EP1180046A2 - Capsule de medicament pour injecteur sans aiguille - Google Patents

Capsule de medicament pour injecteur sans aiguille

Info

Publication number
EP1180046A2
EP1180046A2 EP00931402A EP00931402A EP1180046A2 EP 1180046 A2 EP1180046 A2 EP 1180046A2 EP 00931402 A EP00931402 A EP 00931402A EP 00931402 A EP00931402 A EP 00931402A EP 1180046 A2 EP1180046 A2 EP 1180046A2
Authority
EP
European Patent Office
Prior art keywords
drug
plastics
layer
needleless injector
capsule
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00931402A
Other languages
German (de)
English (en)
Inventor
Terence Edward Weston
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aradigm Corp
Original Assignee
Weston Medical Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB9911663.4A external-priority patent/GB9911663D0/en
Priority claimed from GBGB9924533.4A external-priority patent/GB9924533D0/en
Application filed by Weston Medical Ltd filed Critical Weston Medical Ltd
Publication of EP1180046A2 publication Critical patent/EP1180046A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/3129—Syringe barrels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/30—Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
    • A61J1/202—Separating means
    • A61J1/2044—Separating means having slits
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2096—Combination of a vial and a syringe for transferring or mixing their contents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3117—Means preventing contamination of the medicament compartment of a syringe
    • A61M2005/3118—Means preventing contamination of the medicament compartment of a syringe via the distal end of a syringe, i.e. syringe end for mounting a needle cannula
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3117—Means preventing contamination of the medicament compartment of a syringe
    • A61M2005/3118—Means preventing contamination of the medicament compartment of a syringe via the distal end of a syringe, i.e. syringe end for mounting a needle cannula
    • A61M2005/312—Means preventing contamination of the medicament compartment of a syringe via the distal end of a syringe, i.e. syringe end for mounting a needle cannula comprising sealing means, e.g. severable caps, to be removed prior to injection by, e.g. tearing or twisting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3123—Details having air entrapping or venting means, e.g. purging channels in pistons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/1782—Devices aiding filling of syringes in situ
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
    • A61M5/2053—Media being expelled from injector by pressurised fluid or vacuum

