Delivery of small droplets to the respiratory system via electronic breath actuated droplet delivery device
An ejector mechanism of a droplet delivery device includes a piezoelectric actuator coupled to an acoustic horn and an aperture plate including a plurality of openings. At least the fluid entrance side of one or more of the plurality of openings is configured to provide a surface contact angle of less than 90 degrees and the piezoelectric actuator is operable to oscillate the aperture plate at a frequency to thereby generate an ejected stream of droplets such that at least about 50% of the droplets have an average ejected droplet diameter of less than about 6 microns during use. A sealing mechanism is provided at an interface of the aperture plate and a detachable fluid cartridge.
1 . An ejector mechanism comprising:
a piezoelectric actuator coupled to an acoustic horn;
an aperture plate having a plurality of openings formed through its thickness and a fluid entrance side of one or more of said plurality of openings configured to provide a surface contact angle of less than 90 degrees;
a removable fluid cartridge detachably coupled to the aperture plate; and
a sealing mechanism at an interface of the fluid cartridge and the aperture plate;
wherein the piezoelectric actuator is operable to oscillate the aperture plate at a frequency to thereby generate an ejected stream of droplets such that at least about 50% of the droplets have an average ejected droplet diameter of less than about 6 microns during use.
2 . The ejector mechanism of claim 1 , wherein the surface contact angle of less than 90 degrees at the fluid entrance side of one or more of said plurality of openings is obtained by a surface coating with a hydrophilic material, a surface structural modification, or a combination thereof.
3 . The ejector mechanism of claim 2 , wherein the hydrophilic material is selected from siloxane based coatings, isocyante based coatings, ethylene oxide based coatings, polyisocyanate based coatings, hydrocyclosiloxane based coatings, hydroxyalkylmethacrylate based coatings, hydroxyalkylacrylate based coatings, glycidylmethacrylate based coatings, propylene oxide based coatings, N-vinyl-2-pyrrolidone based coatings, latex based coatings, polyvinylchloride based coatings, or polyurethane based coatings.
4 . The ejector mechanism of claim 1 , wherein the aperture plate is configured such that at least the fluid entrance side of one or more of said plurality of openings is configured to provide the surface contact angle of between 2 and 80 degrees.
5 . The ejector mechanism of claim 1 , wherein the aperture plate is configured such that at least the fluid entrance side of one or more of said plurality of openings is configured to provide the surface contact angle of between 2 and 60 degrees.
6 . The droplet delivery device of claim 1 , wherein at least a portion of an interior of one or more of said plurality of openings is configured so as to provide a surface contact angle of less than 90 degree.
7 . The ejector mechanism of claim 1 , wherein the aperture plate is configured such that at a fluid exit side of one or more of said plurality of openings is configured to provide a surface contact angle of greater than 90 degrees.
8 . The ejector mechanism of claim 7 , wherein the aperture plate is configured such that at the fluid exit side of one or more of said plurality of openings is surface treated to provide the surface contact angle of between 90 degrees and 140 degrees.
9 . The ejector mechanism of claim 7 , wherein at least a portion of an interior of one or more of said plurality of openings is configured to provide a surface contact angle of greater than 90 degrees.
10 . The ejector mechanism of claim 7 , wherein the surface contact angle of greater than 90 degrees at the fluid exit side of one or more of said plurality of openings is obtained by a surface coating with a hydrophobic polymer.
11 . The ejector mechanism of claim 10 , wherein the hydrophobic polymer is selected from the group consisting of polytetrafluoroethylene, a siloxane, paraffin, and polyisobutylene.
12 . The ejector mechanism of claim 1 , wherein the aperture plate is composed of a material selected from the group consisting of poly ether ether ketone (PEEK), polyimide, polyetherimide, polyvinylidine fluoride (PVDF), ultra-high molecular weight polyethylene (UHMWPE), nickel, nickel-cobalt, nickel-palladium, palladium, platinum, metal alloys thereof, and combinations thereof.
13 . The ejector mechanism of claim 1 , wherein one or more of the plurality of openings have different cross-sectional shapes or diameters to thereby provide ejected droplets having different average ejected droplet diameters.
14 . An electronically actuated droplet delivery device for delivering a fluid composition as an ejected stream of droplets to a respiratory system of a subject, the device comprising:
a housing comprising a power source and a control board;
a mouthpiece positioned at an airflow exit of the device;
an ejector mechanism of claim 1 configured to generate the ejected stream of droplets; and
at least one differential pressure sensor positioned within the device, the at least one differential pressure sensor configured to activate the ejector mechanism upon sensing a pre-determined pressure change within the device to thereby generate the ejected stream of droplets;
wherein the ejector mechanism is configured to generate the ejected stream of droplets;
wherein the at least about 50% of the droplets have the average ejected droplet diameter of less than about 6 microns, such that at least about 50% of a mass of the ejected stream of droplets is delivered in a respirable range to the respiratory system of the subject during use.
15 . The droplet delivery device of claim 14 , wherein the mouthpiece and ejector mechanism are oriented such that an exit side of the aperture plate is perpendicular to a direction of air flow and the stream of droplets is ejected in parallel to the direction of air flow.
16 . The droplet delivery device of claim 14 , wherein the mouthpiece and ejector mechanism are oriented such that a fluid exit side of the aperture plate is oriented at an angle relative to a direction of air flow and the stream of droplets is ejected at an angle to the direction of air flow.
17 . The droplet delivery device of claim 14 , wherein the mouthpiece is removably coupled to the fluid cartridge.
18 . A method for delivering fluid composition as an ejected stream of droplets in a respirable range to a respiratory system of a subject, the method comprising:
(a) generating the ejected stream of droplets from a fluid composition via an electronically actuated droplet delivery device of claim 14 , wherein the at least about 50% of the ejected stream of droplets have the average ejected droplet diameter of less than about 6 μm; and
(b) delivering the ejected stream of droplets to the respiratory system of the subject such that the at least about 50% of the mass of the ejected stream of droplets is delivered in the respirable range to the respiratory system of a subject during use.
19 . The method of claim 18 , wherein the fluid composition comprises a medicament, and is delivered to a subject to treat or ameliorate a disease, condition or disorder selected from the group consisting of asthma, COPD epilepsy, seizure disorders, pain, chronic pain, neuropathic pain, headache, migraine, arthritis, multiple sclerosis, anorexia, nausea, vomiting, anorexia, loss of appetite, anxiety, or insomnia.
20 . The method of claim 18 , wherein the at least about 50% of the ejected stream of droplets have an average ejected droplet diameter of less than about 3.2 μm.
21 . The method of claim 18 , wherein the ejected stream of droplets is delivered over a period of time less than about 2 seconds.