Application arrangement with a medicinal substance fluid

Abstract

A pharmaceutical product includes a delivery syringe comprising a plastic receptacle and an oxygen-tight envelope which envelopes the delivery syringe in an oxygen-tight manner, wherein the plastic receptacle is filled with an oxygen-sensitive active pharmaceutical ingredient fluid and an inner surface of the plastic receptacle is siliconized at least in sections.

Claims

1. A pharmaceutical product comprising: a delivery syringe comprising a transparent plastic receptacle, wherein the plastic receptacle is filled with an oxygen-sensitive active pharmaceutical ingredient fluid; and an oxygen-tight envelope which envelopes the delivery syringe in an oxygen-tight manner, wherein the oxygen-tight envelope has an oxygen transmission rate of less than or equal to 10 cm3/m2 d bar and a water vapor transmission rate of less than or equal to 10 g/m2 d.

2. The pharmaceutical product of claim 1, wherein the oxygen-sensitive active pharmaceutical ingredient fluid is an active pharmaceutical ingredient emulsion.

3. The pharmaceutical product of claim 1, wherein the active pharmaceutical ingredient fluid comprises an active pharmaceutical ingredient having a water solubility in which at least 30 ml of water are required to dissolve 1 g of active pharmaceutical ingredient.

4. The pharmaceutical product of claim 1, wherein the active pharmaceutical ingredient fluid comprises propofol.

5. The pharmaceutical product of claim 1, wherein the plastic receptacle is formed from plastic comprising cyclic olefin copolymer, cyclic olefin polymer, Crystal Clear Polymer, or a combination thereof.

6. The pharmaceutical product of claim 1, wherein the delivery syringe comprises a plastic plunger rod storable in a shiftable manner in the plastic receptacle.

7. The pharmaceutical product of claim 6, wherein the plastic plunger rod is formed from plastic comprising cyclic olefin copolymer, cyclic olefin polymer, Crystal Clear Polymer, polypropylene, or a combination thereof.

8. The pharmaceutical product of claim 1, wherein the plastic receptacle and/or the plastic plunger rod is/are stored in an at least axially shiftable manner in the oxygen-tight envelope.

9. The pharmaceutical product of claim 1, wherein the plastic receptacle and/or the plastic plunger rod are stored at least separately by means of at least one flexible spacer.

10. The pharmaceutical product of claim 1, wherein the oxygen-tight envelope comprises an ethylene-vinyl alcohol copolymer barrier.

11. The pharmaceutical product of claim 1, wherein the oxygen-tight envelope comprises a shell which is thermoformed from thermoplastic, and wherein the shell forms a molding for the formfitting accommodation of the delivery syringe.

12. The pharmaceutical product of claim 11, wherein the thermoplastic comprises an amorphous polyethylene terephthalate film comprising an ethylene-vinyl alcohol copolymer barrier or biaxially oriented polyester comprising an ethylene-vinyl alcohol copolymer barrier.

13. The pharmaceutical product of claim 11, wherein the shell is sealed in an oxygen-tight manner with a peelable polyethylene film or a polyethylene film comprising an ethylene-vinyl alcohol copolymer barrier.

14. The pharmaceutical product of claim 1, wherein the plastic receptacle is sealed in a fluid-tight manner at the distal and proximal ends by a detachable closure.

15. The pharmaceutical product of claim 1, comprising an oxygen absorber.

16. A pharmaceutical product comprising: a delivery syringe comprising a plastic receptacle, wherein the plastic receptacle is transparent and filled with an oxygen-sensitive active pharmaceutical ingredient fluid; and an oxygen-tight envelope which envelopes the delivery syringe in an oxygen-tight manner, wherein the oxygen-tight envelope has an oxygen transmission rate of less than or equal to 10 cm.sup.3/m.sup.2 d bar and a water vapor transmission rate of less than or equal to 10 g/m.sup.2 d, wherein the oxygen-sensitive active pharmaceutical ingredient fluid is an active pharmaceutical ingredient emulsion and comprises propofol and wherein the plastic receptacle is formed from plastic comprising cyclic olefin copolymer, cyclic olefin polymer, Crystal Clear Polymer, or a combination thereof; and wherein an inner surface of the plastic receptacle is siliconized at least in sections.

Description

(1) Further embodiments are more particularly elucidated with reference to the attached drawings. What are shown are:

(2) FIG. 1 a diagrammatic view of a delivery arrangement;

(3) FIG. 2a, b diagrammatic side views of a delivery arrangement; and

(4) FIG. 3 a flowchart of a production method for producing a delivery arrangement.

(5) FIG. 1 shows diagrammatically a delivery arrangement according to one embodiment. The delivery arrangement comprises a delivery syringe 100 comprising a plastic receptacle 101 and a plastic plunger rod 103. The plunger rod 103 comprises, at the distal end thereof, an insert 105 which is introducible into a plunger 113. Here, for example, the plastic plunger rod 103 is stored outside the plastic receptacle 101.

