WO2025098590A1

WO2025098590A1 - Delivery device for delivering a drug

Info

Publication number: WO2025098590A1
Application number: PCT/EP2023/080872
Authority: WO
Inventors: Christoph Stecher; Eva LITTRINGER
Original assignee: Revive Medtech GmbH
Current assignee: Revive Medtech GmbH
Priority date: 2023-11-06
Filing date: 2023-11-06
Publication date: 2025-05-15
Anticipated expiration: 2026-05-06

Abstract

A delivery device (100) for delivering a drug is proposed. The delivery device (100) comprises at least one mixing device (102) defining a mixing chamber (104) and comprising a mixing piston (108) moveable arranged within the mixing chamber (104). The mixing device (102) is connectable to a solvent reservoir (142) and configured to suck solvent from the solvent reservoir (142) into the mixing chamber (104) by means of moving the mixing piston (108). The delivery device (100) further comprises at least one transporting device (112) configured to be connected to at least one cartridge (114) filled with a pharmaceutical formulation in solid form, particularly in powder form. The transporting device (112) is configured to transport a predetermined amount of the pharmaceutical formulation to the mixing chamber (104). The mixing device (102) is further configured to mix the predetermined amount of the pharmaceutical formulation with a predetermined amount of the solvent so as to provide the drug. The mixing device (102) is further configured to deliver the drug by means of moving the mixing piston (108).

Description

Delivery device for delivering a drug

Technical Field

The present invention relates to a delivery device for short term, continuous or prolonged delivery of a drug, particularly parenteral delivery of a drug e.g. antibiotics in hospital or home setting such as outpatient parenteral antibiotic therapy setting. Particularly, the present invention relates to a mobile, autonomous dosing device for short term, extended or continuous parenteral administration of a drug containing a pharmaceutical formulation having a reduced decomposition profile allowing superior treatment of antibiotic infections or other diseases and enabling optimized delivery of drugs e.g. antibiotics or biopharmaceutics in terms of pharmacokinetic / pharmacodynamic profile or with respect to the handling or work effort of delivery (no need for compounding) and environmental sustainability (energy saving).

Background art

Several medicines have to be parenterally administered. This applies in particular to medicines, which are deactivated or have their efficiency remarkably decreased by oral administration, e.g. biopharmaceutics (such as insulin, growth hormones, interferons), carbohydrates (e.g. heparin), antibodies and the majority of vaccines, certain antibiotics and new modalities. Such medicines are predominantly parenterally administered by means of syringes or delivery devices e.g. medicament pumps, pens, autoinjectors.

The user of such delivery devices can range from healthcare professionals to the medicament-recipient themselves, the latter ranging from children to elderly persons. The medicinal injections may include repetitive or multiple injections of a particular dose (e.g. a vaccine in multi-dosage regimen) to a single injection of a single dose (e.g. a vaccine or in an emergency hydrocortisone).

As medicament pumps, usually elastomeric, peristaltic or mechanic pumps are used. Despite the advantages provided by delivery devices using such pumps, pens or autoinjectors, there are still some drawbacks. All drug delivery devices using conventional medicament pumps, pens or autoinjectors have in common that the drug has to be either provided as liquid formulation or needs to be transferred into a liquid formulation (e.g. reconstitution of a lyophilized product in vial) filling into the delivery device and subsequent administration (with the exception of pens working with dual-chamber systems). Thus, there is a risk of contamination and they are work intensive (considerable amount of working time of health care professionals is required for e.g. reconstitution and filling of pumps). Further, due to limited stability of many drugs in the liquid state compared to the solid state there is the risk of decomposition once in the liquid form and toxic, allergic or hazardous degradation products may form in addition to reduced activity due to lower content of the active, which in some cases can be prevented by cold chain storage (e.g. storage at 2-8°C, -20°C or -80°C), however is often impossible in the home setting. Limited stability upon reconstitution is well known for many drugs, e.g. antibiotics. However, recent studies have shown beneficial effects of prolonged or continuous delivery of parenteral antibiotic solutions, or delivery on demand based on measured blood or interstitial fluid levels, at intensive care stations as well as in the OP AT (outpatient parenteral antibiotic treatment) setting. However, due to limited stability of many antibiotics in solution, especially at room temperature, it is difficult to provide prolonged or continuous treatment options. Further, many of the common known drug delivery device require a predetermined orientation such as with respect to gravity to properly work. Still further, some known drug delivery devices are not capable of reliably or properly mixing of antibiotics with the infusion solution, such as by creating bubbles. Furthermore, known drug delivery devices do not allow to monitor the antibiotics concentration.

Problem to be solved

It is therefore desirable to provide a delivery device configured to minimize or eliminate the above drawbacks. Particularly, it is an object to provide a delivery device configured to prepare a bubble free predetermined amount of a drug to be administered as required independent on the orientation of the drug delivery device. Further, it is an object to provide a delivery device configured to monitor a drug concentration such as an antibiotics concentration. Such a drug delivery device is particular used for short term, continuous or prolonged delivery of a drug, preferably antibiotics, biopharmaceuticals or new modalities, in hospital or home setting such as outpatient parenteral antibiotic therapy setting. The new delivery device will help to save energy required for cooling and production of the drug.

Summary

This problem is addressed by a drug delivery device and a kit with the features of the independent claims. Advantageous embodiments which might be realized in an isolated fashion or in any arbitrary combinations are listed in the dependent claims as well as throughout the specification.

As used in the following, the terms “have”, “comprise” or “include” or any arbitrary grammatical variations thereof are used in a non-exclusive way. Thus, these terms may both refer to a situation in which, besides the feature introduced by these terms, no further features are present in the entity described in this context and to a situation in which one or more further features are present. As an example, the expressions “A has B”, “A comprises B” and “A includes B” may both refer to a situation in which, besides B, no other element is present in A (i.e. a situation in which A solely and exclusively consists of B) and to a situation in which, besides B, one or more further elements are present in entity A, such as element C, elements C and D or even further elements.

Further, it shall be noted that the terms “at least one”, “one or more” or similar expressions indicating that a feature or element may be present once or more than once typically will be used only once when introducing the respective feature or element. In the following, in most cases, when referring to the respective feature or element, the expressions “at least one” or “one or more” will not be repeated, non-withstanding the fact that the respective feature or element may be present once or more than once.

Further, as used in the following, the terms "preferably", "more preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features, without restricting alternative possibilities. Thus, features introduced by these terms are optional features and are not intended to restrict the scope of the claims in any way. The invention may, as the skilled person will recognize, be performed by using alternative features. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features, without any restriction regarding alternative embodiments of the invention, without any restrictions regarding the scope of the invention and without any restriction regarding the possibility of combining the features introduced in such way with other optional or non-optional features of the invention.

According to a first aspect of the present disclosure, there is provided delivery device for delivering a drug. The delivery device comprises at least one mixing device. The mixing device defines a mixing chamber. The mixing device comprises a mixing piston moveable arranged within the mixing chamber. The mixing device is connectable to a solvent reservoir. The mixing device is configured to suck solvent from the solvent reservoir into the mixing chamber by means of moving the mixing piston. Thus, by actuating the mixing piston, solvent may be sucked into the mixing chamber for being used with a mixing process.

The delivery device further comprises at least one transporting device. The transporting device is configured to be connected to at least one cartridge filled with a pharmaceutical formulation in solid form, particularly in powder form. The transporting device is configured to transport a predetermined amount of the pharmaceutical formulation to the mixing chamber. Thus, the transporting device is used to transport a predetermined amount of the pharmaceutical formulation to the mixing chamber in order for the pharmaceutical formulation to be used with a mixing process with the solvent.

In addition, it has to be noted that a solid state drug is usually more stable than a liquid drug which allows development of drug formulations that are stable at higher temperatures e.g. biologies that can be stored at room temperature instead of requiring a cold chain storage during the whole product life time, or change from -20°C storage to higher temperatures. As cold chain storage and transport, apart from being error prone, requires a lot of energy the potential of formulations which are stable at higher temperatures contributes to solving the emerging problem of climate change by saving energy for the cooling process. Furthermore, a lot of waste caused by cold chain transport ( e.g. Styrofoam boxes) can be avoided.

The mixing device is further configured to mix the predetermined amount of the pharmaceutical formulation with a predetermined amount of the solvent so as to provide the drug. The mixing device is further configured to deliver the drug by means of moving the mixing piston. Thus, by actuating the mixing piston, the mixing process is carried out. Further, as the solvent and the pharmaceutical formulation are supplied to the mixing chamber, the drug to be delivery may be prepared fresh and when it is needed so as to avoid any potential degradation thereof. Further, with the provision of the mixing chamber and the mixing piston therein, the mixing process may be reliably carried out independent on the orientation of the delivery device.

