U.S. patent application number 16/229518 was filed with the patent office on 2019-04-18 for aerosol generating assembly.
This patent application is currently assigned to Philip Morris USA Inc.. The applicant listed for this patent is Philip Morris USA Inc.. Invention is credited to David Ammann, Donald Brookman, Gary Grollimund, Niranjan Maharajh, Douglas D. McRae, F. Murphy Sprinkel, JR., Sudarsan Srinivasan.
Application Number | 20190111231 16/229518 |
Document ID | / |
Family ID | 39166806 |
Filed Date | 2019-04-18 |
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United States Patent
Application |
20190111231 |
Kind Code |
A1 |
Srinivasan; Sudarsan ; et
al. |
April 18, 2019 |
AEROSOL GENERATING ASSEMBLY
Abstract
An aerosol generating assembly is disclosed, which includes a
heater assembly including, a heater body extending in a
longitudinal direction, and at least one heater in the heater body;
a capillary tube extending longitudinally through at least a
portion of the heater body, the capillary tube in fluid
communication with a reservoir, the at least one heater configured
to heat the capillary tube; a thermocouple in the heater body; and
a temperature controller configured to control a heating
temperature.
Inventors: |
Srinivasan; Sudarsan;
(Richmond, VA) ; Ammann; David; (Richmond, VA)
; Brookman; Donald; (Richmond, VA) ; Maharajh;
Niranjan; (Richmond, VA) ; Grollimund; Gary;
(Chesterfield, VA) ; Sprinkel, JR.; F. Murphy;
(Glen Allen, VA) ; McRae; Douglas D.;
(Chesterfield, VA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Philip Morris USA Inc. |
Richmond |
VA |
US |
|
|
Assignee: |
Philip Morris USA Inc.
Richmond
VA
|
Family ID: |
39166806 |
Appl. No.: |
16/229518 |
Filed: |
December 21, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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13555810 |
Jul 23, 2012 |
10188823 |
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16229518 |
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11866283 |
Oct 2, 2007 |
8251055 |
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13555810 |
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60849038 |
Oct 2, 2006 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 15/025 20140204;
A61M 11/001 20140204; A61M 16/1075 20130101; A61M 11/007 20140204;
A61M 11/042 20140204; A61M 2205/3368 20130101; A61M 16/0808
20130101; A61M 16/1065 20140204; A61M 11/041 20130101; A61M
2205/505 20130101; A61M 16/14 20130101; A61M 16/024 20170801; A61M
15/00 20130101; A61M 2205/128 20130101 |
International
Class: |
A61M 16/14 20060101
A61M016/14; A61M 16/10 20060101 A61M016/10; A61M 16/00 20060101
A61M016/00; A61M 11/00 20060101 A61M011/00; A61M 15/00 20060101
A61M015/00; A61M 11/04 20060101 A61M011/04; A61M 15/02 20060101
A61M015/02 |
Claims
1. An aerosol generating assembly comprising: a heater assembly
including, a heater body extending in a longitudinal direction, and
at least one heater in the heater body; a capillary tube extending
longitudinally through at least a portion of the heater body, the
capillary tube in fluid communication with a reservoir, the at
least one heater configured to heat the capillary tube; a
thermocouple in the heater body; and a temperature controller
configured to control a heating temperature.
2. The aerosol generating assembly of claim 1, wherein the heater
body comprises: an upper assembly; and a lower assembly configured
to mate with the upper assembly.
3. The aerosol generating assembly of claim 2, wherein the upper
assembly and the lower assembly define at least one longitudinally
extending bore.
4. The aerosol generating assembly of claim 3, wherein the at least
one heater is in the at least one longitudinally extending
bore.
5. The aerosol generating assembly of claim 2, wherein the upper
assembly, the lower assembly, or both the upper assembly and the
lower assembly are formed of a thermally conductive material.
6. The aerosol generating assembly of claim 1, wherein the at least
one heater comprises: a heater cartridge.
7. The aerosol generating assembly of claim 1, wherein the
capillary tube has an inner diameter of about 0.05 millimeters to
about 0.53 millimeters.
8. The aerosol generating assembly of claim 1, wherein the
capillary tube has a length ranging from about 90 mm to about 120
mm.
9. The aerosol generating assembly of claim 1, wherein the
capillary tube is formed of metal.
10. The aerosol generating assembly of claim 1, further comprising:
a heater holder surrounding at least a portion of the heater
body.
11. The aerosol generating assembly of claim 10, wherein the heater
holder comprises: a top heater holder; and a bottom heater holder
configured to connect with the top heater holder.
12. A delivery system comprising: a pumping unit; and an aerosol
generating assembly including, a heater assembly including, a
heater body extending in a longitudinal direction, and at least one
heater in the heater body; a capillary tube extending
longitudinally through at least a portion of the heater body, the
pumping unit configured to deliver a liquid to the capillary tube,
the at least one heater configured to heat the capillary tube to a
temperature sufficient to volatilize at least a portion of the
liquid delivered to the capillary tube; a thermocouple in the
heater body; and a temperature controller configured to control a
heating temperature.
13. The delivery system of claim 12, wherein the pumping unit
comprises: a syringe pump.
14. The delivery system of claim 12, further comprising: a power
source configured to supply power to the at least one heater.
15. The delivery system of claim 12, wherein the heater body
comprises: an upper assembly; and a lower assembly configured to
mate with the upper assembly.
16. The delivery system of claim 15, wherein the upper assembly and
the lower assembly define at least one longitudinally extending
bore.
17. The delivery system of claim 16, wherein the at least one
heater is in the at least one longitudinally extending bore.
18. The delivery system of claim 15, wherein the upper assembly,
the lower assembly, or both the upper assembly and the lower
assembly are formed of a thermally conductive material.
19. The delivery system of claim 12, wherein the at least one
heater comprises: a heater cartridge.
20. The delivery system of claim 12, wherein the capillary tube has
an inner diameter of about 0.05 millimeters to about 0.53
millimeters.
21. The delivery system of claim 12, wherein the capillary tube has
a length ranging from about 90 mm to about 120 mm.
22. The delivery system of claim 12, wherein the capillary tube is
formed of metal.
23. The delivery system of claim 12, further comprising: a heater
holder surrounding at least a portion of the heater body.
24. The delivery system of claim 23, wherein the heater holder
comprises: a top heater holder; and a bottom heater holder
configured to connect with the top heater holder.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This is a continuation application of U.S. patent
application Ser. No. 13/555,810, filed on Jul. 23, 2012, which is a
continuation application of U.S. patent application Ser. No.
11/866,283 filed on Oct. 2, 2007, now U.S. Pat. No. 8,251,055,
which claims priority to U.S. Provisional Application No.
60/849,038, filed Oct. 2, 2006, the entire contents of all three of
which is incorporated herein by reference.
BACKGROUND
[0002] Capillary aerosol technology and capillary aerosol
generators have been described in U.S. Pat. No. 5,743,251, the
contents of which are hereby incorporated by reference in their
entirety.
SUMMARY
[0003] In accordance with one embodiment, a drug delivery system,
comprises: an aerosol generator unit wherein a liquid formulation
is partially volatilized to form an aerosol; a pumping unit adapted
to supply a liquid formulation to the aerosol generator unit; a
flow passage having an inlet end in fluid communication with an
outlet of the aerosol generator unit and an outlet adapted for
connection to a patient interface which supplies ventilation gas to
a patient's lungs; at least one condensate collector adapted to
collect condensed liquid or liquid produced by the aerosol
generator unit; and a transition adapter arranged to mix aerosol
produced by the aerosol generator unit with heated air or
ventilation gas and directs the mixed aerosol into the inlet end of
the flow passage.
[0004] In accordance with a further embodiment, a drug delivery
system, comprises: an aerosol generator unit wherein a liquid
formulation is partially volatilized to form an aerosol; a pumping
unit adapted to supply a liquid formulation to the aerosol
generator unit at high pressures; a disposable assembly that
operates at high pressures; a flow passage having an inlet end in
fluid communication with an outlet of the aerosol generator unit
and an outlet adapted for connection to a patient interface which
supplies ventilation gas to a patient's lungs; at least one
condensate collector adapted to collect condensed liquid or liquid
produced by the aerosol generator unit; and a transition adapter
arranged to mix aerosol produced by the aerosol generator unit with
heated air or ventilation gas and directs the mixed aerosol into
the inlet end of the flow passage.
[0005] In accordance with another embodiment, an apparatus to
produce an aerosol comprises: a heated capillary aerosol generator;
an arrangement to produce a flow of heated air or ventilation gas;
and a mixer to mix the flow of heated air or ventilation gas with
an output of the heated capillary aerosol generator.
[0006] In accordance with a further embodiment, a method of
producing an aerosol comprises: generating an aerosol with a heated
capillary; and admixing heated air or ventilation gas with the
generated aerosol so as to reduce condensation.
[0007] In accordance with another embodiment, a method of
delivering an aerosol of a drug continuously to a remote location
comprises: generating an aerosol of the drug with a heated
capillary; admixing heated air or ventilation gas with the
generated aerosol so as to produce a heated aerosol of increased
flow rate; and communicating said heated aerosol along a passage to
said remote location.
[0008] In accordance with an embodiment, a delivery system is
disclosed, which includes a pumping unit; and an aerosol generating
assembly including, a heater assembly including, a heater body
extending in a longitudinal direction, and at least one heater in
the heater body, a capillary tube extending longitudinally through
at least a portion of the heater body, the pumping unit configured
to deliver a liquid to the capillary tube, the at least one heater
configured to heat the capillary tube to a temperature sufficient
to volatilize at least a portion of the liquid delivered to the
capillary tube, a thermocouple in the heater body, and a
temperature controller configured to control a heating.