(6) The plastic receptacle 101 is, as indicated in FIG. 1, filled with an active pharmaceutical ingredient fluid 107, preferably with propofol. The plastic receptacle 101 comprises, at the proximal side, a nozzle 109 which is sealed with a closure 111, for example with a plastic cap. The nozzle 109 has a, preferably male, Luer connector or Luer-Lock connector.

(7) The plastic receptacle 101 is, at the distal side, closed off with a plunger 113 into which it is possible to introduce, for example screw in, the insert 105. In this way, the plastic plunger rod 103 can be completed by the plunger 113. The plunger 113 therefore also simultaneously serves as a distal closure of the plastic receptacle 101. In one embodiment, the plastic plunger rod 103 can already have a plunger instead of the insert 105. In this case, the plunger receptacle 101 is provided at the distal side with a further closure.

(8) Also at the distal side, the plastic receptacle 101 comprises side wings 115, 117 which allow not only manual administration but also use of the delivery syringe in a pump system.

(9) The delivery arrangement further comprises an oxygen-tight envelope 119 which can, for example, be formed as a blister or as packaging and envelopes the delivery syringe 100 completely and in an oxygen-tight manner.

(10) In one embodiment, the oxygen-tight envelope 119 can comprise an oxygen-tight shell 121 and also an oxygen-tight film 123 which seals the shell 121 in an oxygen-tight manner along an edge 125 of the shell 121.

(11) To this end, the shell 121 can be formed from a transparent thermoforming film based on an APET film comprising an EVOH barrier (EVOH: ethylene vinyl alcohol) and a peelable sealing layer composed of polyethylene. The shell 121 is therefore a good oxygen barrier and has high rigidity and also good thermoforming behavior, allowing the shell 121 to be designed as a molding. The shell 121 can have at least one of the following technical properties:

(12) Total thickness: 500 μm, DIN 53370; basis weight: 646 g/m.sup.2, ISO 2286-2; oxygen transmission rate: <1 cm.sup.3/m.sup.2 d bar, 23° C./35% r.h., DIN 53380; water vapor transmission rate: <1 g/m.sup.2 d, 23° C./85% r.h., DIN 53122.

(13) The film 123 can, for example, be a polyethylene film comprising an EVOH barrier and, as result, likewise be oxygen-tight. The film 123 can further likewise be produced on the basis of an APET film (APET: amorphous polyethylene terephthalate), making it possible to realize an elevated rigidity. The film 123 is, for example, joined along the edge 125 to the shell 121 in an oxygen-tight manner, for example by welding or adhesive bonding.

(14) The shell 121 can be provided as a molding for the formfitting accommodation of the plastic receptacle 101 and the plunger 113. To this end, the shell 121 can comprise an accommodating recess 127 for the accommodation of the plastic receptacle 101 and an accommodating recess 129 for the accommodation of the plastic plunger rod 103.

(15) To hold the plastic receptacle 101, the accommodating recess 127 can comprise clamping projections 131. The accommodating recess 129 can comprise clamping projections 133 to hold the plastic plunger rod 103. The clamping projections 131, 133 are elastic and therefore able to be pushed in upon application of the plastic receptacle 101 and the plastic plunger rod 103, respectively. Owing to the elasticity of the clamping projections 131, 133, they exert a force, for example in a radial direction, on the plastic receptacle 101 and on the plastic plunger rod 103, respectively, making it possible to fix these elements. In one embodiment, the elements 101 and/or 103 can be fixed such that they cannot fall out of the holder, but are at the same time still shiftable in an axial direction. As a result, in the event of an axial impact for example, it is possible for the plastic receptacle 101 and/or the plastic plunger rod 103 to carry out an axial compensatory movement, more particularly without themselves being damaged and/or without the shell 121 being damaged.

(16) The accommodating recess 127 for the accommodation of the plastic receptacle 101 and the accommodating recess 129 for the accommodation of the plastic plunger rod 103 are arranged separately by means of at least one spacer 130. In the embodiment shown, they are arranged separately by means of two spacers 130. Arranged on the spacers 130 are the aforementioned clamping projections 131, 133. The spacers 130 are flexible, preferably elastic. As a result, impacts in a direction transverse to the longitudinal axis of the plastic receptacle 101 and/or the plastic plunger rod 103 can be cushioned. The two spacers 130 are each provided by a type of wall section.