The delivery device is particularly configured for short term, continuous or prolonged delivery of a drug, particularly parenteral delivery of a drug. In this respect, a short term delivery may mean a delivery within 0-30 min as of preparation of the drug, a continuous delivery may mean a delivery for 24 hours and a prolonged delivery may mean a delivery between 30 min and several hours.

The transporting device may be configured to provide a predetermined force to the cartridge so as to compact the pharmaceutical formulation to ensure the right powder density. Thus, any gas such as air between the particles of the pharmaceutical formulation may be reduced or significantly removed. Further, it is ensured that the correct dose of the pharmaceutical formulation is provided. The transporting device may be further configured to transport the predetermined amount of the pharmaceutical formulation to the mixing chamber in a compacted state. Thus, it is ensured that the correct dose of the pharmaceutical formulation is supplied to the mixing chamber in order to provide a correct concentration of the pharmaceutical formulation when being mixed with the solvent.

The transporting device may comprise a spring configured to provide the predetermined force to the cartridge. Alternatively or in addition, the transporting device may comprise a pressurized gas source configured to supply pressurized gas to the cartridge so as to provide the predetermined force to the cartridge. The predetermined force may be used for compacting and transporting the pharmaceutical formulation within the cartridge.

The delivery device may further comprise a pressure sensor configured to detect a pressure present within the cartridge. Thus, it can be checked whether a target pressure within the cartridge is present for compacting the pharmaceutical formulation.

The delivery device may further comprise a mixing chamber pressure sensor configured to detect a pressure present within the mixing chamber. Thereby, control of sucking the solvent into the mixing chamber, venting the mixing chamber, discharging any fluid from the mixing chamber is allowed.

The transporting device may comprise a dosing wheel configured to provide the predetermined amount of the pharmaceutical formulation. The dosing wheel may be a dosing barrel. Thus, the correct target dose of the pharmaceutical formulation may be provided with a rather simple constructional member.

The transporting device may comprise a transport chamber and a discharge piston moveable within the transport chamber. The transport chamber may be connected to the mixing device. The transporting device may be configured to move the discharge piston so as to transport the predetermined amount of the pharmaceutical formulation to the mixing chamber. Thus, the correct target dose of the pharmaceutical formulation supplied to the transport chamber may be transported to the mixing chamber with a rather simple constructional member.

The mixing chamber may comprise at least one fluid inlet and at least one fluid outlet. The mixing device may be configured to suck solvent from the solvent reservoir into the mixing chamber through the fluid inlet by means of moving the mixing piston. The mixing device may be further configured to deliver the drug through the fluid outlet by means of moving the mixing piston. Thus, the supply of solvent and discharging of the mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent or drug may be realized.

The mixing device may be configured to discharge a mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent from the mixing chamber through the fluid outlet and to return the mixture to the mixing chamber through the fluid inlet. Thereby, a kind of pumping process for causing the mixing effect may be realized.

The delivery device may further comprise a secondary mixing device. The mixing device may be configured to discharge the mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent from the mixing chamber through the fluid outlet to the secondary mixing device and to return the mixture from the secondary mixing device to the mixing chamber through the fluid inlet. The secondary mixing device may be used for enhancing the mixing effect.

The secondary mixing device may be a mixing bag. The mixing bag may be made of any material inert with respect to the pharmaceutical formulation and the solvent such as a plastic material. Thus, a rather costs effective constructional member may be used for enhancing the mixing effect. The mixing chamber may further comprise at least one gas outlet configured to vent the mixing chamber. Thus, any gas or air may be removed from the mixing chamber. The fluid inlet and/or the fluid outlet and/or the gas outlet may be provided with a membrane made of a hydrophobic material. Thus, any adhering of the liquid solvent may be avoided.

The hydrophobic material may be PTFE. Such a material is broadly available and cost effective.

The delivery device may further comprise a bubble trap configured to remove gas bubbles, particularly air bubbles, from the drug delivered from the mixing chamber. Thus, any bubbles which might cause and errors in a detection of a concentration of the pharmaceutical formulation may be removed.

The delivery device may further comprise a gas sensor configured to detect gas bubbles, particularly air bubbles, and/or particles such as visible and subvisible particles, impurities, metabolites, decomposition products or degradation products within the drug delivered from the mixing chamber. Thus, the mixing process may be carried out as long as the presence of any bubbles and/or particles is detected.

The delivery device may further comprise a concentration sensor configured to detect a concentration of the pharmaceutical formulation within the drug delivered from the mixing chamber. Thus, it is ensured that a patient will receive the correct dose of the drug.

The concentration sensor may be an UVvis sensor. Such a sensor is rather simple, reliable and cost effective.

The concentration sensor may be configured to detect gas bubbles, particularly air bubbles, and/or particles within the drug delivered from the mixing chamber. Thus, the concentration sensor may be used to measure the concentration of the pharmaceutical formulation within the solvent and to detect any bubbles and/or particles.

The delivery device may further comprise a waste container configured to at least partially receive the drug delivered from the mixing chamber. Thus, the drug may be disposed if any deviation from its target quality is detected.

The delivery device may further comprise a sterilizing device configured to sterilize the drug delivered from the mixing chamber. Thus, any infectious hazard of the drug may be avoided. The sterilizing device may be a UVC light source. Such a device is rather compact which reduces the overall size of the delivery device.

Alternatively or in addition, the sterilizing device may be a sterile or sterilizing filter. Thus, any potential infection of the patient may be avoided.

The transporting device may be configured to be connected to more than one cartridge filled with a pharmaceutical formulation in solid form, particularly in powder form. Thus, the operation time may be prolonged as the number of replacements of the cartridge is reduced. Further, two different types of pharmaceutical formulation may be provided so as to increase the variety of drugs to be delivered.

The delivery device may further comprise at least two mixing devices and at least two transporting devices. Thus, a redundant process of providing the drug may be realized. Further, different types of pharmaceutical formulation may be provided so as to increase the variety of drugs to be delivered.

The delivery device may further comprise a controller configured to control operation of at least one of the transporting device and the mixing device. The controller allows the operation of the delivery device to be adjusted as appropriate.

The controller may comprise an interface configured to provide a communication link between the controller and a remote electronic device. Thus, the delivery device may be remotely controlled such as by a health care professional without need that the health care professional is present on site.

The communication link may be realized in a wireless or wired manner. Thus, the remote control may be realized as appropriate.

The delivery device may further comprise an input device configured to allow a user to input instructions to the controller. Thus, the operation of the delivery device may be adjusted by inputting respective commands at the input device.

The input device may comprise a display, a keyboard and/or buttons configured to allow a user to input instructions to the controller. Thus, the input of commands may be realized in a broad range of ways. The delivery device may further comprise a power source, particularly a rechargeable power source, configured to supply electrical power to at least one of the transporting device, the controller and the mixing device. Thus, it is ensured that sufficient power for operating the delivery device is provided.

The delivery device may be a portable delivery device. Thus, the delivery device may be designed in a rather compact or small manner to be lightweight.

The delivery device may be configured to communicate with an in-situ sensor. The in-situ sensor may be a blood or interstitial fluid sensor. Thus, depending on the characteristics of the blood or interstitial fluid, the drug may be produced on demand and fresh.

The mixing chamber may be at least partially made of a transparent material or comprise a portion made of a transparent material. Such a transparent portion may be a window. The formation of a transparent material or the provision of a transparent material at the mixing chamber allows a user to optically inspect or monitor whether the pharmaceutical formulation is completely solved in the solvent or not.

The delivery device may further comprise a housing. The transporting device and the mixing device may be arranged within the housing. Thus, the delivery device may be protected from any exterior influence.

The drug may be used for parenteral application e.g. intravenous or sub cutaneous application. With other words, the delivery device may be used for delivering a drug configured to be used with e.g. an intravenous, sub cutaneous, intramuscular, intrathecal, intraperitoneal application.

According to a second aspect of the present disclosure, there is provided a kit. The kit comprises a delivery device according to any of the embodiments described before or hereinafter and at least one cartridge filled with a pharmaceutical formulation in solid form, particularly in powder form, and/or a solvent reservoir filled with solvent.

The term “delivery device” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to any device configured to deliver or administer a drug to a patient. Particularly, the delivery device is configured to deliver or administer a predetermined dose of a drug used for infusion or any other form of administration to a patient such as parenterally.

