Inhalation formulations of 1`-cyano substituted carba-nucleoside analogs

Abstract

The present disclosure provides pharmaceutical formulations of the compound of Formula I, Formula Ia, or Formula Ib, or a pharmaceutically acceptable salt thereof, and an aqueous vehicle. The pharmaceutical formulations of the disclosure are useful in treatment and prevention of viral infections in subjects in need thereof and are for administration by inhalation.

1 .- 49 . (canceled) 
     
     
         50 . A kit comprising
 (a) pharmaceutical formulation comprising:   i. a compound selected from a compound of Formula I, a compound Formula Ia, or a compound Formula Ib:   
       
         
           
           
               
               
           
         
          or a pharmaceutically acceptable salt thereof; 
         ii. water; and 
         iii. cyclodextrin;
 wherein the pharmaceutical formulation is suitable for administration via inhalation; and 
 
         (b) instructions for using the pharmaceutical formulation via inhalation administration. 
       
     
     
         51 . The kit of  claim 50 , wherein the compound is the compound of Formula Ia: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         52 . The kit of  claim 50 , wherein the pharmaceutical formulation is suitable for administration via inhalation in a nebulized form. 
     
     
         53 - 81 . (canceled) 
     
     
         82 . A kit comprising (a) lyophilized pharmaceutical formulation comprising:
 i. a compound selected from a compound of Formula I, a compound Formula Ia, or a compound Formula Ib:   
       
         
           
           
               
               
           
         
          or a pharmaceutically acceptable salt thereof; and 
         ii. cyclodextrin; and 
         (b) instructions for using the pharmaceutical formulation via inhalation administration. 
       
     
     
         83 . The kit of  claim 82 , wherein the compound is the compound of Formula Ia. 
     
     
         84 . The kit of  claim 82 , wherein the lyophilized formulation comprises the compound of Formula I, the compound of Formula Ia, or the compound of Formula Ib in an amount of 1% to 10% w/w and cyclodextrin in an amount of from 90% to 99% w/w. 
     
     
         85 . The kit of  claim 82 , wherein the lyophilized formulation comprises the compound of Formula I, the compound of Formula Ia, or the compound of Formula Ib in an amount of 5% to 10% w/w and cyclodextrin in an amount of from 90% to 95% w/w. 
     
     
         86 . The kit of  claim 82 , wherein the lyophilized formulation comprises the compound of Formula I, the compound of Formula Ia, or the compound of Formula Ib in an amount of 5% to 7% w/w and cyclodextrin in an amount of from 93% to 95% w/w. 
     
     
         87 . The kit of  claim 82 , wherein the lyophilized formulation comprises the compound of Formula I, the compound of Formula Ia, or the compound of Formula Ib in an amount of 6% to 7% w/w and cyclodextrin in an amount of from 93% to 94% w/w. 
     
     
         88 . The kit of  claim 82 , wherein the lyophilized formulation comprises the compound of Formula I, the compound of Formula Ia, or the compound of Formula Ib in an amount of 6.25% w/w and cyclodextrin in an amount of from 93.75% w/w. 
     
     
         89 . The kit of  claim 82 , wherein the lyophilized formulation comprises the compound of Formula I, the compound of Formula Ia, or the compound of Formula Ib in an amount of 1% to 5% w/w and cyclodextrin in an amount of from 95% to 99% w/w. 
     
     
         90 . The kit of  claim 82 , wherein the lyophilized formulation comprises the compound of Formula I, the compound of Formula Ia, or the compound of Formula Ib in an amount of 2% to 4% w/w and cyclodextrin in an amount of from 96% to 98% w/w. 
     
     
         91 . The kit of  claim 82 , wherein the lyophilized formulation comprises the compound of Formula I, the compound of Formula Ia, or the compound of Formula Ib in an amount of 3% to 3.6% w/w and cyclodextrin in an amount of from 96.5% to 97% w/w. 
     
     
         92 . The kit of  claim 82 , wherein the cyclodextrin is a beta-cyclodextrin. 
     
     
         93 . The kit of  claim 82 , wherein the cyclodextrin is a beta-cyclodextrin selected from a group consisting of sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, and hydroxypropyl-beta-cyclodextrin. 
     
     
         94 . The kit of  claim 82 , wherein the cyclodextrin is betadex-sulfobutylether sodium. 
     
     
         95 . The kit of  claim 82 , wherein the lyophilized formulation comprises the compound of Formula I, the compound of Formula Ia, or the compound of Formula Ib in an amount of 3.2% w/w, and the cyclodextrin betadex-sulfobutylether sodium in an amount of 96.8% w/w. 
     
     
         96 .- 105 . (canceled)