Drug delivery device and mixing method

Abstract

A drug delivery device is provided that includes a drug container assembly including a drug container 17 containing a drug 18, a needle 4, a plunger rod 8, a first energy source 5, a stored energy source for needle insertion 10, and an actuation means. Movement of the actuation means releases the stored energy source for needle insertion 10 to move the needle 4 from a pre-needle insertion position to a needle insertion position, and releases the first energy source 5 to move the plunger rod 8 relatively toward the drug container assembly, whereby the drug container assembly applies a force to the drug 18 before the needle reaches the needle insertion position. A method of mixing drugs is also provided.

Description

[Technical Field]

[0001] The present invention relates to drug delivery devices, such as auto-injectors, and methods of mixing drugs within drug delivery devices. [Background technology]

[0002] Autoinjectors can automate either or both needle insertion and drug delivery. Early autoinjector designs tended to have a single spring that simultaneously inserted the needle into the patient and delivered the drug. One drawback of this approach is that the force required for drug delivery is typically much greater than the force required for needle insertion. Therefore, using a single spring for both drug delivery and needle insertion can result in noise and shock during needle insertion, which can be significant to the patient and can undermine the reliability of the autoinjector.

[0003] Modern autoinjector designs typically employ two separate springs: an insertion spring for inserting the needle and a delivery spring for delivering the medication. This allows both springs to be optimized for their respective purposes. To prevent premature delivery of medication to the wrong body compartment, these springs are sequenced so that the delivery spring is not activated until the needle is fully inserted into the patient and in the correct compartment. This means that the medication is not pressurized until the needle is effectively fully inserted into the patient.

[0004] It is important that the drug is delivered to the patient through the needle only after the needle is inserted into the correct body compartment, e.g., intramuscularly or subcutaneously (if appropriate), as administering the drug to the wrong body compartment can adversely affect the efficacy of the drug and cause unwanted side effects.

[0005] In some autoinjectors, it may be beneficial to agitate the drug before administering it to the patient. This can reduce the likelihood of drug suspensions settling, separating, or causing needle blockage, reducing delivery inconsistency. Some drugs may exhibit non-Newtonian viscosity or gelling effects, which can lead to large variations in delivery rate or even delivery failure. Applying shear and mixing forces to the drug before delivering it to the patient can significantly reduce the adverse effects of these issues.

[0006] One approach to agitating a drug prior to delivery involves the user shaking the autoinjector before use. Disadvantages of this approach include the fact that the available energy is limited by the user's (potentially ill) ability to shake the product, and the energy applied can vary dramatically depending on how an individual user interprets the instructions. Additionally, many drug suspensions remain opaque even when most of the solid components have settled, preventing the user from visually determining whether they have sufficiently shaken the product to resuspend the settled formulation. Summary of the Invention [Problem to be solved by the invention]

[0007] It is an object of the present invention to overcome or mitigate one or more of the problems set forth above. [Means for solving the problem]

[0008] The present invention is defined in the accompanying independent claims, to which reference is made. Optional features of the invention are defined in the dependent claims. Aspects, embodiments or examples falling outside the scope of the accompanying independent claims are included for purposes of illustration or description.

[0009] According to a first aspect of the present disclosure, there is provided a drug delivery device. The device may include a housing portion. The device may include a drug container assembly including a drug container that contains a drug. The device may include a needle through which the drug is expelled in use. The needle may be movable relative to the housing portion, for example from a pre-needle insertion position to a needle insertion position. The device may include a plunger rod. Optionally, the plunger rod may be spaced apart from the drug container assembly before the needle is moved from the pre-needle insertion position. The device may include a first stored energy source. The device may include a stored energy source for needle insertion. The device may include an actuation means. The drug container may include an outlet through which the drug is expelled in use. The outlet may be sealed before the needle is moved from the pre-needle insertion position. The device may be configured such that movement of the actuation means from the first position to the second position releases the stored energy source for needle insertion and moves the needle from the pre-needle insertion position to the needle insertion position. The device may be configured such that movement of the actuation means from the first position to the second position releases the first stored energy source and moves the plunger rod toward and relative to the drug container assembly, causing the drug container assembly to apply a force to the drug before the needle reaches the needle insertion position. Thus, the device may be configured such that movement of the actuation means from the first position to the second position releases the needle insertion stored energy source and moves the needle from the pre-needle insertion position to the needle insertion position, and releases the first stored energy source and moves the plunger rod toward and relative to the drug container assembly, causing the drug container assembly to apply a force to the drug before the needle reaches the needle insertion position.