The term “drug” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a pharmaceutical formulation containing one or more pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally pharmaceutically acceptable excipients. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. The term “drug” may be used synonymously to the term “medicament” herein. 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 wellbeing. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

The term “outlet” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a constructional member allowing the escape or discharge of something. The outlet may be or comprise an opening, orifice, vent or similar passage allowing escape or discharge of the drug.

The term “cartridge” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a preformed packaging for pharmaceuticals. Specifically, the cartridge may refer to container including or storing a pharmaceutical formulation in solid form. Particularly, the cartridge contains the pharmaceutical formulation in powder form.

The term “pharmaceutical formulation” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an ingredient in a pharmaceutical drug that is biologically active. Some drugs or medicines may contain more than one active ingredient. Specifically, the term “pharmaceutical formulation” may refer to an active pharmaceutical formulation, a biopharmaceutical and/or new modalities. The term “active pharmaceutical formulation” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an ingredient in a pharmaceutical drug that is biologically active. Some drugs or medicines may contain more than one active ingredient or active pharmaceutical formulation. Specifically, the term “active pharmaceutical formulation” may refer to an antimicrobial substance active against bacteria and suitable excipients.

The term “biopharmaceutical” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, they include vaccines, whole blood, blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living medicines used in cell therapy. Biologies can be composed of sugars, proteins, nucleic acids, or complex combinations of these substances, or may be living cells or tissues. They (or their precursors or components) are isolated from living sources — human, animal, plant, fungal, or microbial. They can be used in both human and animal medicine. The term is also known as biological medical product or biologic.

The term “new modality” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to gene and cell therapies, RNA drugs, radioligands, antibody-drug conjugates and other complex biologies or small molecules deviates.

The term “powder” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a conglomeration of discrete solid particles having a particle size D50 of less than 1.0 mm. These fine particles may be the result of reducing dry substance by pounding, grinding, triturating, freeze-drying, spray-drying, crystallization, solvent evaporation etc. It is explicitly stated that the term “powder” may also refer to compacted powder. For example, the compacted powder may be provided as a capsule, tablet or the like.

The term “solvent” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a substance that dissolves a solute, i.e. a chemically distinct liquid, solid or gas, resulting in a solution. A solvent is usually a liquid.

The term “transporting mechanism” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to any device configured to transport a predetermined amount of the pharmaceutical formulation from a cartridge connected thereto to the mixing chamber. The transporting device may further be configured to compact the pharmaceutical formulation and to transport the predetermined amount of the pharmaceutical formulation to the mixing chamber in a compacted state. For compacting the pharmaceutical formulation, the transporting device may be configured to provide a predetermined force to the cartridge such as by means of a spring and/or a pressurized gas source.

The term “mixing device” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a device that is configured to provide a mixture. Mixing is a unit operation that involves manipulation of a heterogeneous physical system with the intent to make it more homogeneous. A mixture is a material made up of two or more different substances which are physically combined. A mixture is the physical combination of two or more substances in which the identities are retained and are mixed in the form of solutions, suspension and colloids. Mixtures are one product of mechanically blending or mixing chemical substances such as elements and compounds, without chemical bonding or other chemical change, so that each ingredient substance retains its own chemical properties and makeup. Mixtures can be either homogeneous or heterogeneous. A mixture in which its constituents are distributed uniformly is called homogeneous mixture. A mixture in which its constituents are not distributed uniformly is called heterogeneous mixture. Specifically, the term “mixture” may refer to a combination of two components such as the solvent and the pharmaceutical formulation representing or forming the drug. The mixing device may also comprise or include a mixing sensor configured to detect the quality of the solution provided by the mixing device such as the degree and/or homogeneity of the thus prepared solution.

The term “chamber” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a room or spaced used for a special purpose. Specifically, a mixing chamber is a room or space used for mixing purpose.

The term “mixing piston” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an engineering component of engines, pumps and delivery or dosing devices. It is a moving component that is contained by a cylinder and that may be made gas-tight or liquid tight by piston rings. The movement of the piston is particularly a reciprocating movement. In an engine, its purpose is to transfer force from expanding gas in the cylinder to the crankshaft via a piston rod and/or connecting rod. In a pump, the function is reversed and force is transferred from the crankshaft to the piston for the purpose of compressing or ejecting the fluid in the cylinder. In some engines, the piston also acts as a valve by covering and uncovering ports in the cylinder. In a dosing or delivery device, the piston is used for suctioning a fluid such as a solvent into the mixing chamber providing the cylinder and eject or discharge the sucked fluid from the mixing chamber. As the piston of the present application is part of the mixing device and takes part in a mixing process, it is called mixing piston. The mixing piston may be formed cylindrically or may basically have any shape as appropriate.

The term “inlet” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a constructional member allowing the entry or supply of something. The inlet may be or comprise an opening, orifice, vent or similar passage allowing escape or discharge of the solvent.

The term “pressure sensor” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a device configured to measure the pressure of gases or liquids. Pressure sensors can alternatively be called pressure transducers, pressure transmitters, pressure senders, pressure indicators, piezometers and manometers, among other names. Pressure is an expression of the force required to stop a fluid from expanding, and is usually stated in terms of force per unit area. A pressure sensor usually acts as a transducer; it generates a signal as a function of the pressure imposed. Pressure sensors can vary drastically in technology, design, performance, application suitability and cost. There is also a category of pressure sensors that are designed to measure in a dynamic mode for capturing very high speed changes in pressure. Example applications for this type of sensor would be in the measuring of combustion pressure in an engine cylinder or in a gas turbine. These sensors are commonly manufactured out of piezoelectric materials such as quartz. In the present disclosure, a pressure sensor may be a device configured to detect or measure a pressure within the cartridge and/or mixing chamber. The pressure within the cartridge may be provided by a fluidic medium such as a gas. Non limiting examples of pressure sensors that may be used with the present disclosure are Force collector types. These types of electronic pressure sensors generally use a force collector such as a diaphragm, piston, bourdon tube, or bellows to measure strain or deflection due to applied force over an area (pressure). To this kind of pressure sensors belong piezoresistive strain gauge sensors which use the piezoresistive effect of bonded or formed strain gauges to detect strain due to an applied pressure, electrical resistance increasing as pressure deforms the material. Common technology types are silicon (monocrystalline), poly silicon thin film, bonded metal foil, thick film, silicon-on-sapphire and sputtered thin film. Generally, the strain gauges are connected to form a Wheatstone bridge circuit to maximize the output of the sensor and to reduce sensitivity to errors. This is the most commonly employed sensing technology for general purpose pressure measurement. Further, to this kind of pressure sensors belong capacitive sensors which use a diaphragm and pressure cavity to create a variable capacitor to detect strain due to applied pressure, capacitance decreasing as pressure deforms the diaphragm. Common technologies use metal, ceramic, and silicon diaphragms. Capacitive pressure sensors are being integrated into CMOS technology and it is being explored if thin 2D materials can be used as diaphragm material. Further, to this kind of pressure sensors belong electromagnetic sensors which measure the displacement of a diaphragm by means of changes in inductance (reluctance), linear variable differential transformer (LVDT), Hall effect, or by eddy current principle. Further, to this kind of pressure sensors belong piezoelectric sensors which uses the piezoelectric effect in certain materials such as quartz to measure the strain upon the sensing mechanism due to pressure. This technology is commonly employed for the measurement of highly dynamic pressures. As the basic principle is dynamic no static pressures can be measured with piezoelectric sensors.

The term “dosing wheel” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a cylindrical constructional member longer than it is wide. The dosing wheel is rotatable around its longitudinal axis. The dosing wheel is configured to provide the predetermined amount of the pharmaceutical formulation, i.e. fulfills a dosing function.

The term “dosing barrel” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a cylindrical constructional barrel with a bulging center, longer than it is wide. The dosing wheel is rotatable around its longitudinal axis. The dosing barrel is a dosing wheel with a varying cross- sectional area along its longitudinal axis, particularly with a maximum at its center along the longitudinal axis, that is configured to provide the predetermined amount of the pharmaceutical formulation, i.e. fulfills a dosing function.

