Note: Descriptions are shown in the official language in which they were submitted.
CA 02202620 1997-04-14
R'O 96/18478 PCTlUS95115677
1
METHOD AND APPARATUS FOR FORMING
DISPENSER DELIVERY PORTS
TECHNICAL FIELD
This invention relates to the use of a laser to form a delivery port in a
beneficial agent dispenser, and more particularly to a method and apparatus
for forming a delivery port having a maximal passage area while requiring
minimal mass removal and minimal laser energy.
BACKGROUND ART
Saunders et al US Patent 4,063,064; Theeuwes et al US Patent
4,088,864; and Geerke et al US Patent 5,294,770 all disclose machines for
transporting pharmaceutical tablets from a tablet reservoir to a laser
treatment (ie, drilling) station where the tablets are treated (ie, drilled)
by a
laser. US Patent 5,294,770 additionally discloses laser drilling (ie, by
burning) of multiple drug release ports in a single pharmaceutical tablet.
Each delivery port is formed by a single pulse of a laser beam. Each port is
formed independently of the other delivery ports on the tablet. Thus, the
combined delivery port area of these multiple ports is simply the sum of the
area of each of the ports. Since the area burned away by each laser pulse is
dependent of the power of the laser pulse, the laser drilling of multiple
ports
requires proportionally more power.
In general the diameter of a laser drilled release port, such as
disclosed in US 5,019,397, is limited by the laser power available and the
thickness and composition of the material being laser drilled. Osmotic drug
dispensers typically have very thin (eg, less than 2 mm thickness) polymeric
(eg, cellulose-based polymers) membrane walls. At present, most
CA 02202620 1997-04-14
WO 96/18478 PCT/US95115677
2
commercially sold lasers have a maximum power output of up to about 500
watts. Thus, a laser operating at 500 watts power output drilling through a
cellulosic membrane having a thickness of only 0.1 mm can only drill an
orifice having a diameter of up to about 0.7 mm. Unfortunately, dispensers
are now beirig developed which require orifices having diameters of up to
about 10 mm and even larger.
DISCLOSURE OF THE INVENTION
The present invention provides an improved method for forming
delivery ports in beneficial agent dispensers using a laser.
This invention further provides such a method which forms delivery
ports having maximal passage area while requiring minimal laser energy.
This invention further provides a method of laser drilling delivery ports
having diameters greater than the drilling diameter of conventional drilling
laser beams using conventional lasers having drilling beams of conventional
power and drilling diameter.
In addition to a laser drilling method and apparatus, the present
invention also provides an improved method and apparatus for marking leg,
placing an identification symbol on) a workpiece, such as a pharmaceutical
tablet or a beneficial agent dispenser, using a laser.
Briefly, the present invention provides a method of forming a delivery
port in a beneficial agent dispenser. The dispenser has a compartment
formed by a wall and containing the beneficial agent to be delivered. A laser
beam having an effective burning diameter burns at least partially through the
CA 02202620 2005-08-08
67696-232
3
wall. The dispenser is conveyed along a path to a point
where the laser is aimed at a predetermined port site on the
dispenser (ie, the laser beam path intersects the
predetermined port site on the dispenser). The laser source
is energized and scribing relative motion is established
between the laser beam path and the dispenser for scribing a
delivery port proximate the port site. The laser source
emits a laser beam during at least a portion of the scribing
motion to burn the dispenser wall. The laser beam may be
fired continuously or in a pulsed manner during the scribing
motion. If fired in a pulsing mode, preferably the pulsing
of the laser and the speed of the scribing motion are
selected so that a plurality of overlapping burn holes are
formed through the dispenser wall. The dispenser delivery
port is formed by the continuous/pulsed beam burning the
scribed pattern (eg, a line, a circle, a square, etc) in the
dispenser wall.
In a similar manner, the apparatus and method of
the present invention may be used to scribe an identifying
mark (eg, a symbol, a trademark or other identifying text)
on an object such as a pharmaceutical agent dispenser by
laser surface burning, as opposed to laser drilling, the
mark on the object.
One aspect of the invention provides a method of
forming a delivery port in a beneficial agent dispenser,
comprising providing a dispenser having a compartment formed
by a wall, and containing a beneficial agent to be
delivered; providing a laser source which produces laser
energy along a laser energy path, the laser energy being
capable of burning a bore of predetermined dimension at
CA 02202620 2005-08-08
67696-232
3a
least partially through the wall of the dispenser;
positioning the dispenser relative to the laser energy path
such that the laser energy path intersects the dispenser at
a predetermined port site on the dispenser, the method being
characterized by; establishing scribing relative motion
between the laser energy path and the dispenser for scribing
a channel at least partially surrounding a removable central
plug, the channel and the removable plug defining a delivery
port proximate the port site; and energizing the laser
source during the scribing motion to produce laser energy
which forms the delivery port in the wall, the delivery port
having at least one dimension which is greater than the bore
dimension.
