DOSAGE FORM FOR ORAL ADMINISTRATION OF 3-(2-{4-(HEXYLOXYCARBONYLAMINO-IMINO-METHYL)-PHENYLAMINO-METHYL}-1-METHYL-1H-BENZIMIDAZOL-5-CARBONYL)-PYRIDIN-2-YL-AMINO PROPIONIC ACID ETHYL ESTER OR ITS SALTS

摘要

Pharmaceutical composition for oral administration comprises ethyl 3-(2-(4-(hexyloxycarbonylamidino)phenylaminomethyl)-1-methyl-1H-benzimidazole-5-carbonyl)-2-pyridylamino)propionate (I), or a salt of (I), and an organic acid (II) with a water-solubility of more than 1 g/250 ml at 20 [deg]C. Independent claims are also included for: (1) production of such a composition by forming cores from (II), optionally with addition of binders or other additives, by: (a) granulation, pelletization or extrusion/spheronization; (b) coating the cores with an insulating layer comprising a water-soluble polymer and optionally plasticizer, release agent and/or pigment; (c) applying a dispersion containing (I), binder and optionally release agent and simultaneously or subsequently drying the dispersion; (d) optionally applying a coating of film former, plasticizer and optionally pigment; and (e) filling hard capsules with the resulting pellets; (2) the methanesulfonate salt of (I). ACTIVITY : Anticoagulant. Hard gelatin capsules were filled with pellets comprising a core of tartaric acid (61.3 wt.pts.) and gum arabic (3.1 wt.pts.), an insulating layer of gum arabic (2.8 wt.pts.) and talc (5.6 wt.pts.) and a drug layer of talc (3.2 wt.pts.), hydroxypropyl cellulose (4 wt.pts.) and ethyl 3-(2-(4-(hexyloxycarbonylamidino)phenylaminomethyl)-1-methyl-1H-benzimidazole-5-carbonyl)-2-pyridylamino)propionate mesylate (20 wt.pts.). The capsules contained 57.7 mg of the mesylate, corresponding to 50 mg drug free base. In clinical trials, the relative bioavailability in subjects treated with pantoprazol to raise their gastric pH compared with subjects not so treated was 94%, compared with 18% for conventional tablets not containing tartaric acid. MECHANISM OF ACTION : Thrombin inhibitor.