Definitions

  • Needleless injectors are used as an alternative to needle-type hypodermic injectors for injecting liquid drugs through the epidermis and into the underlying tissues.
  • the normal form of construction is a syringe having a small discharge orifice which is placed on the skin, and through which the drug is discharged at sufficiently high pressure to puncture the skin.
  • the force required to pressurise the drug may be derived from a compressed coil spring, compressed gas, explosive charge or other form of stored energy.
  • the pressure induced in the drug during the injection cycle comprises a first phase in which the pressure rises rapidly to a peak, followed by a second phase at lower pressure.
  • the first phase facilitates the penetration of the skin by the drug and the second phase dispenses the drug through the hole thus formed.
  • the pressure reached in the first phase is in the order of 300-400 bars, with a rise time of about 50 ⁇ s, whilst the second phase is completed at a pressure of about 100 bars.
  • the injection cycle for 500 ⁇ l of drug is between 30 and 50ms for water or liquids having similar characteristics to water.
  • the capsule from which the drug is discharged is often in the form of a cylinder containing a free piston (ie 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 drug.
  • the complete injector may be presented as a single use, pre-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.
  • Needleless injectors place heavy demands on the capsule construction because of the extremely high stresses induced during injection.
  • the materials used must be strong, highly transparent so that the drug may be checked visually or by laser inspection instruments for contamination and entrapped gas, and be chemically compatible with the drug to be stored.
  • the ideal material for the capsule is so-called type 1 borosilicate glass, which is very commonly used for needle-type syringes that are pre- filled with drug.
  • glass capsules made to the appropriate specifications have excellent performance, they require rigorous proof testing to eliminate glass containing common flaws such as entrained bubbles and foreign matter, cracks and scratches, and they also require time consuming cleaning and sterilisation before they can be filled.
  • glass capsules are first washed to remove particles and then dry heat sterilised and depyrogenated by heating to around 180°C for at least 6 hours. Glass capsules are therefore expensive to make.
  • Plastics technology allows more precise control of the capsules' dimensions at high production rates.
  • plastics materials introduce a number of problems which are not found in glass, one of which is the problem of drug compatibility.
  • plastics are not suitable for long term drug contact.
  • Plastics are gas permeable, absorb water and contain material which can adversely react with the drug.
  • plastics injection moulding technology typically requires the use of release agents which are not drug compatible requiring time consuming and expensive cleaning and sterilisation of the plastics drug capsule.
  • Many drugs are sensitive to oxygen and so gas permeability must be minimised. The absorption of water would change the concentration of a liquid drug.
  • pyrogen free moulding technology combined with gas sterilisation, typically using ethylene oxide, may be used in place of dry heat sterilisation.
  • gas sterilisation precludes the preassembly of the free piston in the drug capsule to ensure all surfaces can be reached.
  • plastics are sensitive to the sterilisation gas.
  • ethylene oxide is banned in some countries due to public health concerns.
  • a transparent needleless injector drug capsule suitable for pre-filling with a liquid drug comprises a first inner layer of drug compatible transparent plastics defining a chamber for receiving a liquid drug and a second outer layer of transparent plastics forming a supporting sleeve around the first layer of plastics, wherein each of the first and second layers of transparent plastics is resistant to discolouration when irradiated by high energy radiation.
  • the present invention provides a low cost, transparent, needleless injector drug capsule which uses a plastics construction which is capable of being sterilised by high energy irradiation and thereby overcome the production problems associated with conventional glass and plastics drug capsules.
  • Gamma irradiation causes glass and many plastics to assume a brown colour, which impairs visual inspection of the contents after filling.
  • the selection of plastics materials which combine to provide the necessary drug compatibility and strength, and which are also suitable for gamma or other high energy irradiation, provides a cost effective solution to the problems of manufacturing conventional capsules.
  • an alternative material to glass suggested in the prior art is a transparent plastics, but there are very few suitable for long-term contact with most drugs. Those that are potentially chemically compatible have other drawbacks, such as poor resistance to irradiation, intense colouration as a result of irradiation, high water absorption, high gas or vapour transmission, or very low tensile strength. Generally, the plastics most suitable for drug contact are also very brittle, and whilst in theory a single layer, very thick walled capsule could be moulded to provide sufficient strength, this would result in severe post-moulding shrinkage and stress- induced micro-cracks.
  • the first and second layers of plastics are injection moulded, with the first layer being bonded to the second layer at the interface.
  • One reason for bonding the two materials is to prevent the formation of very small air gaps between layers, which would otherwise produce optical interference patterns (Newton's rings) and adversely affect visual or automatic inspection. Even a small gap would adversely affect the barrier properties of the combination.
  • the second layer of plastics has a higher melting point than the first layer of plastics.
