Pulse drug nebulization system, formulations therefore, and methods of use

Abstract

Liquid nebulizer apparatus, systems, and formulation compositions, as well as systems for the nebulized, aerosol delivery of such compositions, for the administration and insufflation of medicinal aerosols into the pulmonary system of a mammal are described. The nebulizing apparatus and system can effectively aerosolize a variety of viscosities of medicinal liquid drug carriers, including those made up of oil, water, or emulsions of oil and water. Drugs dissolved or suspended in the compositions and formulations described and adapted for use herein are not damaged or denatured by the nebulization process when the nebulizer described is used. Further, the nebulization system itself can be adapted for use with both mechanically assisted pulmonary ventilation systems as well as hand-held inhalers and nose/mouth face masks for use in pulmonary drug delivery.

What is claimed is: 
     
         1 . A nebulization system comprising:
 a pressurized gas reservoir;   a pressurized drug reservoir;   a nozzle comprising an outer gas delivery tube and at least one inner microchannel drug delivery tube disposed within the outer gas-delivery tube, wherein the outer gas-delivery tube is in fluid communication with the pressurized gas reservoir and the at least one inner microchannel drug delivery tube is in fluid communication with the pressurized drug reservoir; and   wherein the outer gas delivery tube is concentrically configured around at least one inner delivery tube, such concentric configuration adapted to convey a pressurized flow of gas around a central supply of drug that is injected from the controlled pressurized drug reservoir into the at least one inner microchannel drug delivery tube.   
     
     
         2 . The nebulization system of  claim 1 , wherein the nozzle has an air volume to nebulized droplet volume ratio less than about 60,000:1. 
     
     
         3 . The pulmonary drug delivery system of  claim 1 , further comprising:
 a ventilator fitted onto and in fluid communication with an air stream of a mammalian patient; and   a plurality of control valves including a carrier gas control valve adapted to regulate flow of a carrier gas from the pressurized carrier gas reservoir and a drug control valve flow adapted to regulate a flow of the drug composition from the pressurized drug reservoir,   wherein the control valves are synchronized with the ventilator to provide a cyclic delivery of the carrier gas and the drug composition during an inspiration cycle of the ventilator.   
     
     
         4 . The nebulization system of  claim 1 , wherein the outer gas delivery tube has an inner diameter ranging from about 0.01 inches to about 0.05 inches. 
     
     
         5 . The nebulization system of  claim 1 , wherein the inner microchannel delivery tube has an outer diameter ranging from about 0.01 inches to about 0.04 inches. 
     
     
         6 . The nebulization system of  claim 1 , wherein the system is adapted to produce aerosol droplets of compositions comprising a fatty acid or lipids having particle sizes ranging from about 2 μm to about 12 μm. 
     
     
         7 . A pulmonary drug delivery system capable of nebulizing a drug composition comprising a water-insoluble or substantially water-insoluble drug and a fatty acid or lipid, the system comprising:
 a pressurized drug reservoir;   a pressurized carrier gas reservoir;   a plurality of control valves including a carrier gas control valve adapted to regulate flow of a carrier gas from the pressurized carrier gas reservoir and a drug control valve flow adapted to regulate a flow of the drug composition from the pressurized drug reservoir; and   a nebulizing nozzle in fluid communication with the pressurized drug reservoir and the carrier gas reservoir, wherein the nebulizing nozzle comprises an outer carrier gas delivery tube spaced apart from and disposed around at least one inner drug delivery tube and wherein the outer carrier gas delivery tube and the inner drug delivery tube share a longitudinal axis and are together dimensioned and disposed such that expulsion of the carrier gas through the outer carrier gas delivery tube forms an outer surrounding stream of carrier gas that carries an inner flow of the drug composition from the pressurized drug reservoir in a center of carrier gas flow exiting the nebulizing nozzle.   
     
     
         8 . The pulmonary drug delivery system of  claim 7 , further comprising an assembly fitted onto and in fluid communication with an air stream of a mammalian patient. 
     
     
         9 . The pulmonary drug delivery system of  claim 7 , wherein the nebulizing nozzle can produce aerosol drug containing droplets having a particle size ranging from about 2 μm to about 5 μm. 
     
     
         10 . The pulmonary drug delivery system of  claim 7 , wherein the nozzle has an air volume to nebulized droplet volume ratio less than about 60,000:1. 
     
     
         11 . The pulmonary drug delivery system of  claim 10 , wherein the nozzle has an air volume to nebulized droplet volume ratio less than about 15,000:1. 
     
     
         12 . The pulmonary drug delivery system of  claim 8 , wherein the assembly fitted onto and in fluid communication with an air stream of a mammalian patient comprises a mechanical ventilator. 
     
     
         13 . The pulmonary drug delivery system of  claim 12 , wherein the control valves are synchronized with the ventilator to provide a cyclic delivery of the carrier gas and the drug composition during an inspiration cycle of the ventilator. 
     
     
         14 . The pulmonary drug delivery system of  claim 7 , wherein an intermediate air space between the outer carrier gas delivery tube and the inner drug delivery tube ranges from about 0.000009 in 2  to about 0.001 in 2 . 
     
     
         15 . The pulmonary drug delivery system of  claim 7 , wherein an intermediate air space between the outer carrier gas delivery tube and the inner drug delivery tube ranges from about 0.00000259 in 2  to about 0.001 in 2 . 
     
     
         16 . The pulmonary drug delivery system of  claim 7 , wherein the outer carrier gas delivery tube has an inner diameter ranging from about 0.01 inches to about 0.05 inches. 
     
     
         17 . A pulmonary drug delivery system capable of nebulizing a drug composition comprising a water-insoluble or substantially water-insoluble drug and a fatty acid or lipid, the system comprising:
 a pressurized drug reservoir;   a pressurized carrier gas reservoir;   a nebulizing nozzle in fluid communication with the pressurized drug reservoir and the pressurized carrier gas reservoir, wherein the nebulizing nozzle comprises an outer gas delivery tube and a plurality of individual inner drug delivery tubes disposed within, and sharing a longitudinal axis with, the outer gas delivery tube, whereby expulsion of carrier gas through the outer gas delivery tube will entrain a the drug composition from the drug reservoir into a surrounding stream of carrier gas when carrier gas exits the nebulizing nozzle.   
     
     
         18 . The pulmonary drug delivery system of  claim 17 , wherein the plurality of individual drug delivery tubes ranges from 2 to 12 individual drug delivery tubes disposed within the outer gas delivery tube. 
     
     
         19 . The pulmonary drug delivery system of  claim 17 , where the relative dimensions of the outer gas delivery tube and the plurality of individual inner drug delivery tubes produce aerosol drug containing droplets having a particle size ranging from about 2 μm to about 12 μm in median mass aerodynamic size. 
     
     
         20 . The pulmonary drug delivery system of  claim 17 , further comprising:
 a ventilator fitted onto and in fluid communication with an air stream of a mammalian patient; and   a plurality of control valves including a carrier gas control valve adapted to regulate flow of a carrier gas from the pressurized carrier gas reservoir and a drug control valve flow adapted to regulate a flow of the drug composition from the pressurized drug reservoir,   wherein the control valves are synchronized with the ventilator to provide a cyclic delivery of the carrier gas and the drug composition during an inspiration cycle of the ventilator.