Another aspect of the invention provides an
apparatus for forming a delivery port in a beneficial agent
dispenser, comprising: a conveyor for conveying a dispenser,
said dispenser having a compartment formed by a wall and
containing a beneficial agent to be delivered; a laser
source which produces a laser energy beam; scribing means
for establishing scribing relative motion between the laser
energy beam and the dispenser; and control means for
controlling the scribing means to form a channel at least
partially surrounding a removable central plug, the channel
and the removable plug defining a delivery port.
A further aspect of the invention provides an
apparatus for forming a delivery port in a beneficial agent
dispenser, the apparatus comprising: a laser source
producing laser energy; and means for controlling the laser
source and means for moving the laser energy or the
dispenser to scribe the laser energy on the dispenser to
form a channel at least partially surrounding a removable
CA 02202620 2005-08-08
67696-232
3b
central plug in the dispenser, the channel and the removable
plug defining the delivery port in the beneficial agent
dispenser.
BRIEF DESCRIPTION OF THE DRAWINGS
Further objects and advantages of the present
apparatus and method of forming a delivery port, and/or
forming an identifying mark, on an agent dispenser will
become apparent from the following detailed description and
drawings (not drawn to scale) in which:
Fig. 1 is a side view of a dispenser treating
apparatus showing the basic elements required to form the
delivery ports;
CA 02202620 1997-04-14
WO 96/18478 PC'TICTS95115677
4
Fig. 2 is a top view of the dispenser treating apparatus of Fig. 1;
Fig. 3 is a perspective view ofi two adjacent dispensers, with parts
thereof shown in section, showing (i) the conveyor motion for positioning the
dispensers in the intersection zone with the laser beam path and (ii) the
scribing relative motion for scribing the delivery ports;
Figs. 4A through 4D are perspective views of agent dispensers having
an oval shaped delivery port, a slot shaped delivery port, a bore cluster
delivery port, and a polygon shaped delivery port, respectively, all scribed
in
accordance with the present invention;
Fig. 4E is a perspective view of an agent dispenser having an
identifying marking scribed in accordance with the present invention;
Fig. 5 is a top view of a scribed channel formed by overlapping burn
bores;
Fig. 6 is a top view of a scribed channel formed by spaced burn bores;
Fig. 7 is a partial sectional view of a scribed full depth channel which is
laser drilled in accordance with the present invention;
Fig. 8 is a partial sectional view of a scribed partial depth channel
which is laser drilled in accordance with the present invention;
Figs. 9 and 10 are side and side sectional views of an agent dispenser
having a delivery port scribed and laser drilled in accordance with the
present
invention embodiment;
CA 02202620 2005-08-08
67696-232
Fig. 11 is a perspective view of a laser scanning system showing a
scribing control means including an X deflection mirror and a Y deflection
mirror.
5
MODES FOR CARRYING OUT THE INVENTION
As shown in Figs. 1 and 2, dispenser treatment apparatus 10 treats a
series of dispensers 30 with laser energy proximate a predetermined port site
on each dispenser. An endless conveyer 11 moves individual dispensers 30
along dispenser path 12 (in the direction of the an-ow) from a supply end of
the treatment apparatus to a collection end. Laser source 13 provides laser
energy along a laser beam path 14 which crosses the dispenser path 12
defining an intersection zone 15 common to both paths 12, 14. Relative
motion between each of the dispensers 30 and the laser beam is established
by the motion of the endless conveyer 11 and by a suitable laser scanning
system 16 disclosed in more detail hereinafter (Fig. 11 ).
The treatment apparatus 10 has laser ready windows during which the
laser source 13 may be fired. A controller 17 is responsive to the relative
motion between the dispenser 30 and the laser beam and responsive to the
laser ready windows for energizing the laser beam: A suitable dispenser
treatment apparatus 10 and controller 17 are disclosed in Geerke et al US
Patent 5,294,77Q.
