WO2001058638A1

WO2001058638A1 - A method and apparatus for manufacturing a drug capsule for a needlefree injector

Info

Publication number: WO2001058638A1
Application number: PCT/GB2001/000535
Authority: WO
Inventors: Oliver Alexander Shergold; Toby Stjohn King; Timothy Andrew Large; Mary Jane New
Original assignee: Weston Medical Limited
Priority date: 2000-02-11
Filing date: 2001-02-12
Publication date: 2001-08-16
Also published as: GB0003260D0; AU2001233844A1

Abstract

A method of forming a drug capsule for a needlefree injector, in which a surface of a drug capsule blank (22) is irradiated with light from a high energy laser (18), thereby ablating material to form a discharge orifice in a wall of the drug capsule. The laser preferably operates at a wavelength in the ultraviolet range of the spectrum, and may for example be an excimer laser. An apparatus is described for carrying out this method.

Description

A METHOD AND APPARATUS FOR MANUFACTURING A DRUG CAPSULE FOR A NEEDLEFREE INJECTOR

Background to the Invention

Needlefree injectors are used as an alternative to needle-type hypodermic injectors for injecting liquid drugs through the epidermis and into the underlying tissues. The usual form of construction for such a device is a syringe having a small discharge orifice which is placed in contact with the skin, and through which the drug is injected at a sufficiently high speed to penetrate the skin of the patient. The force required to pressurise the drug may be derived from a compressed coil spring, compressed gas, explosive charge or some other form of stored energy.

The size of the discharge orifice affects the sensation a patient experiences during an injection. Generally speaking, a smaller diameter discharge orifice offers a more comfortable injection, although it is important that the hole is not so small that the injection takes such a long time that it is impractical for the patient to hold the device still in contact with the same part of the skin, or that the drug molecules are damaged by the boundary effects and turbulence within the jet stream.

The capsule from which the drug is discharged is often in the form of a cylinder containing a free piston (i.e. no connecting rod), with the discharge orifice located in an end wall. The orifice may be formed integrally with the cylinder or there may be a separate nozzle in sealing hydraulic contact with the end of the cylinder. The other end of the cylinder may be open to receive a driving push rod which acts on the piston to cause the discharge of the drug. The complete injector may be presented as a single use, p e- filled and disposable device; or as a multiple use actuator with replaceable drug capsules; or as a multi-dose actuator which dispenses successive doses from a bulk supply. An example of a single use, needlefree injector is shown in International publication number WO 96/28202.

One method of manufacturing glass drug capsules for use in needlefree injectors is described in International publication number WO 98/13086 and is now described briefly with reference to Figures 1 and 2. Figure 1 shows a length of glass tubing 2 located over a mandrel 4 having a frustro-conical form 6 terminating in a pin 8 made from tungsten carbide or high performance steel. Located concentrically above the mandrel is a form tool 100 having a forming surface 12. A hole 14 in the forming tool 10 is a close clearance fit relative to the pin 8. In use, the glass tube 2 is heated to a sufficient temperature to soften the glass and when an optimum temperature is reached, the form tool 10 is lowered and pressed onto the softened glass as shown in Figure 2. The mandrel can then be removed leaving the formed drug capsule.

Although this method does provide a reliable and accurate method of producing a discharge orifice in the drug capsule, to reduce the diameter of the orifice further to increase patient comfort requires a corresponding reduction in the diameter of the pin. However, as the diameter of the pin is reduced, the life expectancy of the mandrel is also reduced. Consequently, the cost of manufacture per unit capsule increases substantially as replacement mandrels are needed frequently. It has been found that as the diameter of the discharge orifice is reduced from the conventionally available 0.5 mm to around 0.3 mm or less, the life of a mandrel is reduced significantly.

Summary of the Invention

According to a first aspect of the present invention, there is provided a method of manufacturing a drug capsule for a needlefree injector, comprising the step of: irradiating a surface of the drug capsule with light from a high energy laser, thereby ablating material to form a discharge orifice in a wall of the drug capsule.

According to a second aspect of the present invention there is provided an apparatus for manufacturing a drug capsule for a needlefree injector, comprising a high energy laser arranged to irradiate a surface of the drug capsule and so ablate material from a wall of the drug capsule to form a discharge orifice; and means for supporting a drug capsule in optical alignment with the laser.

In the present invention, a discharge orifice is formed in the wall of a drug capsule by a high energy laser drilling operation that relies on the ablation of the material of the drug capsule in what is effectively a cold process, i.e. the process is one of photo ablation rather than thermal ablation. This allows accurate control of the profile of the discharge orifice which is otherwise very difficult to achieve using conventional forming processes. When manufacturing drug capsules having a discharge orifice which is particularly narrow, the present invention can provide substantial cost savings over conventional forming processes.

Preferably, the drug capsule is formed of a glass such as, borosilicate glass. Alternatively, the drug capsule may be formed of a COC or polycarbonate material.