[0010] Advantageously, the drug container assembly applies a force to the drug before the needle reaches the needle insertion position. Autoinjector designers typically seek to minimize the initial shock, as this can frighten patients and undermine the reliability of the autoinjector. However, analysis conducted by the present inventors surprisingly confirmed that this force has the positive effect of mixing the drug and introducing shear forces into the drug. This can resuspend precipitated solids in the liquid component of a suspended drug and reduce the viscosity of a shear-thinning drug.

[0011] Additionally, there are advantages to providing an initial impact force on the drug before drug delivery through the needle begins, especially when the suspension may settle and form a solid layer on the drug exit path to the needle, which may pose a risk of clogging at the start of drug delivery. The drug container can continue to apply force to the drug after the needle has reached the needle insertion position.

[0012] However, if too much time is allowed between the initial impact force and the onset of drug delivery, the suspended components of the drug may begin to re-sediment, and the viscosity of a shear-thinning drug may increase again as the shear forces in the fluid decrease with time.

[0013] Another advantage of the first embodiment is that movement of the actuation means both moves the needle from the pre-insertion position to the needle insertion position and causes the drug container assembly to apply a force to the drug before the needle reaches the needle insertion position. Thus, the device according to the first embodiment may require only a single user action (movement of the actuation means) to perform needle insertion and mix the drug at the appropriate operational stage. This may simplify device operation. Furthermore, this may prevent problems with some prior art devices, such as drug settling, separation, or viscosity buildup after drug mixing but before needle insertion. This problem may exist, for example, when the drug is manually mixed in a prior art device (e.g., by shaking or tapping the device) and then the drug settles (e.g., while preparing a patient's injection site) before needle insertion and drug delivery.

[0014] As will be appreciated by those skilled in the art from this disclosure, the first stored energy source may be a different stored energy source from the stored energy source for needle insertion, and the first stored energy source may be different or separate from the stored energy source for needle insertion, or both.

[0015] The first stored energy source may be or may include a first spring. The needle insertion stored energy source may be or may include a needle insertion spring. The first spring may be a different spring than the needle insertion spring.

[0016] When the stored energy source for needle insertion moves the needle from a pre-needle insertion position to a needle insertion position, the stored energy source for needle insertion may expand along a stored energy source axis for needle insertion. When the first stored energy source moves the plunger rod toward and relative to the drug container assembly, the first stored energy source may expand along a first stored energy source axis. The stored energy source axis for needle insertion may be different from, and optionally parallel to, the first stored energy source axis.

[0017] According to a first aspect, the plunger rod is spaced from the drug container assembly before the needle moves from the pre-needle insertion position. Unless otherwise specified, the term "spaced" is used herein to mean spatially separated. One or more intermediate components can be located between two spaced apart components. For example, one or more components can be located between the plunger rod and the drug container assembly before the needle moves from the pre-needle insertion position. For example, a compressible component, such as a sponge or foam, can be located between the plunger rod and the drug container assembly before the needle moves from the pre-needle insertion position. Alternatively, or additionally, an air gap can be located between the plunger rod and the drug container assembly before the needle moves from the pre-needle insertion position. Thus, the plunger rod can be spaced from the drug container assembly only by an air gap or partially by an air gap before the needle moves from the pre-needle insertion position.

[0018] The plunger rod may be spaced from the drug container assembly prior to movement of the needle from the pre-needle insertion position such that, in use, the plunger rod is configured to accelerate substantially unopposed toward the drug container assembly under the influence of the first stored energy source. Advantageously, this may allow the drug container assembly to apply a greater force to the drug than if acceleration of the plunger rod toward the drug container assembly were substantially resisted.