Supply hopper 18 is positioned proximate the supply end of the
dispenser path 12 for containing a reserve of untreated dispensers 30 which
are loaded onto the conveyor 11 for treatment with the laser energy. The
CA 02202620 1997-04-14
WO 96/18478 PCT/U595115677
6
endless conveyer 11 is preferably a carrier chain formed by carrier links
extending from the supply hopper 18 through the intersection zone 15 to the
collection end and back to the supply hopper 18 for moving the dispensers 30
along the dispenser path 12 and through the intersection zone 15 for
freatrnent. A supply wheel 19 mounted within the supply hopper 18 engages
the supply end of the conveyer 11, permitting the dispensers 30 to load onto
the carrier chain. A collection wheel 20 mounted proximate the collection end
of the dispenser path 12 engages the collection end of the conveyer 11. The
collection wheel 20 is positioned higher than the supply wheel 19 to create a
positive slope along the dispenser path 12 which raises the dispensers 30 out
of the dispenser supply hopper 18 up to the intersection zone 15.
A suitable drive device such as motor 21 moves the endless carrier
chain around the wheels 19 and 20, and conveys the dispensers 30 along the
dispenser path 12. In the embodiment of Fig. 1, collection wheel 20 is a drive
wheel connected to the drive motor 21 and lower wheel 19 is a free turning
idler wheel. The upper drive wheel 20 pulls against the drag of the chain
links and the idler wheel 19 to hold the carrier chain taut along the inclined
dispenser path 12.
The basic steps of laser scribing a delivery port in a beneficial agent
dispenser is described below.
The apparatus and method of the present invention can be used to
form delivery ports in pharmaceutical agent dispensers, eg, dispensers which
are adapted to be implanted in, or swallowed by, a patient and thereafter
deliver a pharmaceutical agent (eg, a drug) to the patient. Two particularly
useful dispensers which can be used with the present invention are
osmotically driven and are designated by the reference numerals 30a and
CA 02202620 1997-04-14
WO 96118478 PCTIU595115677
7
30b in Fig. 3. Dispenser 30a is an elemeritary osmotic pump dispenser while
dispenser 30b is a push-pull type osmotic dispenser. Dispenser 30a has a
semipermeable membrane wall 31. Wall 31 surrounds and forms an internal
compartment 32. Internal compartment 32 comprises a dispensable drug 33,
identified by dots, and an optional osmagent 34 represented by dashes. Wall
31 is semipermeable, ie, it is permeable to the passage of an exterior fluid
(eg, water) present in the biological environment of use (eg, the gastro-
intestinal (GI) tract of an animal body), and is substantially impermeable to
the passage of drug 33 and optional osmagent 34. Wall 31 preferably
comprises a thin cellulosic membrane. Because wall 31 is substantially
impermeable to drug 33, dispenser 30a must have at least one delivery port
provided through wall 31 at port site 35a in order to deliver drug 33 to the
biological environment of use. When dispenser 30a is placed in an aqueous
environment (eg, when dispenser 30a is swallowed by a patient), water from
the patient's GI tract permeates through wall 31 and forms an aqueous
solution or suspension of drug 33. As more water permeates through wall 31,
the aqueous drug solution or suspension is pumped out of the delivery port
38a, which port is defined by the laser scribed channel 37a, and into the
patient's GI tract.
Like dispenser 30a, dispenser 30b also has a wall 31 which surrounds
and forms an internal compartment 32 containing a drug and an optional
osmagent or osmopolymer 34. However, compartment 32 of dispenser 30b
also comprises an expandable hydrogel 36 identified by vertical lines. The
drug-containing composition 33, 34 and the expandable hydrogel 36 are in
laminar arrangement, and they cooperate with wall 31 for the effective
delivery of drug 33 through the delivery port formed at port site 35b. Like
the
wall 31 of dispenser 30a, the wall 31 of dispenser 30b is semi-permeable, ie,
it is permeable to a liquid solvent (ie, water) present in the environment of
CA 02202620 1997-04-14
WO 96/18478 PGT/US95l15677
8
use but impermeable to the beneficial agent 33 and is preferably a thin
cellulosic membrane. When dispenser 30b is placed in an aqueous
environment (eg, when dispenser 30b is swallowed) water from the
environment permeates through wall 31 and is absorbed by the expandable
hydrogel 36, causing it to swell. As hydrogel 36 swells, it pushes against the
beneficial agent 33 which is thereby forced out of the dispenser 30b through
the delivery port 38b defined by the laser scribed channel 37b and into the
environment of use. In both dispensers 30a and 30b, the outward movement
of the liquid solution or suspension of beneficial agent 33 pushes central
plugs 39a and 39b (positioned within the laser scribed channels 37a and 37b,
respectively) away from the delivery ports 38a and 38b, respectively. In the
push-pull type dispenser 30b, it is important to scribe the delivery port 38b
adjacent to the beneficial agent composition 33, 34 and to position the
expandable hydrogel 36 at the "closed" end of the dispenser 30b.
