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 hydrophilic surfactant.

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 hydrophilic surfactant. 
     
     
         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 , 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  claim 1 , characterised in that the non-ionic hydrophilic surfactant has an HLB-value between 10 and 20, preferably between 12 and 18. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , characterised in that the non-ionic hydrophilic surfactant has a melting point, pour point or melting range between 5° C. and body temperature (37° C.), preferably between room temperature (20° C.) and body temperature (37° C.). 
     
     
         6 . The pharmaceutical composition according to  claim 1 , characterised in that it further comprises colloidal silicon dioxide. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , characterised in that it further comprises lauroyl macrogol glycerides (Gelucire® 44/14). 
     
     
         8 . The pharmaceutical composition according to  claim 1 , characterised in that the composition is in a hard gelatine capsule. 
     
     
         9 . The pharmaceutical composition according to  claim 1 , characterised in that it shows a dissolution of the bendamustine of at least 80% after 60 minutes, as measured with a paddle apparatus at 50 rpm during 30 minutes, followed by 200 rpm during a further 30 minutes, according to the European Pharmacopoeia in 500 ml of a dissolution medium at a pH of 1.5. 
     
     
         10 . The pharmaceutical composition according to  claim 1 , characterised in that it shows a dissolution profile of the bendamustine of at least 60% dissolved after 20 minutes, 70% after 40 minutes and 80% after 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 the dissolution of the bendamustine is at least 80% after 30 minutes, and preferably the dissolution profile of at least 60% bendamustine dissolved after 10 minutes, 70% after 20 minutes and 80% after 30 minutes. 
     
     
         12 . A method of 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 in a person comprising administering the pharmaceutical composition of  claim 1  to the person. 
     
     
         13 . The method of  claim 12 , characterised in that the pharmaceutical composition is 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 method 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 method according to  claim 12 , wherein the pharmaceutical composition is 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 method according to  claim 15 , characterised in that the corticosteroid is prednisone or prednisolone.