  • the materials should have similar coefficients of expansion so that the bond layer doesn't become over stressed during cooling and any subsequent temperature fluctuations.
  • the first layer of plastics is a metallocene catalysed polymer, most preferably a cyclic olefinic copolymer (COC) or a cyclic olefinic polymer (COP).
  • COC cyclic olefinic copolymer
  • COP cyclic olefinic polymer
  • This class of materials exhibits a number of useful properties making it suitable for long term drug contact, including extremely low water absorption, excellent water vapour barrier properties, high transparency, and low birefringence.
  • the material can be sterilised by gamma irradiation without clouding or weakening. However, alone it is too brittle for use as a drug capsule in a needleless injector.
  • the solution is to provide a tough impact resistant sleeve to lend support.
  • the second layer of plastics is a polymer selected from a group consisting of polyesters, copolyesters, polyethylene naphthalate, polyamides, polycarbonates, and polyurethanes. These materials can provide a tough impact resistant transparent plastics support sleeve for the first layer of plastics and which may themselves be sterilised by gamma irradiation without clouding or weakening.
  • the drug capsule further comprises a PTFE piston within the chamber for
  • the first layer of plastics is extended to form an integral filling adapter.
  • the filling adapter includes a frangible tamper evident connection.
  • a needleless injector comprises a drug capsule according to the first aspect of the present invention.
  • the second or outermost layer of plastics is an integral part of the body of the needleless injector.
  • a method of manufacturing a transparent drug capsule for a needleless injector comprises the steps of: forming a multilayer capsule having a first inner layer of drug compatible transparent plastics and a second outer support layer of transparent plastics, each of the first and second layers of transparent plastics being selected so that they are resistant to discolouration when irradiated; and, sterilising the multilayer capsule by high energy irradiation.
  • the first layer of plastics is injection moulded and subsequently the second layer of plastics is moulded onto the first layer so that the two layers are bonded at the interface between them.
  • the second layer of plastics has a higher melting point than the first layer of plastics.
  • the materials should have similar coefficients of expansion so that the bond layer doesn't become over stressed during cooling and any subsequent temperature fluctuations.
  • the drug capsule is preassembled with a PTFE piston located within the capsule, and the entire assembly is sterilised in a vacuum by high energy irradiation.
  • PTFE is usually considered a radiation degradable polymer but it has been found that when irradiated in a vacuum, for example in a vacuum pack, sufficient strength is retained.
  • the PTFE piston is pretreated by gamma or other high energy radiation at an elevated temperature. This treatment causes crosslinking, with a consequent increase in strength and resistance to further irradiation.
  • the method further comprises the step of filling the sterilised drug capsule with a liquid drug in an automated process and subsequently sealing the capsule in a manner suitable for transport and long term storage.
  • a drug capsule for a needleless injector comprises a body having a main chamber for receiving a liquid drug and for retaining a free piston in a sealing fit for subsequent use in the discharge of a drug, the body also having an extension chamber having an opening for receiving the free piston in a loose fit.
  • a multichamber drug capsule which allows a free piston, typically a PTFE piston, to be preassembled within it in a loose fit. Since the piston is initially assembled in a loose fit, and therefore not under mechanical stress, it would not be degraded by normal levels of gamma radiation.
  • a free piston typically a PTFE piston
  • the clearance provided by the initial loose fitting of the piston allows penetration by a sterilization fluid.
  • the drug capsule is capable of being assembled in clean conditions and subsequently sterilized by any known method. Once sterilized, the free piston is pushed into position prior to filling so that it is located and retained in a sealing fit within the main chamber for subsequent use in the discharge of a drug.
  • the drug capsule further comprises a stop to retain the free piston within the extension chamber.
  • the stop comprises a number of integral stakes formed by thermal or ultrasonic displacement of material at the opening of the extension chamber.
  • the stop could be a separate fitting which is connected to the opening of the extension chamber.
  • the extension chamber comprises a tapered section.
  • the extension chamber may be tapered over its entire length or alternatively comprise a parallel section and a tapered section, the tapered section being provided at a transition between the main chamber and the extension chamber.
  • the drug capsule is a transparent plastics drug capsule in accordance with the first aspect of the present invention.
  • a drug capsule in accordance with the fourth aspect of the present invention and a free piston.
  • a method of manufacturing a drug capsule comprises the steps of: forming a drug capsule in accordance with the fourth aspect of the present invention; assembling a free piston in the extension chamber in a loose fit; sterilising the drug capsule assembly; and, locating the free piston within the main chamber in a sealing fit.
  • the drug capsule is then filled.
  • the piston may either be pushed to the discharge end and the capsule then filled with injectate thereby returning the piston to the other end of the main chamber under the pressure of the injectate.
  • the injectate may be introduced by first evacuating the volume of the main chamber and then filling the main chamber with the injectate.
  • Sterilisation may be carried out using a fluid.
  • the fluid is steam or ethylene oxide.
