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WO2025221761A2 - Récipient de médicament et kit de reconstitution d'un médicament lyophilisé - Google Patents

Récipient de médicament et kit de reconstitution d'un médicament lyophilisé

Info

Publication number
WO2025221761A2
WO2025221761A2 PCT/US2025/024734 US2025024734W WO2025221761A2 WO 2025221761 A2 WO2025221761 A2 WO 2025221761A2 US 2025024734 W US2025024734 W US 2025024734W WO 2025221761 A2 WO2025221761 A2 WO 2025221761A2
Authority
WO
WIPO (PCT)
Prior art keywords
container
medicament
diluent
sidewall
outlet
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.)
Pending
Application number
PCT/US2025/024734
Other languages
English (en)
Other versions
WO2025221761A3 (fr
Inventor
Daniel Auernhammer
Yvonne WANNER
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.)
Genzyme Corp
Original Assignee
Genzyme Corp
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
Application filed by Genzyme Corp filed Critical Genzyme Corp
Publication of WO2025221761A2 publication Critical patent/WO2025221761A2/fr
Publication of WO2025221761A3 publication Critical patent/WO2025221761A3/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61J1/2089—Containers or vials which are to be joined to each other in order to mix their contents

Definitions

  • the present disclosure relates to the field of reconstituable drug formulations, and in particular to medicament containers and kits for reconstituting a lyophilized medicament. In a further aspect the present disclosure relates to methods of preparing a reconstituable injectable medicament.
  • IV infusions Patients suffering from certain diseases like, for example, haemophilia or requiring enzyme replacement therapy have to take regular intravenous (IV) infusions.
  • IV infusions often have to be mixed and prepared, sometimes to the specific needs of the patient, (and sometimes a short time before drug administration) which may include reconstitution of the drug powder from multiple vials using an exact amount of sterile liquids like water and/or saline.
  • this preparation process is typically complex and tedious, it is usually performed by a health care professional in a clinic or pharmacy, potentially using lab equipment.
  • administering a medicament by way of infusion may require a rather clean or sterile environment.
  • a patient may therefore have to regularly visit an ambulance or health care center.
  • Self-medication or home-medication for administering a medicament through infusion or injection is and remains quite challenging but is very attractive for patients thereby avoiding problems and circumstances involved in visiting a health care center.
  • a patient or user e.g. intending to establish a vascular access to a patient's body, may be obliged to use only one hand, which might be rather cumbersome and thus challenging.
  • the present disclosure relates to a medicament container.
  • the medicament container comprises or defines a container cavity for a soluble substance.
  • the soluble substance comprises an active pharmaceutical ingredient and the soluble substance is soluble by a diluent.
  • the soluble substance is a lyophilized medicament contained inside the container cavity.
  • the medicament container also comprises the soluble substance inside the container cavity.
  • the medicament container further comprises a boundary structure confining the container cavity.
  • the boundary structure is insoluble with respect to the diluent.
  • the boundary structure comprises a sidewall.
  • the sidewall may constitute or may contribute to the boundary structure.
  • the boundary structure comprises the sidewall or is constituted by the sidewall.
  • the medicament container further comprises an inlet for introducing the diluent into the container cavity.
  • the inlet may extend through the boundary structure. It may extend through the sidewall or may be located at an end section, e g., at a first end section of the sidewall.
  • the medicament container further comprises an outlet.
  • the outlet is in flow communication with the container cavity.
  • the outlet may extend through the boundary structure. In some examples the outlet may be located at a further end of the side wall or it may extend through the sidewall.
  • the medicament container also comprises a flow channel extending from the inlet to the outlet.
  • the flow channel is configured to direct the diluent from the inlet through the container cavity to the outlet.
  • the flow channel may be configured to direct via fluid flow the diluent from the inlet through the container cavity to the outlet.
  • the container cavity e.g., the hollow space defined by the container cavity, may be occupied by the flow channel and by the soluble substance located inside the container cavity.
  • the boundary structure is configured or formed in such a way to define or to confine a liquid tight and insoluble outer boundary for the container cavity such that the diluent, which is initially located outside the medicament container is allowed to enter the container cavity via the inlet.
  • the flow channel extending from the inlet to the outlet is configured as a flow-through channel for the diluent.
  • the container cavity and hence the medicament container is configured such that the soluble substance located inside the boundary structure and hence inside the container cavity is inoperable to block or to impede a flow-through of the diluent from the inlet towards and through the outlet.
  • the diluent is configured to dissolve at least a portion or fraction of the soluble substance located inside the container cavity.
  • the flow channel is of persistent nature.
  • the flow channel In an initial configuration, and wherein the container cavity is void of a diluent the flow channel extends unobstructed from the inlet through the container cavity to the outlet. Upon introducing the diluent into the container cavity via the inlet the flow channel does not collapse but remains unaltered. During a flow of the diluent through the flow channel the cross-section of the flow channel may even increase since the soluble substance is either dispersed or dissolved in the diluent.
  • the container cavity is configured to receive and/or to adhere the soluble substance to an inside of the sidewall of the boundary structure thereby providing a flow channel through the container cavity. In this way and even though the container cavity is partially occupied by the soluble substance there is always provided a flow channel for the diluent to flow from the inlet through the flow channel and hence through the container cavity to the outlet.
  • the unobstructed and unimpeded flow of the diluent from the inlet through the container cavity to the outlet may be accompanied by dissolving at least a portion of the soluble substance in the diluent. Dissolved portions or fractions of the soluble substance that have been dissolved or released, i.e. dispersed, in the diluent as the diluent flows from the inlet through the container cavity to the outlet, are transported by the diluent from the inside of the container cavity towards and through the outlet of the medicament container.
  • the container cavity of the medicament container may provide a dissolving or mixing chamber inside which, and in an initial state, there is provided a soluble substance, e.g. in powdered or granular form.
  • the flow-through channel extending from the inlet to the outlet allows and supports an unobstructed flow of the diluent through the container cavity, which flow of the diluent is accompanied by releasing or dissolving at least a portion or a fraction of the soluble substance in the diluent, which is then transported by the flow of the diluent towards and through the outlet. In this way the medicament container provides a twofold function.
  • It provides a mixing or dissolving of the soluble substance, e.g., of a lyophilized medicament with a diluent and further provides a transportation of the dissolved or released medicament, e.g. of the reconstituted medicament out of the medicament container, e.g. towards and into an injection or infusion device.
  • the sidewall of the medicament container comprises an inside surface facing towards at least one of the container cavity and the flow channel.
  • the sidewall may be a closed sidewall. It may be impenetrable for the soluble substance as well as for the diluent.
  • the medicament container is configured such that the diluent is exclusively introducible into the container cavity via the inlet. Also, the diluent and/or the soluble substance, e.g., dissolved in the diluent, may exclusively leave the container cavity via the outlet.
  • the medicament container may define an unidirectional flow for the diluent from the inlet towards the outlet and through the outlet out of the container cavity.