The term “secondary mixing device” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a device that is configured to provide a mixture. Mixing is a unit operation that involves manipulation of a heterogeneous physical system with the intent to make it more homogeneous. A mixture is a material made up of two or more different substances which are physically combined. A mixture is the physical combination of two or more substances in which the identities are retained and are mixed in the form of solutions, suspension and colloids. Mixtures are one product of mechanically blending or mixing chemical substances such as elements and compounds, without chemical bonding or other chemical change, so that each ingredient substance retains its own chemical properties and makeup. Mixtures can be either homogeneous or heterogeneous. A mixture in which its constituents are distributed uniformly is called homogeneous mixture. A mixture in which its constituents are not distributed uniformly is called heterogeneous mixture. Specifically, the term “mixture” may refer to a combination of two components such as the solvent and the pharmaceutical formulation representing or forming the drug. The mixing device may also comprise or include a mixing sensor configured to detect the quality of the solution provided by the mixing device such as the degree and/or homogeneity of the thus prepared solution. The secondary mixing device is configured to fulfil a secondary mixing function, i.e. not the main part of a mixing process but is used as assistance in the mixing process.

The term “mixing bag” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a bag shaped constructional member in which a mixing process can be carried out.

The term “bubble trap” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to any device configured to remove gas bubbles, particularly air bubbles, from the drug delivered from the mixing chamber.

The term “UVvis sensor” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a sensor that is configured to measure the amount of ultraviolet (UV) and visible light that is absorbed by a sample. UVvis sensors work by passing a beam of light through the sample and measuring the amount of light that is absorbed at each wavelength. The amount of light absorbed is proportional to the concentration of the absorbing compound in the sample.

The term “UVC light source” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a source configured to emit light with a wavelength of 100 nm to 280 nm.

The term “sterilizing device” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a device used to make something completely clean and free from bacteria.

The sterilizing device may be a UVC light source. Such a device is rather compact which reduces the overall size of the delivery device.

The term “housing” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a shell or material at least partially enclosing or surrounding other or further constructional members.

The term “portable” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to the dimensions and weight of the delivery device allowing a user such as a human being to lift or carry the device.

The term “wearable” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to the dimensions and weight of the delivery device allowing a user such as a human being to wear or carry the delivery device at the user’s body.

The term “in-situ” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a Latin phrase that translates literally to "on site" or "in position." It can mean "locally", "on site", "on the premises", or "in place" to describe where an event takes place and is used in many different contexts. Particularly, the term may describe the way a measurement is taken, that is, in the same place the phenomenon is occurring without isolating it from other systems or altering the original conditions of the test. More particularly, this term means to examine the phenomenon exactly in place where it occurs i.e., without moving it to some special medium.

The term “in-situ sensor” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to any sensor configured to detect or measure characteristics within a human or animal body. The term may particularly refer to a blood sensor or interstitial fluid sensor.

The term “blood sensor” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a sensor that is configured to measure any characteristics of animal or human blood or interstitial fluid. The characteristics may be at least one characteristics selected from the group consisting of a person's blood oxygen saturation, the concentration of glucose in the blood (glycemia), blood pressure such as arterial blood pressure, CRP value (CRP - C-reactive protein).

Summarizing and without excluding further possible embodiments, the following embodiments may be envisaged:

Embodiment 1 : A delivery device for delivering a drug, comprising at least one mixing device defining a mixing chamber and comprising a mixing piston moveable arranged within the mixing chamber, wherein the mixing device is connectable to a solvent reservoir and configured to suck solvent from the solvent reservoir into the mixing chamber by means of moving the mixing piston, at least one transporting device configured to be connected to at least one cartridge filled with a pharmaceutical formulation in solid form, particularly in powder form, wherein the transporting device is configured to transport a predetermined amount of the pharmaceutical formulation to the mixing chamber, wherein the mixing device is further configured to mix the predetermined amount of the pharmaceutical formulation with a predetermined amount of the solvent so as to provide the drug, wherein the mixing device is further configured to deliver the drug by means of moving the mixing piston.

Embodiment 2: The delivery device according to the preceding embodiment, wherein the transporting device is configured to provide a predetermined force to the cartridge so as to compact the pharmaceutical formulation, wherein the transporting device is further configured to transport the predetermined amount of the pharmaceutical formulation to the mixing chamber in a compacted state.

Embodiment 3 : The delivery device according to the preceding embodiment, wherein the transporting device comprises a spring configured to provide the predetermined force to the cartridge and/or a pressurized gas source configured to supply pressurized gas to the cartridge so as to provide the predetermined force to the cartridge.

Embodiment 4: The delivery device according to according to any preceding embodiment, further comprising a pressure sensor configured to detect a pressure present within the cartridge.

Embodiment 5: The delivery device according to any preceding embodiment, further comprising a mixing chamber pressure sensor configured to detect a pressure present within the mixing chamber.

Embodiment 6: The delivery device according to any preceding embodiment, wherein the transporting device comprises a dosing wheel, particularly a dosing barrel, configured to provide the predetermined amount of the pharmaceutical formulation. Embodiment 7: The delivery device according to any preceding embodiment, wherein the transporting device comprises a transport chamber and a discharge piston moveable within the transport chamber, wherein the transport chamber is connected to the mixing device, wherein the transporting device is configured to move the discharge piston so as to transport the predetermined amount of the pharmaceutical formulation to the mixing chamber.

Embodiment 8: The delivery device according to any preceding embodiment, wherein the mixing chamber comprises at least one fluid inlet and at least one fluid outlet, wherein the mixing device is configured to suck solvent from the solvent reservoir into the mixing chamber through the fluid inlet by means of moving the mixing piston, wherein the mixing device is further configured to deliver the drug through the fluid outlet by means of moving the mixing piston.

Embodiment 9: The delivery device according to the preceding embodiment, wherein the mixing device is configured to discharge a mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent from the mixing chamber through the fluid outlet and to return the mixture to the mixing chamber through the fluid inlet.

Embodiment 10: The delivery device according to the preceding embodiment, further comprising a secondary mixing device, wherein the mixing device is configured to discharge the mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent from the mixing chamber through the fluid outlet to the secondary mixing device and to return the mixture from the secondary mixing device to the mixing chamber through the fluid inlet.

Embodiment 11 : The delivery device according to the preceding embodiment, wherein the secondary mixing device is a mixing bag.

Embodiment 12: The delivery device according to any one of embodiments 6 to 9, wherein the mixing chamber further comprises at least one gas outlet configured to vent the mixing chamber, wherein the fluid inlet and/or the fluid outlet and/or the gas outlet is provided with a membrane made of a hydrophobic material. Embodiment 13: The delivery device according to the preceding embodiment, wherein the hydrophobic material is PTFE.

Embodiment 14: The delivery device according to any preceding embodiment, further comprising a bubble trap configured to remove gas bubbles, particularly air bubbles, from the drug delivered from the mixing chamber.

Embodiment 15: The delivery device according to any preceding embodiment, further comprising a gas sensor configured to detect gas bubbles, particularly air bubbles, and/or particles within the drug delivered from the mixing chamber.

Embodiment 16: The delivery device according to any preceding embodiment, further comprising a concentration sensor configured to detect a concentration of the pharmaceutical formulation within the drug delivered from the mixing chamber.

Embodiment 17: The delivery device according to the preceding embodiment, wherein the concentration sensor is an UVvis sensor.

Embodiment 18: The delivery device according to any of the two preceding embodiments, wherein the concentration sensor is configured to detect gas bubbles, particularly air bubbles, and/or particles within the drug delivered from the mixing chamber.

Embodiment 19: The delivery device according to any preceding embodiment, further comprising a waste container configured to at least partially receive the drug delivered from the mixing chamber.

Embodiment 20: The delivery device according to any preceding embodiment, further comprising a sterilizing device configured to sterilize the drug delivered from the mixing chamber.

Embodiment 21 : The delivery device according to the preceding embodiment, wherein the sterilizing device is a UVC light source and/or a sterile filter. Embodiment 22: The delivery device according to any preceding embodiment, wherein the transporting device is configured to be connected to more than one cartridge filled with a pharmaceutical formulation in solid form, particularly in powder form.

Embodiment 23 : The delivery device according to any preceding embodiment, further comprising at least two mixing devices and at least two transporting devices.

Embodiment 24: The delivery device according to any preceding embodiment, further comprising a controller configured to control operation of at least one of the transporting device and the mixing device.

Embodiment 25: The delivery device according to the preceding embodiment, wherein the controller comprises an interface configured to provide a communication link between the controller and a remote electronic device.

Embodiment 26: The delivery device according to the preceding embodiment, wherein the communication link is realized in a wireless or wired manner.

Embodiment 27: The delivery device according to any of the three preceding embodiments, further comprising an input device configured to allow a user to input instructions to the controller.

Embodiment 28: The delivery device according to the preceding embodiment, wherein the input device comprises a display, a keyboard and/or buttons configured to allow a user to input instructions to the controller.