  • the drug capsule may be sterilized by exposure to high energy radiation.
  • the drug capsule may be formed of glass.
  • the drug capsule is a plastics drug capsule.
  • a needleless injector comprises a drug capsule in accordance with the fourth aspect of the present invention.
  • Figure 1 shows a first example of a plastics drug capsule in accordance with the present invention
  • Figures 2 and 3 show the filling of the drug capsule of Figure 1 ;
  • Figure 4 shows the drug capsule of Figure 1 assembled to the body of a needleless injector;
  • Figure 5 shows an example of a needleless injector incorporating a second example of a plastics drug capsule in accordance with the present invention
  • Figure 6 shows a third example of a drug capsule in accordance with the present invention.
  • FIGS 7 and 8 show the filling of the drug capsule of Figure 6.
  • the capsule 1 comprises an inner liner 2 and a sleeve 3.
  • a screw thread 4 for attaching the capsule to an actuator is provided, although a snap fit, bayonet or other well- known connection may be used as an alternative.
  • the liner 2 has an orifice 5 at one end through which the injectate is dispensed, and is in frangible and hydraulic connection at 7 with the filling connector 6.
  • the materials of the liner 2 and connector 6 are preferably the same, and suitable for contact with the drug.
  • the bore 9 of the liner 2 is substantially parallel, and has a surface finish to be compatible with a material of a piston (see Figure 2).
  • the capsule 1 is shown with a piston 10 assembled therein.
  • the piston 10 seals and slides in the bore 9 of the liner 2 and is of a quality to prevent microbial contamination of the drug.
  • Piston 10 is shown in position suitable for vacuum filling, whereby the volume 11 is evacuated via orifice 5, and then filled with liquid drug through the orifice 5. The friction of the piston 5 within the bore 9 is sufficient to prevent its movement during evacuation.
  • An alternative to vacuum filling is to position the piston as at 10b, in which case the small void is first evacuated and the drug then introduced through orifice 5 at a pressure sufficient to force the piston 10 along the bore 9 to the required position.
  • the configuration of the connector 6 may be adapted to suit the filling machine, and a suitable filling method is described in our co-pending application PCT/GB96/03017.
  • Figure 3 shows the capsule described above filled with a liquid drug 12 and sealed.
  • the drug 12 is filled as described, with a small excess in chamber 14 to permit thermally induced volume fluctuations.
  • An elastomeric seal 13 is placed in the bore 8 of connector 6, or (not shown) a small sealing plug may be inserted in the chamber 14.
  • Alternative methods of sealing are a cap 13a, or by thermally softening the walls of the connector 6 and crimping to provide an hermetic seal.
  • There are still other sealing methods such as ultrasonically welding and radio frequency bonding of a foil membrane which may be used, the object in each case to effect a seal against microbial contamination.
  • Figure 4 shows the capsule 1 assembled to an injector actuator 15, and connector 6 together with the seal 13 snapped off at the frangible connection 7, exposing the orifice 5 of the capsule 1.
  • the injector is thus prepared for giving an injection by placing the orifice 5 onto the patient's skin, and operating the actuator to release the stored energy therein, which causes the push-rod 16 to act on piston 10 and dispense the injectate 12 through the orifice 5.
  • a complete injector 100 is shown in Figure 5.
  • the liner 2 is moulded integrally with the body 200, and is of a similar form to that described above.
  • the energy source is a compressed carbon dioxide cartridge 101 (although other liquified gases may be used) having a frangible tube 102.
  • a cap 201 welded or otherwise fixed to body 200 retains the cartridge 101 in situ.
  • This injector is operated by removing the filling connector 6 together with seal 13, and pressing the orifice 5 against the skin. Acting on the lever 103 to push rod 104 against the frangible tube 102 sufficiently to snap the tube 102 causes the release of carbon dioxide gas from the cartridge.
  • the piston 105 is attached to a push-rod 16, and the compressed gas acts on the piston 105 to drive it forward to first strike the piston 10 to create a rapid pressure rise, and then to continue to push the piston 10 to discharge the injectate.
  • a hole 107 prevents excessive back-pressure which would reduce the force of the piston 105, and a hole 106 is positioned so that the piston 105 just passes it at the end of the injection to exhaust residual compressed carbon dioxide.
  • a compressed coil spring or gas spring may be used, and the simple energy release trigger may be replaced by a release mechanism that operates in response to pressure of the orifice on the skin. The latter feature is desirable since it reduces the skill required to achieve a reproducible contact force on the skin, which has a direct effect on injection quality.
  • the material for the inner liner of the capsule must be compatible with the drug and the material for the outer sleeve must be tough and impact resistant. Both materials should be susceptible to sterilisation. Furthermore, the properties of both materials should enable a bond to form at the interface.
  • the preferred material for the inner liner is a cyclic olefin copolymer (COC) known as Topaz (RTM) and manufactured by Ticona (Germany). This material is a
  • Topaz the bulky norbornene group stiffens the chain resulting in a totally amorphous structure where no melting point is observed.
  • a particularly preferred grade of Topaz (RTM) is Topas 6015 (RTM) which is a clear general propose grade with a heat deflection temperature HDT/B of 150°C.
  • the change in yellow index measured according to DIN 6187 ( ⁇ YI) is 1-2 and the change of the haze measured according to ASTM 1003 ( ⁇ Haze) is less than 0.4.
  • Topaz (RTM) can be processed on conventional injection moulding machines.