The beneficial agent or drug 33 may be a pharmaceutical substance
(eg, a drug) which is placed in the dispensers 30a and/or 30b for metered
release in vivo over time. Other potential applications of the dispensers 30a
and/or 30b include the release of a catalyst for a chemical process, the
release of nutrients for aquatic feeding, and the release of fertilizer for
agricultural growth.
The next step in the method of the present invention is to provide a
laser source which produces laser energy eg, in the form of a beam along a
laser energylbeam path. The laser beam has sufficient power to be capable
of burning an effective burning bore at least partially through the wall 31.
The
energy of the laser beam is absorbed by the wall 31 at the intersection zone
15 creating sufficient heat to vaporize the wall material. Laser beams
typically have a circular cross-section with most of the energy being
CA 02202620 1997-04-14
WO 96/18478 PCTIU595/15677
9
concentrated in the center of the beam. The effective burning bore of the
laser beam is the diameter of the hole formed in wall 31 when there is no
relative motion between the dispenser and the beam. The effective burning
bore depends on the cross-sectional area of the laser beam at the
intersection zone 15, the power of the laser and the thickness and
composition of the wall material being laser drilled.
The next step in the method of the present invention is to position
dispenser 30a and/or the laser beam such that the laser beam path intersects
dispenser 30a of a predetermined port site 35a on the dispenser. The laser
source is usually turned off (un-energized) durihg the positioning step. The
positioning of the laser beam is controlled by laser scanning system 16, while
the positioning of the dispenser 30a is controlled by the movement of
conveyor 11 (conveyor 11 is not shown in Fig. 3 for ease of illustration)
which
conveys the dispensers 30a and 30b along the X axis in the direction of the
arrow in Fig. 3. The positioning of the laser beam path 14 and the positioning
of the dispensers 30a and 30b determines the position of the delivery ports
38a and 38b, respectively, on the dispensers 30a and 30b, respectively. The
positioning motion also moves the dispensers 30a and 30b relative to the
laser beam path 14 such that the beam is aimed initially at dispenser 30a and
subsequently at dispenser 30b, ie, the laser beam path 14 is initially aimed
at
port site 35a on dispenser 30a, and following the scribing of channel 37a, the
laser beam path is aimed at port site 35b on dispenser 30b which is the next
dispenser in line on conveyer 11. Alternatively, the positioning motion may
move the laser path 14 and/or the dispensers such that the laser beam path
14 is subsequently aimed at a second or third site on the same dispenser to
produce a multi-port dispenser.
CA 02202620 1997-04-14
WO 96118478 PGT/US95/15677
The next step in the method of the present invention is to establish
scribing relative motion between the laser beam path 14 and the dispenser
30a for scribing a channel 37a proximate the port site 35a. During the
scribing motion, the laser source 13 is turned on (energized) producing a
5 laser beam which causes burn removal of the wall material proximate the port
site 35a. The scribing motion is controlled by (i) the movement of the
dispenser 30a in the X direction, which movement is controlled by the
movement of conveyor 11, (ii) the movement of the laser beam path, which
movement is controlled by the scanning system 16, or a combination thereof.
10 The scribing motion determines the size and shape of the delivery port. The
scribing motion causes the laser beam to move relative to dispenser 30a,
from the port site 35a along a generally circular course 37a and back to the
port site 35a. The scribing motion causes the laser beam to burn the wall 31
along channel 37a which defines delivery port 38a. The thus formed delivery
port 38a allows subsequent delivery of the beneficial agent or drug 33
therethrough.
As shown in Fig. 3, the port site 35a is the starting point of the circular
course 37a and preferably is also the terminal point. As such, the channel
37a forms a closed course which completely surrounds round central plug 39
of wall material. The term "closed" in connection with a laser scribed channel
refers to a scribed channel of any shape which starts at a starting point and
returns the laser beam to substantially the same starting point. Plug 39a is
adapted to be removed to allow drug 33 to be dispensed through port 38a.
Plugs 39a and 39b on osmotic dispensers 30a and 30b are pushed away
from ports 38a and 38b, respectively, by the osmotic pumping of drug solution
or suspension out of dispenser 30a. In non-osmotic dispensers it may be
necessary to remove the central plug 39 before the dispenser can become
fully operative.
