PROCESS FOR PRODUCING A SOLID DISPERSION OF AN ACTIVE INGREDIENT
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.