Method for producing a controlled release preparation

Abstract

The invention concerns a method for producing a controlled-release pharmaceutical preparation with a particle-containing coating, the coating being derived from an aqueous dispersion of a film-forming water insoluble polymer and a water soluble pore-forming agent. By suspending, instead of dissolving the pore-forming agent, the resulting coating will contain particles of pore-formers with a predetermined size that creates, when disintegrated or dissolved in the body fluid, canals or a network of pores through the polymer film. Due to this network, the film will get a good mechanical stability and are left intact after the release of the drug

1 . A controlled-release pharmaceutical preparation comprising: 
 a drug-containing solid core; and    a coating on the solid core, said coating having a water insoluble polymer with the predetermined amount of particles of a pore-forming agent dispersed therein, said pore-forming agent having a balanced solubility in an aqueous dispersion of a film-forming, essentially water insoluble polymer    wherein the mean particle size of the pore-forming agent is 0.5-100 μm; and    wherein the amount of the pore-forming agent is 40-95% by weight of the total weight of the dry coating and;    wherein the coating provides good mechanical strength requiring a force of from 18 N to 27 N to break, compared to a force below 1 N.    
   
   
       2 . A controlled-release pharmaceutical preparation according to  claim 1 , wherein the pore-forming agents is a member selected from the group consisting of: potassium bitartrate, creatine, aspartic acid, glutamic acid, inosine, aspargine, glutamine, leucin, neroleucine, isoleucine, magnesium phosphate, magnesium carbonate, magnesium hydroxide, chitosan and poly (butyl methacrylate, (2-dimethyl aminoethyl) methacrylate, methyl methacrylate) 1:2:1 or a composition wherein at lease one component is selected from one of these substances.  
   
   
       3 . A controlled-release pharmaceutical preparation according to  claim 1 , wherein the amount of the pore-forming agents is 50-90% by weight of the total weight of the dry coating.  
   
   
       4 . A controlled-release pharmaceutical preparation according to  claim 1 , wherein the polymer is ethylcellulose, celluloseacetate, celluloseacetatebutyrate, celluloseacetatepropionate, nitrocellulose, polymethylmethacrylate, poly(ethylacrylate, methylmethacrylate), polyvinylacetate, polyvinylchloride, polyethylene, polyisobutylene, poly(ethyacrylate, methylmethacrylate, trimethylamonioethyl methacrylate chloride), block- or copolymer of the polymers or a composition wherein at least one of the components is selected from these polymers.  
   
   
       5 . A controlled-release pharmaceutical preparation according to  claim 1 , wherein the coating polymer is a copolymer consisting of 50-100% by weight of polyviny1 chloride and 0-50% by weight of polyvinyl acetate.  
   
   
       6 . A controlled-release pharmaceutical preparation according to  claim 1 , wherein the coating polymer is a copolymer consisting of 80-95% by weight of polyvinylchloride, 0.5-19% by weight of polyvinylacetate, and 0.5-10% by weight of polyvinylalcohol.  
   
   
       7 . A controlled-release pharmaceutical preparation according to  claim 1 , where the amount of pore-forming agent is 55-88% by weight of the total weight of the dry coating.