CA 02202620 1997-04-14
WO 96118478 PGTIUS95115677
11
In Fig. 3, the scribing motion causes the burning of the wall 31 by the
laser beam, forming a circular channel 37a surrounding a central plug 39a of
wall material. The passage area of the large delivery port 38a is equal to the
area of central plug 39a plus the area of burned channel 37a. The central
plug 39a is pushed out of the delivery port 38a by osmotic pressure and
represents delivery port area that does not require burning by the laser. That
is, most of the passage area of the delivery port 38a is formed by the central
plug 39a, rather than the area of the burned channel 37a, and hence most of
the area of the delivery port 38a is created without burning of wall 31 by the
laser, and without generating burned debris or requiring laser energy. The
larger passage area permits delivery of larger quantities of the beneficial
agent per unit of time into the environment of use.
In the embodiment shown in Fig. 3, the scribing motion moves the
laser beam along generally circular channels 37a and 37b to scribe generally
round delivery ports 38a and 38b. The channel 37 may be non-circular as
shown in Figs. 4A through 4D. A round delivery port has the maximum
passage area for the amount of laser drilling (burn removal mass) and is the
preferred shape. That is, a circular channel 37 produces a round delivery
port 38 with the least debris per square unit of port area. The scribed
channel may be slightly out-of-round due to manufacturing tolerances. The
endless conveyer 11 may vary in speed during manufacture, or generally
slow down with age. The laser scanning system 16 may be impertect, or
vibrate during operation, or drift out of calibration. In practice, a circular
channel 37 resulting in a round delivery port 38 may be merely a desirable
goal which is theoretically possible.
CA 02202620 1997-04-14
WO 96/18478 PC1'/US95/15677
12
Alternatively, the delivery port may be non-circular, such as the
polygon shaped port 48 shown in Fig. 4D, or the channel defining the delivery
port may be non-closed such as the C-shaped channel 64 shown in Fig. 4A
or the slot shaped delivery port 40 shown in Fig. 4B. The C-shaped channel
64 forms a delivery port 46 having a generally oval shape with a major port
dimension and a minor port dimension. The unburned wall portion 62
functions as a hinge permitting the central plug 63 to fold away to the hinged
side like a flap under the force of the internal osmotic pressure. Unlike
plugs
39a and 39b, which are shed when osmotic dispensers 30a and 30b begin
pumping the liquid solution or suspension of drug 33, the hinged central plug
63 remains attached to the dispenser and is not shed into the environment of
use.
The minimum minor port dimension of a delivery port formed according
to the present invention may be only one burning bore diameter while the
minimum major port dimension of the delivery port is at least about twice the
burning bore diameter and preferably at least about 5 times the burning bore
diameter. An example of a delivery port 40 having a minor port dimension of
only one burning bore diameter and a major port dimension comprising a
plurality of burning bore diameters is shown in Fig. 4B. Since the minor port
dimension (ie, the width) of delivery port 40 is limited to the diameter of
the
burn bore, the area of port 40 is limited. Thus, elongated slot shaped
delivery port 40 is typically used only when small area ports are needed or
when drilling a flexible wall material which allows the slot shaped port 40 to
bulge open during the dispensing of the beneficial agent or drug 33.
Fig:-4C shows a delivery port 47 having a major port dimension of
about 2 burning bore diameters and a minor port dimension of about 2
burning bore diameters. Port 47 is formed by a pulsed laser beam which
CA 02202620 1997-04-14
WO 96/18478 PGTIUS95/15677
13
produces a cluster of four adjacent laser burned bores. The minimum
number of adjacent or clustered bum bores forming a delivery port according
to the present invention may be as few as two to four (see for example
delivery port 47 in Fig. 4C) or as many as several hundred or even several
thousand when forming large polygon shaped ports (such as port 48 in Fig.
4D) using a pulsed firing laser. The minimum dimension of the delivery port
may be much greater than the effective burning bore of the laser beam,
resulting in a large oval shaped delivery port 46 as shown in Fig. 4A or a
large polygon shaped delivery port 48 shown in Fig. 4D. Port 48 is formed by
scribing a series of straight lines with the laser. The polygon-shaped port 48
may alternatively have another geometric shape such as a triangle, square,
pentagon, etc.
The user source energization may be continuous during the scribing
motion to continuously burn the wall creating a continuous scribed channel.
The preferred speed of the scribing motion for a continuously energized laser
beam is a function of burn removal factors such as the power of the laser, the
effective burning bore, the thickness and composition of the wall, and the
desired depth of the channel. If the scribing motion is too fast, the laser
beam will remove too little wall material and the channel will be too shallow.
If the scribing motion is too slow, the laser beam will remove all of the wall
and burn info the beneficial agent formulation, ie, the channel will be too
deep. Overly deep channels generate unnecessary debris, utilize
unnecessary laser power, andlor unnecessarily slow down the speed of
conveyor 11 and hence the manufacturing line. The following is illustrative of
a typical scribing motion speed: using a laser having a power output of 25
watts and a burning bore diameter of 0.15 mm, for drilling a semipermeable
cellulosic membrane having a thickness of about 0.1 mm, the scribing motion
speed is about 1 m/sec.
