Aerosol delivery systems, compositions and methods

Abstract

An aerosol preparation assembly includes an entrainment chamber defining an entrainment volume. The entrainment chamber includes a gas inlet port, an aerosol inlet port and an outlet port. The entrainment chamber is configured such that a velocity of a flow of a gas within the entrainment volume is less than a velocity of the flow of the gas within the gas inlet port. The entrainment chamber is configured such that at least a portion of inlet aerosol is entrained into the flow of the gas within the entrainment volume to produce an entrained aerosol flow at the outlet port. The particle selection chamber is configured to receive the entrained aerosol flow and produce an outlet aerosol flow. The particle selection chamber and nozzle are collectively configured such that a volumetric median diameter of the outlet aerosol flow is less than a volumetric median diameter of the inlet aerosol.

1 . An aerosol suspension of liquid particles comprising an active agent and a buffering agent; wherein the aerosol particles have a volume median diameter (VMD) from about 0.5 μm to about 2.5 μm and there are not more than about 10% aerosol particles larger than 4 μm based on volume normalized amounts; and the aerosol particles produce a deposition efficiency of greater than about 3% on lung airway surfaces via transnasal administration and maintain the physiological pH of lung airway surfaces upon delivery. 
     
     
         2 . The aerosol suspension of  claim 1 , wherein the aerosol particles have a VMD from about 1 μm to about 2 μm; or about 1.2 μm to about 1.6 μm; or about 1.4 μm. 
     
     
         3 . The aerosol suspension of  claim 1 , wherein there are not more than about 5%, or 2.5%, or 1% aerosol particles larger than 4 μm based on volume normalized amounts. 
     
     
         4 . The aerosol suspension of  claim 1 , wherein the aerosol particles produce a deposition efficiency of greater than about 10%, or greater than about 15%, or greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or up to about 80%. 
     
     
         5 . The aerosol suspension of  claim 1 , wherein the aerosol particles produce a deposition rate of less than about 10 mg/min, or less than about 3 mg/min, or less than about 2 mg/min, or less than about 1 mg/min of the active agent on lung airway surfaces. 
     
     
         6 . The aerosol suspension of  claim 1 , wherein the active agent is selected from the group consisting of osmolytes, secretagogues, sodium channel blockers, mucus modifying agents (mucolytics) such as Pulmozyme and NAC, anti-infective agents including type II antibiotics such as meropenem, anti-virals such as ribavirin, anti-inflammatory agents, bronchodilators including beta-agonists and muscarinic receptor antagonists, steroids such as beclamethasone, budesonide, ciclesonide, flunisolide, fluticasone and mometasone, triamcinolone, anti-fungal agents such as amphotericin, intraconazol and voriconazol, anti-rejection drugs such as cyclosporine, tacrolimus and sirolimus, siRNAs, microRNAs, microRNA mimics, surfactants, therapeutic proteins and antibodies, gene therapy vectors, aptamers, endothelin-receptor antagonists, alpha-1-antitrypsin, prostacyclins, vaccines, and combinations thereof. 
     
     
         7 . The aerosol suspension of  claim 1 , wherein the active agent is hypotonic saline, isotonic saline, or hypertonic saline. 
     
     
         8 . The aerosol suspension of  claim 7 , wherein the active agent is hypertonic saline having a concentration ranging of about 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% by weight (grams/mL). 
     
     
         9 . The aerosol suspension of  claim 1 , wherein the buffering agent is a compound comprising an anionic component which is able to maintain a pH from about 6.8 to about 7.6, or from about 6.9 to about 7.5, or from about 7.0 to about 7.4. 
     
     
         10 . The aerosol suspension of  claim 9 , wherein the anionic component comprises carbonate or bicarbonate. 
     
     
         11 - 52 . (canceled)