Process for producing a solid dispersion of an active ingredient

Abstract

A process for producing a solid dispersion of an active ingredient which comprises feeding the active ingredient and a matrix-forming agent to an extruder and forming a uniform extrudate, wherein the extruder comprises at least two rotating shafts ( 2 ), each of the shafts ( 2 ) carrying a plurality of processing elements disposed axially one behind the other, the processing elements defining (i) a feeding and conveying section (A), (ii) at least one mixing section (B), and (iii) a discharging section (E), wherein the processing element(s) defining the mixing section (B) comprise(s) a mixing element ( 11, 12, 13 ) that is derived from a screw type element (FIG. 2 ).

1 . A process for producing a solid dispersion of an active ingredient which comprises feeding the active ingredient and a matrix-forming agent to an extruder and forming a uniform extrudate, wherein the extruder comprises at least two rotating shafts, each of the shafts carrying a plurality of processing elements disposed axially one behind the other, The processing elements defining
 (i) a feeding and conveying section,   (ii) at least one mixing section, and   (iii) a discharging section,   
     wherein The processing element(s) defining the mixing section comprise(s) a mixing element that is derived from a screw type element. 
   
   
       2 . The process of  claim 1 , wherein the mixing element has recesses formed in the screw flight of the screw type element. 
   
   
       3 . The process of  claim 1 , wherein the mixing element does not have a plane surface area with a normal that is parallel and opposite to the general conveying direction. 
   
   
       4 . The process of  claim 1 , wherein the mixing element does not have a face that is perpendicular to the general conveying direction. 
   
   
       5 . The process of  claim 1 , wherein the mixing element does not have abutting faces that are perpendicular to the general conveying direction. 
   
   
       6 . The process of  claim 1 , wherein the mixing element has a plurality of concentric ring portions formed by grooves turned into the screw type element. 
   
   
       7 . The process of  claim 1 , wherein the processing elements additionally comprise at least one backpressure element. 
   
   
       8 . The process of  claim 7 , wherein the backpressure element is positioned downstream to the mixing section. 
   
   
       9 . The process of any on of the preceding  claim 1 , wherein the shafts are co-rotating. 
   
   
       10 . The process of any on of  claim 1 , wherein the shafts are counter-rotating. 
   
   
       11 . The process of any on of the preceding  claim 1 , wherein the processing elements define
 (i) a feeding and conveying section,   (ii) a first mixing section,   (iii) an intermediate conveying section,   (iv) a second mixing section, and   (v) a discharging section.   
   
   
       12 . The process of  claim 11 , wherein the processing elements additionally comprising a backpressure element positioned downstream and adjacent to the second mixing section. 
   
   
       13 . The process of  claim 1 , wherein at least part of the matrix-forming agent is fed to a hopper of the extruder and at least one component selected from
 (i) the remainder of the matrix-forming agent,   (ii) an active ingredient,   (iii) an additive, and   (iv) combinations thereof,   
     is introduced into the extruder through an opening in the extruder barrel at a position upstream of or in a mixing section. 
   
   
       14 . The process of  claim 13 , wherein the at least one component is introduced into the extruder at a position at or close to the junction of the feeding and conveying section and a mixing section. 
   
   
       15 . The process of  claim 13 , wherein the at least one component is liquid or liquefied. 
   
   
       16 . The process of any on of  claim 13 , wherein the at least one component comprises a pharmaceutically acceptable surfactant. 
   
   
       17 . The process of  claim 1 , wherein the active ingredient is dispersed in a polymer in a state of a solid solution. 
   
   
       18 . The process  claim 1 , wherein the matrix-forming agent comprises a pharmaceutically acceptable polymer. 
   
   
       19 . The process of  claim 18 , wherein the pharmaceutically acceptable polymer is selected from the group consisting of homopolymers of N-vinyl lactams, copolymers of a N-vinyl lactam and one or more comonomers selected from nitrogen-containing monomers and oxygen-containing monomers, cellulose esters and cellulose ethers, high molecular polyalkylene oxides, polyacrylates and polymethacrylates, oligo- and polysaccharides, poly(hydroxy acids), or mixtures thereof. 
   
   
       20 . The process of  claim 1 , wherein the matrix-forming agent comprises a member selected from polyols, waxes and lipids. 
   
   
       21 . The process of  claim 1 , additionally comprising feeding at least one additive selected from the group consisting of flow regulators; lubricants, fillers, disintegrants, plasticizers, stabilizers or preservatives into the extruder. 
   
   
       22 . The process of  claim 1 , wherein the extrudate is directly shaped into a dosage form. 
   
   
       23 . The process of  claim 22 , wherein shaping is carried out by calendaring, injection moulding or profile extrusion. 
   
   
       24 . The process of  claim 1 , additionally comprising grinding the solidified extrudate. 
   
   
       25 . The process of  claim 24 , additionally comprising compressing said solid dispersion product into a tablet or filling said solid dispersion product into a capsule shell. 
   
   
       26 . The process of  claim 25 , additionally comprising applying a film-coat to the tablet.