Apparatus and method for generating fine particle aerosols with heliox
11524126 · 2022-12-13
Assignee
Inventors
Cpc classification
A61M11/02
HUMAN NECESSITIES
F26B3/12
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
B05B7/0416
PERFORMING OPERATIONS; TRANSPORTING
A61M11/002
HUMAN NECESSITIES
A61M11/006
HUMAN NECESSITIES
International classification
A61M11/00
HUMAN NECESSITIES
B05B7/04
PERFORMING OPERATIONS; TRANSPORTING
A61M11/02
HUMAN NECESSITIES
Abstract
An aerosol generating system for generating a respirable dry powder aerosol from a liquid solution or liquid suspension, having: a liquid aerosol generating nozzle having a nozzle input end designed to receive the liquid solution or liquid suspension, and having a nozzle heliox supply designed to receive nozzle heliox, the liquid aerosol generating nozzle further having a nozzle output end for outputting a liquid aerosol suspended in the nozzle heliox; and a cylindrical evaporation chamber having a cylindrical evaporation chamber input end that is connected to the nozzle output end and connected to a dilution heliox supply for receiving both the liquid aerosol suspended in the nozzle heliox and for receiving the dilution heliox, and the cylindrical evaporation chamber having a cylindrical evaporation chamber output end outputting a first intermediate dry powder aerosol at a first intermediate dry powder aerosol volume flow of a specific concentration.
Claims
1. An aerosol generating system for generating a respirable dry powder aerosol from a liquid solution or liquid suspension, comprising: a liquid aerosol generating nozzle having a nozzle input end designed to receive the liquid solution or liquid suspension, and having a first heliox supply designed to supply the liquid aerosol generating nozzle with a first heliox volume flow, the liquid aerosol generating nozzle further having a nozzle output end for outputting a liquid aerosol suspended in the first heliox volume flow supplied to the liquid aerosol generating nozzle; and a cylindrical evaporation chamber having a cylindrical evaporation chamber input end that is connected to the nozzle output end and connected to a second heliox supply for receiving both the liquid aerosol suspended in the first heliox volume flow and for receiving a second heliox volume flow from the second heliox supply diluting the liquid aerosol suspended in the first heliox volume flow, and the cylindrical evaporation chamber having a cylindrical evaporation chamber output end outputting a dry powder aerosol as a dry powder aerosol volume flow having a dry powder aerosol particle concentration.
2. The system according to embodiment 1 wherein the dry powder aerosol volume flow is between 80 and 200 I/min.
3. The system according to claim 1 wherein the liquid solution or liquid suspension contains a surfactant.
4. The system according to claim 1 wherein the system is designed to output from the cylindrical evaporation chamber the dry powder aerosol having fine particles of a size of 1.5-4 μm MMAD suspended in heliox.
5. The system according to claim 1 wherein the system is designed to aerosolize the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
6. The system according to claim 1 wherein the first heliox volume flow has a first heliox pressure between 207 and 414 kPa.
7. The system according to claim 1 further comprising a counter flow tube, an infrared radiation source, a reflector, and an aerosol collection cone.
8. The system according to claim 1 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
9. The system according to claim 8 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
10. A method for generating a respirable dry powder aerosol from a liquid solution or liquid suspension, comprising: feeding liquid solution or liquid suspension and a first heliox volume flow into a liquid aerosol generating nozzle; outputting from the liquid aerosol generating nozzle a liquid aerosol suspended in the first heliox volume flow into a cylindrical evaporation chamber; feeding a second heliox volume flow into the cylindrical evaporation chamber for diluting the liquid aerosol suspended in the first heliox volume flow; and outputting from the cylindrical evaporation chamber a dry powder aerosol having fine dry powder particles that allow respirable particles containing a medically active agent and are suspended in heliox as a dry powder aerosol volume flow having a dry powder aerosol particle concentration.
11. The method according to claim 10 further comprising generating the dry powder aerosol volume flow at between 80 and 200 I/min.
12. The method according to claim 10 further comprising providing a surfactant as a constituent of the liquid solution or liquid suspension.
13. The method according to claim 10 further comprising outputting from the cylindrical evaporation chamber the dry powder aerosol at a fine particles of a size of 1.5-4 μm MMAD suspended in heliox.
14. The method according to claim 10 further comprising aerosolizing the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
15. The method according to claim 10 further comprising supplying the first heliox volume flow at a first heliox pressure between 207 and 414 kPa.
16. The method according to claim 10 further comprising providing a counter flow tube, an infrared radiation source, a reflector, and an aerosol collection cone.
17. The method according to claim 10 further comprising supplying the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
18. The method according to claim 10 further comprising supplying the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION OF THE DRAWINGS
(38) A first configuration of the incident invention comprises an aerosol generating system that includes a liquid aerosol generating nozzle 3, a counter-flow tube 54, a flow distributer 5, and a cylindrical evaporation chamber 6 is shown in
(39) A second configuration of the incident invention comprises an aerosol generating system that includes the liquid aerosol generating nozzle 3, the counter-flow tube 54, the flow distributer 5, the cylindrical evaporation chamber 6, and a cylindrical single linear slit aerosol concentrator 9, is shown in
(40) A third configuration of the incident invention comprises an aerosol generating system that includes the liquid aerosol generating nozzle 3, the counter-flow tube 54, the flow distributer 5, the cylindrical evaporation chamber 6, and a cylindrical radial multi-slit aerosol concentrator 24 that are connected as shown in
(41) A fourth configuration the incident invention is an aerosol generating system that comprises the liquid aerosol generating nozzle 3, the counter-flow tube 54, the flow distributer 5, the cylindrical evaporation chamber 6, and a two-stage concentrator 96 that includes the cylindrical radial multi-slit aerosol concentrator 24, and the cylindrical single linear slit aerosol concentrator 9 is shown in
EXAMPLES
(42) The following data were generated using the incident invention operated with the aerosol processing system aligned horizontally atop its control console.
(43) To evaluate the performance of the incident invention, various concentrations of polyvinylpyrridolidone (PVP), a polymeric excipient that can be obtained in a wide range of molecular weights were used. PVP was used both as a surrogate for surfactant and other medications which form solutions or suspensions within the range of viscosities studied. Surfactant suspensions provided by Molecular Express were used that comprise the phospholipids contained in Minisurf. The particle size was measured with a Maple-Miller cascade impactor and expressed as mass median aerodynamic diameter, MMAD. The heliox used in these experiments was 80% helium and 20% oxygen.
(44) The effects on particle size of aerosol generation and processing with heliox compared to air were evaluated in the third configuration of the incident invention where the cylindrical radial multi-slit aerosol concentrator was incorporated in the incident invention.
(45) To evaluate the effects of gas pressure particles were generated with nozzles KB-N-500 and KB-N-600 using 10% 8 kDa PVP at 1 ml/min. The first intermediate dry powder aerosol volume flow were in the range of 160-200 l/min. Additionally, the respirable dry powder aerosol volume flow was controlled as 30 l/min. There was a marked reduction in MMAD of the output of the incident invention using the radial-slit concentrator when heliox is used compared to air as the aerosol generating and processing gas (
(46) To evaluate the effects of aerosolization rate on particle size with air and heliox aerosols generated from 9.33% surfactant suspensions and 10% 8 kDa PVP solutions using nozzle KB-N-500 at compressed air/heliox pressure of 40 psi. At all aerosolization rates (AR) between 0.5 and 3 ml/min, the MMAD of the aerosols generated by and processed with heliox is below 3 μm for both the PVP solutions and surfactant suspensions (
(47) As the viscosity of surfactant suspensions increases rapidly with increasing surfactant concentration was evaluated the effect of fluid viscosity on particles size using heliox as the aerosol generation and processing gas. The viscosities of 10% and 20% solutions of PVP of nominal molecular weights of 8, 29, 40 and 58 kDa were measured with a capillary rheometer and expressed in cSt. The Ohnesorge number, Oh, is proportional to the liquid dynamic viscosity. At large Oh (Oh>0.01), the liquid deformation and breakup are inhibited due to increased damping by liquid viscous forces. Using nozzle KB-N-700 at compressed heliox pressure of 40 psi to aerosolize PVP solutions at 1 ml/min the MMAD there was a modest increase in particle size with increasing viscosity (pr) between 4 and 39 cSt (
(48) To examine the aerosol particles output efficiency by air and heliox using the cylindrical radial multi-slit aerosol concentrator, 10% PVP solution and 9.33% surfactant suspension were aerosolized with the KB-N-500 nozzle at 40 psi and collected with a respirable dry powder aerosol volume flow of 44 l/min. It can be seen in Table 1 that the output of 10% PVP increases to 192 mg/min at 3 ml/min. The output was marginally increased to 198 mg/min with heliox despite the predictable decrease in particle size. When heliox is used as the aerosolizing gas, the output efficiencies for surfactant and PVP were essentially identical.