CA 02202620 1997-04-14
WO 96/18478 PCTJUS95/15677
14
The laser source energization may also be pulsed during the scribing
motion to create the channel. The channel may be a continuous channel 41
formed by a series of overlapping (or tangent) burn bores 42 as shown in Fig.
5. Channel 41 is shown as a straight channel suitable for forming a linear
(ie,
slot shaped) port or one side of a polygon shaped port. Channel 41 could
also be formed as a curved channel suitable for defining a round or oval
delivery port. Alternatively an intermittent channel 43 formed by a series of
closely spaced burn bores 44 can be scribed as shown in Fig. 6. The
scribing motion between pulses of the laser leaves narrow connecting bridges
45 of wall material between adjacent bum bores 44. The connecting bridges
45 are sufficiently narrow that they break open between adjacent burn bores
44 when the dispenser begins dispensing the beneficial agent. Channel 43 is
shown as a straight channel but could also be formed as a curved channel
suitable for forming a segment of a round or oval shaped port.
Figs. 7 and 8 are cross sectional views of portions of wall 31 and
compartment 32 of dispenser 30 and illustrate variations in the depth of laser
drilling which may be used in the method of the present invention. The laser
source 13 may be of sufficient power or have a sufficient on-time to produce a
laser beam which burns completely through the wall 31 as shown in Fig. 7
creating a deeply burned channel 37d. Deep channel 37d extends
completely through the wall 31 from the outer surface down to the beneficial
agent within the compartment 32. When forming a deep channel having a
closed shape (eg, a deep channel having a circular shape similar to channel
37a in Fig. 3), the central plug 39a may flake off prior to use, particularly
if the
adhesion of wall 31 to the beneficial agent formulation is weak.
CA 02202620 1997-04-14
R'O 96118478 PCT/U595/15677
Alternatively, the laser source 13 may be of lower power or have a
shorter on-time and burn only partially through the wall 31, as shown in
Fig. 8, creating a shallow burned channel 37e. Shallow channel 37e extends
only partially through the wall 31 leaving floor 47 along the bottom of the
5 channel 37e. The beneficial agent in compartment 32 is not exposed to the
laser due to the cover provided by the floor 47.
Unlike the deep channel embodiment (Fig. 7), the shallow channel and
intermittent channel embodiments (Figs. 8 and 6), when formed in a closed
10 (eg, circular) shape, retain the central plug of wall material in place in
the
delivery port opening until the time of use. Thus, the channel floor 47 of the
shallow channel 37e and the connecting bridges 45 of the intermittent
channel 43 retain the central plug 39a of wall material (see Fig. 3) in
position
in the delivery port 38a during manufacture and storage of the dispenser 30a,
15 thereby affording greater protection (eg, against light or UV degradation)
to'
the beneficial agent in compartment 32. The floor 47 of the partial channel is
sufficiently thin to permit the osmotic pressure that develops within the
compartment 32 when the dispenser is placed in an aqueous environment to
break the wall material forming the floor 47. Likewise the connecting bridges
45 between the spaced burn bores 44 of the intermittent channel 43 are
spaced sufficiently close to permit the osmotic pressure that develops within
the compartment 32 when the dispenser is placed in an aqueous environment
to break the wall material forming the bridges 45. The pumping of the
beneficial agent solution or suspension then pushes the central plug 39 away
from the delivery port 38. The optimum floor 47 thickness and bridge 45
_ length for this "break-away" mode depends on the strength and thickness of
the wall material and on the internal pressure generated within the
compartment.
CA 02202620 1997-04-14
W O 96!18478 PCTIUS95115677
16
A channel floor and connecting bridges may be employed on the same
break-away central plug. That is, the connecting bridge may be partially
burned away forming a partial channel between the spaced bum bores. The
filoor, bridge and hinged flap embodiments generate less burn removal per
square unit of passage area, and therefore require less laser energyfor the
same size delivery port.
Another example of an implantable osmotically driven delivery system
is shown in Figs. 9 and 10 and is identified by the number 50. Fig. 9 is a
side
view of system 50 while Fig. 10 is a side sectional view of system 50.
