Compositions, methods & systems for respiratory delivery of two or more active agents

Abstract

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, 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 .- 61 . (canceled) 
     
     
         62 . A pharmaceutical composition deliverable from a metered dose inhaler, comprising:
 a pharmaceutically acceptable propellant;   a first species of respirable active agent particles comprising glycopyrrolate, or a pharmaceutically acceptable salt thereof;   a second species of respirable active agent particles comprising formoterol, or a pharmaceutically acceptable salt thereof;   a third species of respirable active agent particles comprising budesonide, or a pharmaceutically acceptable salt thereof; wherein the glycopyrrolate, formoterol and budesonide, or pharmaceutically acceptable salts thereof, are included in the composition in a concentration of between about 0.05 mg/mL and about 5 mg/mL;   a plurality of respirable suspending particles comprising 1,2-distearoyl-sn-glycero-3-phosphocholine and calcium chloride in a concentration of between about 3 mg/mL and about 10 mg/mL; and   wherein the pharmaceutical composition provides a clinically significant increase in forced expiratory volume (FEV 1 ) upon administration to a subject in need thereof.   
     
     
         63 . The pharmaceutical composition of  claim 62 , wherein the glycopyrrolate, or a pharmaceutically acceptable salt thereof is present in a concentration of between about 0.04 mg/L and about 2.25 mg/mL. 
     
     
         64 . The pharmaceutical composition of  claim 62 , wherein the glycopyrrolate, or a pharmaceutically acceptable salt thereof, is present in a concentration sufficient to provide a delivered dose of up to 10 μg upon actuation of the metered dose inhaler. 
     
     
         65 . The pharmaceutical composition of  claim 62 , wherein the pharmaceutically acceptable salt of glycopyrrolate is 3-[(cyclopentyl-hydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide. 
     
     
         66 . The pharmaceutical composition of  claim 62 , wherein the formoterol, or a pharmaceutically acceptable salt thereof, is present in a concentration of between about 0.01 mg/mL and about 0.5 mg/mL. 
     
     
         67 . The pharmaceutical composition of  claim 62 , wherein the formoterol, or a pharmaceutically acceptable salt thereof, is present in a concentration of between about 0.03 mg/L and about 0.04 mg/mL. 
     
     
         68 . The pharmaceutical composition of  claim 62 , wherein the formoterol, or a pharmaceutically acceptable salt thereof, is present in a concentration sufficient to provide a delivered dose of between about 1 μg and about 10 μg per actuation of the metered dose inhaler. 
     
     
         69 . The pharmaceutical composition of  claim 62 , wherein the formoterol, is present in a concentration sufficient to provide a delivered dose of between about 2 μg and about 5 μg per actuation of the metered dose inhaler. 
     
     
         70 . The pharmaceutical composition of  claim 62 , wherein the formoterol is present in a concentration sufficient to provide a delivered dose of up to 5 μg per actuation of the metered dose inhaler. 
     
     
         71 . The pharmaceutical composition of  claim 62 , wherein the pharmaceutically acceptable salt of formoterol is formoterol fumarate. 
     
     
         72 . The pharmaceutical composition of  claim 71 , wherein the formoterol fumarate is formoterol fumarate dihydrate. 
     
     
         73 . The pharmaceutical composition of  claim 62 , wherein the budesonide, or a pharmaceutically acceptable salt thereof, is present in a concentration sufficient to provide a delivered dose of between about 30 μg and about 240 μg. 
     
     
         74 . The pharmaceutical composition of  claim 62 , wherein the budesonide, or a pharmaceutically acceptable sat thereof, is present in a concentration sufficient to provide a delivered dose of up to about 240 μg. 
     
     
         75 . The pharmaceutical composition of  claim 62 , wherein the respirable suspending particles are present in the composition in a concentration of between about 5 mg/mL and about 8 mg/mL. 
     
     
         76 . The pharmaceutical composition of  claim 62 , wherein the respirable suspending particles are present in the composition in a concentration of about 6 mg/mL. 
     
     
         77 . The pharmaceutical composition of  claim 62 , wherein the clinically significant increase in forced expiratory volume (FEV 1 ) upon administration to a subject is about 100 mL. 
     
     
         78 . The pharmaceutical composition of  claim 62 , wherein the clinically significant increase in forced expiratory volume (FEV 1 ) upon administration is greater than 100 mL.