[0019] The drug delivery device may include a housing. The housing may house the drug container assembly. The housing may house the needle in a pre-needle insertion position. The housing may house the plunger rod. The housing may house the first stored energy source. The housing may house the needle insertion stored energy source. The housing may be configured to be held by a user, for example, during operation. The drug delivery device may be a handheld drug delivery device. Advantageously, the housing may make the drug delivery device easier to use. Advantageously, the housing may help to protect the components housed by the housing, for example, from external forces (such as impact forces if the device is dropped) and external contaminants.

[0020] As used herein, the term "pre-needle insertion position" refers to the position of the needle before movement of the actuation means from a first position to a second position. In the pre-needle insertion position, the housing may fully enclose the needle. The pre-needle insertion position may be distal to the needle insertion position. The needle may be configured to move proximally from the pre-needle insertion position to the needle insertion position.

[0021] As used herein, the term "needle insertion position" refers to the position of the needle after movement of the actuation means from a first position to a second position. In the needle insertion position, the housing may house a portion of the needle, e.g., a distal portion. In the needle insertion position, a portion, e.g., a proximal portion, may protrude from the housing. The drug delivery device may be configured to eject the drug only after the needle leaves the pre-needle insertion position, e.g., only after the needle reaches the needle insertion position. The drug delivery device may be configured to eject the drug only while the needle is in the needle insertion position.

[0022] The entire force applied by the drug container assembly to the drug can be applied before the needle reaches the needle insertion position. Alternatively, the drug container assembly can begin applying a force to the drug before the needle reaches the needle insertion position, but not complete applying the force to the drug until the needle reaches the needle insertion position. In either case, the drug container assembly applies a force to the drug before the needle reaches the needle insertion position. Unless otherwise specified, in this specification, application of a force from the drug container assembly to the drug can refer to starting to apply a force from the drug container assembly to the drug or applying the entire force from the drug container assembly to the drug.

[0023] The drug container assembly can apply or begin to apply force to the drug after the needle has moved from the pre-needle insertion position. Advantageously, this can shorten the period between applying force to the drug and the needle reaching the needle insertion position. Additionally, applying force during the needle insertion process can reduce the likelihood of the drug settling, separating, or substantially increasing in viscosity prior to delivery.

[0024] Movement of the actuation means from the first position to the second position can cause the first stored energy source to move the plunger rod toward the drug container assembly. This movement of the plunger rod toward the drug container assembly can cause the plunger rod or the impacting component to impact a collision surface of the drug container assembly. This impact of the collision surface can cause the drug container assembly to apply a force, such as the force described above, to the drug. Advantageously, having the plunger rod impact the collision surface can eliminate the need for an impacting component. Therefore, fewer components are required and the drug delivery device can be more compact.

[0025] The impact surface may be a surface of the drug container. The plunger rod or impacting part may be spaced from the impact surface before the needle moves from the pre-needle insertion position. For example, the plunger rod or impacting part may be spaced from the impact surface by at least 1, 2, 3, 5, 7, or 10 mm before the needle moves from the pre-needle insertion position. Advantageously, a greater separation between the plunger rod or impacting part and the impact surface may allow the plunger rod or impacting part to accelerate over a longer distance before impacting the impact surface. This may allow for a more powerful impact. A more powerful impact may result in a higher degree of mixing of the drug. It is particularly preferred that the plunger rod or impacting part be spaced from the impact surface by at least 5 mm before the needle moves from the pre-needle insertion position. This may allow for a sufficiently strong impact.

[0026] The plunger rod or impacting element may impact the impact surface with a momentum difference. This momentum difference between the plunger rod or impacting element and the impact surface may be at least 0.005 or 0.01 kg·m / s (kilogram meters per second), preferably at least 0.02 kg·m / s. Advantageously, a greater momentum difference between the plunger rod or impacting element and the impact surface may allow for greater energy transfer to the drug. Greater energy transfer to the drug may result in a greater degree of drug mixing.

[0027] The plunger rod or impact surface can impact the impact surface at a relative velocity of at least 5 m / s (meters per second), preferably at least 10 or 13 m / s, relative to the impact surface. Advantageously, the greater the relative velocity between the plunger rod or impact surface and the impact surface, the greater the transfer of energy to the drug. This can result in a greater degree of drug mixing.

