Caspofungin Composition

Abstract

The present invention relates to a composition comprising caspofungin or a pharmaceutical acceptable salt thereof and succinate or lactate as a buffering agent.

1 . A composition comprising:
 a) a pharmaceutically effective amount of caspofungin or a pharmaceutically acceptable salt thereof;   b) a pharmaceutically acceptable amount of one or more pharmaceutically acceptable excipients effective to form a lyophilized cake; and   c) a pharmaceutically effective amount of a buffering agent selected from the group consisting of lactate and succinate.   
     
     
         2 . A composition according to  claim 1 , wherein the pharmaceutically acceptable salt of caspofungin is an acetate salt. 
     
     
         3 . A composition according to  claim 1 , wherein the buffering agent is succinate. 
     
     
         4 . A composition according to  claim 1 , wherein the buffering agent is lactate. 
     
     
         5 . A composition according to  claim 1 , wherein the one or more excipients is selected from the group consisting of diluents, antioxidants, and preservatives. 
     
     
         6 . A composition according to  claim 1 , wherein the excipients is selected from the group consisting of sucrose, mannitol; and a combination thereof. 
     
     
         7 . A compositing according to  claim 1 , wherein the composition comprises:
 a) a pharmaceutically acceptable amount of caspofungin or a pharmaceutically acceptable salt thereof;   b) about 10-200 mg/ml of one or more pharmaceutically acceptable excipients effective to form a lyophilized cake;   c) a pharmaceutically effective amount of lactate or succinate effective to provide a pharmaceutically acceptable pH.   
     
     
         8 . A composition according to  claim 7 , wherein the composition comprises an amount of caspofungin or a salt thereof corresponding to about 42 mg/ml caspofungin. 
     
     
         9 . A composition according to  claims 8 , wherein the composition comprises:
 a) about 46 mg/ml diacetate salt of caspofungin;   b) about 30 mg/ml sucrose and about 20 mg/ml mannitol; and   c) about 1.5 mg/ml succinate or about 1.15 mg/ml lactate.   
     
     
         10 . A process for making a caspofungin composition according to  claim 1  comprising the steps of:
 a) mixing an aqueous solution comprising a pharmaceutically acceptable amount of one or more excipients with a pharmaceutically effective amount of a buffering agent selected from the group consisting of lactate and succinate; 
 b) optional adjusting the pH by adding a base to obtain a pharmaceutically acceptable pH; 
 c) adding to the mixture of a) a pharmaceutically acceptable amount of caspofungin or a pharmaceutically acceptable salt thereof; 
 d) optional adjusting the pH by adding a base to obtain a pharmaceutically acceptable pH; 
 e) filtering the solution obtained in d). 
 
     
     
         11 . A process for making a caspofungin composition according to  claim 9 , wherein step a) is performed by firstly preparing an aqueous solution comprising a pharmaceutically effective amount of a buffering agent selected from the group consisting of lactate and succinate; and then adding to said solution of buffering agent a pharmaceutically acceptable amount of one or more excipients dissolved in water. 
     
     
         12 . A process for making a caspofungin composition according to  claim 9 , wherein step a) is performed by firstly dissolving a pharmaceutically acceptable amount of one or more excipients in water; then adding to said solution of exipient(s) a pharmaceutically effective amount of a buffering agent selected from the group consisting of lactate and succinate. 
     
     
         13 . A process according to  claim 9 , wherein the pH is adjusted to 5.0-5.7 in step b). 
     
     
         14 . A process according to  claim 9 , wherein the pH is adjusted to about 6 in step d). 
     
     
         15 . A process according to  claim 9 , wherein caspofungin diacetate is added in step c). 
     
     
         16 . A lyophilized formulation consisting of a composition which prior to lyophilization corresponds to a composition according to  claim 9 . 
     
     
         17 . A formulation for parenteral administration consisting of a lyophilized formulation according to  claim 16 , wherein said lyophilized formulation is dissolved in a pharmaceutically acceptable reconstitution solution suitable for parenteral administration to a patient in need thereof. 
     
     
         18 . A formulation for parenteral administration according to  claim 17 , wherein the pharmaceutically acceptable reconstitution solution is selected from the group consisting of distilled water, sterile water, physiologic saline, and bacteriostatic water. 
     
     
         19 . A kit comprising a first container comprising the lyophilized formulation according to  claim 15  and a second container comprising a parenterally acceptable solvent for reconstitution thereof, and optionally a container comprising means for administrating the reconstituted solution to a patient in need thereof. 
     
     
         20 . A method of treating or preventing a fungal infection, comprising parenterally administering to an individual in need thereof a composition according to  claim 8 . 
     
     
         21 . The method according to  claim 20 , wherein the infections is caused by a fungus belonging to the species  Candida  or  Aspergillus.    
     
     
         22 . The method according to  claim 21 , wherein the infections is caused by a fungus belonging to the species infection is caused by  C. albicans, C. tropicalis, C. krusei, C. glabrata, A. fumigatus, A. flavus  and  A. nigerc .