  • Typical plastics which can be moulded onto the inner layer are copolyesters such as Eastar GN007 manufactured by Eastman (USA), polyethylene napthalate, polyurethanes, nylon 12 and polycarbonate.
  • a particularly preferred material for the outer layer is a specific grade of polycarbonate, Makrolon Rx-1805 (RTM) with colour additive 45/311 manufactured by Bayer (Germany). This material is a transparent high viscosity polycarbonate based on Bisphenol A with a specialised additive system.
  • This material has high chemical resistance and resistance to gamma irradiation. It has a tensile modulus according to ISO 527 of 2400 MPa and a IZOD notched impact strength at 23 °C according to ISO 180-4A of 95 KJ/m 2 - Makrolon Rx-1805 (RTM) can be sterilised by the usual methods, for example with steam, ethylene oxide gas or gamma irradiation. It has high colour stability after gamma irradiation. This material can be processed on all modern injection moulding machines.
  • a drug capsule is manufactured using Topaz 6015 (RTM) as the inner layer and Makrolon Rx-1805 (RTM) as the outer layer.
  • Any conventional injection moulding machine can be used.
  • preferred processing parameters are as follows.
  • injection moulding should be carried out at a tool temperature of 110-150° C, an injection speed of 5-40 cm 3 /s, a shot volume of 27-30 cm 3 , an injection time of 0.80 s, a holding pressure of 200-600 bar, a holding time of 2-3.5 s and a back pressure of 60 bar.
  • the preferred processing parameters are a barrel temperature of 240-300°C, a mould temperature of 80-120°C, an injection pressure of 500-1000 bar, an injection time of 0.5-1.0 s, a back pressure of 20-100 bar, a holding pressure of 150-450 bar and a holding time of 1.5-3.0 s.
  • the liner would be moulded first, allowed to cool slightly, and the outer layer then moulded around it.
  • the liner would typically have a thickness of 1-2 mm, preferably 1.5 mm, and the outer layer a thickness of 2-4 mm, preferably 3 mm.
  • the temperatures should be selected so that the second moulding slightly melts and bonds to the first and the inner liner formed thereafter.
  • the design of the capsule or injector may dictate that the outer part is moulded first. Again, it is important that the coefficients of expansion of the two materials are in the correct range, so that there are no large stresses produced as a result of differential thermal expansion. Additional layers or features may be moulded onto the capsule,
  • plastics that change colour when irradiated to provide a visual indication that the device has been sterilised.
  • the inner layer may also be formed from a liquid crystal polymer or from a poly- para-xylylene (parylene). These materials are suitable for long term drug contact and are opaque or translucent when moulded in thin layers.
  • Preferred liquid crystal polymers are selected from the aromatic copolyesters exemplified by commercial products such as Vectra (RTM) (Hoechst-Celanese), Xydan (RTM) (Amoco Performance Products), HX type liquid crystal polymers (DuPont), Eikonol (RTM) and Sumikasuper (RTM) (Sumitomo Chemical), Rodrun (RTM) (Unitika) and Granlar (RTM).
  • a thin layer of liquid crystal polymer may be obtained by co-extending the liquid crystal polymer with the plastics material forming the outer layer of the drug capsule, such as polycarbonate, for example. This results in a tubular form which is thermo-formed into a desired shape.
  • Parylene coatings are formed from an active monomer gas which is capable of polymerising on the surface of the pre-moulded outer sleeve. It may be formed in layers typically from a few molecules to 75 microns thick.
  • a preferred material for the piston is poiytetrafluoroethylene (PTFE), which has low stiction (coefficients of dynamic and static friction are similar) and excellent chemical resistance. It is easily deformed so that a piston made from the material may be inserted to provide an interference fit in the capsule bore, yet it has a high modulus of elasticity at the high strain rates induced during the first part of the injection. The latter property ensures a high coefficient of restitution and maximum transfer of energy from the actuator into the drug.
  • PTFE poiytetrafluoroethylene
  • Figure 6 shows another example of a drug capsule.
  • the capsule 2 has a bore 9, enlarged at the open end at 9A.
  • Bore 9 A is shown as a taper, for ease of manufacture, but it may be a parallel bore connected to bore 9 by a short tapered section.
  • the piston 10 is a loose fit within the bore 9 A and is retained therein by staking the rim 2 A of capsule 2.
  • Other suitable retaining means may be used instead.
  • the staking 20 may be formed by thermal or ultrasonic displacement of the rim 2A.
  • the preferred material for the piston 10 is PTFE, and because the piston 10 is a loose fit within the bore 9A, and therefore not under mechanical stress, it would not be degraded by normal levels of gamma radiation, ie up to 40 kGys.
  • the clearance between the piston 10 and bore 9 A allows penetration of steam for autoclaving or gasing by ethylene oxide, both common alternatives for sterilising devices for parenteral delivery of drugs.
  • the piston and capsule may be assembled in clean conditions and subsequently sterilised by any known method. After sterilisation, the capsule is filled. As shown in Figure 7, the piston 10 is pushed from the enlarged bore 9A into the substantially parallel bore 9, so that the ribs 10b make sealing contact with the bore 9.
  • the piston may be pushed to the discharge end of the capsule at 10A.
  • the capsule is then filled with injectate 12, as shown in Figure 8, and sealed by a plug 13 or cap 13 A.
  • the plug 13 may have a projection 13B which seals on the filling orifice 21.
  • plastics' is used in the generic sense as for certain organic substances, mostly synthetic or semi-synthetic (casein and cellulose derivatives) condensation or polymerisation products, and also certain natural substances (shellac, bitumen, but excluding natural rubber), which under heat and pressure become plastic, and can then be shaped or cast in moulds, or extruded.