[0009] In accordance with another embodiment, a delivery system is
disclosed comprising: a pumping unit; and an aerosol generating
assembly including, a heater assembly including, a heater body
extending in a longitudinal direction, and at least one heater in
the heater body, a capillary tube extending longitudinally through
at least a portion of the heater body, the pumping unit configured
to deliver a liquid to the capillary tube, the at least one heater
configured to heat the capillary tube to a temperature sufficient
to volatilize at least a portion of the liquid delivered to the
capillary tube, a thermocouple in the heater body, and a
temperature controller configured to control a heating.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 is a perspective view of a drug delivery system in
accordance with one embodiment having a disposable assembly housing
in an open position.
[0011] FIG. 2 is a perspective view of the drug delivery system of
FIG. 1 with the disposable assembly housing in a closed
position.
[0012] FIG. 3 is an exploded view of the drug delivery system of
FIGS. 1 and 2.
[0013] FIG. 4 is another exploded view of the drug delivery
system.
[0014] FIG. 5 is a perspective view of a disposable assembly of the
drug delivery system of FIG. 1.
[0015] FIG. 6 is a side view of the disposable assembly of FIG.
5.
[0016] FIG. 7 is an exploded view of the disposable assembly of
FIG. 5.
[0017] FIG. 8A is a perspective view of the valve assembly of the
disposable assembly of FIG. 5.
[0018] FIG. 8B is a schematic diagram of the valve assembly.
[0019] FIGS. 8C-8E are schematic diagrams of the valve assembly and
the syringe pumps in accordance with an embodiment.
[0020] FIG. 9 is a chart showing the benefit and effectiveness of
periodically increasing the flow rate.
[0021] FIG. 10 is a cross-sectional view of one of the valves of
the valve assembly as shown in FIG. 8A.
[0022] FIG. 11 is a perspective view of a drug delivery system in
accordance with another embodiment.
[0023] FIG. 12 is a top view of the base unit of the drug delivery
system of FIG. 11.
[0024] FIG. 13 is a side view of the base unit of the drug delivery
system of FIG. 11.
[0025] FIG. 14 is a perspective view of the heater body or
subassembly of the drug delivery system of FIG. 11.
[0026] FIG. 15 is a perspective view of the disposable assembly of
the drug delivery system of FIG. 11.
[0027] FIG. 16 is an exploded view of the disposable assembly of
FIG. 15.
[0028] FIG. 17 is a block diagram of a drug delivery system in
accordance with an embodiment.
[0029] FIG. 18 is a chart of a drug delivery system showing drug
concentration (milligrams per liter of air) versus flow rate (liter
per minute) in accordance with an embodiment.
DETAILED DESCRIPTION
[0030] Aerosols are useful in a wide variety of applications. For
example, it is often desirable to treat respiratory ailments with,
or deliver drugs by means of, aerosol sprays of finely divided
particles of liquid and/or solid, e.g., powder, medicaments, etc.,
which are inhaled into a patient's lungs. Aerosols can be generated
from a heated capillary aerosol generator by feeding a solution or
suspension in a liquid state to a capillary while heating the
capillary sufficiently such that the solution (or the carrier
portion of the suspension) is volatilized, so that upon discharge
from the heated capillary, the solution (or suspension) is in the
form of an aerosol. The length of the capillary can depend on heat
requirements dictated by, among other factors, the composition of
the aerosol to be generated. A potential problem associated with
directly heated capillary aerosol generators is broad temperature
variations inside the capillary tube that may lead to overheating
and substandard aerosol formation, resulting in clogging of the
capillary tube and/or failure of a capillary aerosol generator.
[0031] In accordance with one embodiment, the aerosol generating
system can be used to aspirate a liquid material or formulation
from a disposable assembly (i.e., a container closure system), and
dispense it through an aerosol generator or capillary tube
sub-assembly for delivery of a continuous aerosolization.
[0032] In accordance with another embodiment, a thermally
conductive heater block encases a capillary passage through a
block, such as a capillary tube, such that the thermally conductive
heater block maximizes heat transfer substantially evenly and
uniformly from the thermally conductive heater block to the
capillary tube. In accordance with one embodiment, the thermally
conductive heater block is preferably a stainless steel block
having an upper half and a lower half, which is adapted to receive
an aerosol generator in the form of a capillary tube, and heater
cartridges and electrical leads attached to the heater cartridges.
The electrical leads are connected to a power source. The power
source is selected in view of the characteristics of the components
of the aerosol generator.
[0033] In accordance with a further embodiment, the drug delivery
system is able to provide a method for controlling the fluid flow
from a source to an output at high pressure and to allow fluid flow
and stop flow under high pressure (i.e., at least 2000 psi) in a
disposable and low cost system.
[0034] In operation, the electrical leads transfer power from the
power source to the heater cartridges that are inserted into the
thermally conductive heater block, thereby heating the thermally
conductive heater block. When heated, the thermally conductive
heater block transfers heat to the aerosol generator or capillary
tube and thus substantially evenly and uniformly heats the
capillary tube to a temperature sufficient to at least partially
volatilize the liquid material or the liquid formulation that is
introduced to the heated capillary tube. For example, the at least
partially volatilized liquid material or liquid formulation can be
driven through a restrictor to atomize the liquid material or
formulation. The volatilized material mixes with ventilation gas
supplied by a heated sheath gas source within an aerosol
confinement member at a distal end of the heater block and forms an
aerosol.
[0035] Liquid material is preferably introduced into the capillary
tube through an inlet of the capillary tube connected to a source
of liquid material. The volatilized material is driven out of the
capillary tube through the outlet of the capillary tube, i.e., the
back pressure of the liquid from the source of liquid material
causes the liquid to be ejected from the outlet.
[0036] Electrical current passed directly through a conductive
capillary tube may provide uneven heating across the length of the
capillary tube, with temperature variations inside the capillary
tube on the order of about 50 degrees Celsius (.degree. C.) to 100
degrees Celsius (.degree. C.). In contrast, a heater block and
heated capillary aerosol generator provides substantially even and
uniform heating across the heated length of the capillary tube.
Because the thermally conductive material of the heater block has a
mass that is preferably at least about ten times the mass of
.sub.the capillary tube and the heater cartridges are preferably
positioned longitudinally within the heater block, the temperature
inside the capillary tube preferably varies by less than about
5.degree. C. Further, by providing electrical energy to the heater
cartridges in a controlled manner, the temperature inside the
capillary tube can be accurately maintained.
[0037] Since the heater block provides substantially even and
uniform heat distribution along the length of the capillary tube,
liquid material or volatilized liquid material can be heated to a
desired temperate range without overheating the liquid. Overheating
can impair aerosol formation and/or result in clogging of the
capillary tube and/or failure of an aerosol generator.
[0038] In accordance with one embodiment, the drug delivery system
includes an aerosol generator and a heater block, wherein the
temperature of the heater block and the thermally conductive
material is heated to and maintained at an operating temperature
(i.e., a temperature at which liquid material in the capillary tube
is volatilized), which is in the range of about 250.degree. C. to
400.degree. C. Accordingly, it would be desirable to provide a
constant, uniform temperature source for a medical or drug delivery
system having an aerosol generator, and wherein a liquid
formulation is partially volatilized to form an aerosol for
inhalation.
[0039] FIG. 1 shows a perspective view of a drug delivery system 10
(or aerosol generation system) in accordance with one embodiment.
As shown in FIG. 1, the drug delivery system 10 comprises a base
unit 20, which is adapted to receive a disposable assembly 40 in
the form of a sterile disposable fluid system. The base unit 20 is
comprised of a housing 22, a disposable assembly housing 30 adapted
to receive the disposable assembly 40, a compact reconfigurable
input/output (I/O) controller assembly 36 (FIG. 3) and a user
interface 24. The user interface 24 can be a touch screen panel as
shown in FIG. 1, or other suitable interface system for input of
information and receiving of operational data from the system
10.
[0040] The disposable assembly housing 30 is preferably comprised
of a clam-shell like housing, which is adapted to receive the
disposable assembly 40. The disposable assembly 40 preferably
includes a heater block subassembly 90 with an aerosol generator
unit 50 (FIG. 7) therein. As shown in FIG. 1, the disposable
assembly housing 30 in the base unit 20 is comprised of an upper or
first half 32 and a lower or second half 34, which is adapted to
surround the disposable assembly 40 in a clam-shell configuration,
including a handle for ease of opening and closing of the housing
30. The disposable assembly 40 fits within the lower or second half
of the housing 30, and ensures that the components of the
disposable assembly 40 are matched to their respective connections
within the base unit 20.
[0041] In use, the heater block subassembly 90 has an indirect
heating block 150 (FIG. 7), which encases an aerosol generator (or
aerosol generating unit) 50, for heating a liquid material or
liquid formulation, which is pumped through the aerosol generator
unit 50 at a constant and continuous rate by a pumping unit 260. In
accordance with an embodiment, the pumping unit 260 includes two
syringe pumps 262, 264 and a valving arrangement or assembly 60
operable to supply liquid formulation into an inlet of one syringe
pump 262, 264 during delivery of liquid formulation to the aerosol
generator unit 50 by the other syringe pump 262, 264.
