Compositions for pulmonary delivery of long-acting b2 adrenergic receptor agonists and associated methods and systems

Abstract

Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting β 2 adrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

1 .- 54 . (canceled) 
     
     
         55 . A pharmaceutical composition deliverable from a metered dose inhaler, comprising:
 a pharmaceutically acceptable HFA suspension medium;   a plurality of respirable suspending particles;   a plurality of active agent particles comprising formoterol, or a pharmaceutically acceptable salt thereof, in a concentration of between about 0.01 mg/mL and about 0.5 mg/mL; and   a plurality of active agent particles comprising glycopyrrolate, or a pharmaceutically acceptable salt thereof, in a concentration of between about 0.04 mg/mL and about 2.25 mg/mL;   wherein the respirable suspending particles are formed separately from the active agent particles and are substantially insoluble in the suspension medium; and   wherein the respirable suspending particles are present in the suspension medium at a concentration of between about 5 mg/mL and about 8 mg/mL and at a weight ratio of total mass of the respirable suspending particles to total mass of active agent particles that ranges from 1:1 to 200:1.   
     
     
         56 . The pharmaceutical composition of  claim 55 , wherein the concentration of the formoterol active agents particles is between about 0.03 and about 0.4 mg/mL. 
     
     
         57 . The pharmaceutical composition of  claim 55 , wherein the pharmaceutically acceptable salt of formoterol is formoterol fumarate. 
     
     
         58 . The pharmaceutical composition of  claim 55 , wherein the pharmaceutically acceptable salt of glycopyrrolate is 3-[(cyclopentyl-hydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide. 
     
     
         59 . The pharmaceutical composition of  claim 55 , wherein the concentration of the suspending particles is about 6 mg/mL. 
     
     
         60 . The pharmaceutical composition of  claim 55 , wherein the concentration of the suspending particles is between 5.8 and 6.1 mg/mL. 
     
     
         61 . The pharmaceutical composition of  claim 55 , wherein the suspending particles comprise 1,2-distearoyl-sn-glycero-3-phosphocholine and calcium chloride. 
     
     
         62 . A method of treating a pulmonary disease or disorder in a subject comprising providing a metered dose inhaler comprising the pharmaceutical composition of  claim 55  to the subject and administering the pharmaceutical composition by actuating the metered dose inhaler. 
     
     
         63 . The method of  claim 62 , wherein the pulmonary disease or disorder is chronic obstructive pulmonary disease. 
     
     
         64 . The method of  claim 62 , wherein the pulmonary disease or disorder is asthma.