Colchicine compositions and methods

Abstract

Stable ultrapure colchicine compositions comprising ultrapure colchicine and a pharmaceutically acceptable excipient are described. The compositions can be tablets. Methods for preparing such compositions and methods of use are also disclosed. Methods of treating gout flares with colchicine compositions are also disclosed.

We claim: 
     
         1 . A colchicine dosage form, comprising
 colchicine; and   a pharmaceutically acceptable excipient;   wherein the colchicine dosage form comprises no more than 0.42% N-deacetyl-N-formyl colchicine.   
     
     
         2 . The dosage form of  claim 1 , wherein the colchicine dosage form further comprises no more than 2.0% of Impurity B. 
     
     
         3 . The dosage form of  claim 2 , wherein the colchicine dosage form further comprises no more than 1.5% of Impurity B. 
     
     
         4 . The dosage form of  claim 1 , wherein the pharmaceutically acceptable excipient is a filler, a binder, a disintegrant, a lubricant, or a combination comprising at least one of the foregoing excipients. 
     
     
         5 . The dosage form of  claim 4 , wherein the filler is microcrystalline cellulose, starch, lactose, sucrose, glucose, mannitol, dextrose, silicic acid, or a combination comprising at least one of the foregoing fillers. 
     
     
         6 . The dosage form of  claim 5 , wherein the filler is present in an amount of about 10 wt % to about 99 wt %, based on the total weight of the dosage form. 
     
     
         7 . The dosage form of  claim 4 , wherein the binder is pregelatinized starch, carboxymethylcellulose, alignate, gelatin, polyvinylpyrrolidone, acacia, or a combination comprising at least one of the foregoing binders. 
     
     
         8 . The dosage form of  claim 7 , wherein the binder is present in an amount of about 10 wt % to about 99 wt %, based on the total weight of the dosage form. 
     
     
         9 . The dosage form of  claim 4 , wherein the disintegrant is sodium starch glycolate, sodium croscarmellose (cross-linked carboxy methyl cellulose), crosslinked polyvinylpyrrolidone (PVP-XL), anhydrous calcium hydrogen phosphate, agar-agar, potato or tapioca starch, alginic acid, or a combination comprising at least one of the foregoing disintegrants. 
     
     
         10 . The dosage form of  claim 9 , wherein the disintegrant is present in an amount of about 1 to about 20 wt %, based on the total weight of the dosage form. 
     
     
         11 . The colchicine dosage form of  claim 1 , wherein the colchicine is present in an amount of about 0.6 mg. 
     
     
         12 . The colchicine dosage form of  claim 1  compressed into a tablet. 
     
     
         13 . The colchicine dosage form of  claim 1 , wherein the percent N-deacetyl-N-formyl colchicine in the colchicine dosage form is determined in an HPLC assay under the following conditions:
 the mobile phase is pH 4.5 Ammonium Acetate Buffer:methanol gradient;   the column is a Waters XBridge C18, 250 mm×4.6 mm, 5 μm particle size;   the flow rate is 0.9 mL/min;   the column temperature is 10±3.5 C and the sample temperature is 10±2 C;   the detection is at 246 nm;   the injection volume is 75 μL; and   the run time is 60 minutes.   
     
     
         14 . A method for treating a patient in need of colchicine therapy, wherein the method comprises
 administering to a patient in need of colchicine therapy a therapeutically effective amount of the colchicine dosage form of  claim 1 .   
     
     
         15 . The method of  claim 14 , wherein administering comprises
 orally administering 1.2 mg colchicine to a human patient at onset of a gout flare; and then   orally administering 0.6 mg colchicine to the patient about one hour after the first administration.   
     
     
         16 . A method of determining response of patients having a gout flare to colchicine therapy, comprising
 administering a dosing regimen to a patient having a gout flare; and   determining likelihood of percent improvement in pain of the patient at 24 hours after the first dose;   wherein the dosing regimen is a first dosing regimen consisting of two colchicine tablets at the onset of the gout flare, followed by one colchicine tablet in about one hour or a second dosing regimen consisting of two colchicine tablets at the onset of the gout flare, followed by one colchicine tablet every hour for 6 hours,   wherein a colchicine tablet comprises about 0.6 mg colchicine.