(49) TABLE-US-00001 TABLE 1 The PVP and surfactant mass output rate and efficiency for PVP and surfactant aerosols by air and heliox. Dose rate/efficiency Aerosolization rate mg/min/% ml/min Air heliox 10% 8 kDa PVP 1 64/64 66/66 2 128/64 132/66 3 192/64 198/66 9.33% Surfactant 1 59/63 62/66 2 118/63 123/66 3 165/59 182/65
(50) To demonstrate that large masses of particles could be processed using the cylindrical radial multi-slit aerosol concentrator 10 ml and 20 ml 10% 8 kDa PVP solution at an aerosolization rate of 3 ml/min with nozzle KB-N-500 at compressed air pressure of 40 psi. Output masses of, 0.7 and 1.2 g were collected in 3.3 and 6.7 min, respectively. These data demonstrate that potentially clinically relevant doses of surfactant and other molecules can be delivered with the incident invention.
(51) In the second configuration of the incident invention, the single slit aerosol concentrator replaced the cylindrical radial multi-slit aerosol concentrator to evaluate the effect of CGP on MMAD, the effect of increasing aerosolization rates on the dose rate (DR), as well as to evaluate the effects of respirable dry powder aerosol volume flow (RAVF) on the output mass concentration (MC) and the output efficiency (OE) of the aerosol processing system. The first intermediate dry powder aerosol volume flow in these experiments were 160-200 l/min and respirable dry powder aerosol volume flow was 12-44 l/min.
(52) Aerosols were generated with heliox with nozzle KB-N-500 at an aerosolization rate 3 ml/min to aerosolize 10% 8 kDa PVP solutions and 8.85% surfactant suspensions. In both cases, the MMAD decreased with increasing CGP (
(53) The single slit aerosol concentrator used with heliox with the respirable dry powder aerosol volume flow of 44 l/min delivered particles of PVP up to 258 mg/min with the efficiency up to 86% (
(54) To demonstrate that large masses of particles could be processed using the single slit aerosol concentrator 10 ml and 30 ml of 10% 8 kDa PVP were aerosolized at 3 ml/min using nozzle KB-N-500 at compressed heliox pressure of 40 psi. Output masses of 0.86 g and 2.2 g were collected at output in 3.3 min and 10 min, respectively.
(55) These data demonstrate that the incident invention has the potential to provide 3 mg/s of particles less than 3 μm MMAD throughout each and every breath with total output doses of ˜2 g of surfactant in ˜10 minutes. Using the cylindrical linear single slit aerosol concentrator, the aerosol deposition on the orifices was minimal. Aerosol losses to the walls of the cylindrical linear single slit aerosol concentrator were minimal with the diverging output channel having the highest wall deposition. This particle-wall interaction on the diverging output channel at these very high particle concentrations did not appear to effect the performance of the concentrator over the ranges of particles sizes, concentrations and total masses processed reported herein. Thus, using the cylindrical linear single slit aerosol concentrator with heliox enabled higher total particle masses to be concentrated than with the cylindrical radial multi-slit concentrator.
(56) To attain high particle concentrations, the relative utilities of the third configuration using cylindrical radial multi-slit aerosol concentrator and the fourth configuration comprising a series combination of the cylindrical radial multi-slit aerosol concentrator and the cylindrical linear single slit aerosol concentrator to form a two-stage concentrator were evaluated at a high ratio of first intermediate dry powder aerosol volume flow to respirable dry powder aerosol volume flow. The respirable dry powder aerosol volume flow of 12 l/min was chosen.
(57) The third configuration using cylindrical radial multi-slit aerosol concentrator was evaluated using air as the aerosol generating and dilution gas. Using nozzle KB-N-400 and a fluid flow of 1 ml/min of 10% 8 kDa PVP together with a first intermediate dry powder aerosol volume flow of 80 l/min the output mass concentration was 2.2 mg/l with an output efficiency of 26% with an estimated MMAD of 3.3 μm. The output pressure was 0.4 cm of water. When the total first intermediate dry powder aerosol volume flow was increased to 160 l/min, the mass concentration was 1.5 mg/l with an output efficiency of <20%. It is notable that when an aerosol was generated from 5% 8 kDa PVP using the KB-N-400 nozzle together with the cylindrical linear single slit aerosol concentrator and a total airflow of 60 l/min and an aerosolization rate of 0.5 ml/min a mass concentration of 0.9 mg/l was attained. The pressure at the output was 6 cm of water. The MMAD was estimated at about 2.9 μm.
(58) The fourth configuration comprising the two-stage concentrator was evaluated using air. The first intermediate dry powder aerosol volume flow of 160 l/min of air and a respirable dry powder aerosol volume flow limited to 12 l/min was evaluated. In this case, when using nozzle KB-N-500 and an aerosolization rate of 3 ml/min of 10% 8 kDa PVP, the mass concentration was 9.3 mg/l with the over al two stage concentrator output efficiency of 37%. The output pressure was 1.5 cm of water. The MMAD was about 3.2 μm.
(59) Additionally, using the second configuration with heliox as the processing gas together with nozzle KB-N-500 and with cylindrical linear single slit aerosol concentrator, the first intermediate dry powder aerosol volume flow of 160-200 l/min and the respirable dry powder aerosol volume flow limited to 12 μmin and an aerosolization rate of 3 ml/min the output mass concentration was 14.5 mg/l with an output efficiency of 58% (
(60) Together, these data demonstrate that it is advantageous to use the two-stage concentrator when generating high concentrations of aerosol with air. It is notable that when heliox is available, the efficiency and output of the single stage cylindrical linear single slit aerosol concentrator is far superior, especially when aerosols of 2-3 μm MMAD are being generated.
(61) The portioning gas flows within the fourth configuration comprising the two-stage concentrator was evaluated using either air or heliox in the absence of aerosolization. When operating in this mode with air with a first intermediate dry powder volume flow of 160 l/min, the ratio of the first intermediate aerosol dry powder aerosol volume flow to second intermediate dry powder volume flow was estimated as 2.7 for the cylindrical radial multi-slit aerosol concentrator. The ratio of the second intermediate dry powder volume flow to respirable dry powder volume flow was estimated to be 4.9 for the cylindrical linear single slit aerosol concentrator. When using this two-stage configuration was operated with heliox using the first intermediate dry powder aerosol volume flow of 210 l/min and respirable dry powder aerosol volume flow limited to 12 l/min, the input flow/output gas flows were 4.9 for the cylindrical radial multi-slit aerosol concentrator first stage and 3.6 for the cylindrical linear single slit aerosol concentrator with an overall two-stage concentrator efficiency of 41%. The output pressure was 0.6 cm. This demonstrates the versatility and practical utility of this two-stage concentrator.