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  • Health & Medical Sciences (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Apparatus For Disinfection Or Sterilisation (AREA)

Abstract

L'invention concerne une capsule de médicament transparente pour injecteur sans aiguille, conçue pour être pré-remplie d'un médicament liquide et comprenant une première couche intérieure de plastique transparent compatible avec le médicament, délimitant une chambre destinée à recevoir un médicament liquide, et une deuxième couche extérieure de plastique transparent formant une gaine de support autour de la première couche de plastique. Les première et deuxième couches de plastique transparent résistent à la décoloration lorsqu'elle sont irradiées par un rayonnement à grande énergie. Ainsi, on produit une capsule de médicament transparente pour injecteur sans aiguille, de faible coût, et pouvant être stérilisée par une irradiation à grande énergie. La capsule peut définir un corps possédant une chambre principale destinée à recevoir un médicament liquide et à loger un piston libre à ajustement étanche, destiné à être utilisé ultérieurement dans la décharge d'un médicament, le corps possédant également une chambre d'extension dotée d'une ouverture pour la réception du piston libre en ajustement libre. L'ajustement libre initial du piston permet la pénétration par un fluide de stérilisation, de sorte que la capsule de médicament puisse être assemblée dans des conditions de propreté et stérilisée ultérieurement par un procédé connu, quel qu'il soit.
EP00931402A 1999-05-19 2000-05-19 Capsule de medicament pour injecteur sans aiguille Withdrawn EP1180046A2 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GB9911663 1999-05-19
GBGB9911663.4A GB9911663D0 (en) 1999-05-19 1999-05-19 Needleless injector drug capsule
GB9924533 1999-10-15
GBGB9924533.4A GB9924533D0 (en) 1999-10-15 1999-10-15 Needleless injector drug capsule
PCT/GB2000/001922 WO2000071185A2 (fr) 1999-05-19 2000-05-19 Capsule de medicament pour injecteur sans aiguille

