Enteric Soft Capsules

Abstract

A gel mass is provided that is useful in manufacturing enteric soft or hard capsules, or enteric tablets without coating.

What is claimed is: 
     
         1 . An enteric oral dosage form comprising an enteric soft capsule comprising a capsule shell encapsulating a fill, the capsule shell formed from a gel mass composition comprising:
 (a) a gelatin,   (b) an acid-insoluble polymer;   (c) an alkaline aqueous solvent; and   (d) one or more plasticizers;   wherein   a weight ratio range of the acid-insoluble polymer to the gelatin in the gel mass composition is from about 30% to about 40%;   a weight ratio of a combined weight of the plasticizers to a combined weight of the gelatin and the acid-insoluble polymer in the gel mass composition is about 1:2; and   a final pH of the gel mass composition is less than or equal to about 9 pH units.   
     
     
         2 . The enteric oral dosage form of  claim 1 , wherein a moisture content of the enteric soft capsule shell is from about 2% to about 10% by weight of the gel mass composition. 
     
     
         3 . The enteric oral dosage form of  claim 1 , wherein the gelatin comprises about 25% to about 36% by weight of the gel mass composition. 
     
     
         4 . The enteric oral dosage form of  claim 1 , wherein the gelatin comprises about 30% by weight of the gel mass composition. 
     
     
         5 . The enteric oral dosage form of  claim 1 , wherein the gelatin is has a Bloom value of about 100 to about 250. 
     
     
         6 . The enteric oral dosage form of  claim 1 , wherein the acid-insoluble polymer comprises about 8% to about 20% by weight of the gel mass composition. 
     
     
         7 . The enteric oral dosage form of  claim 1 , wherein the acid-insoluble polymer comprises about 10% by weight of the gel mass composition. 
     
     
         8 . The enteric oral dosage form of  claim 1 , wherein a weight ratio of the plasticizer to the gelatin is from about 1:9 to about 1:1 by weight. 
     
     
         9 . The enteric oral dosage form of  claim 1 , wherein the acid-insoluble polymer is selected from the group consisting of acrylic and methacrylic acid copolymers and cellulose acetate esters. 
     
     
         10 . The enteric soft capsule of  claim 9 , wherein the cellulose acetate esters are selected from the group consisting of phthalate, butyrate, hydroxypropyl methylcellulose phthalate, and salts thereof. 
     
     
         11 . The enteric soft capsule of  claim 9 , wherein the acid-insoluble polymer is a methacrylic acid copolymer. 
     
     
         12 . The enteric soft capsule of  claim 1 , wherein the plasticizer comprises sorbitol, glycerol, polyethylene glycol, poly-alcohols with 3 to 6 carbon atoms, citric acid, citric acid esters, or triethyl citrate, or combinations thereof. 
     
     
         13 . The enteric oral dosage form of  claim 12 , wherein the citric acid ester is triethyl citrate. 
     
     
         14 . The enteric oral dosage form of  claim 1 , wherein the alkaline aqueous solvent comprises ammonia, sodium hydroxide, potassium hydroxide, ethylenediamine, hydroxylamine, or tri-ethanolamine. 
     
     
         15 . The enteric oral dosage form of  claim 1 , wherein the alkaline aqueous solvent comprises a volatile alkali. 
     
     
         16 . The enteric oral dosage form of  claim 15 , wherein the volatile alkali comprises ammonia and ethylenediamine. 
     
     
         17 . The enteric oral dosage form of  claim 1 , wherein the alkaline aqueous solvent is a hydroalcoholic solution. 
     
     
         18 . The enteric oral dosage form of  claim 1 , wherein a thickness of the capsule shell is from about 0.015 inches to about 0.050 inches. 
     
     
         19 . The enteric oral dosage form of  claim 1 , wherein the enteric soft capsule is stable at pH 1.2 for at least 2 hr. 
     
     
         20 . The enteric oral dosage form of  claim 1 , wherein the enteric soft capsule dissolves at pH 6.8 within 30 min. 
     
     
         21 . The enteric oral dosage form of  claim 1 , wherein the capsule shell is clear or transparent. 
     
     
         22 . The enteric oral dosage form of  claim 1 , wherein the enteric soft capsule delays a release of an active pharmaceutical ingredient. 
     
     
         23 . The enteric oral dosage form of  claim 1 , wherein the capsule shell is transparent and colored. 
     
     
         24 . The enteric oral dosage form of  claim 1 , wherein the fill comprises food or medicine. 
     
     
         25 . The enteric oral dosage form of  claim 1 , wherein the fill comprises a hydrophilic solution, a hydrophilic suspension, a hydrophobic solution, a hydrophobic suspension or a combination of a hydrophilic solution and a hydrophobic solution. 
     
     
         26 . The enteric oral dosage form of  claim 25 , wherein the hydrophobic solution comprises an oil, a shortening, or a wax or combinations thereof. 
     
     
         27 . The enteric soft capsule of  claim 26 , wherein the oil comprises a soybean oil, a medium chain triglyceride, a Cremophor, or a shortening, or combinations thereof. 
     
     
         28 . The enteric soft capsule of  claim 25 , wherein the hydrophilic solution comprises a polyethylene glycol. 
     
     
         29 . The enteric soft capsule of  claim 28 , wherein the polyethylene glycol comprises polyethylene glycol 3350 or polyethylene glycol 400 or combinations thereof. 
     
     
         30 . A process of manufacturing enteric soft capsules, the process comprising:
 (a) preparing a gel mass composition comprising
 (a) a gelatin, 
 (b) an acid-insoluble polymer; 
 (c) an alkaline aqueous solvent; and 
 (d) one or more plasticizers; 
 wherein 
 a weight ratio range of the acid-insoluble polymer to the gelatin in the gel mass composition is from about 30% to about 40%; 
 a weight ratio of a combined weight of the plasticizers to a combined weight of the gelatin and the acid-insoluble polymer in the gel mass composition is about 1:2; and 
 a final pH of the gel mass composition is less than or equal to about 9 pH units; 
   (b) casting the gel mass composition into films using heat-controlled drums or surfaces; and   (c) forming a soft capsule using rotary die technology.   
     
     
         31 . The process of  claim 30 , wherein the preparing comprises mixing the gelatin with the acid-insoluble polymer, and the plasticizers to form a homogeneous mixture, in presence of a solvent. 
     
     
         32 . The process of  claim 30 , wherein the preparing does not require cross-linking.