  • the medicament container may define an unidirectional flow, which may be rather turbulent or laminar, e.g. depending on the surface structure provided by the soluble substance adhered or provided at the inside surface of the sidewall.
  • the inside surface of the sidewall may be particularly configured to store and/or to deposit the dissolvable or soluble substance inside the container cavity. In this way, and by adhering or otherwise depositing or fixing the soluble substance to the inside surface of the sidewall there can be provided a flow channel inside the container cavity and inside the boundary structure that extends from the inlet to the outlet.
  • the medicament container In some examples and as seen from a radial center of the medicament container, e.g., in a direction perpendicular to the flow direction as defined by the flow channel and hence by a direction perpendicular to the elongation of the flow channel there may be centrally provided the flow channel, which is at least partially enclosed by the soluble substance.
  • the soluble substance may be adhered or fastened to an inside surface of the sidewall and the sidewall may form or constitute a boundary structure to seal the container cavity in relation to the outside environment of the medicament container.
  • the soluble substance at least in part adjoins the flow channel or encloses at least a part of the flow channel.
  • the soluble substance may be located in the interface between the boundary structure and the flow channel such that the diluent flowing through the flow channel gets in contact with the soluble substance, thereby dissolving or dispersing the soluble substance in the diluent.
  • the soluble substance is provided on or is adhered to the inside surface of the sidewall.
  • the inside surface of the sidewall provides a carrier or a substrate for adhering or for fixing the soluble substrate inside the boundary structure and hence inside the container cavity.
  • an unobstructed flow channel extending from the inlet through the container cavity to the outlet.
  • a well-defined amount or fraction of the soluble substance may get in contact with the diluent as the diluent flows through the flow channel from the inlet towards and/or through the outlet.
  • the soluble substance is homogeneously distributed across the inside surface of the sidewall.
  • the soluble substance may be equally distributed across the inside surface of the sidewall.
  • the medicament container comprises a layer of the soluble substance adhered to or provided on the inside surface of the sidewall.
  • the layer may comprise a layer thickness.
  • the layer of the soluble substance may effectively consist of the soluble substance.
  • the layer may comprise a compressed powder or the layer may be provided as a kind of an inside coating on the inside surface of the sidewall.
  • the layer of the soluble substance may provide or may comprise a homogeneous distribution of the soluble substance.
  • a continuous and/or homogeneous layer of the soluble substance on the inside surface of the sidewall may provide a well-defined reconstitution rate for the reconstituable medicament as the diluent flows through the flow channel, thereby getting in a dissolving contact with the soluble substance of the layer, thus leading to a well-defined dissolving or reconstitution of the soluble substance by the diluent inside the container cavity.
  • the soluble substance is distributed inside the sidewall and/or the sidewall is doped with the soluble substance.
  • the inside surface of the sidewall gets in contact with the diluent flowing through the flow channel or flowing through the container cavity at least a fraction of the soluble substance may be dissolved or released by the diluent.
  • the soluble substance may be integrated or embedded in the sidewall such that the soluble substance is free to diffuse towards the inside surface of the sidewall and/or to get in a dissolving contact with the diluent flowing through the flow channel and/or flowing through the container cavity.
  • the medicament container an inside surface of the layer, which faces away the inside surface of the sidewall and adjoins or encloses the flow channel.
  • the inside surface of the layer may directly enclose the flow channel and may thus confine the flow channel in a direction perpendicular to the elongation of the flow channel. In this way there can be provided a direct mutual contact between the diluent flowing through the flow channel and the soluble substance as provided on or inside the layer.
  • the soluble substance is provided on or in a perforated or porous carrier structure located inside the container cavity.
  • the carrier structure may be insoluble with respect to the diluent. It may provide a mechanical stabilization for introducing the soluble substance into the container cavity while simultaneously maintaining a persisting flow channel inside the container cavity.
  • the carrier structure such may be hollow and may provide a longitudinal through opening acting as a part of the flow channel.
  • the perforation of the carrier structure may provide the flow channel inside of the container cavity.
  • the carrier structure may comprise a scaffold, the details of which will be described below.
  • the carrier structure may be inherently stiff at least to such a degree that it remains dimensionally stable under the effect of gravitation. It may comprise at least one of a rigid, flexible or elastically deformable body.
  • the carrier structure may be connected to an inside of the sidewall or may be supported by the sidewall.
  • the carrier structure may be loosely arranged inside the container cavity and may be subject to a rather free floating when the diluent is introduced into the container cavity.
  • the inside surface of the sidewall comprises a roughened surface structure. By way of a roughened surface structure the overall surface of the sidewall can be effectively increased. Moreover, adhesion of the soluble substance to the inside surface of the sidewall can be improved.
  • a roughened surface structure may provide an increased inside surface for the substance or for fixing the soluble substance, e.g. soluble particles of the soluble substance to the inside surface of the sidewall.
  • the roughened surface structure of the inside surface of the sidewall is chemically or physically roughened.
  • the inside surface of the sidewall is or has been subject to plasma etching or plasma treatment to provide a roughened surface structure.
  • the inside surface of the sidewall is roughened by chemical treatment, e.g. by chemical agents, e.g. by a suitable acid or solvent.
  • the sidewall and/or the boundary structure comprises or constitutes a hollow tube extending from the inlet to the outlet.
  • the sidewall and hence the boundary structure may comprise a tubular structure.
  • the sidewall and/or the boundary structure may comprise a circular symmetric cross section.
  • the sidewall may comprise a continuous or homogeneous cross section as seen from the inlet towards the outlet.
  • the medicament container may comprise an elongated hollow tube formed by the sidewall and extending from the inlet provided at one longitudinal end of the tube towards an opposite longitudinal end, which is provided with the outlet.
  • the hollow tube may comprise a flexible hollow tube.
  • the hollow tube may comprise a hose, e.g., a flexible hose, extending from the inlet to the outlet.
  • the hollow tube may comprise a diameter less than 2 cm, less than 1.5 cm, less than 1 cm or less than 0.5 mm.
  • the hollow tube may define a well-defined flow channel extending through the elongation of the hollow tube.
  • the hollow portion of the tube may form or may constitute the container cavity, which may be a readily occupied by the soluble substance, and/or by dissolvable active pharmaceutical ingredient.
  • a hollow tube with one of the above-mentioned maximum diameters is beneficial for establishing a connection to at least one of a diluent container and an administering container.
  • the rather small diameter provides and supports an unidirectional, rather laminar flow through the container cavity.
  • An elongated hollow tube is easy to manufacture. It may be made of a variety of different materials or material classes.
  • the hollow tube comprises geometric structure that requires only a minimum of storage space and/or transportation space.
  • the medicament container comprising or constituting a hollow tube only allows and provides a rather densely packed configuration for the purpose of storage, shipment and retail.
  • At least one of the boundary structure and the side wall of the medicament container is flexible and/or elastically deformable.
