Hard capsule

Abstract

A method of manufacturing a hard capsule made mainly of a polymer or copolymer obtained includes polymerizing or copolymerizing at least one polymerizable vinyl monomer in the presence of polyvinyl alcohol and/or a derivative thereof. Unlike conventional hard capsules, this hard capsule can be filled with a solvent (e.g., polyethylene glycol) for a sparingly soluble drug ingredient.

1 . A method of producing a hard capsule made mainly of a polymer or copolymer, comprising: 
 polymerizing or copolymerizing at least one polymerizable vinyl monomer in the presence of polyvinylalcohol and/or a derivative thereof; and    forming a hard capsule using a polymer or copolymer obtained by the polymerizing or copolymerizing step.    
     
     
         2 . The method according to  claim 1 , wherein the polyvinylalcohol and/or derivative is present in an amount of 20-95 wt %, and the polymerizable vinyl monomer(s) is/are used in an amount of 5-80 wt %.  
     
     
         3 . The method according to  claim 1 , wherein the polymerizing or copolymerizing step comprises (i) dissolving the polyvinylalcohol and/or derivative in water, and (ii) adding the polymerizable vinyl monomer(s) and a polymerization initiator to the polyvinylalcohol and/or derivative-dissolved water.  
     
     
         4 . The method according to  claim 1 , wherein the polyvinylalcohol derivative is polyvinylalcohol having a thiol group at an end thereof.  
     
     
         5 . The method according to  claim 1 , wherein the polymerizable vinyl monomer(s) is/are at least one selected from the group consisting of: 
 (1) acrylic acid, methacrylic acid, fumaric acid, maleic acid, and itaconic acid;    (2) sodium salts, potassium salts, ammonium salts and alkylamine salts of the compounds in (1); and    (3) methyl methacrylate, methyl acrylate, ethyl methacrylate, ethyl acrylate, butyl methacrylate, butyl acrylate, isobutyl methacrylate, isobutyl acrylate, cyclohexyl methacrylate, cyclohexyl acrylate, 2-ethylhexyl methacrylate, 2-ethylhexyl acrylate, acrylonitrile, acrylamide, dimethylacrylamide, styrene, vinyl acetate, hydroxyethyl methacrylate, hydroxyethyl acrylate, an ester formed by polyethylene glycol and methacrylic acid, an ester formed by polyethylene glycol and acrylic acid, an ester formed by polypropylene glycol and methacrylic acid, an ester formed by polypropylene glycol and acrylic acid, N-vinylpyrrolidone, and acryloyl morpholine.    
     
     
         6 . The method according to  claim 1 , wherein the polymerizable vinyl monomer is at least one member selected from the group consisting of sodium salt, potassium salt, ammonium salt and alkylamine salt of acrylic acid; sodium salt, potassium salt, ammonium salt and alkylamine salt of methacrylic acid; and a compound represented by general formula [1] 
         H 2 C═C(R 1 )—COOR 2   [1] 
       wherein R 1  represents a hydrogen atom or a methyl group, and R 2  represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.  
     
     
         7 . The method according to  claim 1 , wherein the polymerizable vinyl monomers are methyl methacrylate; and at least one member selected from the group consisting of acrylic acid, sodium salt, potassium salt, ammonium salt and alkylamine salt of acrylic acid thereof and methacrylic acid, sodium salt, potassium salt, ammonium salt and alkylamine salt thereof; and the at least one member is 5 to 50 wt % of the total amount of the polymerizable vinyl monomers, and the methyl methacrylate is 50 to 95 wt % of the total amount of the polymerizable vinyl monomers.  
     
     
         8 . The method according to  claim 3 , wherein the polymerization initiator is selected from the group consisting of an azo compound, a persulfate, an organic peroxide, and a redox initiator.  
     
     
         9 . The method according to  claim 1 , wherein the forming step comprises providing a solution containing the polymer or copolymer, a gelating agent, and optionally a gelation auxiliary, and pulling a molding pin to form a capsule.  
     
     
         10 . The method according to  claim 9 , wherein the gelating agent is selected from the group consisting of kappa carrageenan, iota carrageenan, lambda carrageenan, tamarind seed polysaccharide, pectin, curdlan, gelatin, furcellaran, agar, xanthan gum, locust bean gum, and jielan gum.  
     
     
         11 . The method according to  claim 9 , wherein the gelation auxiliary for kappa carrageenan is selected from the group consisting of, a water-soluble compound containing one or two or more of potassium ions, ammonium ions and calcium ions, and the gelation auxiliary for iota carrageenan is selected from the group consisting of a water-soluble compound containing calcium ions.  
     
     
         12 . The method according to  claim 1 , further comprising filling the hard capsule with polyethylene glycol having a degree of polymerization of 2000 or less or a derivative thereof.  
     
     
         13 . The method according to  claim 1 , further comprising filling the hard capsule with a polyoxyethylene sorbitan fatty acid ester.  
     
     
         14 . The method according to  claim 1 , further comprising filling the hard capsule with a fatty acid having 6 to 12 carbon atoms or a salt thereof.  
     
     
         15 . The method according to  claim 1 , further comprising filling the hard capsule with polyoxyethylene castor oil.  
     
     
         16 . The method according to  claim 1 , further comprising filling the hard capsule with an ether derivative of diethylene glycol.