Embodiment 29: The delivery device according to any of the five preceding embodiments, further comprising a power source, particularly a rechargeable power source, configured to supply electrical power to at least one of the transporting device, the controller and the mixing device. Embodiment 30: The delivery device according to any preceding embodiment, wherein the delivery device is a portable and/or wearable delivery device.

Embodiment 31 : The delivery device according to any preceding embodiment, wherein the delivery device is configured to communicate with an in-situ sensor, particularly a blood or interstitial fluid sensor.

Embodiment 32: The delivery device according to any preceding embodiment, wherein the mixing chamber is at least partially made of a transparent material or comprises a portion made of a transparent material.

Embodiment 33: The delivery device according to any preceding embodiment, further comprising a housing, wherein the transporting device and the mixing device are arranged within the housing.

Embodiment 34: The delivery device according to any preceding embodiment, wherein the drug is configured to be used for parenteral application, particularly an intravenous or sub cutaneous application.

Embodiment 35: A kit comprising a delivery device according to any preceding embodiment and at least one cartridge filled with a pharmaceutical formulation in solid form, particularly in powder form, and/or a solvent reservoir filled with solvent.

Embodiment 36: Use of the delivery device according to any preceding embodiment referring to a delivery device for delivering a drug, particularly with a parenteral application, more particularly an intravenous or sub cutaneous application.

Short description of the Figures Further optional features and embodiments will be disclosed in more detail in the subsequent description of embodiments, preferably in conjunction with the dependent claims. Therein, the respective optional features may be realized in an isolated fashion as well as in any arbitrary feasible combination, as the skilled person will realize. The scope of the invention is not restricted by the preferred embodiments. The embodiments are schematically depicted in the Figures. Therein, identical reference numbers in these Figures refer to identical or functionally comparable elements.

In the Figures:

Figure 1 shows a block diagram of a delivery device for delivering a drug according to the present invention;

Figure 2 shows a perspective view of the delivery device;

Figure 3 shows a side view of the delivery device;

Figure 4 shows a front view of the delivery device;

Figure 5 shows a top view of the delivery device;

Figure 6 shows a cross-sectional view of the delivery device taken along line A- A of

Figure 5;

Figure 7 shows a cross-sectional view of the delivery device taken along line B-B of Figure 5;

Figure 8 shows a perspective view of the dosing wheel;

Figure 9 shows a top view of the dosing wheel;

Figure 10 shows a front view of the dosing wheel;

Figures 11 to 28 show a block diagram of the delivery device with the constructional members thereof in different operation states.

Detailed description of the embodiments Figure 1 shows a block diagram of a delivery device 100 for delivering a drug according to the present invention. The drug is configured to be used for a parenteral application The parenteral application preferably includes an intravenous application. Alternatively or in addition, the parenteral application may include a sub cutaneous application. Figure 2 shows a perspective view of the delivery device 100. Figure 3 shows a side view of the delivery device 100. Figure 4 shows a front view of the delivery device 100. Figure 5 shows a top view of the delivery device 100. The delivery device 100 is a portable and/or wearable delivery device 100. The delivery device 100 comprises at least one mixing device 102. The mixing device 102 defines a mixing chamber 104. The mixing chamber 104 comprises a mixing chamber inlet 106.

Figure 6 shows a cross-sectional view of the delivery device 100 taken along line A- A of Figure 5. Figure 7 shows a cross-sectional view of the delivery device 100 taken along line B-B of Figure 5. The mixing device 102 comprises a mixing piston 108 moveable arranged within the mixing chamber 104. Particularly, the mixing piston 108 is linearly moveable by means of a mixing piston drive 110 such as a linear actuator.

The delivery device 100 further comprises at least one transporting device 112. The transporting device 112 is configured to be connected to at least one cartridge 114 filled with a pharmaceutical formulation in solid form such as an active pharmaceutical formulation, a biopharmaceutical formulation or new modalities. The pharmaceutical formulation is particularly in powder form. Such a cartridge 114 comprises a cartridge piston 116 such as a powder piston moveable such as linearly moveable within the cartridge 114. The cartridge 114 may comprise an elliptical cross-section in its interior. The cartridge piston 116 may also comprise an elliptical cross-section in order to prevent rotation within the cartridge 114. The transporting device 112 is configured to transport a predetermined amount of the pharmaceutical formulation to the mixing chamber 104.

The transporting device 112 is configured to provide a predetermined force to the cartridge 114 so as to compact the pharmaceutical formulation. More particularly, the transporting device 112 is configured to provide a predetermined force to the cartridge piston 116 so as to compact the pharmaceutical formulation. The transporting device 112 is further configured to transport the predetermined amount of the pharmaceutical formulation to the mixing chamber 104 in a compacted state. The transporting device 112 comprises a spring (not shown in detail) configured to provide the predetermined force to the cartridge 114. Alternatively or in addition, the transporting device 112 comprises a pressurized gas source 118 configured to supply pressurized gas to the cartridge 114 so as to provide the predetermined force to the cartridge 114. In the latter case, the cartridge 114 comprises a gas inlet 120 for supplying the pressurized gas. The cartridge piston 116 is driven by the force of the spring or by the air pressure provided by the pressurized gas source 118. Optionally, the delivery device 100 further comprises a pressure sensor (not shown in detail) configured to detect a pressure present within the cartridge 114.

The transporting device 112 comprises a dosing wheel 122 configured to provide the predetermined amount of the pharmaceutical formulation. The dosing wheel 122 may be a dosing barrel 124. Figure 8 shows a perspective view of the dosing wheel 122. Figure 9 shows a top view of the dosing wheel 122. Figure 10 shows a front view of the dosing wheel 122. As is shown in Figures 8 to 10, the dosing wheel 122 comprises two depressions 126. The two depressions 126 are located opposite to one another with a longitudinal axis 128 of the dosing wheel 122 therebetween. The depressions 126 each form a dosing wheel inlet 130 into the dosing wheel 122. As is particularly shown in Figure 8, the dosing wheel inlet 130 is a circular radial inlet. Further, the dosing wheel 122 comprises a dosing wheel outlet 132. As is particularly shown in Figure 10, the dosing wheel outlet 132 is a circular axial outlet. The predetermined amount or dose of the pharmaceutical formulation is defined by rotating the dosing wheel 122 at 180° clockwise or counter-clockwise around the longitudinal axis 128. The dosing wheel 122 is rotatable around its longitudinal axis 128 by means of a dosing wheel drive 134.

As is further shown in Figure 6, the transporting device 112 further comprises a transport chamber 136 and a discharge piston 138. The predetermined amount or dose of the pharmaceutical formulation is conveyed to the transport chamber 136 by rotating the dosing wheel 122 at 180° clockwise or counter-clockwise around the longitudinal axis 128. The discharge piston 138 is linearly moveable within the transport chamber 136. It is explicitly stated that the dosing barrel 124 does not have an ellipsoid or spherical shape. Rather, the dosing barrel 124 has a bulging center along the longitudinal axis 128. With the specific shapes for the dosing wheel inlet 130 and the dosing wheel outlet 132, the overall cross-sectional area of the cartridge 114 may be used for feeding the dosing barrel 124 such as from above. Thus, no edges or narrowing portions located within the infeed where any powder may adhere or retain and obstruct the infeed are present. Further, the pharmaceutical formulation such as a powder may be supplied from the dosing wheel outlet 132 to the transport chamber 136 by whipping off by means of a simple linear movement of the discharge piston 138. The discharge piston 138 preferably has a circular cross-section facilitating the manufacturing and any sealing thereof if compared to the presence of any edges or radii. With the dosing barrel 124, the flow of the pharmaceutical formulation from the dosing wheel inlet 130 to the dosing wheel 132 outlet is turned at 90° within the dosing barrel 124. The specific shape of the depressions 126 is advantageous in that it allows an easy supply to the dosing wheel 122 as well as an easy discharge from the dosing wheel 122. If depressions 126 were formed as pockets, the shape thereof may be adapted to the shape of the cartridge 114 so as to reduce the resistance within the conveying flow of the pharmaceutical formulation but the pharmaceutical formulation may not be easily discharged at the dosing wheel outlet 132.