  • the flexibility or elasticity of the sidewall and/or of the boundary structure may be predominately governed by the material the boundary structure and/or the sidewall is made of.
  • parameters, such as a variable thickness of the sidewall may have a respective influence on the elasticity and/or flexibility of the medicament container.
  • the flexible or elastically deformable boundary structure or sidewall of the medicament container may be of particular benefit during production, manufacturing, transportation and storage.
  • a flexible or elastically deformable medicament container may inherently provide mechanical shock absorption. It may be rather insensitive to mechanical shock or mechanical impact.
  • the flexible or elastically deformable boundary structure or sidewall of the medicament container may be less prone step to breakage or disintegration compared to medicament containers made of a vitreous material, such as glass.
  • a flexible and/or elastically deformable sidewall or boundary structure of the medicament container may be also beneficial to assist a mixing or dissolving processes when the diluent is introduced into to the container cavity.
  • a dissolving or reconstituting process may be supported and/or improved.
  • the container cavity and/or the sidewall and/or the boundary structure comprises an elongated structure comprising a first longitudinal end and a second longitudinal end opposite to the first longitudinal end.
  • the opposite longitudinal ends may be provided with the inlet and with the outlet, respectively.
  • the opposite longitudinal ends may further provide a direct access to the container cavity from outside the medicament container.
  • the container cavity may be accessible via both longitudinal ends.
  • the sidewall may be of tubular shape, it may be produced by extrusion of a sidewall material and/or by folding a planar flexible sidewall substrate into a tubular shape and by fixing the folded sidewall substrate in a wrapped or tubular configuration.
  • the inlet is provided at the first longitudinal end and the outlet is provided at the second longitudinal end.
  • the container cavity, the sidewall and/or the boundary structure may define an unidirectional flow of the diluent from the inlet through the boundary structure and hence through the flow channel towards the outlet.
  • the medicament container comprises a perforated or porous scaffold inside the container cavity.
  • the scaffold is enclosed or encapsulated by a liquid tight outside cover.
  • the scaffold may belong or may contribute to the sidewall.
  • the scaffold may be separate from the sidewall or boundary structure.
  • the liquid tight outside cover may form or constitute at least one of the outer boundary structure and the sidewall.
  • the scaffold may be located inside the container cavity. It may be in flow communication with the flow channel that extends from the inlet to the outlet.
  • the scaffold is dimensionally stable. In further examples the scaffold is flexible and/or deformable. The scaffold may improve the mechanical stability of the medicament container. Moreover, the scaffold may provide a structure for adhesion or for depositing the soluble substance. In some examples the scaffold may provide a substrate for adhesion of the soluble substance to an outside and/or inside surface of the scaffold. The scaffold may be penetrable by the soluble substance. It may comprise at least one of a perforated or porous structure. Typically, and in some examples the diluent may flow through the perforated or porous scaffold. In some examples the soluble substance is adhered to or is provided on at least one of an inside or outside surface of the scaffold. In some examples the soluble substance may be distributed inside or across the perforated or porous scaffold.
  • the soluble substance may be mechanically fixed and/or mechanically supported inside the container cavity.
  • the liquid tight outside cover may form or constitute the boundary structure.
  • the scaffold may also contribute to the boundary structure and/or to the sidewall. In further examples the scaffold may be located inside the container cavity and may neither contribute to the boundary structure nor to the sidewall of the container cavity.
  • the sidewall and/or the boundary structure comprises at least one of the perforated or porous scaffold and the liquid tight outside cover.
  • the perforated and/or porous scaffold comprises a fabric provided with the soluble substance.
  • the perforated or porous scaffold may comprise a textile or otherwise woven or nonwoven material. It may comprise numerous fibers provided in a fabric structure.
  • the fabric may be penetrable by the diluent.
  • the fabric may be therefore impregnated with the soluble substance. Hence, particles of the soluble substance may adhere to the fibers or other constituents of the fabric of the perforated or porous scaffold.
  • the total amount of soluble substance inside the container cavity can be increased.
  • the scaffold itself may comprise a tubular structure that matches with the tubular structure of at least one of the sidewall and the boundary structure of the medicament container.
  • the perforated and/or porous scaffold may comprise a hollow interior and may thus provide or constitute the flow channel extending from the inlet to the outlet of the medicament container.
  • the elongation of the scaffold and hence the elongation of the fabric may be as large as the longitudinal distance between the inlet and the outlet of the medicament container.
  • the elongation, hence the longitudinal extent of the perforated or porous scaffold may be shorter than the total elongation of the container cavity that extends from the inlet to the outlet.
  • the sidewall of the medicament container comprises a pliable substrate, e.g. a planar pliable substrate, comprising an outside surface and comprising an opposite inside surface.
  • a pliable substrate e.g. a planar pliable substrate
  • the recesses being each configured to receive at least a portion or a fraction of the soluble substance, hence, of the lyophilized medicament.
  • the pliable substrate may be further wrappable into a hollow tubular structure to thereby form or constitute the sidewall of the boundary structure.
  • the substrate is no longer planar but assumes a tubular or cylindrical, and hence a wrapped configuration.
  • the sidewall of the medicament container may comprise a wrapped or coiled tubular substrate that has been wrapped or coiled from a planar pliable or flexible substrate.
  • the pliable or flexible substrate may comprise a plastic foil.
  • the pliable substrate is typically insoluble with respect to the diluent. It may be liquid tight.
  • Opposite circumferential ends of the pliable substrate may be brought in an overlapping or otherwise abutment configuration.
  • Oppositely located circumferential ends of the folded or of the wrapped hollow tubular structure may be mutually connected, e.g., welded, or otherwise sealed so as to form or to constitute a liquid tight hollow tubular structure that may serve or that may constitute the sidewall or boundary structure of the medicament container.
  • the recesses as provided on the inside surface are sealed by an inside cover, which is one of disposable or disintegrable by the diluent or solvent.
  • an inside cover it can be provided that during transportation and storage the soluble substance, which may be provided in a powdered or granular form, is hindered to fall out of the recesses.
  • the inside cover the soluble substance is entrapped in the recesses and is hindered to escape prematurely from the recesses. In this way it can be provided that the flow channel is and remains unobstructed at least during transportation and storage of the medicament container.
  • the inside cover is and remains intact and effectively entraps or encloses the soluble substance in the recesses.
  • the inside cover is successively dissolved or disintegrated by the diluent, thereby disseminating and releasing the soluble substance from the receptacles or recesses.
  • the inside cover is at least one of biocompatible, pharmaceutically inert and physiologically inert. The same may apply to the material that forms the container cavity.
  • the material of the sidewall and/or the material of the boundary structure, at least the material fraction or material portion forming or constituting the inside surface of the sidewall, and which is in direct contact with the container cavity and/or with the flow channel is made of a biocompatible material a pharmaceutically inert material answers or is made of a physiologically inert material.
  • any material or material fraction that may be dissolved by the diluent and which may enter or contribute to the reconstituted medicament does not harm a patient and does not have a physiological effect when the reconstituted medicament is administered to a patient.
