Novel crystalline forms of gatifloxacin

Abstract

Provided are novel crystalline forms of gatifloxacin denominated forms A, B, C, D, E1, F, G, H, I, and J, and methods for their preparation. Also provided are methods for making known crystalline forms of gatifloxacin, in particular forms omega and T2RP.

1 - 75 . (canceled)  
     
     
         76 . A crystalline form of gatifloxacin characterized by x-ray reflections at about 7.1°, 7.3°, 10.8°, 15.7°, 16.4°, and 18.1°±0.2° 2θ.  
     
     
         77 . The crystalline form of  claim 76  containing acetonitrile, water, or mixtures thereof up to about 10% by weight.  
     
     
         78 . A method of making the crystalline form of gatifloxacin of  claim 77  comprising the step of treating E1-ACN in a fluidized bed apparatus.  
     
     
         79 . The method of  claim 78  wherein the E1-ACN treated with moist gas at a temperature greater than about 30° C.  
     
     
         80 . A method of making the crystalline form of gatifloxacin of  claim 81  comprising the step of exposing E1-ACN to 60% relative humidity.  
     
     
         81 . The crystalline form of gatifloxacin of  claim 77 , designated E1 hydrate, comprising about 7.5% to 10% by weight water.  
     
     
         82 . A method of making the crystalline form of gatifloxacin of  claim 81  comprising the step of treating E1-ACN with moist gas in a fluidized bed apparatus at a temperature greater than about 30° C.  
     
     
         83 . The method of making the crystalline form of gatifloxacin of  claim 82  wherein the gatifloxacin treated is first treated with moist gas at 20° to 30° C.  
     
     
         84 . A method of making the crystalline form of gatifloxacin of  claim 81  comprising the step of exposing E1-ACN to 60% relative humidity.  
     
     
         85 - 87 . (canceled)  
     
     
         88 . A method of making the crystalline form of gatifloxacin a  claim 80  comprising the steps of: 
 a) providing a solution of gatifloxacin in acetonitrile having about 5 wt % or less water at reflux,    b) cooling the solution to a seeding temperature of about 57° to 70° C.,    c) seeding the solution at the seeding temperature,    d) cooling the seeded solution, and    e) isolating the crystalline form of gatifloxacin.    
     
     
         89 . The method of  claim 88  wherein the seeded solution is maintained at the seeding temperature for a seeding time of at least about 30 minutes.  
     
     
         90 . The method of  claim 88  wherein the seeding temperature is about 60° C.  
     
     
         91 . The method of  claim 88  wherein the seeded solution is cooled to about 5° C. or below.  
     
     
         92 . The method of  claim 88  wherein the solution of gatifloxacin in acetonitrile has about 4.5 mt % or less water.  
     
     
         93 . A method of making the crystalline form of gatifloxacin of  claim 80  comprising the step of incubating gatifloxacin in acetonitrile vapors.  
     
     
         94 . A crystalline form of gatifloxacin, denominated E1-ACN, having up to about 10% acetonitrile and characterized by x-ray reflections at about 7.1°, 7.3°, 10.8°, 15.7°, 16.4°, and 18.1°±0.2° 2θ, wherein the crystalline form is made by a process comprising the steps of: 
 a) providing a solution of gatifloxacin in acetonitrile having about 5 wt % or less water at reflux,    b) cooling the solution to a seeding temperature of about 57° to 70° C.,    c) seeding the solution at the seeding temperature,    d) cooling the seeded solution, and    e) isolating the crystalline form of gatifloxacin.    
     
     
         95 . The crystalline form of gatifloxacin of  claim 94  wherein the solution of gatifloxacin in acetonitrile has about 4.5 wt % or less water.  
     
     
         96 . The crystalline form of  claim 94  wherein the seeded solution is maintained at the seeding temperature for a seeding time of at least about 30 minutes.  
     
     
         97 . The crystalline form of  claim 94  wherein the seeding temperature is about 60° C.  
     
     
         98 . The crystalline form of  claim 94  wherein the seeded solution is cooled to about 5° C. or below.  
     
     
         99 - 107 . (canceled)  
     
     
         108 . A method of making a hydrated gatifloxacin form E1 comprising the step of treating gatifloxacin form E1-ACN solvate with a moist gas at a temperature from ambient temperature to about 60° C.  
     
     
         109 . The method of  claim 108  wherein the treating is at about 20° to about 30° C. and the E1 dihydrate has a water content of about 7.5% to about 10% on a weight basis.  
     
     
         110 . The method of  claim 108  wherein the moist gas has a relative humidity between about 55% and about 75%.  
     
     
         111 . The method of  claim 108  wherein the treating is at about 50° C.  
     
     
         112 . The method of  claim 108  wherein the treating is effected in a fluidized bed drying apparatus.  
     
     
         113 . A hydrated crystalline form of gatifloxacin having up to about 10% water or a mixture of water and acetonitrile and characterized by x-ray reflections at about 7.1, 7.3, 10.8, 15.7, 16.4, and 18.1×0.2 2ÿ, wherein the crystalline form is made by a process comprising the step of treating gatifloxacin E1-ACN with moist gas at a temperature from ambient to about 60 C.  
     
     
         114 . The crystalline form of gatifloxacin of  claim 113  wherein the treating is at about 20 to about 30 C and the crystalline form contains about 5% to about 7% water.  
     
     
         115 . The crystalline form of  claim 113  wherein the relative humidity of the moist gas is about 55% to about 75%.  
     
     
         116 . The crystalline form of gatifloxacin of  claim 113  wherein the treating is at about 50 C.  
     
     
         117 . The crystalline form of  claim 113  wherein the treating is in a fludized bed apparatus.  
     
     
         118 - 131 . (canceled)