Oral solid formulation containing irinotecan and method of preparing the same

Abstract

An oral solid formulation includes irinotecan or a pharmaceutically acceptable salt thereof as an active ingredient, and an acidifying agent. A method of preparing an oral solid formulation includes forming granules containing irinotecan or a pharmaceutically acceptable salt thereof, a diluent, and a binder, mixing the granules with a disintegrant and a lubricant to obtain a mixture, and includes adding an acidifying agent in step of forming granules and/or mixing the granules.

1 . An oral solid formulation comprising:
 irinotecan or a pharmaceutically acceptable salt thereof; and   an acidifying agent.   
     
     
         2 . The oral solid formulation of  claim 1 , wherein the acidifying agent is a C 2 -C 20  organic acid including a carboxyl group (COOH) or a sulfonic acid group (SO 3 H). 
     
     
         3 . The oral solid formulation of  claim 2 , wherein the acidifying agent is selected from the group consisting of acetic acid, adipic acid, citric acid, ascorbic acid, erythorbic acid, lactic acid, propionic acid, tartaric acid, fumaric acid, formic acid, oxalic acid, camsylic acid, malic acid, maleic acid, edisylic acid, palmitic acid, stearic acid, and any combinations thereof. 
     
     
         4 . The oral solid formulation of  claim 2 , wherein the acidifying agent is selected from the group consisting of acetic acid, citric acid, lactic acid, and any combinations thereof. 
     
     
         5 . The oral solid formulation of  claim 1 , wherein, when a dissolution test takes place using the paddle method in the U.S. Pharmacopoeia (USP) with 900 mL of purified water, the dissolution medium of the oral solid formulation has a pH of about 1 to 5 in 30 minutes of the dissolution test. 
     
     
         6 . The oral solid formulation of  claim 1 , wherein the amount of the acidifying agent is from about 0.2 parts to about 10 parts by weight based on 1 part by weight of the irinotecan or pharmaceutically acceptable salt thereof. 
     
     
         7 . The oral solid formulation of  claim 1 , wherein the oral solid formulation is in the form of granules, a capsule, or a tablet. 
     
     
         8 . The oral solid formulation of  claim 1 , wherein the oral solid formulation further comprises a pharmaceutically acceptable additive selected from the group consisting of a diluent, a binder, a disintegrant, a lubricant, and any combinations thereof. 
     
     
         9 . The oral solid formulation of  claim 8 , wherein the oral solid formulation comprises about 20 wt % to about 80 wt % of the diluent, about 1 wt % to about 10 wt % of the binder, about 2 wt % to about 7 wt % of the disintegrant, or about 0.5 wt % to about 5 wt % of the lubricant based on a total weight of the oral solid formulation. 
     
     
         10 . The oral solid formulation of  claim 1 , wherein, when a dissolution test takes place using the paddle method in the U.S. Pharmacopoeia (USP) with 900 mL of purified water, a dissolution rate of an active ingredient in the solid formulation is about 80% or greater in 30 minutes of the dissolution test. 
     
     
         11 . The oral solid formulation of  claim 1 , wherein the oral solid formulation is for the treatment of cancer. 
     
     
         12 . A method of preparing an oral solid formulation according to  claim 1 , the method comprising:
 forming granules comprising irinotecan or a pharmaceutically acceptable salt thereof, a diluent, and a binder;   mixing the granules with a disintegrant and a lubricant to obtain a mixture; and   optionally, formulating the resultant mixture,   wherein, in the step of forming granules and/or mixing the granules, an acidifying agent is added.   
     
     
         13 . The method of  claim 12 , wherein the step of forming granules is performed by wet granulation or dry granulation. 
     
     
         14 . The method of  claim 13 , wherein the wet granulation comprises forming granules by granulating a mixture of the irinotecan or pharmaceutically acceptable salt thereof and the diluent in combination with a binding solution including the binder, wherein the acidifying agent is added to the mixture and/or the binding solution.