  • the inside cover of the medicament container comprises or is made of a polylactide.
  • a polylactide material is easily dissolvable by the diluent, e.g., by water for injection and does not have a physiological or pharmaceutical effect on a patient.
  • the sidewall of the medicament container and hence the boundary structure may comprise or may be made of at least one of a polyvinylchloride and a thermoplastic elastomer. Both materials are suitable for the short-term as well as long term storage of soluble substances, and in particular of reconstituable medicaments that are provided in powdered or granular form. Polyvinylchloride and thermoplastic elastomers may also provide an excellent container closure integrity and sealability of the medicament container with regards to the outer environment. Such materials are further characterized of being pharmaceutically inert and/or physiologically inert. They may also exhibit an excellent degree of biocompatibility. Moreover, they are available at moderate cost and they may further provide a sidewall and hence a boundary structure that is at least one of flexible and elastically deformable.
  • the sidewall of the medicament container is transparent or translucent. It may be at least partially transparent or partially translucent.
  • An at least partially transparent configuration of the sidewall and hence of the boundary structure of the medicament container allows for a visual inspection of the soluble substance and a visual inspection of the flow channel as well as of the container cavity located inside the boundary structure or sidewall. In this way, introduction of the diluent into the container cavity as well as the process of dissolving of the soluble substance inside the container cavity can be at least visually inspected.
  • At least one of the inlet and the outlet is closed or is closable by a closure.
  • the closure is at least one of detachable from at least one of the inlet and the outlet or the closure is transferable into an open configuration.
  • the closure In an initial configuration of the medicament container, e.g., when and as long as the medicament container provides medicament storage or medicament transportation, the closure is intact and is in a closed configuration.
  • the closure at least one of the inlet and the outlet is effectively closed or sealed against environmental influences.
  • the diluent and/or at least a fraction or portion of the soluble substance dissolved in or transported by the diluent may leave the container cavity, e.g. through the outlet.
  • the container cavity By closing the inlet and the outlet with a closure the container cavity can be effectively sealed. It may provide a storage environment for the soluble substance inside the container cavity.
  • At least one of the inlet and the outlet comprises a frangible portion, which is frangibly and/or detachably connected to one of the flow channel and the sidewall.
  • a frangible portion By way of a frangible portion the respective inlet or outlet can be transferred from its initial closed configuration into an open configuration.
  • the frangible portion By the frangible portion a resealing of the respective inlet or outlet can be effectively impeded. This prevents a multiple use of the medicament container. Accordingly, and once the frangible portion has been detached or transferred into an open configuration, the entirety of the soluble substance provided inside the container cavity should be used or dissolved by the diluent.
  • the medicament container may be used multiple times. It may be then configured as a reusable medicament container.
  • the medicament container may be also refillable once the soluble substance has been extracted or withdrawn from the container cavity.
  • the sidewall comprises a length indicating scale extending from the inlet to the outlet.
  • the length indicating scale may be provided along a portion of the sidewall located between the inlet and the oppositely located outlet.
  • the length indicating scale is of particular use when the soluble substance is homogeneously distributed inside the container cavity as seen in longitudinal direction, hence as seen from the inlet towards the outlet.
  • the length indicating scale may then be indicative of the amount of the soluble substance located inside the container cavity.
  • the length indicating scale may also allow or supported a well-defined disintegration or separation of the container cavity into multiple parts. With a length indicating scale on the sidewall, a user or a health care professional may be given the opportunity to separate the medicament container into multiple parts, e.g.
  • the medicament container and/or its sidewall may be disintegrated at least into two or more parts, wherein each part may contain an amount of the soluble substance and hence an amount of the lyophilized medicament that corresponds to the elongation of the respective container part.
  • the medicament container may be cut or separated into multiple parts, wherein each part contains a well-defined amount of the soluble substance that is proportional to the length of the separated container part.
  • the length indicating scale the individual dosing is even facilitated and improved.
  • the healthcare professional or end user is immediately provided with an information that a particular length fraction of the sidewall corresponds to a particular and well- defined amount of the soluble substance or medicament.
  • the soluble substance comprises a lyophilized medicament or consists of the lyophilized medicament.
  • the soluble substance is located inside the container cavity.
  • the medicament container may be provided as a drug device combination.
  • the medicament container as such may form or constitute a medical device which is readily provided with a soluble substance and hence with a lyophilized medicament.
  • the medicament container may be of particular use for the process of reconstituting the medicament. This process may be easily provided by introducing a diluent, e.g., water for injection, through the inlet into the container cavity. Inside the container cavity at least a portion or a fraction of the soluble substance may be dissolved or disseminated in the diluent. The respective solution, hence the soluble substance and/or the reconstituted medicament may then leave the container cavity through the outlet.
  • a diluent e.g., water for injection
  • At least one of the inlet and the outlet comprises a connector for connecting the medicament container with at least one of a diluent container, an administering container and another medicament container in a fluid communicating way.
  • the connector may provide a mechanical connection of at least one of the inlet and the outlet of the medicament container to at least one of the above-mentioned supplemental containers, e.g. a diluent container, an administering container or a further medicament container in a fluid communicating way.
  • the connector may provide a fluidic coupling, which provides a fluid communication across at least one of the inlet and the outlet of the medicament container with a cavity of at least one of the diluent container, the administering container and another medicament container.
  • Another medicament container may be provided as a further medicament container as described above.
  • the inlet of the medicament container may be provided with a connector of a first type and the outlet of the medicament container may be provided with a connector of a second type. It may be provided that only connectors of the first and second type may form a fluid transferring fluid coupling and/or a fluid transferring mechanical connection.
  • the connector of a first type may be a male connector.
  • the connector of the second type may be a female connector complementary shaped to the male connector.
  • the connector provided with at least one of the inlet and the outlet may comprise a standardized connecting structure.
  • the connector may be provided as a Luer connector or the like standardized liquid transferring connecting structure.
  • a set of medicament containers comprises a first medicament container as described above comprising a first sidewall of a first length.
  • the set of medicament containers further comprises a second medicament container as described above.
  • the second medicament container comprises a second sidewall of a second length. The second length may differ from the first length.
  • first medicament container and the second medicament container may be of equal type apart from the fact that they may distinguish in length.
  • the medicament located inside the first and second container cavities of first and second medicament containers, respectively, may comprise the same active pharmaceutical ingredient.
  • first and second medicament containers may contain different active pharmaceutical ingredients.
  • the first medicament container and the second medicament container may be combined either directly or indirectly. Due to their difference in length they may contain different amounts of the soluble substance and hence different amounts of the reconstituable medicament.
  • the first medicament container may comprise or contain ten doses of a medicament and the second container may only comprise or contain five doses of a medicament.
  • an injectable medicament comprises 15 doses of the active pharmaceutical substance.
  • the set of medicament containers there may be provided multiple medicament containers, each of which comprising or containing a well-defined amount, e.g. a dose or multiple doses of a medicament.
