Gastric reflux resistant dosage forms

Abstract

Gastric resistant film-forming compositions are described herein. The composition comprises a gastric resistant natural polymer, a film-forming natural polymer, and optionally a gelling agent. Suitable gastric resistant natural polymers include polysaccharides such as pectin and pectin-like polymers. The film-forming composition can be used to prepare soft or hard shell gelatin capsules which can encapsulate a liquid or semi-solid fill material or a solid tablet (Softlet®) comprising an active agent and one or more pharmaceutically acceptable excipients. Alternatively, the composition can be administered as a liquid with an active agent dissolved or dispersed in the composition. The compositions are not only gastric resistant but may also prevent gastric reflux associated with odor causing liquids, such as fish oil or garlic oil, encapsulated in a unit dosage form and esophageal irritation due to the reflux of irritant drugs delivered orally.

1 . A gastric resistant film-forming liquid composition comprising 
 (a) a gastric resistant natural polymer present in an amount less than about 5% by weight of the composition;    (b) a film-forming natural polymer; and    (c) optionally, a gelling agent.    
   
   
       2 . The composition of  claim 1  wherein the gastric resistant natural polymer is pectin.  
   
   
       3 . The composition of  claim 1  wherein the gastric resistant natural polymer is a pectin-like polymer.  
   
   
       4 . The composition of  claim 1  wherein the concentration of the gastric resistant natural polymer is from about 2 to about 4% by weight of the composition.  
   
   
       5 . The composition of  claim 1  wherein the film-forming natural polymer is gelatin.  
   
   
       6 . The composition of  claim 5  wherein the film-forming natural polymer is a gelatin-like polymer.  
   
   
       7 . The composition of  claim 1  wherein the concentration of the film-forming natural polymer is from about 20 to about 40% by weight of the composition.  
   
   
       8 . The composition of  claim 7  wherein the concentration of the film-forming natural polymer is from about 25 to about 40% by weight of the composition.  
   
   
       9 . The composition of  claim 1  comprising a gelling agent.  
   
   
       10 . The composition of  claim 9  wherein the gelling agent is divalent cations selected from the group consisting of calcium salts, magnesium salts, and calcium gelatin.  
   
   
       11 . The composition of  claim 1  comprising a gelling agent at a concentration of less than about 2% by weight of the composition.  
   
   
       12 . The composition of  claim 11  wherein the concentration of the gelling agent is less than about 1% by weight of the composition.  
   
   
       13 . The composition of  claim 1  further comprising one or more plasticizers selected from the group consisting of glycerin, sorbitol, sorbitans, maltitol, glycerol, polyethylene glycol, polyalcohols with 3 to 6 carbon atoms, citric acid, citric acid esters, triethyl citrate and combinations thereof.  
   
   
       14 . The composition of  claim 13  wherein the concentration of the one or more plasticizers is from about 8% to about 30% by weight of the composition.  
   
   
       15 . The composition of  claim 1  further comprising a therapeutic, prophylactic or diagnostic agent dissolved or dispersed in the gastric-resistant film-forming composition.  
   
   
       16 . A gastric resistant protein or polysaccharide gelled composition comprising 
 (a) a gastric resistant natural polymer present in an amount less than about 5% by weight of the composition;    (b) a film-forming natural polymer; and    (c) a gelling agent.    
   
   
       17 . The composition of  claim 18  wherein the composition is a hard or soft capsule shell.  
   
   
       18 . The composition of  claim 16  wherein the gastric resistant natural polymer is pectin.  
   
   
       19 . The composition of  claim 16  wherein the gastric resistant natural polymer is a pectin-like polymer.  
   
   
       20 . The composition of  claim 16  wherein the concentration of the gastric resistant natural polymer is from about 2 to about 4% by weight of the composition.  
   
   
       21 . The composition of  claim 16  wherein the film-forming natural polymer is gelatin.  
   
   
       22 . The composition of  claim 16  wherein the film forming natural polymer is a gelatin-like polymer.  
   
   
       23 . The composition of  claim 16  wherein the concentration of the film forming natural polymer is from about 20 to about 40% by weight of the composition.  
   
   
       24 . The composition of  claim 22  wherein the concentration of the film coating natural polymer is from about 25 to about 40% by weight of the composition.  
   
   
       25 . The composition of  claim 16  wherein the gelling agent is a source of divalent cations selected from the group consisting of calcium salts, magnesium salts, and calcium gelatin.  
   
   
       26 . The composition of  claim 16  wherein the concentration of the gelling agent is less than about 2% by weight of the composition.  
   
   
       27 . The composition of  claim 26  wherein the concentration of the gelling agent is less than about 1% by weight of the composition.  
   
   
       28 . The composition of  claim 16  further comprising one or more plasticizers selected from the group consisting of glycerin, sorbitol, sorbitans, maltitol, glycerol, polyethylene glycol, polyalcohols with 3 to 6 carbon atoms, citric acid, citric acid esters, triethyl citrate and combinations thereof.  
   
   
       29 . The composition of  claim 28  wherein the concentration of the one or more plasticizers is from about 8% to about 30% by weight of the composition.  
   
   
       30 . The composition of  claim 17  further comprising a fill material.  
   
   
       31 . The composition of  claim 30  wherein the fill material is in a form selected from the group consisting of liquid, semi-solid, and solid.  
   
   
       32 . The composition of  claim 30  wherein the fill material comprises one or more therapeutic, prophylactic or diagnostic agents and optionally one or more pharmaceutically acceptable excipients.  
   
   
       33 . A method of manufacturing a gastric resistant protein or polysaccharide gelled composition comprising 
 (a) a gastric resistant natural polymer present in an amount less than about 5% by weight of the composition;    (b) a film-forming natural polymer; and    (c) a gelling agent,    the method comprising    (a) preparing a solution comprising a film-forming natural polymer and a gastric-resistant natural polymer and optionally one or more plasticizers to form a gel mass; and    (b) casting the gel mass into films or ribbons.    
   
   
       34 . A method of manufacturing a gastric resistant protein or polysaccharide capsule composition comprising 
 (a) a gastric resistant natural polymer present in an amount less than about 5% by weight of the composition;    (b) a film-forming natural polymer; and    (c) a gelling agent,    the method comprising    (a) preparing a solution comprising a film-forming natural polymer and a gastric-resistant natural polymer and mixing and optionally one or more plasticizers to form a gel mass;    (b) casting the gel mass into films or ribbons; and    (c) forming a capsule shell.