Film-coated tablet or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound
Film-coated tablet, consisting of a tablet core with a film coating, or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound, preferably imatinib or a pharmaceutically acceptable salt of imatinib, preferably imatinib monomethanesulfonate, wherein (i) the tablet cores and the granules have been produced by pressing of the starting materials and, prior to pressing of the starting materials, at least one of them has been dry-granulated, preferably compacted; (ii) the tablet cores and granule cores contain the active ingredient in a proportion of 25% by weight to 80% by weight, based on the total weight of the tablet cores or granule cores, together with (iii) at least one filler-binder, and optionally contain other additives; and (iv) the mean particle size distribution of at least 80% of the active ingredient is in the range from 0.01 mm to 1.0 mm.
1. A process for the production of a film-coated tablet, said process comprising:
dry granulating an active ingredient consisting of imatinib monomethanesulfonate in alpha crystalline form and at least one compound acting as a filler-binder to obtain a starting material;
compressing or compacting the dry granulated starting material to produce a tablet core; and
coating said tablet core to form a film-coated tablet;
wherein at least 80% the active ingredient has a mean particle size distribution in the range from 0.01 mm to 1.0 mm; wherein said dry granulating is carried out in a compactor at pressures in the range from 10 to 300 bar; and wherein the resulting tablet cores contain the active ingredient in a proportion of 25% by weight to 80% by weight, based on the total weight of the tablet cores.
2. The process according to claim 1 , characterized in that, in the dry granulation of the starting materials, the latter are compacted or compressed with rolls.
3. The process according to claim 1 , characterized in that their film-coated tablet core contains the active ingredient in a proportion of 30% by weight to 80% by weight, based on the total weight of the tablet core or granule core.
4. The process according to claim 1 , wherein the at least one compound acting as filler-binder comprises a water content in the range from 0.5% by weight to 10.0% by weight, based on the total weight of the filler-binder.
5. The process according to claim 1 , characterized in that the filler-binder is selected from the group consisting of sugars, sugar alcohols, polymeric glycosides, starches of different origins and inorganic salts.
6. The process according to claim 1 , characterized in that the filler-binder is selected from the group consisting of: modified starches, modified cellulose, modified sugars, modified sugar alcohols, modified lactose, gelatin, gum arabic, gelatinized starch povidones, and hydroxypovidone.
7. The process according to claim 1 , characterized in that the filler-binder is present in concentrations of 75% by weight to 20% by weight, based on the total weight of the tablet core in addition to the active ingredient present, the sum of the active ingredient and the filler-binder present being 100% by weight.
8. The process according to claim 1 , characterized in that their tablet cores contain other additives selected from the group consisting of: disintegrants, flow regulators, mould lubricants, mould release agents, and filler binder.
9. The process according to claim 1 , characterized in that the film coating contains at least one compound selected from the group consisting of: film-forming substances, hydroxypropyl methyl cellulose, propyl cellulose, methyl cellulose, polyvinyl alcohol, polymethacrylates and carrageen.
10. The process according to claim 1 , wherein at least 80% of the active ingredient has a mean particle size distribution in the range from 0.05 mm to 1.0 mm.