Delivery system 50 comprises a delivery end 51, a trailing end 52 and a
passageway 53 provided at end 51 that connects the exterior environment
with the interior of delivery system 50. Passageway 53 is laser scribed
through the wall of housing section 54 in accordance with the present
invention. Delivery system 50 has an outer housing comprised of a first
housing section 54 and a second housing section 55. The two housing
sections 54, 55 have diameters which are close in size and they form a tight
friction fit therebetween. There is clearance or tolerance in size to allow
section 55 a sliding movement into the receiving means 59 of section 54.
Secfions 54 and 55 can be telescoped completely into a closed and
continuous walled position. Optionally, they can be held together by heat
fusion, by adhesive, or the like. Housing sections 54, 55 surround and define
an internal compartment 56. Housing section 54 surrounds a beneficial agent
formulation which comprises a pharmaceutical agent (eg, a drug) identified by
dots 57, and a pharmaceutically acceptable carrier identified by wavy lines
58. The pharmaceutically acceptable carrier 58 may comprises more than
one ingredient, such as a buffer, a surtactant or other formulation
ingredients.
Housing section 54 at ifs end distant from lead end 51 defines and forms
receiving means 59. Receiving means 59 is enlarged slightly for receiving
CA 02202620 1997-04-14
WO 96/18478 PCT/US95115677
17
housing section 55. The wall of housing section 54 comprises a composition
that is substantially impermeable to the beneficial agent formulation 57, 58
and other ingredients contained in delivery system 50. Housing section 54 is
preferably substantially impermeable to the ingress of any liquids (eg, water)
present in the exterior environment and serves as a means for substantially
protecting a beneficial agent 57 (eg, a protein) that is unstable when exposed
to the liquid. Thus, unlike wall 31 in dispensers 30a and 30b, the wall of
housing section 54 is not a semipermeable membrane and may be formed of
nonpermeable materials such as polymers, plastics, elastomers, etc, which
can be burned by a laser. Housing section 54 substantially restricts and
prevents fluid from passing therethrough and entering into compartment 56 in
the region containing the beneficial agent formulation 57, 58. Housing
section 55 surrounds an expandable driving member 60 (eg, an expandable
hydrogel) identified by slanted lines. Expandable driving member 60
optionally comprises an osmagent, homogeneously or heterogeneously
blended within the expandable driving member 60. Compartment 56
optionally comprises a layer 61, represented by horizontal lines, positioned
between the beneficial agent formulation 57, 58 and the expandable driving
member 60. Layer 61 preferably comprises a composition that is
substantially impermeable to the passage of liquid imbibed into driving
member 60 and it serves to restrict the passage of liquid present in the
expandable driving member 60 into the beneficial agent formulation 57, 58;
and it operates to essentially mainfain the integrity of the beneficial agent
layer and the driving layer. Layer 61 acts also to insure that the expanding
driving force generated by the expandable driving member 60 is applied
evenly and directly against the beneficial agent formulation 57, 58. The wall
of housing section 55 comprises, at least in part, a semipermeable wall
composition that is permeable to the passage of the liquid (eg, water) present
in the exterior environment and for making available fluid to the expandable
CA 02202620 1997-04-14
WO 96/18478 PCT/US95115677
18
driving member 60. The wall of housing section 55 is permeable to the
passage of the liquid (eg, water) present in the exterior environment and it
is
substantially impermeable to the passage of other ingredients contained in
driving member 60. Housing 54, 55 may optionally comprise a plasticizer that
imparts flexibility and workability to the wall. Housing 54, 55 is non-toxic
and
in a preferred embodiment, it maintains its physical and chemical integrity,
that is, housing 54, 55 does not erode during the dispensing period.
In operation, delivery system 50 is placed in a biological environment
of use (eg, system 50 is implanted in the body of a mammal, eg, humans or
livestock) and exposed to an aqueous liquid. The aqueous liquid permeates
through the semipermeable wall of housing section 55 and is absorbed by
driving member 60, as the expandable driving member 60 absorbs and
imbibes fluid, it expands and pushes against layer 61 causing it to slide
within
compartment 56 toward passageway 53. Layer 61 moves towards
passageway 53, pushing the beneficial agent formulation 57, 58 through
passageway 53 for delivery of the beneficial agent 57 into the biological
environment of use.
Fig. 11 shows a schematic illustration of a scanning system for
controlling the scribing motion of a continuously or intermittently fired
laser.
Laser scanning system 16 may be any suitable mechanism for systematically
deflecting the laser beam such as an X-Y scanning device. The positioning
of the dispenser with respect to the laser beam and the scribing relative
motion are established along a first axis by a first scanning mirror and along
a
second axis by a second scanning mirror. The first axis may be along the
direction of motion of endless conveyer 11 (see X axis - Fig. 3), and the
second axis may be traverse to the direction (see Y axis - Fig. 3).