Further, it has to be noted that the dosing wheel inlet 130 is shaped such that the dosing wheel inlet 130 has at a circumference of the dosing barrel 124, i.e. at its outermost point, if seen in an axial direction a normal deviating from a tangent to the circumference of the dosing barrel 124 at this point. Thus, the force vector acting onto the pharmaceutical formulation during rotating the dosing barrel 124 from this edge or point is directed towards an interior of the dosing barrel 124 and the dosing wheel inlet 130, respectively, which prevents the pharmaceutical formulation present within the dosing wheel inlet 130 from being pushed out of the dosing wheel inlet 130 during rotating the dosing barrel 124 but keeps the pharmaceutical formulation within the dosing wheel inlet 130.

The transport chamber 136 is connected to the mixing device 102. Particularly, the mixing chamber 104 communicates with the transport chamber 136 via the mixing chamber inlet 106. The transporting device 112 is configured to move the discharge piston 138 so as to transport the predetermined amount of the pharmaceutical formulation to the mixing chamber 104 through the mixing chamber inlet 106. With other words, the discharge piston 138 is configured to convey the pharmaceutical formulation from the dosing wheel outlet 132 of the dosing wheel 122 to the mixing chamber 104 via the mixing chamber inlet 106 of the mixing chamber 104. The discharge piston 138 is driven or moved by a discharge piston drive 140 such as a linear actuator.

The mixing device 102 is connectable to a solvent reservoir 142 and is configured to suck solvent from the solvent reservoir 142 into the mixing chamber 104 by means of moving the mixing piston 108. The mixing device 102 is further configured to mix the predetermined amount of the pharmaceutical formulation with a predetermined amount of the solvent so as to provide the drug. The mixing device 102 is further configured to deliver the drug by means of moving the mixing piston 108. For this purpose, the mixing chamber 104 comprises at least one fluid inlet 144 and at least one fluid outlet 146. The mixing device 102 is configured to suck solvent from the solvent reservoir 142 into the mixing chamber 104 through the fluid inlet 144 by means of moving the mixing piston 108. Particularly, the solvent reservoir 142 is connectable to the fluid inlet 144 by means of a solvent line 148. The solvent line 148 comprises a solvent line valve 150 configured to selectively block and unblock the solvent line 148. Further, the mixing device 102 is further configured to deliver the drug through the fluid outlet 146 by means of moving the mixing piston 108.

The mixing device 102 is configured to discharge a mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent from the mixing chamber 104 through the fluid outlet 146 and to return the mixture to the mixing chamber 104 through the fluid inlet 144. For this purpose, the delivery device 100 comprises a delivery line 152 connected to the fluid outlet 146 and a return line 154 connected to the fluid inlet 144.

The mixing chamber 104 further comprises at least one gas outlet 156. The gas outlet 156 is configured to vent the mixing chamber 104. Further, the cartridge 114 comprises the gas inlet 120 for supplying a pressurized gas. In this case, the gas outlet 156 may be connected to the gas inlet 120 of the cartridge 114 by means of a first line 158. The first line 158 may include a first valve 160 in order to selectively block and unblock the first line 158. In this case, the mixing chamber 104 and the mixing piston 108 may at least partially fulfil the function of the pressurized gas source 118 configured to supply pressurized gas to the cartridge 114 so as to provide the predetermined force to the cartridge 114 as will be described in further detail below. The first line 158 may further comprise a second valve 162 connected to a surrounding of the delivery device 100. The second valve 162 allows to selectively block and unblock the first line 158 so as to allow a venting of the mixing chamber 104 or to block the mixing chamber 104 from the surrounding. The fluid inlet 144 and/or the fluid outlet 146 and/or the gas outlet 156 are provided with a membrane 164 made of a hydrophobic material. The hydrophobic material is PTFE.

The delivery device 100 further comprises a sterilizing device 166. The sterilizing device 166 is configured to sterilize the drug delivered from the mixing chamber 104. Preferably, the sterilizing device 166 is a UVC light source.

Optionally, the delivery device 100 may further comprise a secondary mixing device 168. The secondary mixing device 168 is a mixing bag 170. The mixing device 102 is configured to discharge the mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent from the mixing chamber 104 through the fluid outlet 146 to the secondary mixing device 168 and to return the mixture from the secondary mixing device 168 to the mixing chamber 104 through the fluid inlet 144. With other words, the mixing device 102 is configured to convey the predetermined amount of the pharmaceutical formulation together with the predetermined amount of the solvent from the mixing chamber 104 to the secondary mixing device 168 and back. For this purpose, the secondary mixing device 168 is connected to the delivery line 152 and the return line 154. In order to prevent solvent from the solvent reservoir 142 or a mixture of the pharmaceutical formulation and the solvent from the mixing chamber 104 flowing into the secondary mixing device 168, the return line 154 comprises a check valve 172. Particularly, the mixing device 102 is configured to discharge the mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent from the mixing chamber 104 through the fluid outlet 146 and the delivery line 152 to the secondary mixing device 168 and to return the mixture from the secondary mixing device 168 to the mixing chamber 104 through the return line 154 and the fluid inlet 144.

The delivery device 100 further comprises an optional bubble trap 174. The bubble trap 174 is configured to remove gas bubbles, such as air bubbles, from the drug delivered from the mixing chamber 104. The bubble trap 174 is connectable to the delivery line 152. The delivery line 152 comprises a third valve 176 located between the fluid outlet 146 and the bubble trap 174 within the delivery line 152. The third valve 176 is configured to selectively block and unblock the delivery line 152. The delivery line 152 further comprises a first switch valve 178. The first switch valve 178 is located downstream of the bubble trap 174. Particularly, the first switch valve 178 is configured to switch or vary its positions so as switch a fluid flow from the bubble trap 174 to the secondary mixing device 168 or further within the delivery line 152. The delivery device 100 further comprises an optional gas sensor (not shown in detail). The gas sensor is configured to detect gas bubbles, such as air bubbles, and/or particles within the drug delivered from the mixing chamber 104. The gas sensor may be located between the bubble trap 174 and the first switch valve 178. The delivery device 100 further comprises an optional concentration sensor 180 configured to detect a concentration of the pharmaceutical formulation within the drug delivered from the mixing chamber 104. The concentration sensor 180 is preferably an UVvis sensor 182. Particularly, the concentration sensor 180 is further configured to detect gas bubbles, such as air bubbles, and/or particles within the drug delivered from the mixing chamber 104. The concentration sensor 180 may be located between the bubble trap 174 and the first switch valve 178. The delivery device 100 further comprises an optional waste container 184. The waste container 184 is configured to at least partially receive the drug delivered from the mixing chamber 104. The waste container 184 is connectable to the delivery line 152. Particularly, the delivery line 152 comprises a second switch valve 186 located downstream of the first switch valve 178. The second switch valve 186 is configured to switch or vary its positions so as switch a fluid flow from the bubble trap 174 and the first switch valve 178 to the waste container 184 or further within the delivery line 152 and to a delivery outlet 188 at a patient’s side.

The delivery device 100 further comprises a controller 190. The controller 190 is configured to control operation of at least one of the transporting device 112 and the mixing device 102. The controller 190 comprises an interface 192 configured to provide a communication link between the controller 190 and a remote electronic device (not shown in detail) such as a computer which bay be located at a doctor’s side. The communication link is realized in a wireless or wired manner. The delivery device 100 further comprises an input device 194 configured to allow a user to input instructions to the controller 190. The input device 194 comprises a display, a keyboard and/or buttons configured to allow a user to input instructions to the controller 190. The delivery device 100 further comprises a power source 196, such as a rechargeable power source, configured to supply electrical power to at least one of the transporting device 112, the controller 190 and the mixing device 102.

The delivery device 100 may be modified as follows. The transporting device 112 may be configured to be connected to more than one cartridge 114 filled with a pharmaceutical formulation in solid form, particularly in powder form. The delivery device 100 may further comprise at least two mixing devices 102 and at least two transporting devices 112. The delivery device 100 may be configured to communicate with an in-situ blood sensor. The delivery device 100 may further comprise a housing. The transporting device 112 and the mixing device 102 may be arranged within this housing. The mixing chamber 104 may be at least partially made of a transparent material or comprise a portion made of a transparent material such as window. The formation of a transparent material or the provision of a transparent material at the mixing chamber allows a user to optically inspect or monitor whether the pharmaceutical formulation is completely solved in the solvent or not. The delivery device 100 may further comprise a mixing chamber pressure sensor 198 configured to detect a pressure present within the mixing chamber. Thereby, control of sucking the solvent into the mixing chamber, venting the mixing chamber, discharging any fluid from the mixing chamber is allowed. The delivery device 100 may be part of a kit which further comprises at least one cartridge 114 filled with a pharmaceutical formulation in solid form, particularly in powder form, and/or a solvent reservoir 142 filled with solvent.

