Novel Preparation of an Enteric Release System

Abstract

Hydrophobic liquids are microencapsulated by an enteric matrix in an environment substantially free of organic solvents, the process including forming an emulsion of the enteric material and hydrophobic liquid in water, the emulsion titrated with an acid to form a particulate precipitate of the microencapsulated hydrophobic liquid in an enteric matrix.

1 . A method of microencapsulating an active ingredient with an enteric matrix, the method comprising:
 a) agitating a combination of water, an enteric matrix material, at a pH above the solubility of the enteric polymers being utilized to maintain complete dissolution, and an emulsifier, the combination substantially free of organic solvents;   b) adding a hydrophobic liquid to the combination;   c) homogenizing the hydrophobic liquid and the combination to create a fine, stable emulsion; and   d) acid titrating the emulsion under agitated conditions in an amount effective to form a particulate precipitate.   
     
     
         2 . The method of  claim 1  wherein the emulsion is acid titrated to a pH in the range of about 3.0 to about 6.5. 
     
     
         3 . The method of  claim 1  further comprising (e) filtering, washing and drying the particulate precipitate to produce a dry powder. 
     
     
         4 . The method of  claim 1  further comprising (b1) agitating the hydrophobic liquid and combination to create a coarse emulsion prior to homogenization. 
     
     
         5 . The method of  claim 1  further comprising (d1) adding a surface oil remover to the particulate precipitate in an amount effective to reduce residual surface oil. 
     
     
         6 . The method of  claim 1  further comprising (a1) adding a base in an amount effective to adjust the pH to about 7.1 to about 12.0. 
     
     
         7 . The method of  claim 6  wherein the base is sodium hydroxide. 
     
     
         8 . The method of  claim 6  wherein the base is potassium hydroxide. 
     
     
         9 . The method of  claim 6  wherein the base is ammonium hydroxide. 
     
     
         10 . The method of  claim 1  wherein the enteric matrix material is selected from the group consisting of zein, shellac, and mixtures thereof. 
     
     
         11 . The method of  claim 10  wherein the enteric matrix material is selected for providing a specific release rate. 
     
     
         12 . The method of  claim 1  wherein the emulsifier is a food grade emulsifier. 
     
     
         13 . The method of  claim 1  wherein the emulsifier is selected from the group consisting of polysorbate, polyglycerol ester, sucrose stearate, sucrose esters, protein, lecithin and mixtures thereof. 
     
     
         14 . The method of  claim 1  wherein the hydrophobic liquid comprises an essential oil. 
     
     
         15 . The method of  claim 1  wherein the hydrophobic liquid comprises linalool and thymol. 
     
     
         16 . The method of  claim 1  wherein the hydrophobic liquid comprises alpha-pinene, para-cymene, linalool and thymol. 
     
     
         17 . The method of  claim 16  wherein the hydrophobic liquid includes a triglyceride. 
     
     
         18 . The method of  claim 1  wherein the hydrophobic liquid comprises linalyl ester and thymyl ester. 
     
     
         19 . The method of  claim 1  wherein the hydrophobic liquid comprises unsaturated and polyunsaturated fatty acids. 
     
     
         20 . The method of  claim 1  wherein the hydrophobic liquid comprises unsaturated and polyunsaturated lipids. 
     
     
         21 . The method of  claim 1  wherein the hydrophobic liquid comprises beta-carotene. 
     
     
         22 . The method of  claim 1  wherein the hydrophobic liquid comprises oil soluble vitamins. 
     
     
         23 . The method of  claim 1  wherein the hydrophobic liquid comprises a triglyceride. 
     
     
         24 . The method of  claim 23  wherein the triglyceride is soybean oil. 
     
     
         25 . The method of  claim 22  wherein the triglyceride is canola oil. 
     
     
         26 . The method of  claim 1  wherein the acid is a food grade acid. 
     
     
         27 . The method of  claim 26  wherein the acid is citric acid. 
     
     
         28 . The method of  claim 1  wherein the combination includes from about 0.01 to about 5.0 percent by weight emulsifier. 
     
     
         29 . The method of  claim 1  wherein the emulsion comprises from about 2.0 to about 7.0 percent by weight hydrophobic liquid. 
     
     
         30 . The method of  claim 1 , wherein the particle precipitate has a particle size ranging from about 1.0 to 1000.0 microns. 
     
     
         31 . A composition comprising:
 a hydrophobic liquid; and   an enteric matrix configured to microencapsulate the hydrophobic liquid therein,   
       wherein the hydrophobic liquid is dispersed throughout the enteric matrix. 
     
     
         32 . The composition of  claim 31  wherein the microencapsulated hydrophobic liquid comprises a dry powder. 
     
     
         33 . The composition of  claim 31  wherein the enteric matrix comprises shellac. 
     
     
         34 . The composition of  claim 31  wherein the enteric matrix comprises zein. 
     
     
         35 . The composition of  claim 31  wherein the microencapulated hydrophobic liquid is coated with an enteric material. 
     
     
         36 . The composition of  claim 31  wherein the enteric matrix comprises a combination of shellac and zein. 
     
     
         37 . The composition of  claim 36  wherein the ratio of shellac to zein ranges from about 20:1 to 1:20. 
     
     
         38 . The composition of  claim 37  wherein the ratio is selected to provide a desired release rate. 
     
     
         39 . The composition of  claim 37  wherein ratio of shellac to zein is 3:1. 
     
     
         40 . The composition of  claim 31  wherein the hydrophobic liquid comprises at least one essential oil. 
     
     
         41 . The composition of  claim 31  having a particle size ranging from about 1.0 to about 1000.0 micrometers. 
     
     
         42 . The composition of  claim 41  wherein the particle size range from about 10.0 to about 500.0 micrometers. 
     
     
         43 . The composition of  claim 42  wherein the particle size range from about 75.0 to about 250.0 micrometers. 
     
     
         44 . The composition of  claim 31  wherein the hydrophobic liquid comprises from about 25.0 to about 35.0 percent by weight para-cymene, from about 1.0 to about 10.0 percent by weight linalool, from about 1.0 to about 10.0 percent by weight alpha-pinene, from about 35.0 to about 45.0 percent by weight thymol, and from about 20.0 to about 30.0 percent by weight soybean oil. 
     
     
         45 . The composition of  claim 31  having a payload ranging from about 5.0 to about 35.0 percent. 
     
     
         46 . The composition of  claim 31  including less than about 1.0 percent by weight surface oil.