[0042] FIG. 2 shows a perspective view of the drug delivery system
10 of FIG. 1 with the disposable assembly housing 30 in a closed
position. The disposable assembly 40 is attachable to a source of
liquid material or liquid formulation 136 (FIG. 5), which is
partially vaporized to form an aerosol. As shown in FIGS. 1 and 2,
the housing 22, the disposable assembly housing 30, the compact
reconfigurable input/output (I/O) controller assembly 36 and the
user interface 24 are preferably part of and/or incorporated into
the base unit 20 of the aerosol generating system 10. It can be
appreciated that since the disposable assembly 40 is disposable,
the aerosol generating system 10 is much more attractive from a
cost standpoint, since the system 10 can be reused in a hospital
setting.
[0043] In accordance with one embodiment, the capillary aerosol
generating system 10 is adapted to continuously deliver a liquid
material or liquid formulation 136 as an aerosol, wherein the
liquid material or formulation 136 is heated in an aerosol
generator 50 to partially volatize at least some of the liquid
material or liquid formulation 136. In accordance with a preferred
embodiment, the liquid material or liquid formulation 136 is
Surfaxin.RTM. manufactured by Discovery Laboratories, Inc. In the
formation of an aerosol, the liquid material or liquid formulation
136 is pumped through an aerosol generator 50 preferably in the
form of a heated capillary tube. The aerosol generating system 10
can be comprised of a base unit 20 and wetted components including
a sterile disposable fluid system or disposable assembly 40. In
accordance with one embodiment, the base unit 20 preferably
includes an enclosure or housing 22, a pumping unit 260 having a
pair of syringe pumps 262, 264, a compact reconfigurable
input/output (I/O) controller assembly 36 and a user interface
24.
[0044] The liquid material or liquid formulation 136 will
preferably be a refrigerated formulations such as a surfactant, or
other suitable material. The liquid material or liquid formulations
136 are preferably contained within a refrigerated dose packet 350
(FIG. 17) having an outer protective foil bag. The refrigerated
liquid material or liquid formulation 136 is preferably heated
using a hot plate/stirrer 300 (FIG. 17) or other suitable heating
device to form a suitable formulation for delivery to the syringe
assembly 70. It can be appreciated that these formulations 136 are
usually quite viscous, although they comprise mostly water.
[0045] FIG. 3 shows an exploded view of the drug delivery system 10
of FIGS. 1 and 2. As shown in FIG. 3, the drug delivery system 10,
the housing 22 is comprised of a front panel assembly 21, a left
side panel assembly 23, a right side panel assembly 25, a base
panel assembly 27 and a back panel assembly 29, a vent panel
assembly 31, a compact reconfigurable input/output (I/O) controller
assembly 36 and a touch screen panel assembly 24. The base unit 20
is adapted to house the electric components, printed circuit boards
(PCB), power source, flow controllers, thermocouple devices and
controls, voltage control coil, motors, fans to cool the unit, and
other related digital and electronic devices for operation of the
drug delivery system 10. The system 10 can also include a flow
controller 41 having a line 43 into the flow controller 41 from a
source of pressurized gas (such as a pressurized ventilation gas
line in a hospital room) and a line 45 from the flow controller 41
to an underside of the housing 30.
[0046] FIG. 4 shows another exploded view of the drug delivery
system 10. As shown in FIG. 4, the base unit 20 includes further
includes a top panel assembly 33 and a top panel assembly cover 35.
The base unit 20 also preferably includes a control system, such as
a compact reconfigurable input/output (I/O) controller assembly 36,
which is operable to activate the aerosol generator unit 50 and the
pumping unit 260.
[0047] In accordance with one embodiment, the compact
reconfigurable input/output (I/O) controller assembly 36 effects an
initial filling of the syringe pumps 262, 264 via retraction of a
first piston 265 of the first syringe pump 262 and a second piston
267 of the second syringe pump 264 while maintaining the first and
third valves 116, 120 (FIG. 6) in an open position and the second
and fourth valves 118, 122 in a closed position. The liquid
formulation 136 is delivered to the aerosol generator unit 50 via
advancement of the first piston 265 while maintaining the first and
fourth valves 116, 122 in a closed position, and activating the
second syringe pump 264 near the end of a delivery cycle of the
first syringe pump 262 via advancement of the second piston 267
while maintaining the fourth valve 122 in an open position and the
third valve 120 in a closed position. The refilling of the first
syringe pump 262 is performed via retraction of the first piston
265 while maintaining the first valve 116 in an open position and
the second valve 118 in a closed position, and activating the first
syringe pump 262 near the end of the delivery cycle of the second
syringe pump 264 via advancement of the first piston 265 while
maintaining the second valve 118 in an open position and the first
valve 116 in a closed position.
[0048] FIG. 5 shows a perspective view of the disposable assembly
40 (or sterile disposable fluid system). As shown in FIG. 5, the
disposable assembly 40 preferably includes a valve assembly 60, a
syringe assembly 70, an input fluid tube assembly 80, a heater
block subassembly 90, and a fluid trap assembly 100. In accordance
with a preferred embodiment, the disposable assembly 40 includes a
combination of disposable and reusable parts. The disposable parts
include a capillary flow tube 158 (FIG. 7) through which the liquid
formulation 136 is ejected as an aerosol, and the wetted parts of
the pumping unit 260, including a screening member (not shown)
operable to trap particles in the liquid formulation 136 above a
predetermined size. In accordance with a preferred embodiment, the
screening member is located upstream of the inlet to the aerosol
generator unit 50.
[0049] It can be appreciated that a fluidic element (not shown) can
be positioned between the valve assembly 70 and the aerosol
generation unit 50 to stabilize the nominal operating pressure
within the capillary passage 158 of the aerosol generating unit 50.
The fluidic element increases the threshold backpressure for
aerosolization (i.e., the minimum pressure needed to keep the flow
consistent and capillary wet) and reduces the pressure oscillation
within the system as a result of the conversion of the liquid
material or formulation 136 to vapor and large particles within the
liquid material or formulation as is disclosed in commonly assigned
copending U.S. patent application (attorney docket 1021238-000960)
filed on Oct. 2, 2007, the disclosure of which is incorporated
herein by reference in its entirety.
[0050] A patient interface in the form of a continuous positive air
pressure ventilator adaptor (e.g., nosepiece or mouthpiece) (not
shown) can also be included with the disposable assembly 40. In
accordance with one embodiment, the continuous positive airway
pressure ventilator adaptor (e.g., nosepiece or mouthpiece) also
includes a pharyngeal tube that cooperates with a ventilator.
Mouthpieces for aerosol generators have been described in U.S. Pat.
No. 6,701,922, the contents of which are hereby incorporated by
reference in their entirety.
[0051] The system 10 also includes at least one condensate
collector or fluid trap assembly 100 adapted to collect condensed
liquid or liquid produced by the aerosol generator 50. The flow
tube 104 includes an inlet end 105 in fluid communication with an
outlet 191 of the aerosol generator 50 and an outlet (not shown)
adapted for connection to a patient interface, which supplies
ventilation gas to a patient's lungs.
[0052] FIG. 6 shows a side view of the disposable assembly 40 as
shown in FIG. 5. As shown in FIG. 6, the disposable assembly 40
includes a 4-valve assembly 60, a syringe assembly 70, an input
fluid tube assembly 80, a heater block subassembly 90, and a fluid
trap assembly 100. As shown in FIG. 6, the disposable assembly 40
also includes a pair of sheath gas inlets 155 on a lower surface of
the heater block subassembly 90.
[0053] The at least one condensate collector or fluid trap assembly
100 includes a bowl or fluid trap 102, a bowl top 103 for the fluid
trap 102, and a flow tube or tubing 104. The flow tube or tubing
104 is attachable to an additional tubing section (not shown),
which is attachable to a patient interface in the form of a CPAP
adaptor, nosepiece or mouthpiece.
[0054] FIG. 7 shows an exploded view of the disposable assembly 40.
As shown in FIG. 7, the valve assembly 60 includes an inlet 110 in
the form of an input barb fitting, a pair of tubing adaptors 112,
114, a plurality of valves 116, 118, 120, 122, and an outlet or
output port 124. The valve assembly 60 also includes a plurality of
flow channel supports 113, 115, 117, which are attached to the pair
of tubing adaptors 112, 114, the plurality of valves 116, 118, 120,
122, and the outlet or output port 124. The valve assembly 60 will
preferably be controlled mechanically through a valve control
assembly or control system.
[0055] The valving arrangement or valve assembly 60 as shown in
FIG. 7 includes an inlet 110 which can be connected to a source of
a liquid formulation 136, first and second flow paths in fluid
communication with the inlet 110, an outlet or output port 124 in
fluid communication with an inlet of the aerosol generator or
aerosol generation unit 50, first and second valves 116, 118 along
the first flow path and third and fourth valves 120, 122 along the
second flow path, the valves 116, 118, 120, 122 arranged such that
the first flow path supplies liquid formulation 136 to the first
syringe pump 262 when the first valve 116 is open and the second
valve 118 is closed, the second flow path supplies liquid
formulation to the second syringe pump 264 when the third valve 120
is open and the second valve 118 is closed, the first flow path
supplying liquid formulation to the aerosol generator 50 when the
first valve 116 is closed and the second valve 118 is open, and the
second flow path supplying liquid formulation to the aerosol
generator 50 when the third valve 120 is closed and the fourth
valve 122 is open.
[0056] The syringe assembly 70 is comprised of a pair of syringes
130, a pair of syringe O-rings 132 and a dual syringe block holder
134. The syringes 130 include a barrel 131 and a plunger (or rod)
133. The plunger or rod 133 of the syringes 130 is adapted to fit
within the syringe pumps 262, 264 of the pumping unit 260. In
accordance with one embodiment, the syringes 130 are preferably
comprised of two 1 ml syringes, which are adapted to aspirate and
dispense the liquid material or formulation 136 from the container
closure system 350. However, it can be appreciated that other size
syringes can be used depending on the different components and uses
of the system 10.