Alternatively a three dimensional (see Z axis - Fig. 3) laser scanning system
CA 02202620 1997-04-14
WO 96/18478 PCTIUS95115677
19
may optionally be used. The focal point of the laser beam can be moved
along the Z axis by appropriately moving a beam focusing lens in the Z
direction.
X axis scanner 90X includes X deflection mirror 92X mounted on
pivoting shaft 94X (extending in the Y direction) which is displaced by X
galvanometer 96X. Y axis scanner 90Y includes Y deflection mirror 92Y
mounted on pivoting shaft 94Y (exfending in the X direction) which is
displaced by Y galvanometer 96Y. The galvanometers are servo-like rotary
drives having low mass with minimal inertia, which are responsive to X-Y
control voltages from controller 17. The displacement of the mirrors may be
smooth in response to a smoothly changing control voltage, to provide a
uniform rate of deflection of the laser beam. Alternatively, the displacement
may be incremental in response to a step change in control voltage, for
deflecting the laser beam by increments.
In a pulsed laser beam embodiment such as Fig. 5 and 6, each
rotational step of the mirrors may coincide with a pulse of laser energy. This
one pulse for one step arrangement provides a progressively spaced but
unique XY location for each laser pulse. Polygon shaped delivery ports (see
Fig. 4D) may be easily formed by rotationally stepped mirrors. The straight
line between each pair of successive vertices is created by a series of
uniform X and Y steps. At each vertice, the values of the X and Y steps
change to create the next straight line forming the polygon. The motion of the
endless conveyer 11 may be constant to provide a constant movement of the
dispensers 30 along the X axis. Alternatively, the conveyer 11 may be step
advanced by a stepping motor.
CA 02202620 1997-04-14
W096118478 PCTIUS95115677
In the embodiment of Fig.-3, the relative motion along the X axis is the
sum of the motion of the endless conveyer 11 plus the motion due to the X
deflection mirror; while the relative motion along the Y axis is due only to
the
Y deflection mirror.
The method of forming a delivery port in an agent dispenser disclosed
herein may also be employed to mark an identification symbol on the surface
of a plurality of workpieces such as dispensers 30 presented in a series. One
difference between forming a delivery port and marking an identification
10 symbol is simply the relative power of the laser which is required. With
delivery port formation, the laser must have sufficient power to burn
substantially through the wall 31. On the other hand, The marking is formed
by burning due to the heat of the laser energy, and may be accomplished by
disturbing, discoloring or carbonizing the surtace material. Alternatively,
the
15 identification symbol maybe formed by burning the interior material as well
as
the surtace material thereover. Such deep burning may form a delivery port
which also functions as an identification marking.
The sequence of steps for laser marking an identification symbol are
20 as follows. First, laser source 13 produces laser energy along a laser beam
path for marking the surtace of each workpiece. Relative positioning between
the laser beam path and the presented workpiece 30 is established for
positioning the laser energy at a predetermined marking site on the
presented workpiece. Scribing relative motion is established between the
laser beam and the workpiece far defining the identification symbol proximate
the marking site. The laser source is energized during the scribing motion to
produce the laser energy for marking the surface forming the identification
symbol thereon for subsequent identification of the workpiece.
CA 02202620 1997-04-14
R'O 96118478 PCTIUS95115677
21
The identification symbol may be a stroke based symbol such as an
alpha-numeric formed by at least one stroke. The simple single stroke
numeral "1" may be formed in substantially the same manner as laser drilled
slot shaped delivery port 40 shown in Fig. 4B. The defining relative motion
defines the stroke (or strokes) for marking the workpiece. The identification
symbol may be at least one solid area formed by a plurality of adjacent
strokes defined by the relative motion. Alternatively, the scribing motion can
define printed text and/or a trademark as shown in Fig. 4E. In the surface
marking embodiments, only the surtace of the workpiece is affected by the
laser energy. Therefore the laser beam may have a larger diameter beam for
forming a wider more visible stroke than in the delivery port drilling
embodiments. This shallow marker burning generates less debris and can be
accomplished by a faster scribed beam with lower energy than the beam
needed to form delivery ports.
It will be apparent to those skilled in the art that the objects of this
invention have been achieved by providing an improved method for forming
delivery ports in beneficial agent dispensers. Clearly various changes may
be made in the structure and embodiments shown herein without departing
from the concept of the invention. Further, features of the embodiments
shown in the various figures may be employed with the embodiments of the
other figures. Therefore, the scope of the invention is to be determined by
the terminology of the following claims and the legal equivalents thereof.