[0028] The medication container assembly may include a piston. During use, the piston may be configured to move relative to the medication container. Movement of the piston relative to the medication container may expel medication through one or both of the medication container's outlet and the needle. During use, the medication may be expelled through the medication container's outlet and the needle. During use, movement of the piston relative to the medication container may expel medication through the medication container's outlet and then through the needle. During use, the medication may be expelled simultaneously through the medication container's outlet and the needle, for example, when the needle extends through the outlet during medication expulsion. During use, movement of the piston relative to the medication container may expel medication simultaneously through the medication container's outlet and the needle. The piston may comprise or consist of a polyethylene material, such as HDPE or LDPE, although other materials are possible.

[0029] The piston may be coated with a lubricating material, which may comprise or consist of a silicone material. Advantageously, the lubricating material may reduce friction between the piston and the medication container during movement of the piston relative to the medication container.

[0030] A surface of the piston may be configured to function as an impact surface. In use, the plunger rod or impacting element may impact the impact surface of the piston. The piston may then apply or begin to apply a force to the drug. That is, the force applied to the drug by the drug container assembly may be applied by the piston. For example, the plunger rod or impacting element may impact the impact surface of the piston, thereby moving the piston relative to the drug. This may cause another surface of the piston, for example, a surface of the piston substantially opposite the impact surface of the piston, to apply or begin to apply a force to the drug, for example, by impacting the drug. Advantageously, it may be convenient for the piston to apply or begin to apply a force to the drug, especially when the piston is already configured to contact the drug and move relative to the drug. Advantageously, impacting the plunger rod or impacting element with the impact surface of the piston may allow force to be transferred from the first stored energy source to the drug through fewer parts. This may result in less dissipated energy and a greater force acting on the drug. As a result, the drug may be more thoroughly mixed.

[0031] After the needle has moved from the pre-needle insertion position, e.g., after the needle has moved from the pre-needle insertion position to the needle insertion position, the first stored energy source may be configured to move a piston relative to the medication container, e.g., to expel medication through the needle. Advantageously, piston movement may not commence until the needle is in the needle insertion position, such that medication is not delivered through the needle until the needle is at a sufficient minimum length, minimizing mis-anatomical or premature delivery.

[0032] In addition to the outlet, the drug container may include an opening. The opening of the drug container may be substantially opposite the outlet of the drug container. An opening seal may be provided across the opening of the drug container. The opening seal may close the opening before movement of the needle from the pre-needle insertion position. The opening seal may be configured to be ruptured or removed during or before use of the drug delivery device. The opening seal may comprise a sealing foil. Advantageously, the opening seal may act as a microbial barrier, reducing the ingress of contaminants into the drug container, for example until ruptured or removed.

[0033] Prior to movement of the needle from the pre-needle insertion position, the piston may be positioned within the drug container, for example, between the opening and the drug or between the opening seal and the drug. The piston may contact the inner surface of the drug container. The piston may provide a sealing interface with the inner surface of the drug container to prevent the drug from passing from one side of the piston to the other. Positioning the piston between the drug and the opening seal may advantageously result in the piston not having to form a microbial seal. This may reduce interference requirements for the piston with the drug container. Lower interference requirements may reduce frictional forces between the piston and the drug container. As a result, a lower required spring force may be required. A lower required spring force may allow a smaller spring to be selected, which may result in a smaller size of the drug delivery device. Advantageously, a lower required interference force may reduce energy dissipation from the drug container assembly to the drug, which may result in a greater transfer of energy to the drug. Greater energy transfer to the drug may result in a greater degree of drug mixing.

[0034] Movement of the first stored energy source can move the plunger rod toward the piston to open the aperture seal, for example, by rupturing, penetrating, displacing, or removing the aperture seal. The plunger rod can be coupled to a piercing piece that can pierce the aperture seal during movement of the plunger rod toward the piston. Advantageously, configuring the plunger rod to enable opening of the aperture seal eliminates the requirement for an additional opening element. This can reduce the number of parts required and result in a cheaper, smaller, and more compact device.

[0035] The drug container may comprise a polymer. The drug container may comprise one or more of a polyethylene polymer and a cyclic olefin polymer. Advantageously, a polymer drug container is less likely to break and can withstand higher forces than a glass drug container. By withstanding greater forces, it may be possible to transmit greater forces to the drug, which may aid in mixing of the drug.