[0057] The input fluid tube assembly 80 is comprised of a spike
140, a spike protector or tube 142, a spike tubing assembly 144,
and a tubing clamp 146. As shown in FIG. 5, the syringe assembly 70
includes an input line 110 from the container closure system 136
(FIG. 7) and an output line 124 to the capillary tube, which is
contained within the heater block subassembly 90. After the initial
priming cycle, at any given time, one syringe 130 will dispense and
the other syringe 130 will aspirate. Each of the syringes 130 will
have two halves, one for the container closure system 350 and the
other to the capillary tube 158 or aerosol generator unit 50.
[0058] The syringe pumps 262, 264 (FIG. 2) will preferably include
drive trains and control electronics to allow simultaneous
operation of the dual syringes 130 in order to dispense liquid
material or liquid formulation 136 continuously. The programmable
automation controller will also preferably generate the signals for
opening and closing of the valves 116, 118, 120, 122. It can be
appreciated that pump parameters such as dispense rate, aspiration
rate, handshake parameters, etc. will preferably reside local to
the automation controller and can be changed by an independent user
interface such a laptop computer or other suitable input device.
The functions of priming, start, stop, and pause for the pumping
unit 260 can also be generated by the main user interface and will
be communicated through a programmable automation controller.
[0059] In accordance with one embodiment, the pumping unit 260
should be able to support backpressures of up to at least 2,000
psi, and more preferably up to 3,000 to 4,000 psi. In addition, the
syringe pumps 262, 264 are preferably mounted in a fluid resistant
enclosure, and can include a force sensor on each syringe-mounting
bracket to monitor the plunger force during fluid delivery. The
syringes 130 can be installed with a minimum of mechanical locking
to the pump, such that the syringes 130 may not require wire
connections on the syringe end of the pump (where the mechanical
valves will be placed). In addition, the programmable automation
controller can include a flow meter (not shown) within the dual
syringe pumps to control the sheath gas flow rate before it enters
the disposal. The pumping capacity of the syringe pumps 262, 264
facilitate handling of highly viscous formulations 136 such as
Surfaxin.RTM..
[0060] The heater block subassembly 90 includes a heater block 150
comprised of an upper or top assembly 152 and a lower or bottom
assembly 154, a thermocouple 156, and an aerosol generator unit 50
in the form of a capillary tube 158. The aerosol generator unit 50
includes a capillary passage in which the liquid formulation 136 is
at least partially volatilized, a heater body or block assembly 150
operable to heat the capillary passage to a temperature range
effective to at least partially volatilize liquid formulation in
the capillary passage or tube 158, and at least one ventilation gas
passage arranged such that air is heated by the heater body or
block 150 and the heated air is combined with the aerosols produced
by the aerosol generator unit 50.
[0061] As shown in FIG. 7, the heater body or heater block 150 is
comprised of two assemblies (i.e., an upper assembly and a lower
assembly) 152, 154, which includes at least one longitudinally
extending bore 165 and more preferably two (2) longitudinally
extending bores 165 adapted to receive a heater element 164. The
heater element 164 is preferably 30-watt heater cartridges;
however, it can be appreciated that any suitable watt heater
cartridge can be used. It can also be appreciated that the heater
block subassembly 90 can include any suitable heating system
including heated coils and/or wires. The two assemblies 152, 154
are preferably constructed of a thermally conductive material, such
as stainless steel or other suitable material. In use, the
thermally conductive material forming the heater body or heater
block 150 is heated to and maintained at an operating temperature
to volatilize at least some of the liquid material therein.
[0062] The thermocouple 156 is preferably incorporated into the
heater block subassembly 90. In accordance with one embodiment, the
thermocouple 156 is preferably incorporated into either the upper
and lower assemblies 152, 154, such that the placement of the
thermocouple 156 ensures accurate temperature monitoring. By
utilizing the thermocouple 156 as a feedback device, a closed loop
temperature control system can be used to control the temperature
of the capillary tube 158.
[0063] The capillary tube 158 can include a feed tube end or
proximal end 160, and a domed capillary end or distal end 162. The
capillary tube 158 preferably has an inside diameter in the range
of about 0.05 to 0.53 millimeters, and more preferably in the range
of about 0.1 to 0.2 millimeters. The feed tube end 160 is
preferably circular in cross-section with a domed capillary end 163
on the distal end 162 of the capillary tube 158. A particularly
preferred inside diameter of the capillary tube 158 is
approximately 0.1905 mm (or 0.0075 inches). In accordance with one
embodiment, the capillary tube 158 has a length of approximately 90
mm to 120 mm, and more preferably 100 mm to 110 mm. However, it can
be appreciated that the length of the capillary tube 158 is based
on the flow rate of the liquid formulation or liquid material 138
within the capillary tube 158.
[0064] In accordance with one embodiment, the capillary tube 158 is
a tipped capillary as described in U.S. Publication No.
20050235991, the contents of which are hereby incorporated by
reference in their entirety. As described in U.S. Publication No.
20050235991, the capillary tube 158 can include a constriction in
the form of a domed capillary end or formed tip 163 at the outlet
or distal end 162 of the flow passage. In accordance with a
preferred embodiment, the distal end 162 of the flow passage has an
opening in the range of 1000 to 5000 square microns and more
preferably, the opening is in the range of 2000 to 3000 square
microns.
[0065] It can be appreciated that the domed capillary end or formed
tip 163 can be formed by any suitable technique. For example, the
domed capillary end or formed tip 163 can be formed by inserting a
mandrel, such as a cylindrical wire, a desired distance into the
flow passage, and then deforming the capillary tube 158 around the
mandrel, such as by crimping. The mandrel can have a desired
cross-sectional shape and cross-sectional area that define the
desired size and shape of the flow section. In alternative
embodiment, the tip 163 of the capillary tube 158 can be formed by
welding closed an end of the capillary tube 158 to form a domed
closure. An opening is then made in the domed closure by drilling,
laser cutting, or electrical discharge machining (EDM) a hole of
desired smaller diameter. Alternatively, a tipped or domed
capillary end or formed tip 163 can be formed by attaching a metal
cap to one end of a capillary by press fitting the cap to the
capillary or by welding the cap in place. Either before or after
attaching the cap to the capillary, a laser can be used to drill an
orifice in the metal cap of a diameter that is less than the
capillary's inner diameter. Another method for forming a tipped
capillary by electrolytic deposition of layers of metal within a
capillary tube, wherein the method involves dipping a desired
length the capillary tube into an appropriate electrolyte solution
and electroplating the dipped length with metal.
[0066] The capillary tube 158 may be comprised of a metallic or
non-metallic tube, however, in one preferred embodiment; the
capillary tube 158 is preferably made of a nickel-based super alloy
such as Inconel.RTM.. In accordance with another embodiment, the
capillary tube 158 may be comprised of stainless steel or
glass.
[0067] Alternatively, the capillary assembly or tube 158 may be
comprised of, for example, fused silica or aluminum silicate
ceramic, or other substantially non-reactive materials capable of
withstanding repeated heating cycles and generated pressures and
having suitable heat conduction properties may also be used. Since
the heater block 150 is in thermal contact with the capillary tube
158, capillary tubes 158 with low or high electrical resistance may
be used. If desired or necessary, an inside wall of the capillary
tube 158 may be provided with a coating for reducing the tendency
of material to stick to the wall of the capillary tube 158, which
may result in clogging.
[0068] The heater block subassembly 90 also can include a ferrule
172, a capillary seal 174, an airway sleeve 176, a peek filter 178,
a front filter holder 180, a back filter holder 182, an electrical
connector 184, a bottom heater holder 186, a top heater holder 188,
an aerosol confinement member or transition adaptor 190, and a
drain tube assembly 192. The drain tube assembly 192 can include
drain bag tubing 194 for the drain bag (not shown), a male
connector 196 and a female connector 198. The female connector 198
is attachable to a drain bed for condensate, which has been
collected by the transition adaptor 190. The bottom heater holder
186 can also include a pair of inlets 187, which are adapted to
releasably engage with the bottom half of the housing 30 and
communicates the output air lines 45 of the air flow controller 41
with an annular channel or gap, which is defined between the heater
block 150 and the heater holder 186, 188. The heater block 150 and
the heater holder 186, 188 are separated by an annular channel or
gap of approximately 0.0125 to 0.50 of an inch, and more preferably
an annular channel or gap of about 0.0625 of an inch.
[0069] In one embodiment, the aerosol confinement member 190
captures the aerosols produced by the capillary tube 158 of the
aerosol generator 50 and directs the aerosol into the inlet end 105
of the flow tube 104. The aerosol confinement member 190 is
preferably sealed to the capillary tube 158 of the aerosol
generator unit 50, and allows heated air delivered to the
transition adaptor 190 to be mixed with the aerosol produced by the
capillary tube 158 of the aerosol generator unit 50. The aerosol
confinement member 190 can include at least one baffle therein
and/or a drainage port 193 at a lower end thereof adapted to attach
to a condensate collection device or drain tube assembly 192.