(62) Assuming that spherical particles with an ideal log-normal distribution were generated, the number of PVP/surfactant particles per liter of heliox for an aerosol of 2.6 μm (σ.sub.g=1.9) in diameter was calculated to be 9.8×10.sup.9, at 14.5 mg/l on the basis of the theory developed by Hatch and Choate. Subsequently, based on the Smoluchowski's approach, the number of particles would decrease due to coagulation by 0.06% after 0.2 sec. Thus, at these concentrations, the effect of coagulation can be neglected in the incident invention.
(63) The surface tensions of the surfactant prior to and following aerosolization by SUPRAER were measured with Contact Angle Analyzer (FTA-200) using the pendant drop shape method. The static surface tensions of 4 mg/ml surfactant prior to and following aerosolization by the incident invention were 22.2 and 22.6 mN/m, respectively. The aerosolization and resuspension processes did not degrade the surface tension of the surfactant.
Use and Application of the Embodiments of the Invention
(64) These data demonstrate the remarkable efficiency of this configuration of the incident invention to deliver high doses of fine particle aerosols 1.5 μm to 4 μm MMAD with 1.6-2.7 geometric standard deviations. The incident invention is able to meet the aerosol delivery needs of adults, children and infants. It also lends itself to the extremely rapid emergency delivery of therapeutic aerosols in other life threatening conditions.
(65) Through the use of the cylindrical linear single slit aerosol concentrator, in conjunction with the use of heliox ability to generate aerosols<3 μm mass median aerodynamic diameter, MMAD, from a 9.33% surfactant suspension (viscosity 34 cP) was accomplished and deliver high payloads of dry powder aerosols containing up to 3 mg/s of pure phospholipids with efficiencies between 69% and 84%. The low surface tension properties of the surfactant are retained following aerosolization and resuspension. The incident invention has the potential to deliver a constant 3 mg/s throughout each and every inspiration over the entire treatment time without interruption. The surfactant dose rate and total dose are 10 to 20 times higher than that attainable by competitive devices. For the first time, a clinically relevant dose of aerosolized surfactant will be attainable for multiple treatments in adults with impaired lung function. Thus this incident invention, together with a surfactant that contains the SPB protein (or mimetic), has the potential to provide life-saving physiological benefits to enable the resolution of the pulmonary inflammatory processes.
(66) According to the invention, heliox more efficiently generates and delivers surfactant aerosols than air. In addition, heliox facilitates deeper penetration of aerosols into the lungs and improves gas exchange, especially in patients with compromised lung function. The physical properties of heliox have enabled us to deliver<3 μm MMAD aerosols at efficiencies up to 86% using cylindrical linear single slit aerosol concentrator, while the efficiency was 69% in the case of air. The lower losses enable us to realize higher total delivered doses of surfactant. Moreover, the process of evaporating water from the aerosols was enhanced due to the fact that heliox has a higher thermal conductivity and specific heat than air. This has enables surfactant to be delivered with high efficiencies even at high delivered doses. When the cylindrical linear single slit aerosol concentrator is used with air rather than heliox at these flow rates (First intermediate dry powder aerosol volume flow: 160-200 l/min; respirable dry powder aerosol volume flow: 44 l/min), the delivered pressure to the patients would be higher than 38 cm H.sub.2O, while this pressure is only 13 cm H.sub.2O when heliox is used. The high aerosol delivery pressure when air is used with the cylindrical linear single slit aerosol concentrator is both undesirable for patients breathing spontaneously and sets a too high lower limit on ventilation with continuous positive airway pressure, CPAP, or positive end expiratory pressure, PEEP, when using in the intensive care unit setting. The cylindrical radial multi-slit aerosol concentrator, when used with air, has an aerosol delivery pressure as low as 3 cm H.sub.2O and has efficiencies between 59 and 64%. To provide a unit to address the needs of clinical facilities that do not have heliox, or choose not to use it, according to the invention as described above it was possible to use in connection with the some of the described embodiments either air or heliox as the aerosol generating and processing gas.
(67) Further embodiments 1-141 of the invention are described in the following:
(68) 1. An aerosol generating system for generating a respirable dry powder aerosol 15 from a liquid solution or liquid suspension at a respirable dry powder aerosol volume flow 91, comprising: a liquid aerosol generating nozzle 3 having a nozzle input end 11 designed to receive the liquid solution or liquid suspension, and having a nozzle gas supply 55 designed to receive nozzle gas 2, the liquid aerosol generating nozzle 3 further having a nozzle output end 36 for outputting a liquid aerosol 13 suspended in the nozzle gas 2; a cylindrical evaporation chamber 6 having a cylindrical evaporation chamber input end 7 that is connected to the nozzle output end 36 and connected to a dilution gas supply 60 for receiving both the liquid aerosol 13 suspended in the nozzle gas 2 and for receiving the dilution gas 4, and the cylindrical evaporation chamber 6 having a cylindrical evaporation chamber output end 8 outputting a first intermediate dry powder aerosol 14 at a first intermediate dry powder aerosol volume flow 89 and a first intermediate dry powder aerosol particle concentration 90; and a cylindrical single linear slit aerosol concentrator 9 having a cylindrical single linear slit aerosol concentrator input end 10 that is connected to the cylindrical evaporation chamber output end 8, the cylindrical single linear slit aerosol concentrator 9 comprising a converging cylindrical single linear slit aerosol concentrator input channel 19 converging from the cylindrical single linear slit aerosol concentrator input end 10 to a cylindrical single linear slit aerosol concentrator input orifice 20 that is connected to a cylindrical single linear slit aerosol concentrator aerosol separation space 40, the cylindrical single linear slit aerosol concentrator aerosol separation space 40 connecting both to a cylindrical single linear slit aerosol concentrator exhaust port 44 and to a cylindrical single linear slit aerosol concentrator output orifice 21, the cylindrical single linear slit aerosol concentrator output orifice 21 being connected to a diverging cylindrical single linear slit aerosol concentrator output channel 22 outputting the respirable dry powder aerosol 15 at the respirable dry powder aerosol volume flow 91 that is lower than the first intermediate dry powder aerosol volume flow 89 and at a respirable dry powder aerosol particle concentration 92 that is higher than the first intermediate dry powder aerosol particle concentration 90.
(69) 2. The system according to embodiment claim 1 wherein at least one of the nozzle gas 2 and the dilution gas 4 is heliox.
(70) 3. The system according to embodiment 1 wherein at least one of the nozzle gas 2 and the dilution gas 4 is air.
(71) 4. The system according to one of the preceding embodiments 1-3 wherein the first intermediate dry powder aerosol volume flow 89 is between 80 and 200 l/min.
(72) 5. The system according to one of the preceding embodiments 1-4 wherein the cylindrical single linear slit aerosol concentrator output orifice 21 is between 1 and 5 cm long and between 1 and 2 mm wide.
(73) 6. The system according to one of the preceding embodiments 1-5 wherein the liquid solution or liquid suspension contains a surfactant.
(74) 7. The system according to one of the preceding embodiments 1-6 wherein the cylindrical single linear slit aerosol concentrator 9 has a cylindrical single linear slit aerosol concentrator aerosol separation space 40 that is less than 2 mm wide and extends between a cylindrical single linear slit aerosol concentrator input orifice 20 and the cylindrical single linear slit aerosol concentrator output orifice 21.
(75) 8. The system according to one of the preceding embodiments 1-7 wherein the converging cylindrical single linear slit aerosol concentrator input channel 19 converges from the cylindrical single linear slit aerosol concentrator input end 10 to a center of the cylindrical single linear slit aerosol concentrator input orifice 20 at a converging cylindrical single linear slit aerosol concentrator input channel angle 52 between 10 and 60 degrees.
(76) 9. The system according to one of the preceding embodiments 1-8 wherein the diverging cylindrical single linear slit aerosol concentrator output channel 22 diverges from the cylindrical single linear slit aerosol concentrator output orifice 21 at a diverging cylindrical single linear slit aerosol concentrator output channel angle 53 between 10 and 60 degrees.