[0036] Conventionally, it is often desirable to minimize the volume of gas bubbles, such as air bubbles, in a drug container of a drug delivery device, or to eliminate gas bubbles entirely. This is because minimizing the volume of gas bubbles can minimize the risk of injecting a significant amount of gas (gas) into a patient. Furthermore, minimizing the volume of gas bubbles is often desirable when the drug is susceptible to degradation in the presence of this gas. For example, if the gas contains oxygen, like air, and the drug is susceptible to oxidation, it may be desirable to minimize the volume of gas bubbles in the drug container. However, contrary to conventional practice in the field of the present invention, the present inventors have discovered that the presence of gas bubbles in a drug container can be beneficial. Specifically, gas bubbles can aid in drug mixing. Gas bubbles can aid in drug mixing when present in a device within the scope of the attached independent claims. Gas bubbles can have two properties that can significantly aid mixing: a specific gravity that is significantly different from that of the drug, and a level of compressibility that the drug does not have. High-speed video and other analytical techniques performed by the inventors have confirmed that the rapid compression, expansion, migration, disintegration, and dispersion of gas bubbles induces turbulent motion throughout the drug, aiding in drug mixing.

[0037] Thus, in addition to the drug in the drug container, gas bubbles may be present in the drug container. The term "gas bubbles" is used herein to mean a volume of undissolved gas. The gas bubbles in the drug container are not necessarily surrounded by the drug. A portion of the gas bubbles may contact the drug. A second portion of the gas bubbles may contact the drug container. Advantageously, the gas bubbles may aid in mixing the drug. Without wishing to be bound by theory, it is understood that the density difference between the gas bubbles and the drug may aid in mixing the drug. When a force is applied to the drug by the drug container assembly, the gas bubbles disperse within the drug container and travel through the drug container, disrupting settled drug particles. Disturbing potentially settled particles may manipulate the drug into a more homogeneous state than before the force was applied.

[0038] The force applied to the drug by the drug container assembly may compress the gas bubble. Compression of the gas bubble may result in one or both of an increase in the pressure of the gas bubble and a decrease in the volume occupied by the gas bubble. The force applied to the drug by the drug container assembly may rapidly compress the gas bubble. Following compression of the gas bubble, the gas bubble may break up, shatter, or "explode" into multiple secondary gas bubbles. These secondary gas bubbles may travel through the drug and aid in mixing the drug.

[0039] As one skilled in the art will appreciate, a compromise must be made regarding the size of the gas bubble present within the drug container. As the volume of the gas bubble increases, the size of the drug container and device must also increase to accommodate the gas bubble. Furthermore, a bubble that is too large may, in some embodiments, act as a cushion or damper and actually reduce the force applied to the drug by the drug container assembly. However, a bubble with a small volume may not significantly aid in mixing the drug within the drug container. The compromise regarding gas bubble size may be affected by the volume of drug within the drug container, the pressure of the gas bubble prior to compression, and the shape of the drug container. Prior to needle movement from the pre-needle insertion position, the gas bubble should be at least 50 or 100 mm at room temperature and atmospheric pressure. 3 Before needle movement from the pre-insertion position, the gas bubble may occupy a volume of 5000 or 2000 mm at room temperature and atmospheric pressure. 3 Prior to needle movement from the pre-insertion position, the gas bubble may occupy a volume of 50-5000 mm at room temperature and atmospheric pressure. 3 , preferably 100 to 2000 mm 3 It can occupy a volume of

[0040] Prior to needle movement from the pre-needle insertion position, the gas bubble may occupy at least 5% of the volume of the medication container. Prior to needle movement from the pre-needle insertion position, the gas bubble may occupy no more than 30% of the volume of the medication container.

[0041] The outlet of the drug container may be sealed before movement of the needle from the pre-needle insertion position. The outlet may be sealed by an outlet seal. The device may include an opening mechanism for opening the outlet of the drug container in use. The opening mechanism may be configured to engage with the outlet seal to open the outlet. For example, the opening mechanism may be configured to rupture, pierce, displace or remove the outlet seal. The opening mechanism may be configured to open the outlet after the needle has moved from the pre-needle insertion position. Advantageously, this ensures that the outlet cannot be opened prematurely, for example while the drug delivery device is not in use or if the drug would be delivered to the wrong body compartment.