[0070] In accordance with another embodiment, the aerosol
confinement member 190 can be adapted to receive a supply of heated
sheath air received from the heater block subassembly 90. The
heater block subassembly 90 preferably includes at least one inlet
155 on a proximal end of the heater block subassembly 90, which
receives a ventilated or hospital air supply, which is inserted
into the heater block subassembly 90 and is heated or warmed by the
heater block 150 forming a circumferential ring or cone of warmed
air, which is admixed with the vaporized or volatized liquid
formulation at the distal end of the heater block subassembly 90
within the aerosol confinement member 190. The admixing of the
heated or warm air with the aerosol reduces condensation of the
formulation. It can be appreciated that since the liquid
formulation 136 is comprised primarily of water (up to 90% or
higher; e.g., the formulation for infants can be approximately 99%
water), the heated or warm air reduces the amount of condensation
produced after vaporization or volatization of the liquid
formulation 136. The admixing of heated air at the transition
adapter 190 allows the warmer air to hold more water and moves the
water-moist system away from saturated conditions, and further the
additional flow rate of air further moves the moist system away
from saturated conditions. Thereby condensation at and about the
capillary discharge is minimized, such that condensate build-up is
minimized and flow rate conditions are made conducive to remote
delivery such as via the aerosol tube or flow tube 104. It can be
appreciated that the air supply is preferably heated to about 125
to 145 degrees Celsius and more preferably about 135 degrees
Celsius.
[0071] In accordance with one embodiment, the heater block 150 is
preferably heated to about 250.degree. C. to 300.degree. C., and
more preferably about 275.degree. C. The hospital air flow can also
be heated by passing air along the heater blocks 152, 154, or other
suitable heating methods including heating the air flow with a
discrete heater that is remote of the capillary tube 158, in lieu
of or in addition to use of the heat generated at or about the
capillary tube 158. It can be appreciated that in an alternative
embodiment, the sheath air supply can be supplied without heating
thereof.
[0072] In accordance with one embodiment, the source of pressurized
air connected to the aerosol confinement member 190 is preferably
supplied via a metering pump that drives an airstream along the
heater block 150 at a predetermined flow rate in the range of about
1 L/min to 6 L/min (liters per minute).
[0073] It can be appreciated that to provide sheath air to entrain
the emitted aerosol efficiently and carry it to a continuous
positive airway pressure (CPAP) adaptor located at the patient.
Typically, a CPAP ventilator, such as the InfantStar 950
manufactured by Puritan-Bennett of Carlsbad, Calif., creates a
backpressure of approximately 6 to 10 inches H.sub.2O (water), at
the continuous positive airway pressure (CPAP) adaptor. This
backpressure at the adaptor requires the sheath air source to be
sealed to provide control of the sheath airflow rate, which can
affect aerosol delivery efficiencies. Accordingly, in accordance
with one embodiment, the heater block subassembly 90 is preferably
injection molded to reduce cost and inserted into the aerosol
generator unit 50 with a pump as shown in FIGS. 1 and 2. It can be
appreciated that by the addition of the heater block subassembly
90, a sheath air sleeve can be formed on an outer periphery of the
heater block 150, such that the sheath air sleeve can be used to
help distribute air more evenly around the disposable assembly
housing 30 as the air is heated as the air flows over the
disposable assembly housing 30.
[0074] It can be appreciated that the valve assembly 60 will
include a valve control assembly, which will preferably be located
inside the dual syringe pumping unit 260, such that the dual
syringe pumping unit 260 and the valve control assembly will
preferably be mechanically aligned. The valve control assembly will
hold the part of the disposal fluid system or disposable assembly
40 that contains the disposable valve block assembly 60 and the
capillary subassembly 90. The programmable automation controller
will perform the control of the flow meter. A valve control box
located within the base unit 20 will preferably include an access
door adapted to keep the disposable closed during the operation,
and to provide a means for mechanical support to hold the
disposables in place inside the box. When the disposables are
installed in the valve box, a secure mechanical connection can be
made between a capillary ring located in the disposable to the
valve control box. An electrical connection can be made from a
printed circuit board (PCB) to the disposable.
[0075] The valve control box will preferably contain a plurality of
drive trains or linear actuators, control valve electronics, a flow
meter and a controller. The drive trains or linear actuators will
preferably be four (4) in number, wherein each of the drive trains
is used to control the opening and closing of the valves 116, 118,
120, 122 in the disposable valve assembly 40. In operation, the
signals to open and close the valves 116, 118, 120, 122 will
preferably come from the pump. The control valve electronics will
consist of four linear actuators, four printed circuit boards
(PCB's), and a stepper drive, which can be driven from a 15V or a
24V power supply. In operation, the pump will preferably generate
speed, direction, and an enabling signal for each stepper drive.
The system 10 will also include an electrical connection between
the stepper drives and each actuator. The flow meter and a
controller can be used to take the air from an outside source and
control it before it enters the disposable valve assembly.
[0076] The system 10 can also include at least two LED fluid
sensors to monitor the flow in the output lines on the disposable
valve assembly 60. One printed circuit board (PCB) for controlling
the LED's. The system 10 also preferably includes a safety device
for ensuring and monitoring that the door is closed, and a safety
device for ensuring and monitoring that the aerosol tube is
connected at the end of the capillary. The heating of the capillary
tube 158 will be controlled by any suitable microprocessor or
programmable automation controller (PAC), such as the Compact RIO
sold by National Instruments.RTM..
[0077] FIG. 8A shows a perspective view of the valve assembly 60.
As shown in FIG. 8, the valve assembly 60 is comprised of an inlet
110 in the form of an input barb fitting, a pair of tubing adaptors
112, 114, a plurality of valves 116, 118, 120, 122, and an outlet
or output port 124. The valve assembly 60 also includes a plurality
of flow channel supports 113, 115, 117, which are attached to the
pair of tubing adaptors 112, 114, the plurality of valves 116, 118,
120, 122, and the outlet or output port 124.
[0078] FIG. 8B shows a schematic diagram of a pumping unit and
valve assembly 60. The valving arrangement or valve assembly 70
includes an inlet 110, which can be connected to a source of a
liquid formulation 136, first and second flow paths 121, 123 in
fluid communication with the inlet 110, and an outlet 124 in fluid
communication with an inlet of the aerosol generator unit 50. As
shown in FIG. 8B, the first and second valves 116, 120 are located
along the first flow path 121, and the third and fourth valves 118,
122 are located along the second flow path 123. In accordance with
one embodiment, the valves 116, 118, 120, 122 are arranged such
that the first flow path 121 supplies liquid formulation 136 to the
first syringe pump when the first valve 116 is open and the second
valve 118 is closed, while the second flow path 123 supplies liquid
formulation 136 to the second syringe pump when the third valve 120
is open and the fourth valve 122 is closed. The first flow path 121
also supplies liquid formulation 136 to the aerosol generator unit
50 when the first valve 116 is closed and the second valve 118 is
open. In addition, the second flow path 123 supplies liquid
formulation to the aerosol generator unit 50 when the third valve
120 is closed and the fourth valve 122 is open.
[0079] More particularly, now referring to FIGS. 8C, 8D and 8E, the
first and second syringe pumps 130a and 130b are alternately
communicated with the capillary 158 of the aerosol generator system
50 during their respective delivery strokes and alternately are
communicated with the fluid (formulation) source 136 during their
respective drawing (aspirating) stokes, with all such actions being
executed in cooperation with valves 116, 118, 120, 122.
[0080] Referring specifically to FIG. 8C, when the first syringe
pump 130a is discharging, its output is directed along a flow path
"x1" from the first syringe pump 130a to the capillary 158. The
flow path x1 is established by closure of the valve 116 and the
opening of valve 118. At the same time, the second syringe pump
130b is executing its aspirating stroke to draw fluid from the
source 136 through channel 144 and inlet 110 along a path
designated "x2" in FIG. 8C. In order to establish this flow path
x2, the valve 120 is opened and the valve 122 is closed.
[0081] Referring to FIG. 8D, the system is approaching the end of
the discharge stroke of the first syringe pump 130a; and in
accordance with handshake parameters, the system is executing at
the same time for a brief period simultaneous initiation of a new
discharge stroke in syringe pump 130b. In this mode, the output of
the first syringe 130a is directed along the first flow path "y1"
to the capillary 158 which is established by closure of the valve
116 and the opening of the valve 118. Likewise, the output of the
second syringe pump 130b is directed along a path "y2" to the
capillary 158 via closure of the valve 120 and the opening of the
valve 122.
[0082] Referring now to FIG. 8E, the first syringe pump 130a is
executing its aspiration stroke wherein formulation is drawn from
the fluid source 136 along a path "z1" which is established by the
opening of valve 116 and closure of valve 118. At the same time,
the second syringe 130b continues to execute its discharge stroke
to supply the formulation along a path to "z2" to the capillary 158
via closure of valve 120 and the opening of the valve 122.
[0083] It is to be realized that as the second syringe pump 130b
completes its discharge stroke, the first syringe pump 130a will
have already completed its aspirating stroke and will have
initiated its discharge stroke in accordance with handshake
parameters. At that point, the flow through the system will
resemble that shown in FIG. 8D, except that the first syringe pump
130a will be in initiating its discharge stroke and the second
syringe pump 130b will be just completing its discharge stroke.
[0084] It can be appreciated that when dispensing certain liquids
through the capillary passage, with or without the intent to
aerosolize, the properties of the liquid or liquid formulation may
cause a coating, agglomeration, or deposits to form on the inside
the capillary passage 158. In addition, accumulation of such
material within the capillary or capillary passage can also lead to
clogging of the capillary or capillary passage. Accordingly, it
would be desirable to have a system and method of modulating or
changing the flow of the liquid formulation periodically to enable
a cleaning or flushing of any potential material within the system.
The modulating or changing of the flow of the liquid formulation
can also maintain a stable nominal operating pressure for the
system and provide a reliable aerosol of consistent quality.