Hereinafter, an operation of the delivery device 100 is described.

Figures 11 to 28 each show a block diagram of the delivery device 100 with the constructional members thereof in different operation states. Figure 1 shows an initial state of the delivery device 100 after the constructional members have fulfilled a so called reference run. The reference run is an absolute job that serves to zero the drive for subsequent positioning tasks. A reference run is used to mechanically move a motor (connected to a mechanism) to a specific position on the machine, called the "reference position". In this state, the first valve 160 and the second valve 162 are in a blocking position in which the first line 158 to the gas inlet 120 of a cartridge 114 and to the surrounding is blocked. Further, the third valve 176 is in its blocking position in which the delivery line 152 to the bubble trap 174 is blocked. The first switch valve 178 is in a first position in which the delivery line 152 to the second switch valve 186 is unblocked. Further, the second switch valve 186 is in a second position in which the delivery line 152 is connected to the waste container 184. The solvent line valve 150 is in a blocking position in which the solvent line 148 is blocked. The discharge piston 138 is in its rear position. The mixing piston 108 is in its rear position. A cartridge 114 filled with the pharmaceutical formulation is connected to the transporting device 112.

Then, as shown in Figure 11, the mixing chamber 104 is discharged from any residues therein by moving the discharge piston 138 to its front position and moving the mixing piston 108 towards its front position, i.e. towards the fluid outlet 146. Further, the third valve 176 is moved in its unblocking position in which the delivery line 152 to the bubble trap 174 is unblocked. Thereby, any residues from the mixing chamber 104 are conveyed to the waste container 184.

Then, as shown in Figure 12, the third valve 176 is moved into its blocking position in which the delivery line 152 to the bubble trap 174 is blocked. Further, the mixing piston 108 sucks any residues from the secondary mixing device 168 through the return line 154 and the check valve 172.

Then, as shown in Figure 13, the third valve 176 is moved in its unblocking position in which the delivery line 152 to the bubble trap 174 is unblocked. Further, the mixing piston 108 moves further towards its front position. Thereby, any residues from the secondary mixing device 168 and the mixing chamber 104 are conveyed to the waste container 184.

Then, as shown in Figure 14, the third valve 176 is moved into its blocking position in which the delivery line 152 to the bubble trap 174 is blocked. Further, the second valve 162 is moved in its unblocking position in which the gas outlet 156 of the mixing chamber 104 is connected to the surrounding. Further, the mixing piston 108 sucks air from the surrounding through the gas outlet 156, the fluid inlet 144 and the fluid outlet 146 by moving towards its rear position. Then, as shown in Figure 15, the second valve 162 is moved into its blocking position in which the first line 158 to the surrounding is blocked. Further, the mixing piston 108 moves towards its front position. Thereby, the pressure within the mixing chamber 104 increases.

Then, as shown in Figure 16, the first valve 160 is moved into its unblocking position in which the first line 158 to the gas inlet 120 of the cartridge 114 is unblocked. The mixing piston 108 moves further towards its front position. Thereby, the cartridge piston 116 of the cartridge 114 is pressurized via the gas outlet 156 of the mixing chamber 104 by actuating the mixing piston 108.

Then, as shown in Figure 17, the first valve 160 is moved into its blocking position in which the first line 158 to the gas inlet 120 of the cartridge 114 is blocked. The second valve 162 is moved into its unblocking position in which the first line 158 to the surrounding is unblocked. The mixing piston 108 is moved in its rear piston. Thereby, the discharge piston 138 is wiped off by the mixing piston 108.

Then, as shown in Figure 18, the second valve 162 is moved into its blocking position in which the first line 158 to the surrounding is blocked. The discharge piston 138 is moved into its rear position. Further, the mixing piston 108 is slightly moved forwards so as to block the mixing chamber inlet 106. Then, the predetermined amount or dose of the pharmaceutical formulation is provided by rotating the dosing wheel 122. Particularly, the predetermined amount or dose of the pharmaceutical formulation is conveyed into the blocked transport chamber 136 through the dosing wheel 122.

Then, as shown in Figure 19, the discharge piston 138 is slightly moved forwards so as to block the outlet of the dosing wheel 122. Thus, the dosing wheel 122 is blocked.

Then, as shown in Figure 20, the mixing piston 108 is moved into its rear position. Thereby, the mixing chamber inlet 106 is unblocked. The second valve 162 is moved into its unblocking position in which the first line 158 to the surrounding is unblocked. Further, the discharge piston 138 is moved into its front position. Thus, the mixing chamber 104 is loaded the predetermined amount or dose of the pharmaceutical formulation via the mixing chamber inlet 106 by actuating the discharging piston and subsequently the mixing piston 108. Then, as shown in Figure 21, the mixing piston 108 is slightly moved forwards so as to block the mixing chamber inlet 106. Thereby, any pharmaceutical formulation adhering at the discharge piston 138 is wiped off.

Then, as shown in Figure 22, the mixing piston 108 is moved into its front position. As the first line 158 to the surrounding is unblocked, the mixing chamber 104 is vented.

Then, as shown in Figure 23, the second valve 162 is moved into its blocking position in which the first line 158 to the surrounding is blocked. Further, the solvent line valve 150 is moved into its unblocking position, in which the solvent line 148 is unblocked. Further, the mixing piston 108 is moved towards its rear position. Thus, a predetermined amount of solvent is sucked into the mixing chamber 104 through the solvent line 148 and the fluid inlet 144.

Then, as shown in Figure 24, the solvent line valve 150 is moved into its blocking position, in which the solvent line 148 is blocked. Further, the third valve 176 is moved into its unblocking position, in which the delivery line 152 to the bubble trap 174 is unblocked. Further, the first switch valve 178 is moved into its second position, in which the bubble trap 174 is connected to the secondary mixing device 168. The mixing piston 108 is moved towards its front position. Thus, the predetermined amount of the pharmaceutical formulation and the predetermined amount of solvent is conveyed into the secondary mixing device 168 through the bubble trap 174 and the concentration sensor 180. Thereby any gas bubbles are removed at the bubble trap 174 and the predetermined amount of the pharmaceutical formulation and the predetermined amount of solvent are mixed.

Then, as shown in Figure 25, the third valve 176 is moved into its blocking position, in which the delivery line 152 to the bubble trap 174 is blocked. Further, the first switch valve 178 is moved into its first position, in which the bubble trap 174 is connected to the second switch valve 186. The mixing piston 108 is moved rearwards so as to suck the mixture of the pharmaceutical formulation and the predetermined amount of solvent back into the mixing chamber 104 through the return line 154 and the check valve 172.

Then, as shown in Figure 26, the mixing piston 108 moves so as to compensate the resulting negative pressure. The steps shown in Figures 24 to 26 may be repeated as appropriate. Thus, the predetermined amount of the pharmaceutical formulation is mixed with the solvent via the fluid outlet 146 and fluid inlet 144 by actuating the mixing piston 108 back and forth. Thereby, the predetermined amount of the pharmaceutical formulation and the predetermined amount of the solvent are conveyed out of the mixing chamber 104 and back into the mixing chamber 104 which causes turbulences providing a mixing effect. During this conveying or pumping process, any bubbles are removed from thus provided dispersion by means of the bubble trap 174. Further, the homogeneity is checked by means of the mixing sensor and the concentration of the thus provided drug is checked by means of the concentration sensor 180. Still further, the presence of any bubbles is checked by means of the gas sensor being an UVvis sensor 182 while mixing. The step of conveying the dispersion back and forth as well as the checks of the quality of the dispersion, the concentration of the dispersion and the presence are carried out until the target homogeneity, the target concentration and absence of bubbles are reached.

Then, as shown in Figure 27, the third valve 176 is moved into its unblocking position, in which the delivery line 152 to the bubble trap 174 is unblocked. Further, the first switch valve 178 is moved into its first position, in which the bubble trap 174 is connected to the second switch valve 186. Further, the second switch valve 186 is moved into its first position, in which the delivery line 152 is connected to the delivery outlet 188 at the patient’s side. Thus, the drug may be delivered to the patient such as by means of infusion. With other words, finally, the thus provided drug is inject into a patient via the fluid outlet 146 by actuating the mixing piston 108.