[0042] The opening mechanism may open the outlet after the drug container assembly applies a force to the drug. Advantageously, this may prevent premature expulsion of the drug due to the application of the force to the drug. For example, the opening mechanism may be configured to open the outlet at least 5 ms (milliseconds), preferably at least 12 ms, after the force is applied or the application of the force begins. Opening the outlet at least a predetermined time after the force is applied may advantageously allow sufficient time for mixing to occur before drug delivery.

[0043] The opening mechanism may open the outlet after the needle has advanced at least a predetermined distance from the pre-needle insertion position, for example at least 10 mm or 20 mm from the pre-needle insertion position, or at least 50%, 75% or 90% of the distance from the pre-needle insertion position to the needle insertion position. Advantageously, this may allow sufficient time for the medication to mix before the outlet is opened and the medication is expelled.

[0044] The opening mechanism may be operated to open the outlet after the needle has reached the needle insertion position, which may advantageously reduce the risk of premature expulsion of the drug through the needle and delivery of the drug to the wrong body compartment.

[0045] The opening mechanism may be configured to open the outlet at least 10 ms or 20 ms after the actuation means reaches the second position, advantageously allowing sufficient time to lapse to ensure the drug is well mixed before expelling it through the outlet.

[0046] The opening mechanism may include a needle. In use, the needle, e.g., the distal end of the needle, may pierce the outlet seal to open the outlet. At least a portion of the outlet seal, and optionally the drug container, may move relative to the needle so that the needle pierces the outlet seal. At least a portion of the outlet seal, and optionally the drug container, may move proximally relative to the needle so that the distal end of the needle pierces the outlet seal. At least a portion of the outlet seal, and optionally the drug container, may move relative to the needle so that the needle pierces the outlet seal after the needle moves from a pre-needle insertion position or after the needle reaches a needle insertion position. This may allow the needle to pierce the outlet seal and open the outlet after the needle leaves the pre-needle insertion position or after the needle reaches the needle insertion position. In one example, after the needle reaches the needle insertion position, the drug container and outlet seal move proximally relative to the needle so that the distal end of the needle pierces the outlet seal and open the outlet.

[0047] During use, the outlet seal may flex. For example, the outlet seal may flex outward or away from the medication container. The outlet seal may flex under increased pressure within the medication container, for example, when the piston moves relative to the medication container. This flexing may cause the outlet seal, or at least a portion of the outlet seal, to move relative to the needle, allowing the needle to penetrate the outlet seal.

[0048] The outlet may be initially sealed by a valve. In use, the valve may be opened to unseal the outlet. The valve may be opened as a result, for example indirectly, of moving the actuation means from the first position to the second position.

[0049] The drug container assembly may apply or begin to apply force to the drug at least 5 ms or 10 ms before the needle reaches the needle insertion position, advantageously allowing more time for the force to mix the drug before delivering the drug through the outlet.

[0050] The medication container assembly may apply or begin to apply force to the medication before the needle moves a predetermined distance from the pre-needle insertion position, for example, before the needle moves a distance of 5 mm or 10 mm from the pre-needle insertion position, or before the needle moves 25% or 50% of the distance from the pre-needle insertion position to the needle insertion position. Advantageously, this allows more time for the force to mix the medication before delivering the medication through the outlet.

[0051] The first stored energy source can be released to relatively move the plunger rod toward the drug container assembly. The first stored energy source can be released after movement of the needle from the pre-needle insertion position. The first stored energy source can be released before the needle reaches the needle insertion position. Advantageously, this can ensure that the force applied to the drug by the drug container assembly is applied at an appropriate stage in the operation of the device, for example, after the needle leaves the pre-needle insertion position and before the needle reaches the needle insertion position.

[0052] The drug delivery device may include a housing. The actuation means may include a skin sensor element movable relative to the housing. Movement of the actuation means from a first position to a second position may include distal movement of the skin sensor element relative to the housing. The housing may be configured to be held by a user.

[0053] When the needle is in the pre-needle insertion position, the skin sensor element may be biased to a proximal position relative to the housing, for example, by a skin sensor element biasing spring.