[0085] In accordance with one embodiment, an aerosolization system
or drug delivery system 10 having improved reliability and the
robustness of a capillary aerosol generation system, can be
obtained by modulating or changing the flow of the aqueous or
liquid formulation 50 for a short duration to enable cleaning or
flushing of any potential material within the capillary passage or
capillary tube 158. In an aerosolization system or drug delivery
system 10 as shown in FIG. 7, the capillary passage and/or
capillary tube 158 is heated. When the aerosol is generated, the
system 10 can generate significant backpressure in the order of
1100 to 1200 psi, due to vaporization of the aqueous or liquid
formulation 136 and the pumping of the vapor/liquid formulation 136
through a reduced orifice or tipped capillary at the exit of the
aerosol generation unit 50. Large particles in the aqueous or
liquid formulation 136, and sub optimal vaporization can also cause
a gradual increase in pressure in the system up to 3000 to 3500
psi, at which point the material (or clogging particles) either is
ejected from the capillary passage or irreversibly clogs the
capillary passage or capillary tube 158.
[0086] In accordance with an embodiment, a method of dispensing a
liquid formulation in a drug delivery system to an aerosol
generation unit 50, includes the steps of dispensing a liquid
formulation 136 to a pumping unit 260; supplying the liquid
formulation 136 from the pumping unit 260 to a capillary tube 158
of an aerosol generation unit 50 at a first flow rate; vaporizing
at least a portion of the liquid formulation 136 within the
capillary tube 158 of the aerosol generation unit 50; and
periodically increasing the flow rate from a first flow rate to a
second flow rate. The flow rate returns to the first flow rate
after each of these short durations of increased flow. In
accordance with a preferred embodiment, the second flow rate is
preferably at least twice the first flow rate. It can also be
appreciated that the by increasing the flow rate within the system
10, the system 10 experiences an increase in the operating pressure
within the capillary passage of the aerosol generation unit 50.
[0087] In use with the system 10 as shown in FIG. 7, an example of
a system and/or method of dispensing a liquid formulation 136 to
maintain a clog free capillary can be achieved by periodically
increasing the flow rate from a pumping unit 260 to an aerosol
generation unit 50 with a defined pump cycle. In accordance with
one embodiment, a clog free capillary passage can be achieved by
the cleaning or flushing of any potential material within the
capillary or capillary passage by increasing the flow rate (i.e.,
the first flow rate, e.g., 20 microliters per second) from the
valving assembly 60 to a second flow rate. In accordance with one
embodiment, the second flow rate is at least two times the first
flow rate (i.e., approximately 40 microliters per second). In
addition, the increased flow rate is preferably for a short
duration (i.e., two (2) to four (4) seconds for a pump cycle of
approximately 50 seconds).
[0088] In a preferred embodiment, the periodic increase in flow
rate within the capillary or capillary passage does not include any
reduction in pressure within the capillary. It can be appreciated
that a reduction in pressure within the capillary can lead to
clogging of the capillary. Accordingly, the increase in flow rate
preferably coincides with the maintenance of the pressure within
the capillary and/or an increase in pressure within the capillary
tube 158.
[0089] For example, in accordance with one embodiment, the pumping
unit 260 dispenses the liquid formulation 136 at approximately 20
microliters per second (.mu.l/s) to a valving assembly 60 for
delivery to the capillary passage or capillary tube 158. The
valving assembly 60 includes a pair of syringes 130, wherein one
syringe dispenses for fifty seconds, after which it refills and the
other syringe dispenses for fifty (50) seconds. Thus, the natural
periodic handshake of syringes every fifty (50) seconds can be
taken advantage of as a convenient opportunity to increase the
liquid formulation 136 flow rate from 20 to 40 microliters per
second (.mu.l/s) for a short duration.
[0090] In accordance with another embodiment, the increase in flow
rate can be accomplished by dispensing from the second syringe
while the first syringe is still dispensing. In particular, an
overlap or increase in flow rate can occur for between two (2) to
four (4) seconds. In addition to increasing or doubling the flow
rate, the system 10 also preferably pressurizes the fluid or liquid
formulation 136 in the syringe to a value close to the operating
pressure before the syringe begins dispensing the liquid
formulation 136 to the aerosol generator 50.
[0091] In an alternative embodiment, a single syringe pump unit 130
can be used, wherein the flow rate is increased as part of the
delivery cycle. In accordance with a single syringe pump system,
the system 10 has a defined fill cycle, upon which a short burst or
periodic increase in the flow rate increases the operating pressure
and ejecting any material that may be accumulated inside the
capillary or capillary passage.
[0092] It can be appreciated that the timing of the periodic
increase in flow can be a function of the properties or
concentration of the liquid material or formulation 136, the flow
rate, and the aerosolization parameters. For example, a liquid
material or formulation 136 having a higher concentration (of
medicaments or other materials) will preferably require more
frequent increases in flow rate (i.e., flushes) than a liquid
formulation 136 having a lower concentration.
[0093] In accordance with another embodiment, the modulating or
changing of the first flow ale to a second flow rate can be
performed in a plurality of short bursts, wherein each of the
plurality of short bursts occurs for less than one second at a
frequency of one burst every 10 seconds or less. In addition, it
can be appreciated that by increasing the flow rate, an increase of
10 to 20 percent in the operating pressure within the system can be
achieved, which can prevent the buildup of any significant amount
of large accumulation inside the capillary tube 158.
[0094] An example of the benefit and effectiveness of a periodic
increase in flow rate in an aerosolization system is shown in FIG.
9. The first plot 81 shows the typical capillary pressure behavior
without any changes in flow rate. Due to any number of failure
modes, such as formulation particle size, sub optimal
aerosolization, etc., it can be seen that the pressure within the
capillary tube 158 rises over a period of a few seconds. In
accordance with one embodiment, the obstruction within the
capillary tube 158 is ejected from the capillary or results in an
irreversible clog. The second plot 83 shows the behavior when the
flow rate is doubled every 50 seconds. The doubling of the flow
rate for two (2) to four (4) seconds results in 10 to 20 percent
increase in the operating pressure of the liquid formulation, which
keeps the capillary clog free by preventing the buildup of any
significant amount of large particles inside the capillary. The
periodic increase in flow rate not only helps maintain a clog free
capillary, but can also provides a stable nominal operating
pressure and produces aerosols of consistent quality.
[0095] FIG. 10 shows a cross-sectional view of one of the plurality
of valves 116, 118, 120, 122. As shown in FIG. 10, the plurality of
valves 116, 118, 120, 122 are preferably comprised of a flexible
membrane 220 that can be pushed down to fill an inner cavity or
void 222 within a fluid passageway 224. The squeezing action plugs
both an entrance or entry port 226 and the exit port 228 of the
passageway 224. In addition, by keeping the cross sectional area of
the entrance and exit ports 226, 228 small, the forces necessary to
keep the flexible membrane 220 closed and stop the fluid flow is
relatively small. The small ports 226, 228 also reduce dead volume,
which improves system function by minimizing air pockets and
reducing priming time.
[0096] Since the flexible membrane 220 is considerably larger than
the entrance and exit ports 226, 228 it will see substantially
larger forces. It can be appreciated that the flexible membrane 220
must be mechanically restrained yet allow for movement in order to
fill the ridged cavity (upon closure). As shown, the membrane 220
is captured within a housing 230 that pinches an outer ring making
a fluid tight seal. The inner cavity 222 has a passage so that a
pusher 238 can actuate the membrane 220. A spring (not shown) can
be included to assure that the membrane 220 is always open when no
pressure (or vacuum) is present in the fluid lines. The spring
pushes against the pusher 238, which is embedded within the
membrane 220 to keep the membrane 220 in an open position. It can
be appreciated that any number of valve assemblies can be used into
a system to control the flow of fluid at different points in the
system 10. For example, as shown in FIG. 8A, the system 10 includes
a four (4)-valve assembly in conjunction with a dual syringe pump
to pump fluid at a constant rate at high pressure.
[0097] FIG. 11 is a perspective view of a drug delivery system 10
in accordance with another embodiment. As shown in FIG. 11, the
drug delivery system 10 includes a base unit 20, which is adapted
to receive a disposable assembly 40 in the form of a sterile
disposable fluid system. The base unit 20 is comprised of a lower
assembly or base 500 and a hinged upper assembly or cover 502
(i.e., pump top assembly). The base 500 and the hinged upper
assembly or cover 502 preferably include a latch mechanism or
system 506, which allows the hinged upper assembly or cover 502 to
be secured to the base 500 during use.
[0098] The base unit 20 includes a heater body or subassembly 400
comprised of a lower or bottom heater subassembly 410, an upper or
top heater subassembly 420, a lower or bottom sheath air
subassembly 430 and an upper or top sheath air subassembly 440. In
accordance with an embodiment, the lower or bottom subassembly 410
and the lower or bottom sheath air subassembly 430 are housed in
the base 500 of the base unit 20. The upper or top heater
subassembly 420 and the upper or top sheath air subassembly 440 are
housed in the hinged upper assembly or cover 502.
[0099] As shown in FIG. 11, the lower or bottom heater subassembly
410 includes a V-shaped heater core 412 having a channel or groove
413 adapted to receive the capillary tube 158 of the disposable
assembly 40. The lower or bottom heater subassembly 410 also
preferably includes an insulation core subassembly 414, which is
preferably comprised of a two piece insulation core subassembly 414
having a first half 416 and a second half 418, at least one
cartridge heater or heating unit (not shown), and a thermocouple
(not shown). The at least one cartridge heater or heating unit is
preferably comprised of at least two, and more preferably three
cartridge heaters, which are positioned within the insulation core
subassembly 414. The at least one cartridge heater and the
thermocouple preferably extend longitudinally within the insulation
core subassembly 414. It can be appreciated that in accordance with
an alternative embodiment, the heating unit is heated coils and/or
wires.