(77) 10. The system according to one of the preceding embodiments 1-9 further comprising a sculptured plenum 43 that connects the cylindrical single linear slit aerosol concentrator aerosol separation space 40 and the cylindrical single linear slit aerosol concentrator exhaust port 44 and has a sculptured plenum volume between 30 and 300 ml.
(78) 11. The system according to one of the preceding embodiments 1-10 wherein the cylindrical single linear slit aerosol concentrator exhaust port 44 with a diameter of 10-20 mm.
(79) 12. The system according to one of the preceding embodiments 1-11 wherein in use the cylindrical single linear slit aerosol concentrator input orifice 20 and the cylindrical single linear slit aerosol concentrator output orifice 21 extend substantially vertically.
(80) 13. The system according to one of the preceding embodiments 1-12 wherein the system is designed to output from the cylindrical evaporation chamber 6 the first intermediate dry powder aerosol 14 having fine particles of a size of 1.5-4 μm MMAD suspended in gas.
(81) 14. The system according to one of the preceding embodiments 1-13 wherein the system is designed to aerosolize the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
(82) 15. The system according to one of the preceding embodiments 1-14 wherein the nozzle gas 2 has a nozzle gas pressure between 207 and 414 kPa.
(83) 16. The system according to embodiment 2 wherein the respirable dry powder aerosol 15 has a respirable dry powder aerosol pressure of less than 1 cm of water.
(84) 17. The system according to embodiment 3 wherein the respirable dry powder aerosol 15 has a respirable dry powder aerosol pressure of less than 2 cm of water.
(85) 18. The system according to one of the preceding embodiments 1-17 wherein the respirable dry powder aerosol volume flow 91 is 10-15 l/min while concentration efficiency is greater than 30%.
(86) 19. The system according to one of the preceding embodiments 1-18 wherein the system is free of flow controls at the cylindrical single linear slit aerosol concentrator exhaust port 44 of the cylindrical single linear slit aerosol concentrator 9.
(87) 20. The system according to one of the preceding embodiments 1-19 further comprising a counter flow tube 54, an infrared radiation source 39, a reflector 72, and an aerosol collection cone 95.
(88) 21. The system according to one of the preceding embodiments 1-20 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
(89) 22. The system according to embodiment 21 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
(90) 23. The system according to embodiment 22 wherein the system is designed to output the respirable dry powder aerosol volume flow 91 between 12 l/min and 44 l/min, thereby delivering a medication at a medication mass concentration of at least 5 mg/l and up to 14.5 mg/l.
(91) 24. A method for generating a respirable dry powder aerosol 15 from a liquid solution or liquid suspension at a respirable dry powder aerosol volume flow 91, comprising: feeding liquid solution or liquid suspension and nozzle gas 2 into a liquid aerosol generating nozzle 3; outputting from the liquid aerosol generating nozzle 3 a liquid aerosol 13 suspended in the nozzle gas 2 into a cylindrical evaporation chamber 6; feeding dilution gas 4 into the cylindrical evaporation chamber 6; outputting from the cylindrical evaporation chamber 6 a first intermediate dry powder aerosol 14 having fine dry powder particles that allow respirable particles containing a medically active agent and are suspended in gas at a first intermediate dry powder aerosol volume flow 89 and a first intermediate dry powder aerosol particle concentration 90; feeding the first intermediate dry powder aerosol 14 into a cylindrical single linear slit aerosol concentrator 9, the cylindrical single linear slit aerosol concentrator 9 comprising a converging cylindrical single linear slit aerosol concentrator input channel 19 converging to a cylindrical single linear slit aerosol concentrator input orifice 20 and a diverging cylindrical single linear slit aerosol concentrator output channel 22 diverging from a cylindrical single linear slit aerosol concentrator output orifice 21; and outputting the respirable dry powder aerosol 15 at the respirable dry powder aerosol volume flow 91 that is lower than the first intermediate dry powder aerosol volume flow 89 and a respirable dry powder aerosol particle concentration 92 that is higher than the first intermediate dry powder aerosol particle concentration 90.
(92) 25. The method according to embodiment 24 further comprising supplying heliox as at least one of the nozzle gas 2 and the dilution gas 4.
(93) 26. The method according to embodiment 24 further comprising supplying air as at least one of the nozzle gas 2 and the dilution gas 4.
(94) 27. The method according to one of the preceding embodiments 24-26 further comprising generating the first intermediate dry powder aerosol volume flow 89 at between 80 and 200 l/min.
(95) 28. The method according to one of the preceding embodiments 24-27 further comprising providing the cylindrical single linear slit aerosol concentrator output orifice 21 with a length between 1 and 5 cm and a width between 1 and 2 mm.
(96) 29. The method according to one of the preceding embodiments 24-28 further comprising providing a surfactant as a constituent of the liquid solution or liquid suspension.
(97) 30. The method according to one of the preceding embodiments 24-29 further comprising providing the cylindrical single linear slit aerosol concentrator 9 with a cylindrical single linear slit aerosol concentrator aerosol separation space 40 that is less than 2 mm wide and extends between the cylindrical single linear slit aerosol concentrator input orifice 20 and the cylindrical single linear slit aerosol concentrator output orifice 21.
(98) 31. The method according to one of the preceding embodiments 24-30 further comprising providing the converging cylindrical single linear slit aerosol concentrator input channel 19 so that it converges from the cylindrical single linear slit aerosol concentrator input end 10 to a center of the cylindrical single linear slit aerosol concentrator input orifice 20 at a converging cylindrical single linear slit aerosol concentrator input channel angle 52 between 10 and 60 degrees.
(99) 32. The method according to one of the preceding embodiments 24-31 further comprising providing the diverging cylindrical single linear slit aerosol concentrator output channel 22 so that it diverges from the cylindrical single linear slit aerosol concentrator output orifice 21 at a diverging cylindrical single linear slit aerosol concentrator output channel angle 53 between 10 and 60 degrees.
(100) 33. The method according to one of the preceding embodiments 24-32 further comprising providing a sculptured plenum 43 that connects the cylindrical single linear slit aerosol concentrator aerosol separation space 40 and the cylindrical single linear slit aerosol concentrator exhaust port 44 and has a sculptured plenum volume between 30 and 300 ml.
(101) 34. The method according to one of the preceding embodiments 24-33 further comprising providing the cylindrical single linear slit aerosol concentrator exhaust port 44 with a diameter of 10-20 mm.
(102) 35. The method according to one of the preceding embodiments 24-34 further comprising positioning the cylindrical single linear slit aerosol concentrator input orifice 20 and the cylindrical single linear slit aerosol concentrator output orifice 21 such that these extend substantially vertically.
(103) 36. The method according to one of the preceding embodiments 24-35 further comprising outputting from the cylindrical evaporation chamber 6 the first intermediate dry powder aerosol 14 at a fine particles of a size of 1.5-4 μm MMAD suspended in gas.
(104) 37. The method according to one of the preceding embodiments 24-36 further comprising aerosolizing the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
(105) 38. The method according to one of the preceding embodiments 24-37 further comprising supplying the nozzle gas 2 at a nozzle gas 2 pressure between 207 and 414 kPa.
(106) 39. The method according to embodiment 25 further comprising generating the respirable dry powder aerosol 15 at a respirable dry powder aerosol pressure of less than 1 cm of water.
(107) 40. The method according to embodiment 26 further comprising generating the respirable dry powder aerosol 1 at a respirable dry powder aerosol pressure of less than 2 cm of water.
(108) 41. The method according to one of the preceding embodiments 24-40 further comprising generating the respirable dry powder aerosol volume flow 91 at 10-15 l/min while concentration efficiency is greater than 30%.
