Solid pharmaceutical preparations containing copolymers based on polyethers combined with poorly water-soluble polymers
The invention relates to dosage forms which contain preparations of poorly water-soluble substances in a polymer matrix of polyether copolymers, said polyether copolymers being obtained by the radically initiated polymerization of a mixture from 30 to 80% by weight of N-vinyl lactam, 10 to 50% by weight of vinyl acetate and 10 to 50% by weight of a polyether, and at least one poorly water-soluble polymer, the poorly water-soluble substance being present in the polymer matrix as an amorphous substance.
1. A dosage form comprising preparations of slightly water-soluble active substances in a polymer matrix comprising a polyether copolymer and at least one slightly water-soluble polymer, the polyether copolymer being obtained by free radical polymerization of a mixture of from 30 to 80% by weight of N-vinyllactam, from 10 to 50% by weight of vinyl acetate and from 10 to 50% by weight of a polyether, wherein the slightly water-soluble polymers are based on ethyl acrylate and methyl methacrylate, wherein the slightly water-soluble active substance is present in amorphous form in the polymer matrix, and wherein the preparations remain amorphous after storage for 6 months at 30° C./70% relative humidity.
2. The dosage form according to claim 1 , wherein the slightly water-soluble polymers comprise those polymers whose solubility in water is pH-dependent.
3. The dosage form according to claim 1 , wherein the ratio of the polyether copolymer to the slightly water-soluble polymer is from 99:1 to 10:90.
4. The dosage form according to claim 1 , wherein the ratio of the polyether copolymer to the slightly water-soluble polymer is from 90:10 to 30:70.
5. The dosage form according to claim 1 , wherein the ratio of the polyether copolymer to the slightly water-soluble polymer is from 80:20 to 40:60.
6. The dosage form according to claim 1 , in which the polymer matrix further comprises a solubilizer.
7. A process for the production of preparations for dosage forms of slightly water-soluble active substances according to claim 1 , wherein the active substances are present in amorphous form embedded in a polymer matrix based on polyether copolymers of from 30 to 80% by weight of N-vinyllactam, from 10 to 50% by weight of vinyl acetate and from 10 to 50% by weight of a polyether, wherein, in addition to the polyether copolymer, at least one slightly water-soluble polymer based on ethyl acrylate and methyl methacrylate, is incorporated into the polymer matrix, and the polymers are thoroughly mixed with the slightly water-soluble active substances, and wherein the preparations remain amorphous after storage for 6 months at 30° C./70% relative humidity.
8. The process according to claim 7 , wherein the mixture of polymers and active substances is heated above the glass transition temperature of the polyether copolymers.
9. The process according to claim 7 , wherein the mixing of polymers and active substances is effected in an extruder.
10. The process according to claim 7 , wherein the mixing of polymers and active substances is effected in organic solution, and the organic solvents are then removed.
11. The process according to claim 10 , wherein the organic solvents are removed by spray drying.