[0100] The lower or bottom sheath air subassembly 430 is preferably
comprised of a sheath air insulator or insulation member 432 having
a V-shaped groove or channel 434, which receives the sheath gas
tube subassembly 530 (FIG. 15) of the disposable assembly 40. At
least one cartridge heater or heating unit (not shown), and at
least one thermocouple (not shown) are preferably longitudinally
positioned within the lower or bottom sheath air subassembly 430.
The heater subassembly 400 also includes a heater assembly cover
441 and a sheath assembly cover 443 to prevent dissipation of heat
from the heater subassembly 400 to other parts of the system
10.
[0101] The upper or top heater subassembly 420 is preferably
comprised of a wedge core 422 having a protruding V-shaped portion
424, and a top heater insulation member 426. The upper or top
sheath assembly 440 is comprised of a sheath wedge core 442 with a
longitudinally extending channel or groove 444, and a top sheath
insulator or insulation member 446. Upon closing of the hinged
upper assembly or cover 502, the V-shaped portion 424 of the upper
or top heater subassembly 420, and the channel or groove 444 of the
sheath wedge core 424 are in physical contact (i.e., preferably
metal to metal) with the aerosol generator unit 50 and the sheath
gas tube subassembly 530 of the disposable assembly 40,
respectively.
[0102] In accordance with a preferred embodiment, only the lower or
bottom heater subassembly 410 and the lower or bottom sheath air
subassembly 430 include cartridge heaters or heating units and
thermocouples, such that only the lower or bottom heater
subassembly 410 and the lower or bottom air subassembly 430 are
heated. Alternatively, the upper heater subassembly 420 and the
upper sheath air subassembly 440 can also include heater cartridges
or heating units, and thermocouples to provide heat to the upper
heater subassembly 420 and the upper sheath air subassembly
440.
[0103] The heater body or subassembly 400 is preferably constructed
of a thermally conductive material, such as stainless steel or
other suitable material. In use, the thermally conductive material
forming the heater body or subassembly 400 is heated to and
maintained at an operating temperature to volatilize at least some
of the liquid material within the capillary tube 158 and/or heating
of the ventilator or hospital air supply within the sheath gas tube
subassembly 530.
[0104] The lower assembly or base 500 and the hinged upper assembly
or cover 502 also include a disposable assembly housing 30, which
is adapted to receive the disposable assembly 40. The disposable
assembly housing 30 is composed of an upper or first half 32, and a
lower or second half 34. During use, the disposable assembly 40
fits within the lower or second half 34 of the disposable assembly
housing 30 to ensure that the components of the disposable assembly
40 are matched to their respective connections within the
disposable assembly housing 30. The lower assembly or base 500 is
comprised of a housing 22, which houses the compact reconfigurable
input/output (I/O) controller assembly (not shown) and an external
user interface 24.
[0105] The housing 22 also preferably houses the electric
components, printed circuit boards (PCB), power source, flow
controllers, thermocouple devices and controls, voltage control
coil, motors, fans to cool the unit, and other related digital and
electronic devices for operation of the drug delivery system 10. In
accordance with one embodiment, the user interface 24 can include a
digital display and keypad as shown in FIG. 11, a touch pad as
shown in FIG. 1, or other suitable interface system for input of
information and receiving of operational data from the system
10.
[0106] FIG. 12 is a top view of the base unit 20 of FIG. 11 with
the hinged upper assembly or cover 502 in an open position. In
accordance with an embodiment, the disposable assembly housing 30
in the base unit 20 is comprised of an upper or first half 32 and a
lower or second half 34, which is adapted to surround the
disposable assembly 40 in a clam-shell configuration. The
disposable assembly 40 fits within the lower or second half of the
housing 30, and ensures that the components of the disposable
assembly 40 are matched to their respective connections within the
base unit 20. In accordance with one embodiment, the housing 30
includes a pair of valve guides or seats 450, 452.
[0107] The lower portion 32 of the disposable assembly housing 30
also includes a control system (not shown), which activates the
pumping unit 260. As shown in FIG. 12, the pumping unit 260
includes a syringe pump 262, which is housed in the disposable
assembly housing 30. It can be appreciated that pump parameters
such as dispense rate, aspiration rate, handshake parameters, etc.
will preferably reside local to the pump and can be changed by an
independent user interface such a laptop computer or other suitable
input device. In use, the heater assembly 400 encases the aerosol
generator (or aerosol generating unit) 50 and sheath gas tube
subassembly 530, for heating a liquid material or liquid
formulation 136, which is pumped through the aerosol generator unit
50 by the pumping unit 260, and heating a ventilator or hospital
air supply, respectively.
[0108] FIG. 13 is a side view of the base unit 20 of the drug
delivery system of FIG. 11. As shown in FIG. 13, the base unit 20
includes a base 500 and a hinged cover 502, which are attached to
one another via at least one hinge 504, and more preferably a pair
of hinges 504, a latching mechanism 506 and the heater body or
subassembly 400.
[0109] FIG. 14 is a perspective view of the heater body or
subassembly 400 of the drug delivery system of FIG. 11. As shown in
FIG. 14, the heater body or subassembly 400 includes a lower or
bottom heater subassembly 410, an upper or top heater subassembly
420, a lower or bottom sheath air subassembly 430 and an upper or
top sheath air subassembly 440. The lower or bottom heater
subassembly 410 includes a V-shaped heater core 412 having a
channel or groove 413 adapted to receive the capillary tube 158
within the disposable assembly 40. The sheath air subassembly 430
includes a sheath air insulator or insulation member 432 having a
cylindrical groove or channel 434, a cartridge heater (not shown),
and a thermocouple (not shown). The heater subassembly 400 also
includes a heater assembly cover 441 and a sheath assembly cover
443, which prevent the dissipation of heat from the heater
subassembly 400 to other parts of the system 10. The upper or top
heater subassembly 420 is comprised of a V-shaped or wedge core 422
having a V-Shaped portion 424, and a top heater insulation member
426. The upper or top sheath assembly 440 is comprised of a sheath
wedge core 442 with a longitudinally extending cylindrical groove
or channel 444, and a top sheath insulation member 446. The
cylindrical grooves or channels 434, 444 are configured to mate
with the cylindrical surface of the sheath air tube 532 (FIG.
16).
[0110] FIG. 15 is a perspective view of the disposable assembly 40
of the drug delivery system of FIG. 11. As shown in FIG. 14, the
disposable assembly 40 includes a syringe assembly 70 comprised of
a syringe 130, a valving arrangement or valve assembly 60 comprised
of a pair of valves 120, 122, an aerosol generator unit 50 having a
capillary tube 158, a sheath gas tube subassembly 530, and an
aerosol confinement member or transition adapter 190. The
disposable assembly 40 also includes a pair of support members 560,
562, which are attached at one end to the syringe assembly 70/valve
assembly 60 and at the other end to the aerosol confinement member
or transition adapter 190. The aerosol confinement member or
transition adapter 190 is preferably attached to at least one
condensate collector or fluid trap assembly 100 as shown in FIG. 7,
which includes a bowl or fluid trap 102, a bowl top 103 for the
fluid trap 102, and tubing or flow tube 104. The tubing or flow
tube 104 is attachable to an additional tubing section (not shown),
which is attachable to a patient interface in the form of a CPAP
adaptor, nosepiece or mouthpiece.
[0111] In accordance with an embodiment, as shown in FIG. 15, the
disposable assembly 40 preferably includes a syringe assembly 70
comprised of a single (i.e., one) syringe 130, and valve assembly
comprised of a pair of valves 120, 122, which are operable to
supply a liquid formulation 136 (FIG. 5) into a feed tube end or
proximal end 160 of the capillary tube 158 of the aerosol generator
unit 50. As shown in FIG. 15, the pair of valves 120, 122 is
preferably located perpendicular to the syringe 130 and the
capillary tube 158.
[0112] In accordance with one embodiment, the pumping unit 260
should be able to support backpressures of up to at least 2,000
psi, and more preferably up to 3,000 to 4,000 psi. In accordance
with one embodiment, the plunger or rod 580 of the syringe 130 is
adapted to fit within the syringe pump 262 of the pumping unit 260.
In addition, the syringe pump 262 is preferably mounted in a fluid
resistant enclosure, and can include a force sensor on the
syringe-mounting bracket to monitor the plunger force during fluid
delivery.
[0113] In accordance with one embodiment, the syringe assembly 70
preferably is comprised of a syringe barrel or body 588 (FIG. 16)
capable of dispensing approximately 100 microliters to 2000
microliters of liquid material or liquid formulation 136 per pump
cycle from a container closure system 350, and more preferably
about 500 microliters to 1000 microliters of liquid material or
liquid formulation 136. It can be appreciated that the single
syringe assembly 70 as shown in FIGS. 11-16 provides a high
pressure drug delivery system 10 with almost continuous delivery.
In accordance with one embodiment, the single syringe 130 dispenses
a volume of approximately 500 micro-liters to 1000 micro-liters per
pump cycle with an aspiration time of less than 5% of the total
pump cycle.
[0114] The disposable assembly 40 also includes an inlet 536
adapted to receive a ventilated or hospital air supply, which is
fed to the sheath gas tube subassembly 530. The ventilated or
hospital air supply is heater or warmed by the sheath air
subassembly 430, which is admixed with the vaporized or volatized
liquid formulation (i.e., generated aerosol) at the distal end 162
of the capillary tube 158 within the aerosol confinement or
transition adapter 190.
