Method and apparatus for forming dispenser delivery ports

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mate a predetermined port site on each dispenser. An endless conveyer 11 moves individual dispensers 30 along dispenser path 12 (in the direction of the arrow) 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 5 crosses the dispenser path 12 denning 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 10 (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 15 windows for energizing the laser beam A suitable dispenser treatment apparatus 10 and controller 17 are disclosed in Geerke et al U.S. Pat. No. 5,294,770, the disclosures of which are incorporated herein by reference.

Supply hopper 18 is positioned proximate the supply end 20 of the dispenser path 12 for containing a reserve of untreated dispensers 30 which are loaded onto the conveyer 11 for treatment with the laser energy. The endless conveyer 11 is preferably a carrier chain formed by carrier links extending from the supply hopper 18 through the intersection zone 15 25 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 treatment. A supply wheel 19 mounted within the supply hopper 18 engages the supply end of the conveyer 11, permitting the dispensers 30 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 35 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 m 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 4J 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 50 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 55 by the reference numerals 30a and 30b in FIG. 3. Dispenser 30a is an elementary 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 60 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 65 animal body), and is substantially impermeable to the passage of drug 33 and optional osmagent 34. Wall 31 prefer

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ably 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 tag-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 semipermeable, ie, it is permeable to a liquid solvent (ie, water) present in the environment of use but impermeable to the beneficial agent 33 and is preferably a thin cellulosic membrane. When dispenser 30f? 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 382> 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 38£>, respectively. In the push-pull type dispenser 30b, it is important to scribe the delivery port 39b 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 energy/beam 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 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 crosssectional 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