  • the amount of medicament contained inside the respective container cavities may directly correlate with the lengths or elongation of the respective containers. Alone through the elongation or length of the medicament container, the patient or caregiver is immediately and rather intuitively provided with a respective dose size information.
  • each individual medicament container In use of the medicament containers and hence in use of the set of medicament containers the overall length of each individual medicament container is directly indicative of the amount of medicament or soluble substance located therein.
  • the set of medicament containers is exclusively provided by medicament containers as described herein or as described above. Insofar, all features, effects, properties and benefits as described above with regard to the medicament container equally apply to the set of medicament containers.
  • the present disclosure also relates to a kit for reconstituting a lyophilized medicament.
  • the kit comprises a medicament container as described above and a diluent container.
  • the diluent container is filled with a diluent and is connectable with the inlet of the medicament container in a fluid communicating way.
  • an outlet of the diluent container may be provided with a connector, that is complementary shaped to a connector as provided at the inlet of the medicament container.
  • the diluent as provided by the diluent container may be introduced into the container cavity of the medicament container.
  • the diluent may start to dissolve at least a portion or fraction of the soluble substance that is contained inside the container cavity of the medicament container.
  • the diluent and at least a portion of the reconstituted medicament, e.g. at least a portion or fraction of the soluble substance may then leave the container cavity through the outlet of the medicament container.
  • the outlet of the medicament container may be initially sealed.
  • the outlet of the medicament container may be connected or may be connectable to an administering container, which is configured to collect the diluent flowing through the medicament container and the soluble substance that has been dissolved or released in the diluent as the diluent flows through the container cavity of the medicament container.
  • the administering container may provide further mixing or reconstitution of the reconstituable medicament.
  • reconstitution of the lyophilized medicament may require a well-defined mechanical treatment, e.g. a rolling, stirring or shaking motion of the diluent or when in contact with the soluble substance.
  • kit includes a medicament container as described above, all features, properties, effects and benefits as described above in connection with the medicament container equally apply to the kit; and vice versa.
  • the kit also comprises an administering container, which is connectable with the outlet of the medicament container in a fluid communicating way.
  • the administering container is configured to receive at least one of the diluent, the soluble substance, e.g., in form of the lyophilized medicament, and the reconstituted injectable medicament.
  • at least one of the diluent container and the administering container comprises an enclosure.
  • the enclosure may comprise a barrel, e.g. made of a vitreous material.
  • at least one of the diluent container and the administering container comprises a flexible bag.
  • the flexible bag may comprise a flexible or elastically deformable sidewall.
  • the diluent container and/or the administering container may comprise a transparent material so as to visually inspect the diluent as well as the reconstituted injectable medicament provided or collected inside respective cavities of the diluent container and the administering container.
  • the present disclosure also relates to a method of preparing a reconstituable injectable medicament.
  • the method comprises the steps of using or providing a medicament container as described above, wherein the medicament container is provided and/or used with a lyophilized medicament.
  • the lyophilized medicament is provided as the soluble substance inside the container cavity.
  • the inlet of the medicament container is connected with a diluent container. Thereafter, at least a portion of the diluent is directed from the diluent container through the inlet into the container cavity of the medicament container.
  • the lyophilized medicament hence the soluble substance, is at least one of dissolved, released or reconstituted inside the container cavity. Since the method of preparing a reconstituable injectable medicament makes use of the medicament container as described herein, all effects, features, properties and benefits as described above in connection with the medicament container, with the set of medicament containers and with the kit for reconstituting a lyophilized medicament equally apply to the method of preparing the reconstituable injectable medicament; and vice versa.
  • the method also comprises the step of connecting the outlet of the medicament container with an administering container in a fluid communicating or fluid transferring way and guiding at least a portion of the diluent and the dissolvable substance through the outlet of the medicament container into the administering container.
  • the diluent and/or the soluble substance can be collected that has been dissolved or released by the diluent as the diluent flows through the flow channel of the medicament container.
  • the diluent and the soluble substance i.e. the lyophilized medicament, may be further mechanically treated in a well-defined manner to reconstitute the injectable medicament.
  • the reconstituted medicament can be withdrawn from the administering container or can be guided to a further medical device, typically to an injection device for administering the reconstituted liquid medicament into a logical tissue and/or into a human or animal body.
  • drug or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier.
  • An active pharmaceutical ingredient (“API”) in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.
  • a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases.
  • API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.
  • the drug or medicament may be contained in a primary package or “drug container 1 ’ adapted for use with a drug delivery device.
  • the drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., shorter long-term storage) of one or more drugs.
  • the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days).
  • the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20°C), or refrigerated temperatures (e.g., from about - 4°C to about 4°C).
  • the drug container may be or may include a dualchamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber.
  • the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body.
  • the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing.
  • the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.
  • the drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders.
  • disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism.
  • Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.
  • APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (antidiabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.
  • APIs for the treatment and/or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof.
  • an insulin e.g., human insulin, or a human insulin analogue or derivative
  • GLP-1 glucagon-like peptide
  • DPP4 dipeptidyl peptidase-4
  • analogue and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue.
  • the added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues.
  • Insulin analogues are also referred to as "insulin receptor ligands".
  • the term ..derivative refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids.
  • one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.
  • insulin analogues examples include Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Vai or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.
  • insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N- palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega- carboxypentadecanoyl-gamma-L-g
  • GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC- 1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697
  • oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom.
  • DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.
  • hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.
  • Gonadotropine Follitropin, Lutropin, Choriongonadotropin, Menotropin
  • Somatropine Somatropin
  • Desmopressin Terlipressin
  • Gonadorelin Triptorelin
  • Leuprorelin Buserelin
  • Nafarelin Nafarelin
  • Goserelin Goserelin.
  • polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof.
  • a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium.
  • An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.
  • antibody refers to an immunoglobulin molecule or an antigenbinding portion thereof.
  • antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen.
  • the antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody.
  • the antibody has effector function and can fix complement.
  • the antibody has reduced or no ability to bind an Fc receptor.
  • the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region.
  • the term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).
  • TBTI tetravalent bispecific tandem immunoglobulins
  • CODV cross-over binding region orientation
  • fragment refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full- length antibody polypeptide that is capable of binding to an antigen.
  • Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments.
  • Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and immunoglobulin single variable domains. Additional examples of antigen-binding antibody fragments are known in the art.
  • SMIP small modular immunopharmaceuticals
  • immunoglobulin single variable domain (ISV), interchangeably used with “single variable domain”, defines immunoglobulin molecules wherein the antigen binding site is present on, and formed by, a single immunoglobulin domain.
  • immunoglobulin single variable domains are capable of specifically binding to an epitope of the antigen without pairing with an additional immunoglobulin variable domain.
  • the binding site of an immunoglobulin single variable domain is formed by a single heavy chain variable domain (VH domain or VHH domain) or a single light chain variable domain (VL domain).