(109) 42. The method according to one of the preceding embodiments 24-41 further comprising omitting any flow controls at the single linear slit aerosol concentrator exhaust port 44 of the cylindrical single linear slit aerosol concentrator 9.
(110) 43. The method according to one of the preceding embodiments 24-42 further comprising providing a counter flow tube 54, an infrared radiation source 39, a reflector 72, and an aerosol collection cone 79.
(111) 44. The method according to one of the preceding embodiments 24-43 further comprising supplying the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
(112) 45. The method according to embodiment 44 further comprising supplying the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
(113) 46. The method according to embodiment 45 wherein the method is designed to output the respirable dry powder aerosol volume flow 91 between 12 l/min and 44 l/min, thereby delivering a medication at a medication mass concentration of at least 5 mg/l and up to 14.5 mg/l.
(114) 47. The method according to one of the preceding embodiments 24-46 further comprising controlling the volume flow ratios such that the ratio of the first intermediate dry powder aerosol volume flow 89 to the respirable dry powder volume flow 91 is less than 5.
(115) 48. An aerosol generating system for generating a respirable dry powder aerosol 15 from a liquid solution or liquid suspension at a respirable dry powder aerosol volume flow 91, comprising: a liquid aerosol generating nozzle 3 having a nozzle input end 11 designed to receive the liquid solution or liquid suspension, and having a nozzle gas supply 55 designed to receive nozzle gas 2, the liquid aerosol generating nozzle 3 further having a nozzle output end 36 for outputting a liquid aerosol 13 suspended in the nozzle gas 2; a cylindrical evaporation chamber 6 having a cylindrical evaporation chamber input end 7 that is connected to the nozzle output end 36 and connected to a dilution gas supply 60 for receiving both the liquid aerosol 13 suspended in the nozzle gas 2 and for receiving the dilution gas 4, and the cylindrical evaporation chamber 6 having a cylindrical evaporation chamber output end 8 outputting a first intermediate dry powder aerosol 14 at a first intermediate dry powder aerosol volume flow 89 and a first intermediate dry powder aerosol particle concentration 90; a cylindrical radial multi-slit aerosol concentrator 24 comprising at least 3 slits extending from a position at or close to a center of the cylindrical radial multi-slit aerosol concentrator 24 to a position more remote from the center of the cylindrical radial multi-slit aerosol concentrator 24, the cylindrical radial multi-slit aerosol concentrator 24 having a cylindrical radial multi-slit aerosol concentrator input end 25 that is connected to the cylindrical evaporation chamber output end 8, and a cylindrical radial multi-slit aerosol concentrator output end 26 outputting a second intermediate dry powder aerosol 17 at a second intermediate dry powder aerosol volume flow 93 and a second intermediate dry powder aerosol particle concentration 94, the second intermediate dry powder aerosol volume flow 93 being lower than the first intermediate dry powder aerosol volume flow 89 and the second intermediate dry powder aerosol particle concentration 94 being higher than the first intermediate dry powder aerosol particle concentration 90; and a cylindrical single linear slit aerosol concentrator 9 having a cylindrical single linear slit aerosol concentrator input end 10 that is connected to the cylindrical radial multi-slit aerosol concentrator output end 26, the cylindrical single linear slit aerosol concentrator 9 comprising a converging cylindrical single linear slit aerosol concentrator input channel 19 converging from the cylindrical single linear slit aerosol concentrator input end 10 to a cylindrical single linear slit aerosol concentrator input orifice 20 that is connected to a cylindrical single linear slit aerosol concentrator aerosol separation space 40, the cylindrical single linear slit aerosol concentrator aerosol separation space 40 connecting both to a cylindrical single linear slit aerosol concentrator exhaust port 44 and to a cylindrical single linear slit aerosol concentrator output orifice 21, the cylindrical single linear slit aerosol concentrator output orifice 21 being connected to a diverging cylindrical single linear slit aerosol concentrator output channel 22 outputting the respirable dry powder aerosol 15 at the respirable dry powder aerosol volume flow 91 that is lower than the second intermediate dry powder aerosol volume flow 93 and a respirable dry powder aerosol particle concentration 92 that is higher than the second intermediate dry powder aerosol particle concentration 94.
(116) 49. The system according to embodiment 48 wherein at least one of the nozzle gas 2 and the dilution gas 4 is heliox.
(117) 50. The system according to embodiment 48 wherein at least one of the nozzle gas 2 and the dilution gas 4 is air.
(118) 51. The system according to one of the preceding embodiments 48-50 wherein the first intermediate dry powder aerosol volume flow 89 is between 80 and 200 μmin.
(119) 52. The system according to one of the preceding embodiments 48-51 wherein the cylindrical single linear slit aerosol concentrator output orifice 21 is between 1 and 5 cm long and between 1 and 2 mm wide.
(120) 53. The system according to one of the preceding embodiments 48-52 wherein the liquid solution or liquid suspension contains a surfactant.
(121) 54. The system according to one of the preceding embodiments 48-53 wherein the cylindrical single linear slit aerosol concentrator 9 has a cylindrical single linear slit aerosol concentrator aerosol separation space 40 that is less than 2 mm wide and extends between a cylindrical single linear slit aerosol concentrator input orifice 20 and the cylindrical single linear slit aerosol concentrator output orifice 21.
(122) 55. The system according to one of the preceding embodiments 48-54 wherein the converging cylindrical single linear slit aerosol concentrator input channel 19 converges from the cylindrical single linear slit aerosol concentrator input end 10 to a center of the cylindrical single linear slit aerosol concentrator input orifice 20 at a converging cylindrical single linear slit aerosol concentrator input channel angle 52 between 10 and 60 degrees.
(123) 56. The system according to one of the preceding embodiments 48-55 wherein the diverging cylindrical single linear slit aerosol concentrator output channel 22 diverges from the cylindrical single linear slit aerosol concentrator output orifice 21 at a diverging cylindrical single linear slit aerosol concentrator output channel angle 53 between 10 and 60 degrees.
(124) 57. The system according to one of the preceding embodiments 48-56 further comprising a sculptured plenum 43 that connects the cylindrical single linear slit aerosol concentrator aerosol separation space 40 and the cylindrical single linear slit aerosol concentrator exhaust port 44 and has a sculptured plenum volume between 30 and 300 ml.
(125) 58. The system according to one of the preceding embodiments 48-57 wherein the cylindrical single linear slit aerosol concentrator exhaust port 44 with a diameter of 10-20 mm.
(126) 59. The system according to one of the preceding embodiments 48-58 wherein in use the cylindrical single linear slit aerosol concentrator input orifice 20 and the cylindrical single linear slit aerosol concentrator output orifice 21 extend substantially vertically.
(127) 60. The system according to one of the preceding embodiments 48-59 wherein the system is designed to output from the cylindrical evaporation chamber 6 the first intermediate dry powder aerosol 14 having fine particles of a size of 1.5-4 μm MMAD suspended in gas.
(128) 61. The system according to one of the preceding embodiments 48-60 wherein the system is designed to aerosolize the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
(129) 62. The system according to one of the preceding embodiments 48-61 wherein the nozzle gas 2 has a nozzle gas pressure between 207 and 414 kPa.
(130) 63. The system according to embodiment 49 wherein the respirable dry powder aerosol 15 has a respirable dry powder aerosol pressure of less than 1 cm of water.
(131) 64. The system according to embodiment 50 wherein the respirable dry powder aerosol 15 has a respirable dry powder aerosol pressure of less than 2 cm of water.
(132) 65. The system according to one of the preceding embodiments 48-64 wherein a total cylindrical radial multi-slit aerosol concentrator slit length of the cylindrical radial multi-slit aerosol concentrator 24 is at least 4 times longer than a cylindrical single linear slit aerosol concentrator slit length of the cylindrical single linear slit aerosol concentrator 9.