Publications (1)

Publication Number Publication Date
EP1180046A2 true EP1180046A2 (fr) 2002-02-20

Family

ID=26315564

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00931402A Withdrawn EP1180046A2 (fr) 1999-05-19 2000-05-19 Capsule de medicament pour injecteur sans aiguille

Country Status (4)

Country Link
EP (1) EP1180046A2 (fr)
JP (1) JP2003500118A (fr)
AU (1) AU4935800A (fr)
WO (1) WO2000071185A2 (fr)

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Publication number Priority date Publication date Assignee Title
CA2465502C (fr) 2001-11-09 2011-03-22 Pedro De La Serna Auto-injecteur pneumatique
US20070055199A1 (en) 2005-08-10 2007-03-08 Gilbert Scott J Drug delivery device for buccal and aural applications and other areas of the body difficult to access
JP2010508074A (ja) * 2006-11-01 2010-03-18 アルコン，インコーポレイティド 自動ガス充填用消耗品
DK2039382T3 (da) 2007-09-01 2010-09-13 Hoffmann La Roche Ampul med tætning i to kompressionstilstande
GB2467904B (en) * 2009-02-17 2013-06-12 Oval Medical Technologies Ltd Drug container and delivery mechanism
GB2471304B (en) 2009-06-24 2013-12-11 Oval Medical Technologies Ltd A pre-filled syringe or autoinjector
GB2471726B (en) * 2009-07-10 2013-09-11 Oval Medical Technologies Ltd A pre-filled syringe including an oxygen absorber
US20140142500A1 (en) * 2012-04-23 2014-05-22 Zogenix, Inc. Piston closures for drug delivery capsules
JP6040025B2 (ja) 2012-12-28 2016-12-07 株式会社大協精工 医療用の注射器
BE1021349B1 (nl) * 2014-10-10 2015-11-05 Hubert De Backer Nv Afsluitdop met breekrand en injecteerspuit met genoemde afsluitdop
KR101907552B1 (ko) * 2018-05-03 2018-10-12 주식회사 피테크 무바늘 무통 주사 장치

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EP0709105A1 (fr) * 1994-10-27 1996-05-01 Schott Glaswerke Seringue pré-remplie, stérile à usage unique et faible quantité de particles pour l'injection des compositions et procédé pour sa fabrication

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US5312335A (en) * 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
DE4445969C1 (de) * 1994-12-22 1996-03-14 Schott Glaswerke Spritzenzylinder für eine Zweikammer-Fertigspritze, Zweikammer-Fertigspritze und Verfahren zum Herstellen und Füllen derselben
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US5779668A (en) * 1995-03-29 1998-07-14 Abbott Laboratories Syringe barrel for lyophilization, reconstitution and administration
FR2739562B1 (fr) * 1995-10-09 1998-04-24 Moreau Defarges Alain Dispositif d'injection par jet sans aiguille, comportant une cartouche surmoulee
GB9525757D0 (en) * 1995-12-16 1996-02-14 Weston Medical Ltd Needleless injector drug capsule and filling method
WO1997036785A1 (fr) * 1996-04-02 1997-10-09 Weston Medical Limited Procede pour remplir une capsule avec un medicament et produit resultant
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Publication number Priority date Publication date Assignee Title
EP0709105A1 (fr) * 1994-10-27 1996-05-01 Schott Glaswerke Seringue pré-remplie, stérile à usage unique et faible quantité de particles pour l'injection des compositions et procédé pour sa fabrication

Non-Patent Citations (1)

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Title
See also references of WO0071185A3 *

Also Published As

Publication number Publication date
AU4935800A (en) 2000-12-12
WO2000071185A2 (fr) 2000-11-30
JP2003500118A (ja) 2003-01-07
WO2000071185A3 (fr) 2001-04-05

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