  • VH domain or VHH domain single heavy chain variable domain
  • VL domain single light chain variable domain
  • An immunoglobulin single variable domain can be a heavy chain ISV, such as a VH (derived from a conventional four-chain antibody), or VHH (derived from a heavy-chain antibody), including a camelized VH or humanized VHH.
  • the immunoglobulin single variable domain may be a (single) domain antibody, a "dAb” or dAb or a Nanobody® ISV (such as a VHH, including a humanized VHH or camelized VH) or a suitable fragment thereof.
  • Nanobody® is a registered trademark of Ablynx N.V.]; other single variable domains, or any suitable fragment of any one thereof.
  • VHH domains also known as VHHs, VHH antibody fragments, and VHH antibodies, have originally been described as the antigen binding immunoglobulin variable domain of “heavy chain antibodies” (i.e., of “antibodies devoid of light chains”; Hamers-Casterman et al. 1993 (Nature 363: 446-448).
  • VHH domain has been chosen in order to distinguish these variable domains from the heavy chain variable domains that are present in conventional 4- chain antibodies (which are referred to herein as “VH domains”) and from the light chain variable domains that are present in conventional 4-chain antibodies (which are referred to herein as “VL domains”).
  • VHH domains For a further description of VHH’s, reference is made to the review article by Muyldermans 2001 (Reviews in Molecular Biotechnology 74: 277-302).
  • CDR complementarity-determining region
  • framework region refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding.
  • framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.
  • antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).
  • PCSK-9 mAb e.g., Alirocumab
  • anti IL-6 mAb e.g., Sarilumab
  • anti IL-4 mAb e.g., Dupilumab
  • Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device.
  • Pharmaceutically acceptable salts are for example acid addition salts and basic salts.
  • An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608- 1:2014(E). As described in ISO 11608- 1:2014(E), needlebased injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems.
  • the container may be a replaceable container or an integrated non-replaceable container.
  • a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).
  • Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).
  • a single-dose container system may involve a needle-based injection device with a replaceable container.
  • each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation).
  • each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).
  • a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container.
  • each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation).
  • each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).
  • Fig. 1 schematically illustrates an example of the medicament container in connection with a diluent container
  • Fig. 2 shows a cross section A-A of the medicament container as indicated in Fig. 1
  • Fig. 3 shows an example of an outlet of the medicament container
  • Fig. 4 shows a further example of an outlet of the medicament container
  • Fig. 5 shows a kit for reconstituting a lyophilized medicament making use of the medicament container
  • Fig. 6 is a flowchart of a method of preparing a reconstituable injectable medicament
  • Fig. 7 shows a set of medicament containers of different lengths
  • Fig. 8 shows a further example of a medicament container comprising a scaffold
  • Fig. 9 shows a cross-section B-B through the medicament container as indicated in Fig. 8,
  • Fig. 10 shows a transverse cross-section through a further example of a medicament container
  • Fig. 11 shows an example of a pliable substrate for producing or manufacturing a medicament container
  • Fig. 12 shows a cross-section C-C through the substrate of Fig. 11 .
  • Fig. 13 shows the substrate of Figs. 11 and 12 in a coiled or wrapped configuration thereby forming a tubular sidewall structure
  • Fig. 14 shows an example of manufacturing a medicament container according to Figs. 8 and 9.
  • a medicament container 10 that is particularly configured to store a soluble substance 4, such as a lyophilized medicament 2.
  • the medicament container 10 comprises a boundary structure 11 , which is insoluble with respect to a diluent 5.
  • the boundary structure 11 may be provided by a sidewall 12.
  • the sidewall 12 is likewise insoluble with respect to the diluent 5.
  • the diluent 5 may be provided separately in a diluent container 20, which is also shown in Fig. 1.
  • the diluent container 20 may comprise a container cavity 21 , which is encapsulated by an enclosure 22.
  • the enclosure 22 may comprise a bottle and may comprise a respective sidewall.
  • the enclosure 22 comprises a flexible bag 23.
  • the diluent container 20 is provided with an outlet 24.
  • the outlet 24 may be provided with a port 25.
  • the port 25 and/or the outlet 24 may be provided with a standardized connector, e.g. with a fluidic connector that allows for a liquid tight connection to the medicament container 10.
  • the medicament container 10 may comprise a flexible tube 13, which is constituted or formed by a flexible sidewall 12.
  • the sidewall 12 may be made of a polymeric material. It may comprise a polyvinylchloride and/or a thermoplastic elastomer.
  • the sidewall 12 comprises a tubular structure and may thus form an elongated tube 13.
  • the cross-section of the sidewall 12 and hence of the tube 13 may be circular symmetric. In further examples it may comprise an oval structure or cross section.
  • the tube 13 may comprise a polygonal cross-sectional structure or profile.
  • the tube 13 and hence the sidewall 12 comprises a first longitudinal end 18 and a second longitudinal end 19.
  • the longitudinal ends 18, 19 are opposite ends of the elongated tube 13 or sidewall 12. As illustrated in Fig. 1 the first longitudinal end 18 is provided with an inlet 8 or forms an inlet 8 for the diluent 5.
  • the opposite longitudinal end 19 comprises or forms an outlet 9.
  • the medicament container 10 comprises a hollow container cavity 14.
  • the container cavity 14 may be at least partially occupied by a soluble substance 4.
  • the soluble substance 4 comprises an active pharmaceutical ingredient 3.
  • the soluble substance 4 may consist of the active pharmaceutical ingredient 3 and may constitute or comprise a lyophilized medicament 2, which may be provided in a powdered form, a compressed powdered form or in a granular form.
  • the soluble substance 4, e.g. the lyophilized medicament 2 may be adhered or may be fastened to an inside surface 16 of the sidewall 12.
  • the flow channel 15 is unobstructed as seen from the inlet 8 to the outlet 9.
  • the flow channel 15 may provide an unobstructed and/or unimpeded flow of the diluent 5 from the inlet towards the outlet 9 when the diluent 5 is introduced into the container cavity 14 via the inlet 8.
  • both opposite longitudinal ends 18, 19 are sealed by a closure 48, 49.
  • Both closures 48, 49 may comprise a stopper 50.
  • the stopper 50 may be detachably connected to the longitudinal ends 18, 19.
  • the outlet 24 of the diluent container 20 can be connected to the container cavity 14 in a fluid transferring manner.
  • the diluent 5 introduced into the container cavity 14 may leave the container cavity 14, e.g., towards an administering container 30 as e.g. shown in sketch of Fig. 5.
  • the opposite longitudinal ends 18, 19 are sealed in a liquid tight and/or gas tight manner.
  • the container cavity 14 can be sealed against the outside environment and the soluble substance 4 can be protected against environmental influences.
  • the diluent 5 By introducing the diluent 5 into the container cavity 14 the diluent 5 may flow through the flow channel 15. By its way through the flow channel 15 the diluent 5 may get in contact with the soluble substance 4 and may start to dissolve the soluble substance. It may be also that undissolved particles of the soluble substance are released from the inside surface 16 and may be transported by the flow of the diluent 5 towards and/or through the outlet 9.
