Oral Dosage Forms of Bendamustine

Abstract

In the present invention, there is provided an oral pharmaceutical composition, comprising bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient, which is a pharmaceutically acceptable non-ionic surfactant, selected from the group consisting of polyethoxylated castor oil or derivative thereof and a block copolymer of ethylene oxide and propylene oxide.

1 . A pharmaceutical composition for oral administration, the composition comprising bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient, which is 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. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , characterised in that the active ingredient is bendamustine hydrochloride. 
     
     
         3 . The pharmaceutical composition according to  claim 1  or  claim 2 , characterised in that it comprises 10 to 1000 mg, preferably 25 to 600 mg, more preferably 50 to 200 mg and most preferably about 100 mg of the active ingredient. 
     
     
         4 . The pharmaceutical composition according to any one of the preceding claims, characterised in that the polyoxyethylated castor oil or derivative thereof is macrogol glycerol hydroxystearate. 
     
     
         5 . The pharmaceutical composition according to any one of  claims 1  to  3 , characterised in that the polyoxyethylated castor oil or derivative thereof is polyoxyl-35-castor oil. 
     
     
         6 . The pharmaceutical composition according to any one of  claims 1  to  3 , characterised in that the block copolymer of ethylene oxide and propylene oxide is ethylene oxide/propylene oxide block copolymer (Pluronic® L44 NF or Poloxamer® 124). 
     
     
         7 . The pharmaceutical composition according to each of  claim 1 ,  2 ,  3 ,  5  or  6 , characterised in that it further comprises colloidal silicon dioxide. 
     
     
         8 . The pharmaceutical composition according to each of  claims 1 ,  2 ,  3 ,  5  or  6 , characterised in that it further comprises lauroyl macrogol glycerides (Gelucire® 44/14). 
     
     
         9 . The pharmaceutical composition according to any of the preceding claims, characterised in that the composition is in a hard gelatine capsule. 
     
     
         10 . The pharmaceutical composition according to any one of the preceding claims, characterised in that it 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. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , characterised in that it shows a dissolution of at least 60% in 10 minutes, 70% in 20 minutes and 80% in 30 minutes. 
     
     
         12 . The pharmaceutical composition according to any one of the preceding claims characterised in that it is used for the 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, non-small cell lung cancer, and an autoimmune disease. 
     
     
         13 . The pharmaceutical composition according to any one of the preceding claims, characterised in that it is to be administered in combination with at least one further active agent, wherein said further active agent is given prior, concurrently, or subsequently to the administration of the pharmaceutical composition and is selected from the group consisting of an antibody specific for CD20, an anthracyclin derivative, a vinca alkaloid or a platin derivative. 
     
     
         14 . The pharmaceutical composition according to  claim 13 , characterised in that the antibody specific for CD20 is rituximab; the anthracyclin derivative is doxorubicin or daunorubicin; the vinca alkaloid is vincristine and the platin derivative is cisplatin or carboplatin. 
     
     
         15 . The pharmaceutical composition according to any one of  claims 1  to  14 , which is to be administered in combination with at least one corticosteroid, wherein said corticosteroid is given prior, concurrently, or subsequently to the administration of the pharmaceutical composition. 
     
     
         16 . The pharmaceutical composition according to  claim 15 , characterised in that the corticosteroid is prednisone or prednisolone.