[0115] FIG. 16 is an exploded view of the disposable assembly 40 of
FIG. 15. As shown in FIG. 16, the disposable assembly 40 includes a
syringe assembly 70 having a single syringe 130, a valve assembly
60 having a pair of valves 120, 122, an aerosol generator unit 50,
and an aerosol confinement or transition adapter 190.
[0116] The syringe assembly 70 is preferably comprised of a single
syringe 130 comprised of a plunger 580, a test cap 582, an
alignment member 584, a plunger seal 586, and a syringe body 588
having a pair of valve seats 589. Each valve 120, 122 includes a
disposable valve membrane 592, a threaded membrane plug 590, and a
membrane pusher 540. At a distal end of the syringe body 588, the
syringe assembly 70 includes a filter 542 (preferably stainless
steel), which is adjacent to a pressure drop assembly comprised of
an upstream housing member 544, a downstream housing member 548 and
a pressure drop disk 546 positioned therein. The disposable
assembly 40 also includes an air control nut 550, an air controller
base member 552, a ferrule 554, a feed tube nut 556, a domed
capillary tube 158, a capillary end member 570, a two piece end
holder 572, 574, and an aerosol confinement or transition adapter
190. A pair of support members 560, 562 is attached at one end to
the syringe assembly 70/valve assembly 60 and at the other end to
the aerosol confinement member or transition adapter 190. In
addition to providing structure for the syringe assembly 70, the
capillary tube 158, the sheath air tube subassembly 530, and the
aerosol confinement or transition adapter 190, the support members
560, 562 also ensure that the components of the disposable assembly
40 are matched to their respective connections within the base unit
20.
[0117] The disposable assembly 40 also includes a sheath air tube
subassembly 530 comprised of a sheath air tube 532 having an inlet
534 and an outlet 536, and a turbine assembly 538. The turbine
assembly 538 controls the amount of flow of ventilated or hospital
air supply to the aerosol confinement or transition adapter 190
through a valve assembly (not shown). In accordance with an
embodiment, the turbine assembly 538 regulates the flow rate of the
ventilated or hospital air supply by transmitting the rotation
velocity of the turbine assembly 538 in revolutions per minute
(RPM) to the controller assembly 36, by opening, closing or at
least partially obstructing the passage within the valve assembly
to increase or decrease the flow rate and/or supply of ventilated
or hospital air supply to the sheath air tube subassembly 530.
[0118] In accordance with an embodiment, the capillary tube 158 is
a domed capillary tube, which includes a feed tube end or proximal
end 160, and a domed capillary end or distal end 162. The capillary
tube 158 in accordance with an embodiment, preferably has an inside
diameter in the range of about 0.05 to 0.53 millimeters, and more
preferably in the range of about 0.1 to 0.2 millimeters. The feed
tube end 160 is preferably circular in cross-section with a domed
capillary end 163 on the distal end 162 of the capillary tube 158.
A particularly preferred inside diameter of the capillary tube 158
is approximately 0.1905 mm (or 0.0075 inches). In accordance with
one embodiment, the capillary tube 158 is a tipped capillary as
described in U.S. Publication No. 20050235991, the contents of
which are hereby incorporated by reference in their entirety.
[0119] FIG. 17 shows a diagram of the drug delivery system 10. As
shown in FIG. 17, the drug delivery system comprises a formulation
or dose packet 350 (or closed closure system), a hot plate/stirrer
300, a pumping unit 260, a syringe assembly 70, a valve assembly
60, an aerosol generator unit 50 having a heater block 150 and a
capillary tube 158 therein, a transition adaptor 190, and a
condensate trap 100. The system 10 also can include a CPAP adaptor
310 for delivering an aerosol to a patient, an air filter 330 (such
as a HEPA filter), a source of air (CPAP) 320, and a control unit
340. The source of air 320 is preferably from a hospital compressed
airline or pressurized air source, such as a tank of compressed air
with a suitable valve arrangement to achieve a desired air
flow.
[0120] In accordance with one embodiment, a liquid material or
liquid formulation 136, such as Surtaxin.RTM., which is contained
within a formulation or dose packet 350 is prepared for delivery to
a patient by initially heating the packet 350 on the hot
plate/stirrer 300 to liquefy the formulation to a desired viscosity
(i.e., a highly viscous formulation) for delivery to the pumping
unit 260. The pumping unit 260 and the valving assembly 60 supplies
the formulation 136 from the dose packet 350 at a constant and
continuous rate to the aerosol generator unit 50, which includes a
capillary passage in which the liquid formulation 136 is at least
partially vaporized. The heater block 150 heats the capillary
passage to a temperature range effective to at least partially
volatilize liquid formulation 136 in the capillary passage or tube
158 into an aerosol. The aerosol generator unit 50 also preferably
includes at least one air passage arranged such that the source of
air 320 is heated by the heater body or block 150, and wherein the
heated or warmed air is admixed with the aerosol produced by the
aerosol generator unit 50. It can be appreciated that the system 10
can include a separate air heater 312 in the form of a discrete air
heater that is remote to the capillary tube 158, in lieu of or in
addition to the use of the heat generated at or about the capillary
tube 158.
[0121] The transition adaptor or aerosol confinement member 190
captures the aerosols produced by the aerosol generator unit 50 and
the capillary tube 158 and directs the aerosol into a flow tube 104
for delivery to the patient via a CPAP adaptor 310. The CPAP
adaptor 310 preferably delivers aerosols to the patient at about
38.degree. C. to 42.degree. C. and more preferably about 40.degree.
C. for infants. It can be appreciated that be varying the length of
a delivery hose or tubing 104, the delivery temperature of the
aerosols can be delivered at a suitable or desirable temperature.
The aerosol confinement member 190 is preferably sealed to the
aerosol generator unit 50 or capillary tube 158, which prevents
ambient air (in contrast to heated air delivered to the transition
adaptor) from admixing with the aerosol produced by the aerosol
generator unit or capillary tube 158. The transition adaptor or
aerosol confinement member 190 can include a condensate trap 100
having at least one baffle therein and/or a drainage port at a
lower end thereof adapted to attach to a condensate collection
device or drain tube assembly. The admixing of the heated or warm
air with the aerosol produced by the formulation reduces the amount
of condensation from the capillary tube 158 to be able to deliver
an aerosol to the patient located at a remote location from the
system 10 and the aerosol generating unit 50.
[0122] In accordance with another embodiment, a cool air supply
from a fan or other suitable cooling device 370 can be used to cool
the flow tube 104 attached to the continuous positive airway
pressure (CPAP) adaptor 310 or other suitable device. The fan or
other suitable cooling device 370 is preferably located below the
transition adapter 190. A thermocouple or temperature monitoring
device (not shown) located within the patient interface device or
CPAP adaptor 310 monitors the temperature of the admixture of
heated or warm air with the generated aerosol. The temperature of
the admixture of heated air and generated aerosol is then fed to a
temperature controller (not shown) located outside of the base unit
20, or alternatively to a temperature controller located within and
which is an integral part of the base unit 20. During operation of
the system, the temperature controller controls the fan or other
suitable cooling device 370 to initiate cooling or a reduction in
the temperature of the mixture of the heated air and the generated
aerosol in response to the temperature of the heated air and
generated aerosol at the patient interface device or CPAP adaptor
310. In accordance with an embodiment, the cooling of the heated
air and the generated aerosol from the aerosol generator unit 50
can be performed by increasing the fan speed.
[0123] The system 10 preferably in drug delivery applications is
adapted to provide an aerosol having average mass median particle
diameters of less than 3 microns, and more preferably an average
mass median particle diameter of less than 2 microns to facilitate
deep lung penetration. In accordance with a preferred embodiment,
the aerosol has an average mass median particle diameter of between
about 0.2 to 2 microns and more preferably an average mass median
particle diameter of about 0.5 to 1.0 microns. It is also
desirable, in certain drug delivery applications, to deliver
medicaments at high flow rates, e.g., above 1 milligram per second.
It can be appreciated that the source of liquid formulation
preferably contains a lung surfactant adapted for delivery as an
aerosol to an infant's lungs. For example, in accordance with one
embodiment, the liquid formulation is a medicament to treat
Respiratory Distress Syndrome (RDS) in infants.
[0124] In accordance with an embodiment, the system 10 is
preferably capable of delivering an aerosol with a drug
concentration of 2.3 milligrams per liter of air from a liquid
formulation with a drug concentration of 10 milligrams per
milliliter (mg/ml) and commensurately higher aerosol concentrations
from formulations with higher concentrations. In addition, it is
noteworthy that the aerosol generator and/or system 10 as shown
achieves a uniquely high aerosol concentration for a give initial
liquid formulation. For example, as shown in FIG. 18, which is
representative of expected results, which could vary, in accordance
with an embodiment, a drug concentration of 30 milligrams of drug
per milliliter of formulation (mg/ml), one may achieve a delivered
drug aerosol concentration of 7 milligrams of drug aerosol per
liter of air (mg/l) at a sheath air flow rate of 3 liters per
minute (L/min). It can be appreciated that the system efficiency as
shown in FIG. 18, is the ratio of the mass or active medicant as
measured upstream of the CPAP adaptor divided by the mass of the
active medicant pumped into the system.
[0125] While various embodiments have been described, it is to be
understood that variations and modifications may be resorted to as
will be apparent to those skilled in the art. Such variations and
modifications are to be considered within the purview and scope of
the claims appended hereto. For example, a superheated fluid could
be maintained in a superheated liquid condition until discharged
from the capillary, whereupon a flash vaporization will occur.
* * * * *