[0054] The actuation means may be configured to press the skin sensor element against the injection site, causing the skin sensor element to move distally relative to the housing. An actuation means comprising a skin sensor element may advantageously simplify operation of the device. A user may be able to operate the device by pressing the skin sensor against the injection site, thereby moving the actuation means from a first position to a second position.

[0055] The drug may comprise a non-Newtonian fluid. The drug may comprise a non-Newtonian gel. The drug may exhibit shear-thinning properties. For example, the drug may exhibit time-dependent shear-thinning properties. The drug may comprise a thixotropic fluid. The drug may comprise a thixotropic gel.

[0056] The drug may comprise a solute dispersed in a solvent, for example a salt dispersed in water.

[0057] At the lowest energy state of the drug in the drug container, the drug may not be homogeneous. For example, at the lowest energy state of the drug during storage, the drug may not be homogeneous. As used herein, the term "during storage" refers to the state in which the drug is intended to be transported and stored prior to use. Thus, the term "during storage" may refer to one or both of room temperature and atmospheric pressure. Alternatively, if the drug is refrigerated prior to use, the term "during storage" may refer to temperatures below room temperature.

[0058] If left standing for a sufficient time, for example, 24 hours or more, the drug may naturally return to a non-homogeneous state. If left standing for a sufficient time, for example, 24 hours or more, the drug may stratify, i.e., separate into layers. The concentrations of the drug's components may differ between these layers. For example, if the drug comprises a suspension, if left standing for a sufficient time, the lower part of the suspension may have a higher concentration of solid particles than the upper part of the drug. This may occur naturally due to the action of gravity. In this context, the terms "lower part" and "upper part" may be defined relative to the direction in which gravity acts, rather than to a fixed, designated part of the drug container. Thus, if gravity acts in a direction from the top to the bottom of the drug container, gravity may act to increase the concentration of the suspension in the lower part of the drug container compared to the upper part.

[0059] Advantageously, the device may be particularly suitable for drugs having one or more of the characteristics described above, as such drugs may benefit most from being mixed prior to delivery.

[0060] When a force is applied to the drug by the drug container assembly, the dynamic viscosity of the drug may decrease. All references to dynamic viscosity herein refer to the dynamic viscosity measured using the Hagen-Poiseuille equation, although any suitable process may be used. For example, after the drug container assembly applies a force to the drug, the dynamic viscosity of the drug may decrease to less than 10 cP (centipoise, mPa·s), more preferably less than 8 or 4 cP (mPa·s), at room temperature. The dynamic viscosity of the drug may decrease from greater than 15, 20, or 50 cP (mPa·s) to less than 10, 8, or 4 cP (mPa·s) at room temperature after a force is applied to the drug. A decrease in dynamic viscosity may advantageously reduce the force required to deliver the drug through a needle. A decrease in dynamic viscosity may allow the drug to pass through a smaller gauge needle, which may be less noticeable to a patient during needle insertion. A decrease in dynamic viscosity may also allow a given amount of drug to be delivered in less time.

[0061] The drug delivery device may be an auto-injector, which may automate needle insertion and drug delivery. Advantageously, the device being an auto-injector simplifies use of the device and allows the patient to use the device themselves.

[0062] According to a second aspect of the present disclosure, there is provided a method of mixing drugs. The drugs may be mixed in a drug delivery device. The device may include a drug ejection mechanism. The drug ejection mechanism may include a stored energy source. The device may include a drug container containing the drugs. The method may include applying a force to the drugs using the stored energy source to mix the drugs in the drug container and / or increase the homogeneity of the drug in the drug container and / or reduce the kinematic viscosity of the drug in the drug container.

[0063] Advantageously, mixing the drug, increasing the homogeneity of the drug, or decreasing the dynamic viscosity of the drug may reduce the likelihood of the effects mentioned above, such as clogging of the needle or outlet of the drug delivery device, and inconsistent pharmacokinetic profiles.

[0064] Features described in relation to the drug delivery devices above, such as the drug delivery device of the first aspect, are also applicable to the method or drug delivery device of the second aspect.

[0065] The drug delivery device may be a drug delivery device according to the first aspect, in which case the stored energy source of the second aspect may be or comprise the first stored energy source of the first aspect.

