Dry powder formation using a variably constrained, divided pathway for mixing fluid streams
Inventors
GILDELAMADRID, Xuno • Sievers, Robert E.
Assignees
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Publication Number
US-10206873-B1
Publication Date
2019-02-19
Expiration Date
Abstract
Methods of making a dry powder, comprise (a) delivering a liquid solution or suspension and a second, immiscible fluid to a flow path, (b) transporting the liquid solution or suspension and the immiscible fluid along the flow path, wherein the flow path includes two or more flow passages of different diameters, at least one flow divider which divides and diverts the flowing mixture into at least two separate passages, wherein the separate passages subsequently intersect to combine their respective flows into a single flowing stream, (c) rapidly reducing the pressure of the single flowing stream, whereby droplets are formed, and (d) passing the droplets through a flow of inert drying gas to form a dry powder. A nebulizing nozzle includes an inlet, a flow path as described, and a restrictor nozzle outlet.
Core Innovation
The invention relates to a method of making a dry powder by delivering a liquid solution or suspension and an immiscible supercritical or near critical fluid to a flow path, transporting a mixture of the liquid solution or suspension and the immiscible fluid along the flow path, and forming droplets. The flow path includes two flow passages of different diameters, and at least one flow divider divides and diverts the flowing mixture into two separate passages that subsequently intersect to combine their respective flows into a single flowing stream.
The method includes rapidly reducing the pressure of the single flowing stream by passing the stream through a restrictor nozzle, whereby droplets are formed. The droplets are passed through a flow of inert drying gas to form a dry powder. The described result is the formation of low-density particles with an increased hollow-sphere fraction, and the effect is stated to be independent of formulation excipients.
The flow-path arrangement and restriction are implemented using structural relationships between passages and a divided-and-reunified flow pathway to promote thorough mixing and create a fine emulsion and/or bubbles before droplet formation. The partial content also indicates use of computational fluid dynamics (CFD) and SEM comparisons, and contrasts performance with a prior low-volume tee CAN-BD nozzle by reporting an improved hollow-sphere fraction and nozzle performance.
Claims Coverage
The independent claim covers a dry-powder making method combining delivery of a liquid solution or suspension with an immiscible supercritical or near critical fluid into a divided-and-reunified flow path, rapid pressure reduction through a restrictor nozzle to form droplets, and inert drying gas processing to form the dry powder. Dependent claims specify particular fluid and gas embodiments, restrictor and flow-path geometric constraints, and particle-size distribution criteria using an Andersen Cascade Impactor per US Pharmacopeia <601>.
Divided-and-reunified flow path mixing of liquid with immiscible supercritical or near critical fluid
The flow path transports a mixture of a liquid solution or suspension and an immiscible supercritical or near critical fluid, including two flow passages of different diameters, at least one flow divider that divides and diverts into two separate passages, and the separate passages intersect to combine their respective flows into a single flowing stream.
Droplet formation by rapid pressure reduction through a restrictor nozzle
A single flowing stream is rapidly pressure-reduced by passing the stream through a restrictor nozzle, whereby droplets are formed.
Inert drying gas to form a dry powder
The droplets are passed through a flow of inert drying gas to form a dry powder.
Carbon dioxide as the immiscible supercritical or near critical fluid
The supercritical or near critical fluid is carbon dioxide.
Inert drying gas selected as nitrogen or carbon dioxide
The inert drying gas is selected from nitrogen or carbon dioxide.
Andersen Cascade Impactor particle-size criterion for the dry powder
The dry powder contains at least 30% of particles smaller than 5.8 μm as modeled by an Andersen Cascade Impactor according to US Pharmacopeia <601>.
Overall, the claims center on forming droplets from a liquid and immiscible supercritical or near critical fluid using a flow path that divides and reunifies flows into a single stream, followed by rapid pressure reduction via a restrictor nozzle and drying with an inert drying gas to form a dry powder. Dependent claims narrow the fluid and gas embodiments and specify particle-size distribution using Andersen Cascade Impactor per US Pharmacopeia <601>.
Stated Advantages
Increased hollow-sphere fraction in the dry powder.
Low-density particles are produced.
The increased hollow-sphere fraction is independent of formulation excipients.
Improved hollow-sphere fraction and nozzle performance relative to a prior low-volume tee CAN-BD nozzle.
Documented Applications
Production of inhalable dry powders suitable for delivery as dry powders.
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