(17) In one embodiment, the shell 121 and/or the film 123 can be formed from a plastic composite composed of biaxially oriented polyester comprising a coextruded sealing barrier layer composed of polyethylene, EVOH, polyethylene. Such a plastic composite is notable for good transparency. Furthermore, it is possible to realize a broad sealing area and a good oxygen barrier. A film 123 formed in this manner can be used in particular as a lid film for sealing thermoformed shells, for example the shell 121. The film 123 can have at least one of the following technical properties:

(18) total thickness: 100 μm, DIN 53370; basis weight: 107.5 g/m.sup.2, ISO 2286-2; longitudinal tensile strength: 40-60 N/mm.sup.2, ISO 527-3; transverse tensile strength: 35-55 N/mm.sup.2, ISO 527-3; longitudinal elongation at break: 40-120%, ISO 527-3; transverse elongation at break: 40-120%, ISO 527-3; oxygen transmission rate: 1 cm.sup.3/m.sup.2 d bar, 23° C./35% r.h., DIN 53380; CO.sub.2 transmission rate: <4 cm.sup.3/m.sup.2 d bar, 23° C./35% r.h., DIN 53380; N.sub.2 transmission rate: <1 cm.sup.3/m.sup.2 d bar, 23° C./35% r.h., DIN 53380.

(19) In one embodiment, the plastic receptacle 101 is formed from a cyclic polymer. Cyclic polymers have a high purity and also a resistance, ensuring a relatively long storage of active pharmaceutical ingredients. However, cyclic polymers are oxygen-penetrable or oxygen-permeable. This oxygen permeability is disadvantageous not only for oxygen-sensitive products, such as oil-in-water emulsions, but also for oxygen-sensitive active pharmaceutical ingredients, such as propofol.

(20) In one embodiment, this oxygen permeability of the plastic receptacle 101 is compensated for by providing the envelope 119, which can be constructed from a plastic blister and can have a barrier layer with respect to oxygen.

(21) In one embodiment, the plastic receptacle 101 is formed from COC (cyclic olefin copolymer), COP (cyclic olefin polymer) or CCP (Crystal Clear Polymer). These have been found to be resistant to propofol acting as solvent. The plunger 113 and/or the closure 111 is, for example, formed from rubber, more particularly from bromobutyl. The plastic plunger rod 103 can, for example, be formed from polypropylene.

(22) In one embodiment, the plastic receptacle 101 can be a transparent plastic selected from the group of cyclic olefin copolymers or cyclic olefin polymers. The envelope 119 forms an oxygen-impenetrable packaging which encloses the plastic receptacle 101 filled with the active pharmaceutical ingredient fluid 107.

(23) In one embodiment, the inner surface of the plastic receptacle 101 is siliconized or coated with silicone. This increases the sliding capacity thereof. Furthermore, this additionally protects the active pharmaceutical ingredient.

(24) In a further embodiment, plunger 113 is siliconized at least in sections. In one embodiment, the closure 11 is also siliconized at least in sections.

(25) FIGS. 2a and 2b show different side views of the delivery arrangement shown in FIG. 1. In one embodiment, the delivery arrangement can comprise a nonfluidic oxygen absorber 135, which can, for example, comprise iron dust. The oxygen absorber 135 is, for example, arranged at the base of the shell 121.

(26) FIG. 3 shows a chart of a method for producing a delivery arrangement. The method 300 comprises step 301 of providing a delivery syringe comprising a plastic receptacle, step 303 of filling the plastic receptacle with an oxygen-sensitive active pharmaceutical ingredient fluid, for example with propofol or with a propofol fluid, more particularly a propofol emulsion, and oxygen-tight enveloping 305 of the delivery syringe comprising the filled plastic receptacle by means of an oxygen-tight envelope. The method further comprises the step of arranging the prefilled plastic receptacle 101 and the plastic plunger rod 103 in the thermoformed shell 121 and also the oxygen-tight sealing of the shell 121 with the lid film 123 by means of, for example, welding or adhesive bonding.

(27) In one embodiment, an advantage of the delivery arrangement is the ease of use thereof without the need to transfer an active pharmaceutical ingredient to further containers. Furthermore, the delivery syringe can be directly removed and used without the need for further assembly steps. The plastic receptacle 101 has, for example, a capacity of 50 ml, making it possible for the plastic receptacle to be automatically recognized by conventional pump systems. The use of the plastic receptacle achieves a resistance to breakage that is increased with respect to glass. Furthermore, waste quantity can be reduced coupled with simultaneous time savings as a result of elimination of administration preparation steps, which are, for example, caused by transfer of the active pharmaceutical ingredient.

LIST OF REFERENCE SIGNS

(28) 100 Delivery syringe 101 Plastic receptacle 103 Plastic plunger rod 105 Insert 107 Active pharmaceutical ingredient fluid 109 Nozzle 111 Closure 113 Plastic plunger 115 Side wing 117 Side wing 119 Oxygen-tight envelope 121 Shell 123 Film 125 Edge 127 Accommodating recess for the delivery syringe 129 Accommodating recess for the plunger rod 130 Spacer or wall section between the accommodating recess for the delivery syringe and the accommodating recess for the plunger rod 131 Clamping projection 133 Clamping projection 135 Oxygen absorber 300 Method 301 Providing step 303 Filling step 305 Oxygen-tight enveloping