Preferably the laser is one which operates in the ultraviolet region of the spectrum, i.e. at a wavelength of not more than about 400 nun, more preferably in the region from 100 to 400 nm, and still more preferably in the region from 150 nm to 300 nm. Most preferably, the laser is an excimer laser. Excimer lasers typically operate at wavelengths of between 150 nm and 300 nm, and by way of example, excimer lasers operating at wavelengths of 192 nm and 248 nm have been found to perform well in forming an orifice in a glass capsule. The typically low wavelength at which an excimer laser operates offers good control over the definition of small features. Indeed, it is possible to combine the use of an excimer laser with a mask to achieve the required size, shape and number of holes. The process is "cold" in that there is no melting of the material. Instead, material is removed by an ablative process. Other ultraviolet lasers which can be used include higher harmonic neodymium lasers (e.g. frequency tripled or frequency quadrupled Nd: YAG and Nd:YLF lasers), and frequency doubled copper vapour lasers. In contrast, it has surprisingly been found that CO₂ lasers (perhaps the obvious choice for laser drilling), which can be regarded as providing a "hot" process in the context of the present invention, are not satisfactory for the purpose of the present invention. This cheap and readily available form of laser is not suitable for forming an injection orifice in a glass drug capsule because it tends to melt the glass, achieving poor definition (rounded edges) and leaving bubbles in the glass and a degree of thermal stress. Diffraction effects make it difficult to use a mask to project an image of the shape of the required hole onto the capsule in a commercial manufacturing process. Other lasers which are unsuitable include fundamental frequency Nd:YAG lasers and fundamental frequency copper vapour lasers.

Preferably the pulse length of the laser is short (of the order of 1-100 ns), leading to high peak energies, as it gives smaller thermal effects. Also, it is to be noted that in choosing the frequency of the laser, account needs to be taken of the ability of the material, e.g. the glass, in which the orifice is being formed, to absorb that frequency. Preferably, the method further comprises the step of pre-forming a drug capsule blank prior to the step of forming the discharge orifice.

Preferably, the apparatus further comprises a beam splitter arranged to split the laser light into a plurality of laser beams and thereby irradiate each of a plurality of drug capsules simultaneously with a respective one of said beams. An adjustable attenuator, preferably a steplessly adjustable attenuator, can be located in all or some of the beam paths to enable the intensities of the beams to be equalized.

Brief Description of the Drawings

Figures 1 and 2 illustrate the manufacture of a drug capsule using a conventional glass forming process;

Figure 3 shows a schematic representation of an example of an arrangement for manufacturing a drug capsule according to the present invention;

Figures 4 and 5 show a method of laser drilling a discharge orifice in a drug capsule;

Figure 6 shows an example of an arrangement for manufacturing a drug capsule according to the present invention; and

Figures 7 and 8 show a more detailed example of an arrangement for manufacturing a drug capsule according to the present invention.

Detailed Description

Figure 3 shows a schematic representation of an example of an arrangement for manufacturing a drug capsule according to the present invention. The device has a control unit 16 coupled to a laser 18. A preformed drug capsule blank 22 is arranged in optical alignment with the laser 18. Typically, the drug capsule blank is made of a glass such as borosilicate glass which is known to be substantially inert and have the required physical properties so that it is suitable for storing drugs in it over a long period of time. A mandrel 21 is provided to support the drug capsule blank 22 in optical alignment with the laser 18. The mandrel is shown as having a flat end, but more preferably it is part- spherical, e.g. hemispherical. This provides a low area of contact with the capsule, and thus reduces the risk of damage to the capsule, and also serves to align the conical end of the capsule blank in the correct position in relation to the mandrel . The mandrel, whether having a hemispherical end or not, can be accurately aligned with the laser beam before the capsule 22 is located thereon, by having the mandrel provided with a central lengthwise bore (i.e. a bore which runs vertically in the orientation of Fig. 3). A light detector is placed at the lower end of the bore, and when the mandrel is correctly aligned the laser beam is detected by it. The net result is thus that the capsule blank is correctly aligned with the laser beam.

The manufacture of the drug capsule blanks prior to the formation of the discharge orifices may be performed using a conventional glass forming technology. In this method, a glass tube is supported on a rotating mandrel having a flat upper surface. The upper portion of the tube is heated, and at the required temperature a forming tool is lowered to form the drug capsule. The method is analogous to that described above with reference to International publication number WO 98/13086, although in this case there is no pin connected to the mandrel to form an orifice.

The laser 18 is arranged to provide pulses of high energy short wavelength laser light to a predetermined position on the drug capsule blank 22. A lens 24 and a mask 26 may be provided in the optical path to focus the laser light onto the desired area of the wall of the drug capsule blank 22. As the light is incident on the surface of the drug capsule blank 22, the chemical bonds in the material forming the capsule blank are broken by the energy of the photons and dissociated molecules from the drug capsule blank are removed using a vacuum system (not shown). Thus the ablation process is effectively a cold process.

