Process for preparing filled hard-shell capsules with (meth)acrylate copolymer based coatings with a capsule-filling machine

Abstract

A process can be used for preparing a polymer coated hard-shell capsule, filled with a fill containing a biologically active ingredient. The hard-shell capsule contains a body and a cap, and in a closed state, the cap overlaps the body either in a pre-locked state or in a final-locked state. The material of the body and the cap contains an ethyl-, methyl-, or propyl-ether of cellulose, starch, or pullulan. The hard-shell capsule is coated with a coating layer that covers the hard-shell capsule in the pre-locked state. The coating layer contains one or more (meth)acrylate copolymers, where the coating layer is present in an amount of about 1 to 5.8 mg/cm2. The process involves providing the polymer-coated hard-shell capsule in the pre-locked state to a capsule-filling machine, separating the body and the cap, filling the body with the fill, and rejoining the body and the cap in the final-locked state.

1 - 16 . (canceled) 
     
     
         17 : A process for preparing a polymer coated hard-shell capsule, the process comprising:
 providing a hard-shell capsule comprising a body and a cap in a pre-locked state,   coating the hard-shell capsule in the pre-locked state with a coating solution, suspension, or dispersion comprising one or more (meth)acrylate copolymers having a glass transition temperature from −10° C. to 115° C. as determined by differential scanning calorimetry (DSC) according to ISO 11357-2:2013-05, to obtain a coating layer on the hard-shell capsule, and   optionally, drying the coated hard-shell capsule,   wherein a material of the body and the cap is selected from the group consisting of ethyl ether of cellulose, methyl ether of cellulose, propyl ether of cellulose, starch, and pullulan,   wherein the coating layer is present in an amount of about 1 to 5.8 mg/cm 2 , and   wherein a dried film of the coating solution, suspension, or dispersion having a thickness of 250 μm, has an elongation at break of about 15 to 500%.   
     
     
         18 : The process according to  claim 17 , wherein the material of the body and the cap comprises hydroxypropyl methyl cellulose. 
     
     
         19 : The process according to  claim 17 , wherein the one or more (meth)acrylate copolymers is selected from the group consisting of a copolymer of methacrylic acid and ethyl acrylate; a copolymer of methacrylic acid and methyl methacrylate; a copolymer of ethyl acrylate and methyl methacrylate; a copolymer of methacrylic acid, methyl acrylate, and methyl methacrylate; a mixture of a copolymer of methacylic acid and ethyl acrylate, with a copolymer of methyl methacrylate and ethyl acrylate; and a mixture of a copolymer of methacrylic acid, methyl acrylate, and methyl methacrylate, with a copolymer of methyl methacrylate and ethyl acrylate. 
     
     
         20 : The process according to  claim 17 , wherein the coating layer comprises a (meth)acrylate copolymer comprising polymerized units of 40 to 60% by weight of methacrylic acid and 60 to 40% by weight of ethyl acrylate. 
     
     
         21 : The process according to  claim 17 , wherein the coating layer comprises a (meth)acrylate copolymer comprising polymerized units of 60 to 80% by weight of ethyl acrylate and 40 to 20% by weight of methyl methacrylate. 
     
     
         22 : The process according to  claim 17 , wherein the coating layer comprises a (meth)acrylate copolymer comprising polymerized units of 5 to 15% by weight of methacrylic acid, 60 to 70% by weight of methyl acrylate, and 20 to 30% by weight of methyl methacrylate. 
     
     
         23 : The process according to  claim 17 , wherein the coating layer comprises a mixture of
 (meth)acrylate copolymers comprising polymerized units of 40 to 60% by weight of methacrylic acid and 60 to 40% by weight of ethyl acrylate; and a (meth)acrylate copolymer comprising polymerized units of 60 to 80% by weight of ethyl acrylate and 40 to 20% by weight of methyl methacrylate; at a ratio from 10:1 to 1:10 by weight.   
     
     
         24 : The process according to  claim 17 , wherein the coating layer comprises a mixture of
 (meth)acrylate copolymers comprising polymerized units of 5 to 15% by weight of methacrylic acid, 60 to 70% by weight of methyl acrylate, and 20 to 30% by weight of methyl methacrylate; and a (meth)acrylate copolymer comprising polymerized units of 40 to 60% by weight of methacrylic acid and 60 to 40% by weight of ethyl acrylate; at a ratio from 1:1 to 5:1 by weight.   
     
     
         25 : The process according to  claim 17 , wherein the coating layer comprises 2-50% by weight of one or more plasticizers. 
     
     
         26 : The process according to  claim 25 , wherein the one or more plasticizers is selected from the group consisting of alkyl citrate, glycerol ester, alkyl phthalate, alkyl sebacate, sucrose ester, sorbitan ester, glycerol, propylene glycol, and polyethylene glycol. 
     
     
         27 : The process according to  claim 17 , wherein the coating layer comprises 50 to 100% by weight of the one or more (meth)acrylate copolymers and 50 to 0% by weight of pharmaceutical or nutraceutical excipients. 
     
     
         28 : The process according to  claim 27 , wherein the pharmaceutical or nutraceutical excipients comprises one or more detacking agents. 
     
     
         29 : The process according to  claim 28 , wherein the one or more detacking agents is selected from the group consisting of Ca-stearate, Mg-stearate, glycerol monostearate, and talc. 
     
     
         30 : The process according to  claim 17 , wherein the coating layer comprises an emulsifier. 
     
     
         31 : The process according to  claim 30 , wherein an amount of the emulsifier is in a range of 1 to 30% by weight calculated based on a weight of the one or more (meth)acrylate copolymers. 
     
     
         32 : The process according to  claim 30 , wherein the emulsifier is polysorbate 80. 
     
     
         33 : The process according to  claim 17 , wherein the coating layer is present in an amount of about 2 to 5 mg/cm 2 .