(133) 66. The system according to one of the preceding embodiments 48-65 wherein the respirable dry powder aerosol volume flow 91 is 10-15 l/min while concentration efficiency is greater than 30%.
(134) 67. The system according to one of the preceding embodiments 48-66 wherein the system is free of flow controls at a cylindrical radial multi-slit aerosol concentrator exhaust port 51 of the cylindrical radial multi-slit aerosol concentrator 24 and the cylindrical single linear slit aerosol concentrator exhaust port 44 of the cylindrical single linear slit aerosol concentrator 9.
(135) 68. The system according to one of the preceding embodiments 48-67 further comprising a counter flow tube 54, an infrared radiation source 39, a reflector 72, and an aerosol collection cone 95.
(136) 69. The system according to one of the preceding embodiments 48-68 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
(137) 70. The system according to embodiment 69 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
(138) 71. The system according to embodiment 70 wherein the system is designed to output the respirable dry powder aerosol volume flow 91 between 12 l/min and 44l/min, thereby delivering a medication at a medication mass concentration of at least 5 mg/l and up to 14.5 mg/l.
(139) 72. A method for generating a respirable dry powder aerosol 15 from a liquid solution or liquid suspension at a respirable dry powder aerosol volume flow 91, comprising: feeding liquid solution or liquid suspension and nozzle gas 2 into a liquid aerosol generating nozzle 3; outputting from the liquid aerosol generating nozzle 3 a liquid aerosol 13 suspended in the nozzle gas 2 into a cylindrical evaporation chamber 6; feeding dilution gas 4 into the cylindrical evaporation chamber 6; outputting from the cylindrical evaporation chamber 6 a first intermediate dry powder aerosol 14 having fine dry powder particles that allow respirable particles containing a medically active agent and are suspended in gas at a first intermediate dry powder aerosol volume flow 89 and a first intermediate dry powder aerosol particle concentration 90; feeding the first intermediate dry powder aerosol 14 into a cylindrical radial multi-slit aerosol concentrator 24 comprising at least 3 slits extending from a position at or close to a center of the cylindrical radial multi-slit aerosol concentrator 24 to a position more remote from the center of the cylindrical radial multi-slit aerosol concentrator 24; outputting from the cylindrical radial multi-slit aerosol concentrator 24 a second intermediate dry powder aerosol 17 at a second intermediate dry powder aerosol volume flow 93 and a second intermediate dry powder aerosol particle concentration 94, the second intermediate dry powder aerosol volume flow 93 being lower than the first intermediate dry powder aerosol volume flow 89 and the second intermediate dry powder aerosol particle concentration 94 being higher than the first intermediate dry powder aerosol particle concentration 90; feeding the second intermediate dry powder aerosol 17 into a cylindrical single linear slit aerosol concentrator 9, the cylindrical single linear slit aerosol concentrator 9 comprising a converging cylindrical single linear slit aerosol concentrator input channel 19 converging to a cylindrical single linear slit aerosol concentrator input orifice 20 and a diverging cylindrical single linear slit aerosol concentrator output channel 22 diverging from a cylindrical single linear slit aerosol concentrator output orifice 21; and outputting the respirable dry powder aerosol 15 at the respirable dry powder aerosol volume flow 91 that is lower than the second intermediate dry powder aerosol volume flow 93 and a respirable dry powder aerosol particle concentration 92 that is higher than the second intermediate dry powder aerosol particle concentration 94.
(140) 73. The method according to embodiment 72 further comprising supplying heliox as at least one of the nozzle gas 2 and the dilution gas 4.
(141) 74. The method according to embodiment 72 further comprising supplying air as at least one of the nozzle gas 2 and the dilution gas 4.
(142) 75. The method according to one of the preceding embodiments 72-74 further comprising generating the first intermediate dry powder aerosol volume flow 89 at between 80 and 200 I/min.
(143) 76. The method according to one of the preceding embodiments 72-75 further comprising providing the cylindrical single linear slit aerosol concentrator output orifice 21 with a length between 1 and 5 cm and a width between 1 and 2 mm.
(144) 77. The method according to one of the preceding embodiments 72-76 further comprising providing a surfactant as a constituent of the liquid solution or liquid suspension.
(145) 78. The method according to one of the preceding embodiments 72-77 further comprising providing the cylindrical single linear slit aerosol concentrator 9 with a cylindrical single linear slit aerosol concentrator aerosol separation space 40 that is less than 2 mm wide and extends between the cylindrical single linear slit aerosol concentrator input orifice 20 and the cylindrical single linear slit aerosol concentrator output orifice 21.
(146) 79. The method according to one of the preceding embodiments 72-78 further comprising providing the converging cylindrical single linear slit aerosol concentrator input channel 19 so that it converges from the cylindrical single linear slit aerosol concentrator input end 10 to a center of the cylindrical single linear slit aerosol concentrator input orifice 20 at a converging cylindrical single linear slit aerosol concentrator input channel angle 52 between 10 and 60 degrees.
(147) 80. The method according to one of the preceding embodiments 72-79 further comprising providing the diverging cylindrical single linear slit aerosol concentrator output channel 22 so that it diverges from the cylindrical single linear slit aerosol concentrator output orifice 21 at a diverging cylindrical single linear slit aerosol concentrator output channel angle 53 between 10 and 60 degrees.
(148) 81. The method according to one of the preceding embodiments 72-80 further comprising providing a sculptured plenum 43 that connects the cylindrical single linear slit aerosol concentrator aerosol separation space 40 and the cylindrical single linear slit aerosol concentrator exhaust port 44 and has a sculptured plenum volume between 30 and 300 ml.
(149) 82. The method according to one of the preceding embodiments 72-81 further comprising providing the cylindrical single linear slit aerosol concentrator exhaust port 44 with a diameter of 10-20 mm.
(150) 83. The method according to one of the preceding embodiments 72-82 further comprising positioning the cylindrical single linear slit aerosol concentrator input orifice 20 and the cylindrical single linear slit aerosol concentrator output orifice 21 such that these extend substantially vertically.
(151) 84. The method according to one of the preceding embodiments 72-83 further comprising outputting from the cylindrical evaporation chamber 6 the first intermediate dry powder aerosol 14 at a fine particles of a size of 1.5-4 μm MMAD suspended in gas.
(152) 85. The method according to one of the preceding embodiments 72-84 further comprising aerosolizing the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
(153) 86. The method according to one of the preceding embodiments 72-85 further comprising supplying the nozzle gas 2 at a nozzle gas 2 pressure between 207 and 414 kPa.
(154) 87. The method according to embodiment 73 further comprising generating the respirable dry powder aerosol 15 at a respirable dry powder aerosol pressure of less than 1 cm of water.
(155) 88. The method according to embodiment 74 further comprising generating the respirable dry powder aerosol 15 at a respirable dry powder aerosol pressure of less than 2 cm of water.
(156) 89. The method according to one of the preceding embodiments 72-88 further comprising providing as a total cylindrical radial multi-slit aerosol concentrator slit length of the cylindrical radial multi-slit aerosol concentrator 24 a length that is at least 4 times longer than the slit length of the cylindrical single linear slit aerosol concentrator 9.
(157) 90. The method according to one of the preceding embodiments 72-89 further comprising generating the respirable dry powder aerosol volume flow 91 at 10-15 l/min while concentration efficiency is greater than 30%.
(158) 91. The method according to one of the preceding embodiments 72-90 further comprising omitting any flow controls at the cylindrical radial multi-slit aerosol concentrator exhaust port 54 of the cylindrical radial multi-slit aerosol concentrator 24 and the cylindrical single linear slit aerosol concentrator exhaust port 44 of the cylindrical single linear slit aerosol concentrator 9.
(159) 92. The method according to one of the preceding embodiments 72-91 further comprising providing a counter flow tube 54, an infrared radiation source 39, a reflector 72, and an aerosol collection cone 79.
