infection in a subject in need thereof comprising orally administering a solid oral dosage form comprising:
 a mixture comprising:
 a therapeutically effective amount of at least one active pharmaceutical compound classified as BCS Class II, BCS Class III or BCS Class IV, wherein the compound does not include a peptide bond in the compound's molecular structure; 
 an absorption enhancer; and 
 coated organic acid particles, wherein the organic acid particles are coated with a water soluble coat; 
   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 a systemic bioavailability of the least one active pharmaceutical compound when compared to the systemic bioavailability provided by administration of a solid dosage form containing an equal dose of the least one active pharmaceutical compound without the absorption enhancer and the coated organic acid particles.