If any deviations of the mixture of the predetermined amount of the pharmaceutical formulation and the predetermined amount of the solvent from the target homogeneity, the target concentration and/or presence of bubbles is detected after a predetermined number of cycles of the steps shown in Figures 24 to 26, then third valve 176 is moved into its unblocking position, in which the delivery line 152 to the bubble trap 174 is unblocked. Further, the first switch valve 178 is moved into its first position, in which the bubble trap 174 is connected to the second switch valve 186. Further, the second switch valve 186 remains in its second position, in which the delivery line 152 is connected to the waste container 184. Thus, the mixture of the predetermined amount of the pharmaceutical formulation and the predetermined amount of the solvent may be disposed into the waste container 184. List of reference numbers delivery device mixing device mixing chamber mixing chamber inlet mixing piston mixing piston drive transporting device cartridge cartridge piston pressurized gas source gas inlet dosing wheel dosing barrel depression longitudinal axis dosing wheel inlet dosing wheel outlet dosing wheel drive transport chamber discharge piston discharge piston drive solvent reservoir fluid inlet fluid outlet solvent line solvent line valve delivery line return line gas outlet first line first valve second valve membrane sterilizing device secondary mixing device mixing bag check valve bubble trap third valve first switch valve concentration sensor UVvis sensor waste container second switch valve delivery outlet controller interface input device power source mixing chamber pressure sensor

Claims

1. A delivery device (100) for delivering a drug, comprising at least one mixing device (102) defining a mixing chamber (104) and comprising a mixing piston (108) moveable arranged within the mixing chamber (104), wherein the mixing device (102) is connectable to a solvent reservoir (142) and configured to suck solvent from the solvent reservoir (142) into the mixing chamber (104) by means of moving the mixing piston (108), at least one transporting device (112) configured to be connected to at least one cartridge (114) filled with a pharmaceutical formulation in solid form, particularly in powder form, wherein the transporting device (112) is configured to transport a predetermined amount of the pharmaceutical formulation to the mixing chamber (104), wherein the mixing device (102) is further configured to mix the predetermined amount of the pharmaceutical formulation with a predetermined amount of the solvent so as to provide the drug, wherein the mixing device (102) is further configured to deliver the drug by means of moving the mixing piston (108).

2. The delivery device (100) according to the preceding claim, wherein the transporting device (112) is configured to provide a predetermined force to the cartridge (114) so as to compact the pharmaceutical formulation, wherein the transporting device (112) is further configured to transport the predetermined amount of the pharmaceutical formulation to the mixing chamber (104) in a compacted state.

3. The delivery device (100) according to the preceding claim, wherein the transporting device (112) comprises a spring configured to provide the predetermined force to the cartridge (114) and/or a pressurized gas source (118) configured to supply pressurized gas to the cartridge (114) so as to provide the predetermined force to the cartridge (H4).

4. The delivery device (100) according to any preceding claim, further comprising a pressure sensor configured to detect a pressure present within the cartridge (114).

5. The delivery device (100) according to any preceding claim, further comprising a mixing chamber pressure sensor (198) configured to detect a pressure present within the mixing chamber (104).

6. The delivery device (100) according to any preceding claim, wherein the transporting device (112) comprises a dosing wheel (122), particularly, a dosing barrel (124), configured to provide the predetermined amount of the pharmaceutical formulation.

7. The delivery device (100) according to any preceding claim, wherein the transporting device (112) comprises a transport chamber (136) and a discharge piston (138) moveable within the transport chamber (136), wherein the transport chamber (136) is connected to the mixing device (102), wherein the transporting device (112) is configured to move the discharge piston (138) so as to transport the predetermined amount of the pharmaceutical formulation to the mixing chamber (104).

8. The delivery device (100) according to any preceding claim, wherein the mixing chamber (104) comprises at least one fluid inlet (144) and at least one fluid outlet (146), wherein the mixing device (102) is configured to suck solvent from the solvent reservoir (142) into the mixing chamber (104) through the fluid inlet (144) by means of moving the mixing piston (108), wherein the mixing device (102) is further configured to deliver the drug through the fluid outlet (146) by means of moving the mixing piston (108).

9. The delivery device (100) according to the preceding claim, wherein the mixing device (102) is configured to discharge a mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent from the mixing chamber (104) through the fluid outlet (146) and to return the mixture to the mixing chamber (104) through the fluid inlet (144).

10. The delivery device (100) according to the preceding claim, further comprising a secondary mixing device (168), wherein the mixing device (102) is configured to discharge the mixture of the predetermined amount of the pharmaceutical formulation with the predetermined amount of the solvent from the mixing chamber (104) through the fluid outlet (146) to the secondary mixing device (168) and to return the mixture from the secondary mixing device (168) to the mixing chamber (104) through the fluid inlet (144).

11. The delivery device (100) according to the preceding claim, wherein the secondary mixing device (168) is a mixing bag (170).

12. The delivery device (100) according to any one of claims 6 to 9, wherein the mixing chamber (104) further comprises at least one gas outlet (156) configured to vent the mixing chamber (104), wherein the fluid inlet (144) and/or the fluid outlet (146) and/or the gas outlet (156) is provided with a membrane (164) made of a hydrophobic material.

13. The delivery device (100) according to the preceding claim, wherein the hydrophobic material is PTFE.

14. The delivery device (100) according to any preceding claim, further comprising a bubble trap (174) configured to remove gas bubbles, particularly air bubbles, from the drug delivered from the mixing chamber (104).

15. The delivery device (100) according to any preceding claim, further comprising a gas sensor configured to detect gas bubbles, particularly air bubbles, within the drug delivered from the mixing chamber (104).

16. The delivery device (100) according to any preceding claim, further comprising a concentration sensor (180) configured to detect a concentration of the pharmaceutical formulation within the drug delivered from the mixing chamber (104).

17. The delivery device (100) according to the preceding claim, wherein the concentration sensor (180) is an UVvis sensor (182).

18. The delivery device (100) according to any of the two preceding claims, wherein the concentration sensor (180) is configured to detect gas bubbles, particularly air bubbles, and/or particles within the drug delivered from the mixing chamber (104).

19. The delivery device (100) according to any preceding claim, further comprising a waste container (184) configured to at least partially receive the drug delivered from the mixing chamber (104).

20. The delivery device (100) according to any preceding claim, further comprising a sterilizing device (166) configured to sterilize the drug delivered from the mixing chamber (104).

21. The delivery device (100) according to the preceding claim, wherein the sterilizing device (166) is a UVC light source and/or a sterile filter.

22. The delivery device (100) according to any preceding claim, wherein the transporting device (112) is configured to be connected to more than one cartridge (114) filled with a pharmaceutical formulation in solid form, particularly in powder form.

23. The delivery device (100) according to any preceding claim, comprising at least two mixing devices (102) and at least two transporting devices (112).

24. The delivery device (100) according to any preceding claim, further comprising a controller (190) configured to control operation of at least one of the transporting device (112) and the mixing device (102).

25. The delivery device (100) according to the preceding claim, wherein the controller (190) comprises an interface (192) configured to provide a communication link between the controller (190) and a remote electronic device.

26. The delivery device (100) according to the preceding claim, wherein the communication link is realized in a wireless or wired manner.

27. The delivery device (100) according to any of the three preceding claims, further comprising an input device (194) configured to allow a user to input instructions to the controller (190).

28. The delivery device (100) according to the preceding claim, wherein the input device (194) comprises a display, a keyboard and/or buttons configured to allow a user to input instructions to the controller (190).

29. The delivery device (100) according to any of the five preceding claims, further comprising a power source (196), particularly a rechargeable power source, configured to supply electrical power to at least one of the transporting device (112), the controller (190) and the mixing device (102).

30. The delivery device (100) according to any preceding claim, wherein the delivery device (100) is a portable and/or wearable delivery device (100).

31. The delivery device (100) according to any preceding claim, wherein the delivery device (100) is configured to communicate with an in-situ sensor, particularly a blood or interstitial fluid sensor.

32. The delivery device (100) according to any preceding claim, wherein the mixing chamber (104) is at least partially made of a transparent material or comprises a portion made of a transparent material.

33. The delivery device (100) according to any preceding claim, further comprising a housing, wherein the transporting device (112) and the mixing device (102) are arranged within the housing.

34. The delivery device (100) according to any preceding claim, wherein the drug is configured to be used for parenteral application, particularly an intravenous or sub cutaneous application).

35. A kit comprising a delivery device (100) according to any preceding claim and at least one cartridge (114) filled with a pharmaceutical formulation in solid form, particularly in powder form, and/or a solvent reservoir (142) filled with solvent.

36. Use of the delivery device (100) according to any preceding claim referring to a delivery device for delivering a drug, particularly with parenteral delivering of a drug, more particularly with an intravenous or sub cutaneous application.