Pre-mixed, ready-to-use iv bolus nicardipine compositions and methods of use

Abstract

Provided herein are ready-to-use premixed bolus injection pharmaceutical compositions of nicardipine or a pharmaceutically acceptable salt and methods for use in treating cardiovascular and cerebrovascular conditions.

1 - 18 . (canceled) 
     
     
         19 . An inclusion complex of nicardipine or a pharmaceutically acceptable salt thereof and a sulfoalkylated β-cyclodextrin. 
     
     
         20 . The inclusion complex of  claim 19 , wherein the sulfoalkylated β-cyclodextrin is sulfobutylated β-cyclodextrin. 
     
     
         21 . The inclusion complex of  claim 20 , wherein the sulfobutylated β-cyclodextrin is sulfobutylether β-cyclodextrin. 
     
     
         22 . The inclusion complex of  claim 20 , wherein the pharmaceutically acceptable salt of nicardipine is the nicardipine hydrochloride salt. 
     
     
         23 . A pharmaceutical composition comprising an inclusion complex of  claim 19 , wherein the composition is formulated for parenteral bolus administration to a human subject. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the sulfoalkylated β-cyclodextrin is a sulfobutylated β-cyclodextrin having an average of 5 to 8 degrees of sulfobutylation. 
     
     
         25 . (canceled) 
     
     
         26 . The pharmaceutical composition of  claim 23 , comprising a pharmaceutically acceptable salt of nicardipine in an parenterally injectable aqueous carrier containing one or more buffering agents and having a pH within the range from about 3.5 to about 7.5, wherein the concentration of the nicardipine in the composition is from 0.25 mg/ml to 5 mg/ml, inclusive, the concentration of the sulfoalkylated β-cyclodextrin in the composition is from 0.1% to 25% (w/v) inclusive, the concentration of each buffering agent in the composition is 0.1 mM to 100 mM. 
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein the sulfoalkylated β-cyclodextrin is a sulfobutylated β-cyclodextrin having an average of 5 to 8 degrees of sulfobutylation. 
     
     
         28 . (canceled) 
     
     
         29 . The pharmaceutical composition of  claim 26 , wherein the nicardipine is in a concentration of from 0.25 to 1 mg/ml. 
     
     
         30 . The pharmaceutical composition of  claim 26 , wherein the nicardipine concentration is about 0.5 mg/ml. 
     
     
         31 . The pharmaceutical composition of  claim 27 , wherein the sulfobutylated β-cyclodextrin concentration is from 0.5 to 10% (w/v). 
     
     
         32 . The pharmaceutical composition of  claim 27 , wherein the sulfobutylated β-cyclodextrin concentration is from 0.1 to 0.5% (w/v). 
     
     
         33 . The pharmaceutical composition of  claim 26 , wherein the composition is in unit dose format and the unit dose contains the formulation in a volume of from 0.5 to 20 ml, inclusive. 
     
     
         34 . The pharmaceutical composition of  claim 26 , wherein the nicardipine concentration in the aqueous formulation is from 0.3 mg/ml to 0.7 mg/ml, inclusive. 
     
     
         35 . The pharmaceutical composition of  claim 26 , wherein the nicardipine concentration of the aqueous formulation is about 0.5 mg/ml. 
     
     
         36 . The pharmaceutical composition of  claim 26 , wherein the buffering agent is one or more agents selected from the group consisting of acetate, citrate, succinate, and phosphate buffering agents. 
     
     
         37 - 38 . (canceled) 
     
     
         39 . The pharmaceutical composition of  claim 26 , further comprising a tonicity adjusting agent. 
     
     
         40 . (canceled) 
     
     
         41 . The pharmaceutical composition of  claim 26 , wherein the composition further comprises at least one co-solvent in a concentration of 0.1 to 25% (w/v). 
     
     
         42 . The pharmaceutical composition of  claim 41 , wherein concentration of at least one co-solvent is 0.1 to 10% (w/v). 
     
     
         43 . (canceled) 
     
     
         44 . The pharmaceutical composition of  claim 26 , wherein the pH is above a pH of 3.5 and equal to or less than a pH of 5.5. 
     
     
         45 - 51 . (canceled)