Preparation of Aqueous Clear Solution Dosage Forms with Bile Acids

Abstract

Compositions for pharmaceutical and other uses comprising clear aqueous solutions of bile acids which do not form any detectable precipitates over selected ranges of pH values of the aqueous solution and methods of making such solutions. The compositions of the invention comprise water; a bile acid in the form of a bile acid, bile acid salt, or a bile acid conjugated with an amine by an amide linkage; and either or both an aqueous soluble starch conversion product and an aqueous soluble non-starch polysaccharide. The composition remains in solution without forming a precipitate over a range of pH values and, according to one embodiment, remains in solution for all pH values obtainable in an aqueous system. The composition, according to some embodiments, may further contain a pharmaceutical compound in a pharmaceutically effective amount. Non-limiting examples of pharmaceutical compounds include insulin, heparin, bismuth compounds, amantadine and rimantadine

1 . A method for treating gastritis and peptic ulcer disease comprising: 
 (a) administration of an oral liquid dosage form comprising: 
 (i) a first material selected from the group consisting of a bile acid, an aqueous soluble derivative of a bile acid, a bile acid salt, a bile acid conjugated with an amine by an amide linkage, and combinations thereof;  
 (ii) a second material selected from the group consisting of an aqueous soluble starch conversion product and an aqueous soluble non-starch polysaccharide; and  
 (iii) water,  
   wherein the first and second materials both remain in solution for all pH values of the solution within a selected range of pH values.    
     
     
         2 . The method of  claim 1  wherein the dosage form is selected from the group consisting of a syrup, a thick syrup, and a paste.  
     
     
         3 . The method of  claim 1  wherein the oral liquid dosage form additionally comprises a bismuth compound in a pharmaceutically effective amount.  
     
     
         4 . The method of  claim 3  wherein the bismuth compound comprises an aqueous soluble reaction product between a bismuth ion and a chelator.  
     
     
         5 . The method of  claim 4  wherein the chelator is selected from the group consisting of citric acid, tartaric acid, malic acid, lactic acid and eidetic acid and alkalies.  
     
     
         6 . The method of  claim 5  wherein the bismuth compound is selected from the group consisting of an ammonium salt of bismuth sulphate, an ammonium salt of bismuth citrate, and bismuth sodium tartrate.  
     
     
         7 . The method of  claim 1  wherein the first material is selected from the group consisting of ursodeoxycholic acid, chenodeoxycholic acid, cholic acid, hyodeoxycholic acid, deoxycholic acid, 7-oxolithocholic acid, lithocholic acid, iododeoxycholic acid, iocholic acid, tauroursodeoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycoursodeoxycholic acid, taurocholic acid, glycocholic acid, their derivatives at a hydroxyl or carboxylic acid group on the steroid nucleus, their salts, or their conjugates with amines.  
     
     
         8 . The method of  claim 1  wherein the second material is selected from the group consisting of maltodextrin, dextrin, corn syrup corn syrup solid, soluble starch, and dextrans.  
     
     
         9 . The method of  claim 1  wherein the oral liquid dosage form comprises one or more additional bile acids, aqueous soluble derivatives of bile acid, bile acid salts, and amine-conjugated bile acids conjugated by an amide linkage.  
     
     
         10 . The method of  claim 1  wherein the oral liquid dosage form additionally comprises a least one emulsifying agent.  
     
     
         11 . The method of  claim 10  wherein the emulsifying agent is selected from the group consisting of guar gum, pectin, acacia, carrageenan, carboxymethyl cellulose sodium, hydroxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, polyvinyl alcohol, povidone, tragacanth gum, xanthan gum, and sorbitan ester.  
     
     
         12 . The method of  claim 1  wherein the oral liquid dosage form additionally comprises at least one pharmaceutical in a pharmaceutically effective amount.  
     
     
         13 . The method of  claim 12  wherein the pharmaceutical is selected from the group consisting of antibiotics, H 2 -receptor antagonists, and antiprotozoal drugs.  
     
     
         14 . The method of  claim 12  wherein the pharmaceutical is selected from the group consisting of ampicillin, amoxicillin, cefaclor, cefadroxyl, azithromycin, clarithromycin, demeclocycline- HCl, doxycycline, minocycline HCl, tetracycline, oxytetracycline, cimetidine, famotidine, nizatidine, ranitidine, sucralfate, metronidazole, atovaquone, and pentamidine isethionate.  
     
     
         15 - 87 . (canceled)