(160) 93. The method according to one of the preceding embodiments 72-92 further comprising supplying the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
(161) 94. The method according to embodiment 93 further comprising supplying the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
(162) 95. The method according to embodiment 94 wherein the method is designed to output the respirable dry powder aerosol volume flow 91 between 12 l/min and 44l/min, thereby delivering a medication at a medication mass concentration of at least 5 mg/l and up to 14.5 mg/l.
(163) 96. The method according to one of the preceding embodiments 72-95 further comprising controlling the volume flow ratios such that the ratio of the first intermediate dry powder aerosol volume flow 89 to the second intermediate dry powder volume flow 93 and the ratio of the second intermediate dry powder volume flow 93 to the respirable dry powder volume flow 91 are both less than 5.
(164) 97. An aerosol generating system for generating a respirable dry powder aerosol 15 from a liquid solution or liquid suspension, comprising: a liquid aerosol generating nozzle 3 having a nozzle input end 11 designed to receive the liquid solution or liquid suspension, and having a nozzle heliox supply 55 designed to receive nozzle heliox 2, the liquid aerosol generating nozzle 3 further having a nozzle output end 36 for outputting a liquid aerosol 13 suspended in the nozzle heliox 2; and a cylindrical evaporation chamber 6 having a cylindrical evaporation chamber input end 7 that is connected to the nozzle output end 36 and connected to a dilution heliox supply 60 for receiving both the liquid aerosol 13 suspended in the nozzle heliox 2 and for receiving the dilution heliox 4, and the cylindrical evaporation chamber 6 having a cylindrical evaporation chamber output end 8 outputting a first intermediate dry powder aerosol 14 at a first intermediate dry powder aerosol volume flow 89 and a first intermediate dry powder aerosol particle concentration 90; and a cylindrical radial multi-slit aerosol concentrator 24 comprising at least 3 slits extending from a position at or close to a center of the cylindrical radial multi-slit aerosol concentrator 24 to a position more remote from the center of the cylindrical radial multi-slit aerosol concentrator 24, the cylindrical radial multi-slit aerosol concentrator 24 having a cylindrical radial multi-slit aerosol concentrator input end 25 that is connected to the cylindrical evaporation chamber output end 8, and a cylindrical radial multi-slit aerosol concentrator output end 26 outputting the respirable dry powder aerosol 15 at the respirable dry powder aerosol volume flow 91 that is lower than the first intermediate dry powder aerosol volume flow 89 and a respirable dry powder aerosol particle concentration 92 that is higher than the first intermediate dry powder aerosol particle concentration 90.
(165) 98. The system according to embodiment 97 wherein the first intermediate dry powder aerosol volume flow 89 is between 80 and 200 I/min.
(166) 99. The system according to one of the preceding embodiments 97-98 wherein the liquid solution or liquid suspension contains a surfactant.
(167) 100. The system according to one of the preceding embodiments 97-99 wherein the system is designed to output from the cylindrical evaporation chamber 6 the first intermediate dry powder aerosol 14 having fine particles of a size of 1.5-4 μm MMAD suspended in gas.
(168) 101. The system according to one of the preceding embodiments 97-100 wherein the system is designed to aerosolize the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
(169) 102. The system according to one of the preceding embodiments 97-101 wherein the nozzle heliox 2 has a heliox pressure between 207 and 414 kPa.
(170) 103. The system according to one of the preceding embodiments 97-102 wherein the respirable dry powder aerosol 15 has a respirable dry powder aerosol pressure of less than 1 cm of water.
(171) 104. The system according to one of the preceding embodiments 97-103 wherein the respirable dry powder aerosol volume flow 91 is 10-15 μmin while concentration efficiency is greater than 30%.
(172) 105. The system according to one of the preceding embodiments 97-104 wherein the system is free of flow controls at a cylindrical radial multi-slit aerosol concentrator exhaust port 51 of the cylindrical radial multi-slit aerosol concentrator 24.
(173) 106. The system according to one of the preceding embodiments 97-105 further comprising a counter flow tube 54, an infrared radiation source 39, a reflector 72, and an aerosol collection cone 95.
(174) 107. The system according to one of the preceding embodiments 97-106 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
(175) 108. The system according to embodiment 107 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
(176) 109. The system according to embodiment 108 wherein the system is designed to output the respirable dry powder aerosol volume flow 91 between 12 l/min and 44 l/min, thereby delivering a medication at a medication mass concentration of at least 5 mg/l and up to 14.5 mg/l.
(177) 110. A method for generating a respirable dry powder aerosol 15 from a liquid solution or liquid suspension at a respirable system output volume flow 91, comprising: feeding liquid solution or liquid suspension and nozzle heliox 2 into a liquid aerosol generating nozzle 3; outputting from the liquid aerosol generating nozzle 3 a liquid aerosol 13 suspended in the nozzle heliox 2 into a cylindrical evaporation chamber 6; feeding dilution heliox 4 into the cylindrical evaporation chamber 6; and outputting from the cylindrical evaporation chamber 6 a first intermediate dry powder aerosol 14 having fine dry powder particles that allow respirable particles containing a medically active agent and are suspended in gas at a first intermediate dry powder aerosol volume flow 89 and a first intermediate dry powder aerosol particle concentration 90 feeding the first intermediate dry powder aerosol 14 into a cylindrical radial multi-slit aerosol concentrator 24 comprising at least 3 slits extending from a position at or close to a center of the cylindrical radial multi-slit aerosol concentrator 24 to a position more remote from the center of the cylindrical radial multi-slit aerosol concentrator 24; and outputting the respirable dry powder aerosol 15 at the respirable dry powder aerosol volume flow 91 that is lower than the first intermediate dry powder aerosol volume flow 14 and a respirable dry powder aerosol particle concentration 92 that is higher than the first intermediate dry powder aerosol particle concentration 90.
(178) 111. The method according to embodiment 110 further comprising generating the first intermediate dry powder aerosol volume flow 89 at between 80 and 200 l/min.
(179) 112. The method according to one of the preceding embodiments 110-111 further comprising providing a surfactant as a constituent of the liquid solution or liquid suspension.
(180) 113. The method according to one of the preceding embodiments 110-112 further comprising outputting from the cylindrical evaporation chamber 6 the first intermediate dry powder aerosol 14 at a fine particles of a size of 1.5-4 μm MMAD suspended in gas.
(181) 114. The method according to one of the preceding embodiments 110-113 further comprising aerosolizing the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
(182) 115. The method according to one of the preceding embodiments 110-114 further comprising supplying the nozzle heliox 2 at a nozzle heliox 2 pressure between 207 and 414 kPa.
(183) 116. The method according to one of the preceding embodiments 110-115 further comprising generating the respirable dry powder aerosol 15 at a respirable dry powder aerosol pressure of less than 1 cm of water.
(184) 117. The method according to one of the preceding embodiments 110-116 further comprising generating the respirable dry powder aerosol volume flow 91 at 10-15 l/min while concentration efficiency is greater than 30%.
(185) 118. The method according to one of the preceding embodiments 110-117 further comprising omitting any flow controls at the cylindrical radial multi-slit aerosol concentrator exhaust port 54 of the cylindrical radial multi-slit aerosol concentrator 24.
(186) 119. The method according to one of the preceding embodiments 110-118 further comprising providing a counter flow tube 54, an infrared radiation source 39, a reflector 72, and an aerosol collection cone 79.
(187) 120. The method according to one of the preceding embodiments 110-119 further comprising supplying the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
(188) 121. The method according to embodiment 120 further comprising supplying the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
(189) 122. The method according to embodiment 121 wherein the method is designed to output the respirable dry powder aerosol volume flow 91 between 12 l/min and 44l/min, thereby delivering a medication at a medication mass concentration of at least 5 mg/l and up to 14.5 mg/l.