Figure 6 shows another example in which a beam splitter 28 is provided in the optical path to split the light provided by laser 18. Again, each of the drug capsule blanks 22 is in optical alignment with at least one of the split laser beams. This configuration enable discharge orifices in a plurality of drug capsule blanks 22 to be formed simultaneously. Although each laser beam could be used to drill a respective drug capsule blank, more than one laser beam could be used on the same drug capsule blank forming more than one hole in that capsule blank, which is particularly useful for intra- dermal injections. It is also possible to form a plurality of holes in a single capsule blank by means of a single laser beam (which, at least in the case of an excimer laser, is typically wide enough for this purpose), in combination with a mask having a corresponding plurality of holes formed therein.

Figures 7 and 8 show a side view and a cross-sectional side view, respectively, of another example of an arrangement for manufacturing drug capsules in accordance with the present invention.

As shown in the Figures, an array (a 7 x 7 matrix) of drug capsule blanks 30 is supported within a frame 31 on a movable platform 32. The platform 32 can be driven in any one of three mutually orthogonal directions by a respective one of three drive stages

33-35. As before, a laser 36 is positioned above the platform 32 to focus a laser beam 37 onto one or more of the drug capsule blanks 30.

During the process of laser drilling a discharge orifice in a drug capsule blank 30, a vacuum head 38 is applied to an opening 39 on the underside of the platform 32 which communicates with a bore 40 formed in a support mandrel 41 holding the drug capsule blank upright. This allows waste material from the drilling process to be removed. Operation of one or more of the drive states 33-35 subsequent to the completion of a drilling operation to form a discharge orifice in one drug capsule blank repositions the platform 32 to align the laser 36 and vacuum head 38 with the next drug capsule blank in the array.

Instead of using the arrangement shown in Figures 7 and 8, however, it is alternatively possible for the capsule blanks to be held in trays, with a robot gripper being used to pick up blanks one at a time and place them successively on a mandrel of the type shown in Figures 3 to 5.

The method of the present invention enables a discharge orifice having a reduced diameter to be formed in the drug capsule. Therefore, the present invention enables a substantial improvement to be made in the manufacture of drug capsules having a relatively narrow diameter discharge orifice.

Claims

CLAIMS:

1. A method of manufacturing a drug capsule for a needlefree injector, comprising the step of: irradiating a surface of the drug capsule with light from a high energy laser, thereby ablating material to form a discharge orifice in a wall of the drug capsule.

2. A method according to claim 1 , in which the operating wavelength of the laser is in the ultraviolet region of the spectrum.

3. A method according to claim 2, wherein the said operating wavelength is not more than 400 nm.

4. A method according to claim 3, wherein the said operating wavelength is in the region from 100 nm to 400 nm.

5. A method according to claim 4, wherein the said operating wavelength is in the region from 150 nm to 300 nm.

6. A method according to any preceding claim, in which the laser is an excimer laser.

7. A method according to any one of claims 1 to 5, wherein the laser is a higher harmonic neodymium laser.

8. A method according to claim 7, wherein the laser is a frequency tripled or frequency quadrupled NdNAG or Nd: YLF laser.

9. A method according to any one of claims 1 to 5, wherein the laser is a frequency doubled copper vapour laser.

10. A method according to any preceding claim, further comprising the step of providing a mask between the capsule and the laser thereby providing control of the profile of the discharge orifice.

1 1. A method according to any preceding claim, further comprising the step of splitting the laser light provided by the laser into a plurality of laser beams and irradiating a respective drug capsule with each of said laser beams.

12. A method according to any preceding claim, further comprising the step of preforming a drug capsule blank prior to the step of forming the discharge orifice.

13. A method according to any preceding claim, in which the drug capsule is made of glass.

14. An apparatus for manufacturing a drug capsule for a needlefree injector, comprising a high energy laser arranged to irradiate a surface of the drug capsule, and so ablate material from a wall of the drug capsule to form a discharge orifice; and means for supporting a drug capsule in optical alignment with the laser.

15. An apparatus according to claim 14, in which the operating wavelength of the laser is in the ultraviolet region of the spectrum.

16. An apparatus according to claim 15, wherein the said operating wavelength is not more than 400 nm.

17. An apparatus according to claim 16, wherein the said operating wavelength is in the region from 100 nm to 400 nm.

18. An apparatus according to claim 17, wherein the said operating wavelength is in the region from 150 nm to 300 nm.

19. An apparatus according to any one of claims 14 to 18, in which the laser is an excimer laser.

20. An apparatus according to any one of claims 14 to 18, wherein the laser is a higher harmonic neodymium laser.

21. An apparatus according to claim 20, wherein the laser is frequency tripled or frequency quadrupled NdNAG or ΝdNLF laser.

22. An apparatus according to any one of claims 14 to 18, wherein the laser is a frequency doubled copper vapour laser.

23. An apparatus according to any one of claims 14 to 22, further comprising a mask between the capsule and the laser, thereby providing control of the profile of the discharge orifice.

24. An apparatus according to any one of claims 14 to 23, further comprising means for splitting the laser light provided by the laser into a plurality of laser beams each disposed to irradiate a respective drug capsule.