  • the soluble substance 4 may be dissolved in the diluent 5 as the diluent 5 flows unidirectionally from the inlet 8 to and through the outlet 9 into the administering container 30.
  • the administering container 30 may comprise a structure that resembles or that is substantially equal to the structure of the diluent container 20.
  • the administering container 30 comprises a container cavity 31, which in an initial configuration of the administering container 30, may be empty.
  • the administering container 30 also comprises an enclosure 32, which may be provided by a bottle or by a flexible bag 33.
  • the administering container 30 comprises an inlet 34, which is connectable to the outlet 9 of the medicament container 10 in a fluid communicating or fluid transferring manner.
  • the inlet 34 may comprise a port 35 with a standardized connector for establishing a liquid tight fluid transferring or fluid communicating connection between the container cavity 31 and the container cavity 14 of the medicament container 10.
  • the diluent 5 initially located inside the diluent container 20 may be introduced into the container cavity 14 of the medicament container 10 via the inlet 8.
  • the diluent 5 and the soluble substance 4 may dissolve or at least release in the diluent 5 on its way through the container cavity 14 and may then leave the container cavity 14 via and through the outlet 9 into the container cavity 31 of the administering container 30.
  • the administering container 30 may be further connected to an injection device 40.
  • the injection device 40 may comprise an injection needle 42 or an infusion needle for administering the reconstituted medicament 6, as collected or provided inside the administering container 30, into biological tissue.
  • the injection needle 42 and hence the injection device 40 may be connected to the container cavity 31 of the administering container 30 by a fluid transferring fluid line 41.
  • the fluid line 41 may be connectable or may be connected to an outlet 36 of the administering container 30.
  • the outlet 36 may comprise an outlet port 37.
  • the ports 25, 35, 37 as described and mentioned herein may be each provided with a standardized connector, such as a Luer connector thereby providing a liquid proof or liquid tight standardized and detachable connection between the diluent container 20, the medicament container 10, the administering container 30 and the injection device 40, respectively.
  • Fig. 4 there is illustrated an example of the medicament container 10, wherein the outlet 9 and hence the second longitudinal end 19 of the tubular-shaped sidewall 12 is provided with a connector 46.
  • the connector 46 may comprise a nozzle or the like fluid guiding structure.
  • the connector 46 is provided with a detachable protective cap 47. In an initial configuration the protective cap 47 is detachably or frangibly connected to the connector 46 and may seal the connector 46 and hence the outlet 9.
  • the medicament container 10 For connecting the medicament container 10, e.g., to the administering container 38, it is intended to detach or to remove the protective cap 47 and to establish a fluid communicating or fluid transferring connection between the outlet 9 of the medicament container 10 and the inlet 34 of the administering container 30.
  • the longitudinal end 19 and hence the outlet 9 of the medicament container 10 may be provided with a frangible portion 52.
  • the frangible portion 52 may be configured to become detached or to be separated from the sidewall 12, e.g. along a predetermined breaking structure 53.
  • the material of the sidewall 12 may comprise a well- defined structural weakening, which, when exposed to a respective force effect, e.g. when exposed to a shear force, may disintegrate and may provide a separation of the frangible portion 52 from the sidewall 12, thereby opening the longitudinal end 19, which has been hermetically sealed before by the frangible portion 52.
  • the active pharmaceutical ingredient 3 and hence the soluble substance 4 is adhered or is coated on an inside surface 16 of the sidewall 12. In such a way there remains a flow channel 15 inside the center of the container cavity 14.
  • the soluble substance 4 may be provided in or by a layer 17.
  • the layer 17 may be provided or adhered on the inside surface 16 of the sidewall 12.
  • the layer 17 may be dissolvable or may disintegrate when it comes into contact with the diluent 5 as the diluent 5 flows through the flow channel 15.
  • the inside surface 16 of the sidewall 12 may be homogeneously and/or continuously provided with the soluble substance 4.
  • the overall longitudinal length of the medicament container 10 and hence the distance between the inlet 8 and the outlet 9 may be proportional to the total amount of soluble substance 4 and hence of the total amount of the lyophilized medicament 2 located inside the container cavity 14.
  • Fig. 7 there are illustrated three examples of different medicament containers 10, 10', 10" that may each comprise a substantially identical sidewall structure and which may only distinguish with regard to their total elongation, and hence by a distance between the inlet 8 and the outlet 9.
  • the differently sized medicament containers 10, 10', 10" may form or constitute a set of medicament containers with individual medicament containers 10, 10', 10" of different length or elongation.
  • the sidewall 12 of the medicament containers 10, 10', 10" may be provided with a length or size indicating scale 45.
  • the scale 45 extends along the elongation of the sidewall 12. It may extend from the inlet 8 to the outlet 9 and hence from the first longitudinal end 18 to the second and oppositely located longitudinal end 19. Since the elongation of the medicament container 10 as seen in the direction as defined by the distance between the inlet 8 and the outlet 9 is proportional to the total amount of soluble substance 4 located inside the container cavity the length indicating scale is directly indicative of the amount of soluble substance 4 and/or of the amount of lyophilized medicament 2 located inside the container cavity 14.
  • the length indicating scale 45 may further assist or provide the disintegration of a medicament container 10 into two or more pieces. Each piece may then contain a well-defined amount of the soluble substance 4 and hence of the lyophilized medicament, which amount directly correlates to the length of the respective piece.
  • the length indicating scale 45 which may comprise a regular arrangement of length indicating items, e.g. numbers, may help to read or to separate the medicament container into smaller pieces. Each piece separated or torn away from the original medicament container may be likewise connected with at least one of the diluent container 20 and the administering container 30 and may be used in connection with the diluent 5 to produce or to provide a reconstituted medicament 6.
  • a drug concentration of the injectable medicament 6 can be adapted and modified accordingly.
  • the length of the piece separated from the medicament container 10 is directly indicative of the amount of medicament located therein and the medicament container 10 therefore provides a rather intuitive approach of measuring an amount of medicament.
  • the inside surface 16 of the sidewall 12 comprises a roughened surface structure.
  • the inside surface 16 can be roughened in a variety of different ways. It can be mechanically roughened or physically roughened, e.g. by a plasma- assisted or plasma enhanced roughening.
  • the inside surface 16 may be surface roughened by a chemical agent, e.g. by an acid or acid solution.
  • An inside surface being provided with a roughened surface structure is beneficial for improving the adherence and/or fastening of the soluble substance 4 to the inside surface 16. Moreover, by roughening of the inside surface 16 a loading capacity of the inside surface 16 for adhering and/or fixing the soluble substance 4 to the inside surface 16 can be improved.
  • the inside surface 16 of the sidewall 12 comprises one or numerous longitudinally extending projections 65, which projects radially inwardly from the inside surface 16 of the sidewall 12 by a predefined extend.