(190) 123. The method according to one of the preceding embodiments 110-122 further comprising controlling the volume flow ratio such that the ratio of the first intermediate dry powder aerosol volume flow 89 to the respirable dry powder volume flow 91 is less than 5.
(191) 124. An aerosol generating system for generating a respirable dry powder aerosol 15 from a liquid solution or liquid suspension, comprising: a liquid aerosol generating nozzle 3 having a nozzle input end 11 designed to receive the liquid solution or liquid suspension, and having a nozzle heliox supply 55 designed to receive nozzle heliox 2, the liquid aerosol generating nozzle 3 further having a nozzle output end 36 for outputting a liquid aerosol 13 suspended in the nozzle heliox 2; and a cylindrical evaporation chamber 6 having a cylindrical evaporation chamber input end 7 that is connected to the nozzle output end 36 and connected to a dilution heliox supply 60 for receiving both the liquid aerosol 13 suspended in the nozzle heliox 2 and for receiving the dilution heliox 4, and the cylindrical evaporation chamber 6 having a cylindrical evaporation chamber output end 8 outputting a first intermediate dry powder aerosol 14 at a first intermediate dry powder aerosol volume flow 89 and a first intermediate dry powder aerosol particle concentration 90.
(192) 125. The system according to embodiment 124 wherein the first intermediate dry powder aerosol volume flow 89 is between 80 and 200 I/min.
(193) 126. The system according to one of the preceding embodiments 124-125 wherein the liquid solution or liquid suspension contains a surfactant.
(194) 127. The system according to one of the preceding embodiments 124-126 wherein the system is designed to output from the cylindrical evaporation chamber 6 the first intermediate dry powder aerosol 14 having fine particles of a size of 1.5-4 μm MMAD suspended in gas.
(195) 128. The system according to one of the preceding embodiments 124-127 wherein the system is designed to aerosolize the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
(196) 129. The system according to one of the preceding embodiments 124-128 wherein the nozzle heliox 2 has a nozzle heliox pressure between 207 and 414 kPa.
(197) 130. The system according to one of the preceding embodiments 124-129 further comprising a counter flow tube 54, an infrared radiation source 39, a reflector 72, and an aerosol collection cone 95.
(198) 131. The system according to one of the preceding embodiments 124-130 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
(199) 132. The system according to embodiment 131 wherein the system is designed to receive the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
(200) 133. A method for generating a respirable dry powder aerosol 15 from a liquid solution or liquid suspension, comprising: feeding liquid solution or liquid suspension and nozzle heliox 2 into a liquid aerosol generating nozzle 3; outputting from the liquid aerosol generating nozzle 3 a liquid aerosol 13 suspended in the nozzle heliox 2 into a cylindrical evaporation chamber 6; feeding dilution gas 4 into the cylindrical evaporation chamber 6; and outputting from the cylindrical evaporation chamber 6 a first intermediate dry powder aerosol 14 having fine dry powder particles that allow respirable particles containing a medically active agent and are suspended in gas at a first intermediate dry powder aerosol volume flow 89 and a first intermediate dry powder aerosol particle concentration 90.
(201) 134. The method according to embodiment 133 further comprising generating the first intermediate dry powder aerosol volume flow 89 at between 80 and 200 l/min.
(202) 135. The method according to one of the preceding embodiments 133-134 further comprising providing a surfactant as a constituent of the liquid solution or liquid suspension.
(203) 136. The method according to one of the preceding embodiments 133-135 further comprising outputting from the cylindrical evaporation chamber 6 the first intermediate dry powder aerosol 14 at a fine particles of a size of 1.5-4 μm MMAD suspended in gas.
(204) 137. The method according to one of the preceding embodiments 133-136 further comprising aerosolizing the liquid solution or liquid suspension having a liquid solution or liquid suspension viscosity of 4 to 39 cSt.
(205) 138. The method according to one of the preceding embodiments 133-137 further comprising supplying the nozzle heliox 2 at a nozzle heliox 2 pressure between 207 and 414 kPa.
(206) 139. The method according to one of the preceding embodiments 133-138 further comprising providing a counter flow tube 54, an infrared radiation source 39, a reflector 72, and an aerosol collection cone 79.
(207) 140. The method according to one of the preceding embodiments 133-139 further comprising supplying the liquid solution or liquid suspension at a liquid solution or liquid suspension volume flow of 0.1-3 ml/min, delivering a medication at a medication mass flow rate of at least 150 mg/min in form of the solid particles having a dry powder aerosol mass median aerodynamic diameter (MMAD) of 3 μm or less.
(208) 141. The method according to one of the preceding embodiments 133-140 further comprising supplying the liquid solution or liquid suspension at a liquid solution or suspension viscosity exceeding 4 cSt.
LIST OF REFERENCE NUMERALS
(209) nozzle gas 2 liquid aerosol generating nozzle 3 dilution gas 4 flow distributer 5 cylindrical evaporation chamber 6 cylindrical evaporation chamber input end 7 cylindrical evaporation chamber output end 8 cylindrical single linear slit aerosol concentrator 9 cylindrical single linear slit aerosol concentrator input end 10 nozzle input end 11 liquid aerosol 13 first intermediate dry powder aerosol 14 respirable dry powder aerosol 15 first exhaust aerosol 16 second intermediate dry powder aerosol 17 converging cylindrical single linear slit aerosol concentrator input channel 19 cylindrical single linear slit aerosol concentrator input orifice 20 cylindrical single linear slit aerosol concentrator output orifice 21 diverging cylindrical single linear slit aerosol concentrator output channel 22 cylindrical radial multi-slit aerosol concentrator 24 cylindrical radial multi-slit aerosol concentrator input end 25 cylindrical radial multi-slit aerosol concentrator output end 26 nozzle holder 27 central channel 28 fluid nozzle 29 gas entrance orifice 30 gas channels 31 circumferential pressure equalization chamber 32 circumferential converging channel 33 circumferential diverging channel 34 aerosolizing space 35 nozzle output end 36 aerosol plume 37 counter flow orifice 38 infrared source 39 cylindrical single linear slit aerosol concentrator aerosol separation space 40 circular exit 41 sculptured plenum 43 cylindrical single linear slit aerosol concentrator exhaust port 44 radially aligned acceleration nozzles 45 radially aligned deceleration nozzles 46 acceleration slit orifices 47 deceleration slit orifices 48 cylindrical radial multi-slit aerosol concentrator aerosol separation space 49 circular plenum 50 cylindrical radial multi-slit aerosol concentrator exhaust ports 51 converging cylindrical single linear slit aerosol concentrator input channel angle 52 diverging cylindrical single linear slit aerosol concentrator output channel angle 53 counter-flow tube 54 nozzle gas supply 55 channel 56 compressed gas channel 57 constriction orifice 58 counter flow channel 59 dilution gas supply 60 donut shaped chamber 61 holes in a first baffle 62 first baffle 63 second circular chamber 64 second baffle 65 holes in an inner cylindrical chamber 66 inner cylindrical chamber 67 central holes 68 peripheral holes 69 quartz tube 70 half cylinder aluminum reflector 72 lip-seals 73 converging cylindrical single linear slit aerosol concentrator input orifice angle 74 diverging cylindrical single linear slit aerosol concentrator output orifice angle 75 external surface of the converging channel 76 external surface of the diverging channel 77 internal wall 78 collection cone 79 sculptured exhaust channel 80 entrance plate 81 entrance plate channels 82 rear plate 83 rear plate channels 84 converging exhaust channels 85 second exhaust aerosol 86 first intermediate dry powder aerosol volume flow 89 first intermediate dry powder aerosol particle concentration 90 respirable dry powder aerosol volume flow 91 respirable dry powder aerosol particle concentration 92 second intermediate dry powder aerosol volume flow 93 second intermediate dry powder aerosol particle concentration 94 two-stage concentrator 96