ORAL DOSAGE FORMS OF BENDAMUSTINE AND THERAPEUTIC USE THEREOF

摘要

In the present invention there is provided a pharmaceutical composition for oral administration which comprises bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient and which shows a dissolution of the bendamustine of at least 60% in 20 minutes, 70% in 40 minutes and 80% in 60 minutes, as measured with a paddle apparatus at 50 rpm according to the European Pharmacopoeia in 500 ml of a dissolution medium at a pH of 1.5, and wherein the pharmaceutically acceptable excipient is either a pharmaceutically acceptable non-ionic surfactant, selected from the group consisting of a polyethoxylated castor oil or derivative thereof and a block copolymer of ethylene oxide and propylene oxide or a pharmaceutically acceptable saccharide selected from the group consisting of one or more of a monosaccharide, a disaccharide, an oligosaccharide, a cyclic oligosaccharide, a polysaccharide and a saccharide alcohol, wherein the ratio by weight of the active ingredient to the saccharide excipient(s) is in the range of 1:1-5. The invention further relates to the above pharmaceutical composition for use for the oral treatment of a medical condition which is selected from chronic lymphocytic leukemia, acute lymphocytic leukaemia, chronic myelocytic leukaemia, acute myelocytic leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, breast cancer, ovarian cancer, small cell lung cancer and non-small cell lung cancer. The invention moreover relates to the above pharmaceutical composition for the above use wherein the dosage regimen comprises at least the administration of a dose of 100 to 600 mg/m2/per person of bendamustine on day 1 and day 2, optionally a dose of 50 to 150 mg/m2 i.v. or orally of a corticosteroid on days 1 to 5, and optionally a suitable dose of a further active agent selected from the group consisting of an antibody specific for CD20, an anthracyclin derivative, a vinca alkaloid or a platin derivative; and the repetition of said dosage regimen 4 to 15 times after intervals of two to four weeks.