  • Each one of the projections 65 comprises two oppositely located side surfaces 66, 67, that are facing in opposite circumferential directions of the respective projection 65.
  • the total size of the inside surface 16 can be increased and there can be provided an increased surface for adherence of the soluble substance 4 on the respective side surfaces 66, 67 as well as in the intermediate sections between the projections 65 of the tubular shaped inside surface 16 of the sidewall 12.
  • the medicament container 10 comprises a scaffold 60, which is perforated and/or porous.
  • the scaffold 60 may be located inside the boundary structure 11. It may be located inside the sidewall 12 or it may form part of an inside surface 16 of the sidewall 12.
  • the 60 is located inside a liquid tight outside cover 64.
  • the outside cover 64 may be provided by the sidewall 12 or it may form a cladding for the sidewall 12.
  • the perforated or porous scaffold 60 may comprise a fabric 61, which may comprise individual fibers arranged in a fabric like manner. Between the fibers and hence between the perforated or porous scaffold 60 the soluble substance 4 may be entrapped. Specifically, powdered or granular particles of the soluble substance 4 may be entrapped in the perforated or porous scaffold 60, which is penetrable by the diluent 5. The scaffold 60 may be soaked, impregnated or doped with the soluble substance 4, which may dissolve in the diluent 5 as the scaffold 60 gets in contact with the diluent 5.
  • the perforated and/or porous scaffold may be implemented as a kind of a drug eluting structure or drug-eluting scaffold, which allows and supports a dissemination or dispersion of the soluble substance 4 into the diluent 5 as it gets in contact with the diluent 5 or as the scaffold 60 is immersed in the diluent 5.
  • the fabric 61 and hence the scaffold 60 comprises numerous through openings 63.
  • the scaffold 60 may comprise a sidewall 62 with the through openings 63 extending through the sidewall 62.
  • the sidewall 62 of the scaffold 60 may extend parallel or may extend coaxial with the elongation of the liquid tight outside cover 64.
  • the scaffold 60 and the liquid tight outside cover 64 may contribute to the sidewall 12 or may even constitute the sidewall 12.
  • the scaffold 60 may comprise a tubular or cylindrically shaped sidewall 62, which is hollow and which inherently provides and forms a flow channel 15 for the diluent therethrough.
  • a way of manufacturing the medicament container 10 according to the example of Figs. 8 and 9 is schematically illustrated.
  • the fabric or fibers used to produce the fabricbased scaffold 60 may be impregnated or soaked with the soluble substance 4.
  • the soaked or impregnated textile material for producing the scaffold 60 may be then subject to a knitting or weaving process by a respective knitting or weaving tool 58.
  • a pliable boundary 11 e.g. by a boundary structure 11 , which may form or constitute the liquid tight outside cover 64, which may comprise a flexible foil.
  • the outside cover 64 may be sealed or welded along a seam 68 by a welding or sealing tool 69 so as to entirely wrap and enclose the perforated scaffold 60.
  • the arrangement of the scaffold 60 inside the liquid tight outside cover 64 may be provided in an endless manner. Discrete medicament containers may be then provided by cutting the endless band of the scaffold 60 as wrapped in the liquid tight outside cover 64 and by closing the opposite ends of the cut sections by a closure 48, 49.
  • Figs. 11-13 there is shown a further example of a medicament container 10 and a further way of manufacturing such a medicament container 10.
  • the production or manufacturing of the medicament container 10 starts from a planar and pliable substrate 70 as shown in Fig. 11.
  • the substrate 70 comprises an inside surface 76, which is a top surface in the illustration of Fig. 11.
  • Each recess 71 may comprise a sidewall 72 and a closed bottom 73. Each recess 71 may thus form a receptacle configured to receive a well-defined amount of the soluble substance 4.
  • the recesses 71 may be mechanically formed in the substrate 70, e.g. by printing or embossing. After filling the recesses 71 at least partially with the soluble substance 4, the recesses 71 may be effectively closed by an inside cover 74.
  • the inside cover 74 may be welded or otherwise attached on the inside surface 76, thereby closing the recesses 71 that have been filled with the soluble substance 4.
  • the inside cover 74 may be dissolvable or disintegrable by the diluent 5.
  • the substrate 70 may be coiled or wrapped into a tubular structure 78 to such extent that oppositely located longitudinal or circumferential ends of the substrate 70 are joined together along a seam 77.
  • the oppositely located ends of the substrate 70 may be welded or otherwise adhered together along the seam 77 so as to form an elongated tubular hollow structure 78.
  • the inside surface 76 of the substrate 70 faces radially inwardly and encloses a flow channel 15 extending through the elongated tubular structure 78.
  • the opposite longitudinal ends of the tubular structure 78 may be provided with closures 48, 49 and may form or constitute an inlet 8 and an outlet 9, respectively.
  • the soluble substance 4 may be then dissolved or dispersed in the diluent 5 as the diluent 5 flows through the flow channel 15.
  • the flowchart according to Fig. 6 is further illustrative of a method of preparing a reconstituable injectable medicament 6.
  • a medicament container 10 as described herein.
  • the medicament container 10 is filled or provided with a lyophilized medicament 2 as the soluble substance 4.
  • the soluble substance and hence the lyophilized medicament 2 is located inside the container cavity 14 of the medicament container 10.
  • the inlet 8 of the medicament container 10 is connected with a diluent container 20, typically with an outlet 24 of the diluent container 20.
  • step 104 At least a portion of the diluent 5 initially provided in the diluent container 20 is directed from the diluent container 20 through the inlet 8 of the medicament container 10 and into the container cavity 14 of the medicament container.
  • step 106 at least a portion or a fraction of the soluble substance of 4 is dissolved or dispersed in the diluent 5 thereby reconstituting the lyophilized medicament 2 inside the container cavity 14.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

Un aspect de la présente invention concerne un récipient de médicament (10) comprenant : - une cavité de récipient (14) pour une substance soluble (4), la substance (4) comprenant un ingrédient pharmaceutique actif (3) et la substance soluble (4) étant soluble par un diluant (5), - la substance soluble (4) à l'intérieur de la cavité de récipient (14), - une structure de limite (11) confinant la cavité de récipient (14), la structure de limite (11) étant insoluble par rapport au diluant (5) et comprenant une paroi latérale (12), - une entrée (8) pour l'introduction du diluant (5) dans la cavité de récipient (14), - une sortie (9), qui est en communication d'écoulement avec la cavité de récipient (14), et - un canal d'écoulement (15) s'étendant de l'entrée (8) à la sortie (9) et conçu pour diriger le diluant (5) de l'entrée (8) à travers la cavité de récipient (14) vers la sortie (9).
PCT/US2025/024734 2024-04-17 2025-04-15 Récipient de médicament et kit de reconstitution d'un médicament lyophilisé Pending WO2025221761A2 (fr)

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EP24170697.7 2024-04-17
EP24170697 2024-04-17

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