Peptide Pharmaceutical for Oral Delivery

Abstract

Acid-containing oral pharmaceutical compositions are provided wherein the pharmaceutical active agents are peptide compounds (i.e., those that include a plurality of amino acids and at least one peptide bond in their molecular structures). Certain barrier layers and/or particulate coated acid are used to reduce any adverse interactions that might otherwise occur between the acid of the compositions and other components of the composition. Use of these barrier layers and/or use of particulate coated acid is believed to promote a more simultaneous release of the components of the composition than is achieved by prior art acid-protection techniques, thus enhancing, and making more consistent, the bioavailability of the active peptide compounds.

What is claimed is: 
     
         1 . A single dosage form comprising:
 a peptide agent;   at least one pharmaceutically acceptable acid, wherein the acid comprises acid particles coated with a pharmaceutically acceptable protective water soluble coating;   at least one absorption enhancer;   wherein, if the dosage form were 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.   
     
     
         2 . The single dosage form of  claim 1  comprising two or more absorption enhancers. 
     
     
         3 . The single dosage form of  claim 1  wherein the at least one absorption enhancer is a salicylate, a bile acid, an anionic surfactant, a non-ionic surfactant, a phospholipid, a lyso-phospholipid, an acylcarnitine, an acylcholine, an acyl amino acid, a medium-chain glyceride, ethylene-diaminetetraacetic acid, a cationic surfactant, a cationic ion exchange agent, a fatty acid derivative of polyethylene glycol, an alkylsaccharide or a combination thereof. 
     
     
         4 . The single dosage form of  claim 3  wherein the salicylate is sodium salicylate, 3-methoxysalicylate, 5-methoxysalicylate, homovanilate or a combination thereof. 
     
     
         5 . The single dosage form of  claim 3  wherein the bile acid is taurocholic acid, tauorodeoxycholic acid, deoxycholic acid, cholic acid, glycholic acid, lithocholic acid, chenodeoxycholic acid, ursodeoxycholic acid, ursocholic acid, dehydrocholic acid, fusidic acid or a combination thereof 
     
     
         6 . The single dosage form of  claim 3  wherein the non-ionic surfactant is a polyoxyethylene ether, a p-t-octyl phenol, a nonylphenoxypoloxyethylenes, a polyoxyethylene sorbitan ester or a combination thereof. 
     
     
         7 . The single dosage form of  claim 3  wherein the anionic surfactant is dioctyl sodium sulfosuccinate. 
     
     
         8 . The single dosage form of  claim 3  wherein the lyso-phospholipid is lysolecithin, lysophosphatidylethanolamine or a combination thereof. 
     
     
         9 . The single dosage form of  claim 3  wherein the acylcarnitine is lauroylcarnitine, myristoylcarnitine, palmitoylcarnitine or a combination thereof. 
     
     
         10 . The single dosage form of  claim 3  wherein the acylcholine is lauroylcholine, myristoylcholine, palmitoylcholine or a combination thereof 
     
     
         11 . The single dosage form of  claim 3  wherein the acyl amino acid is hexadecyllysine, N-acylphenylalanine or N-acylglycine or a combination thereof. 
     
     
         12 . The single dosage form of  claim 3  wherein the phospholipid is diheptanoylphosphatidylcholine, dioctylphosphatidylcholine or a combination thereof. 
     
     
         13 . The single dosage form of  claim 3  wherein the medium-chain glyceride is a mixture of monoglycerides, diglycerides and triglycerides containing medium-chain-length fatty acids. 
     
     
         14 . The single dosage form of  claim 13  wherein medium-chain-length fatty acid is caprylic acid, capric acid, lauric acid or a combination thereof 
     
     
         15 . The single dosage form of  claim 3  wherein the cationic surfactant is cetylpyridinium chloride. 
     
     
         16 . The single dosage form of  claim 3  wherein the fatty acid derivative of polyethylene glycol is caprylocaproyl macrogol-8 glyceride, a triglyceride medium-chain or a combination thereof. 
     
     
         17 . The single dosage form of  claim 3  wherein the alkylsaccharide is a sucrose ester. 
     
     
         18 . The single dosage form of  claim 3  wherein the alkylsaccharide is lauryl maltoside, lauroyl sucrose, myristoyl sucrose, palmitoyl sucrose or a combination thereof. 
     
     
         19 . The single dosage form of  claim 3  wherein cationic ion exchange agent is protamine chloride or a polycation. 
     
     
         20 . The single dosage form of  claim 1  wherein the acid is citric acid. 
     
     
         21 . A single dosage form comprising:
 a peptide agent;   at least one pharmaceutically acceptable acid, wherein the acid comprises acid particles coated with a pharmaceutically acceptable protective water soluble coating;   two or more absorption enhancers, wherein the two or more absorption enhancers comprise a fatty acid derivative of polyethylene glycol and a sucrose ester;   wherein, if the dosage form were 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.   
     
     
         22 . The single dosage form of  claim 21  wherein the fatty acid is caprylic acid or capric acid. 
     
     
         23 . The single dosage form of  claim 21  further comprising an anionic surfactant. 
     
     
         24 . The single dosage form of  claim 21  wherein the sucrose ester is lauroyl sucrose. 
     
     
         25 . A single dosage form comprising:
 a peptide agent;   citric acid particles coated with a pharmaceutically acceptable protective water soluble coating;   at least one absorption enhancer comprising a fatty acid derivative of polyethylene glycol, a sucrose ester, an anionic surfactant or combinations thereof;   wherein, if the dosage form were 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.   
     
     
         26 . The single dosage form of  claim 25  comprising from 200mg to 400 mg citric acid.