Process for preparing particles containing an antiviral

Abstract

A process for preparing a particle comprising a co-precipitate surrounding a neutral hydrophilic carrier, said process comprising spraying an organic solution on a neutral hydrophilic carrier, said solution comprising at least one triazine or pyrimidine active ingredient having HIV inhibiting properties, one surface active agent, and one hydrophilic polymer, wherein the spraying of whole of the solution occurs in at least two separate steps, each of these steps followed by a grinding step of the product obtained at the end of the preceding step.

1 . A process for preparing a particle comprising a co-precipitate surrounding a neutral hydrophilic carrier, said process comprising spraying an organic solution on a neutral hydrophilic carrier, said solution comprising at least one triazine or pyrimidine active ingredient having HIV inhibiting properties, one surface active agent, and one hydrophilic polymer, wherein the spraying of whole of the solution occurs in at least two separate steps, each of these steps followed by a grinding step of the product obtained at the end of the preceding step.  
   
   
       2 . The process for the preparation of particles according to  claim 1 , comprising the following steps: 
 a) preparing a solution comprising at least one triazine or pyrimidine active ingredient having HIV inhibiting properties, a hydrophilic polymer, and a surface active agent, in an organic solvent;    b) spraying of part of the solution obtained in step a) on a neutral hydrophilic carrier;    c) grinding of the particles obtained in step b);    d) spraying of the remaining quantity of organic solution on the particles obtained in step c), and    e) final grinding of the particles obtained in step d).    
   
   
       3 . The process for the preparation of particles according to  claim 1 , wherein the spraying/grinding sequence (steps b through d) is repeated once, or several times.  
   
   
       4 . The process for the preparation of particles according to  claim 1 , wherein procedures additionally comprise a drying step, either after each spraying step before grinding, or immediately following grinding.  
   
   
       5 . The process for the preparation of particles according to  claim 1 , wherein the inert hydrophilic carrier consists of any chemically or pharmaceutically inert excipient, existing in a particle form, crystalline or amorphous, and selected preferably from the group consisting of sugars, sugar derivatives, celluloses, or mixtures thereof.  
   
   
       6 . The process for the preparation of particles according to  claim 1 , wherein the hydrophilic polymer is selected from the group of polyvinylpyrrolidones, and in particular polymers with a molecular weight ranging from 10,000 to 50,000, cellulose derivatives, preferably hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose phthalate and hydroxypropylmethylcellulose aceto-succinate, acrylic polymers and polyethylene glycols.  
   
   
       7 . The process for the preparation of particles according to  claim 1 , wherein the surface active agent is selected in the group consisting of cationic, anionic, non-ionic or amphoteric agents, separately or as a mixture thereof.  
   
   
       8 . The process for the preparation of particles according to  claim 1 , wherein the organic solvent is selected in the group consisting of ethanol, isopropanol, tetrahydrofuran, isopropyl ether, acetone, methylethylacetone, methylene chloride, and mixtures of these solvents.  
   
   
       9 . The process for the preparation of particles according to  claim 1 , wherein the spraying steps are carried out in a coating pan, in a perforated pan, or on a fluidized bed.  
   
   
       10 . A particle comprising a co-precipitate applied in a layer surrounding a neutral hydrophilic carrier, and comprising at least one antiviral pyrimidine and triazine, at least one surface-active agent, and at least one hydrophilic polymer.  
   
   
       11 . The particle according to  claim 10  obtainable by the process as claimed in  claim 1 .  
   
   
       12 . The particle according to  claim 10 , wherein the surface-active agent is present in the particle in an amount that varies from 1 to 60% by weight.  
   
   
       13 . The particle according to  claim 10 , wherein the inert hydrophilic carrier is present in an amount of up to 95% by weight.  
   
   
       14 . The particle according to  claim 10 , wherein the weight ratio of the hydrophilic polymer to the active ingredient ranges from 10:1 to 1:2.  
   
   
       15 . The particle according to  claim 10 , wherein the surface-active agent is present in an amount that may vary from 0.1 to 20% in weight compared to the total resulting mass.  
   
   
       16 . The particle according to  claim 10 , wherein the unit particle size of the inert hydrophilic carrier ranges from 50 μm to 500 μm, preferably from 90 μm to 200 μm.  
   
   
       17 . A pharmaceutical dosage form, wherein said form contains at least one particle according to  claim 10 , optionally combined with pharmaceutically acceptable excipients.