[0066] Applying a force to the drug may include a plunger rod or a collision part impacting a collision surface. As described above with reference to the first aspect, the drug delivery device may include a plunger rod or a collision part and a collision surface. Configuring the plunger rod to impact the collision surface advantageously reduces the number of components and the size of the drug delivery device.

[0067] The plunger rod or the impacting part can be spaced apart from the impact surface before applying a force to the drug. For example, the plunger rod can be held at a distance of at least 1, 2, 3, 5, 7, or 10 mm from the impact surface before applying a force to the drug. Advantageously, by separating the plunger rod or the impacting part from the impact surface, the acceleration of the plunger rod or the impacting part relative to the impact surface can be increased, thereby increasing the momentum difference at the time of impact. This can increase the impact energy and therefore the degree of mixing of the drug.

[0068] The drug delivery device may include an actuation means. A method of mixing a drug may include moving the actuation means from a first position to a second position to release a stored energy source and apply a force to the drug.

[0069] The medication container may have an outlet through which the medication is expelled during use. Initially, the outlet may be sealed. The method may include unsealing the outlet. The outlet may be unsealed after applying a force to the medication. By configuring the outlet to be sealed before and during application of the force, it may be possible to apply a force to the medication without the medication being expelled from the medication container.

[0070] The outlet may be opened automatically after moving the actuation means from the first position to the second position. Advantageously, this may mean that no further action is required from the user after moving the actuation means from the first position to the second position in order to open the outlet.

[0071] The drug delivery device may include a needle. The method of mixing drugs may include moving the needle from a first needle position to a second needle position. The first needle position may be configured such that the needle resides within the drug delivery device. The second needle position may be arranged such that the needle protrudes from the drug delivery device. The first needle position may correspond to or be a pre-needle insertion position of the device of the first embodiment. The second needle position may correspond to or be a needle insertion position of the device of the first embodiment. Advantageously, moving the needle from the first position to the second position allows for a more user-friendly needle insertion mechanism and improves patient compliance over manual needle insertion mechanisms.

[0072] Movement of the needle from the first position to the second position may be effected by movement of the actuation means from the first position to the second position. Advantageously, this may mean that no further action is required by the user after moving the actuation means from the first position to the second position in order to move the needle from the first needle position to the second needle position.

[0073] A source of stored energy for needle insertion, such as the source of stored energy for needle insertion described in relation to the first embodiment, may move the needle from the first position to the second position.

[0074] As described in relation to the device of the first aspect, the device may include a housing, and the actuation means may include a skin sensor element movable relative to the housing. Movement of the actuation means from the first position to the second position may include distal movement of the skin sensor element relative to the housing. The method may include pressing the skin sensor element against the injection site, which may result in distal movement of the skin sensor element relative to the housing. Prior to movement of the needle from the first needle position, or pre-needle insertion position, the skin sensor element may be biased to a proximal position relative to the housing.

[0075] The method of mixing the drugs may include applying a force to the drugs before the needle reaches the second needle location, which may advantageously allow more time for mixing of the drugs following application of the force to the drugs.

[0076] The force may be applied after the needle has moved from the first needle position, which may advantageously ensure that the drug mixing occurs in a timely manner relative to drug delivery, thereby preventing the mixing effect on the drug from being lost or reversed prior to delivery.

[0077] As used herein, the term "injection site" may refer to the site on a patient through which a drug is delivered.

[0078] As used herein, the term "room temperature" refers to a temperature around 20 degrees Celsius.

[0079] As used herein, front and proximal are used to refer to the same end of the device. The front end may be located at the injection site during use. Similarly, rear and distal are used to refer to the same end of the device. The rear end of the device may be opposite the front end of the device. The rear end may be furthest from the injection site during use.

[0080] The present invention is defined by the claims. However, the following is a non-exhaustive list of numbered items. Any one or more of the features of these items may be combined with any one or more features of any example, embodiment, or aspect described herein, such as any one or more features of the first and second aspects described above. [Section 1] a drug delivery device comprising: a drug container assembly including a housing portion; a drug container containing a drug; a needle through which the drug is expelled in use, the needle being movable relative to the housing portion from a pre-needle-insertion position to a needle-insertion position; a plunger rod spaced from the drug container assembly prior to movement of the needle from the pre-needle-insertion position; a first stored energy source; a stored energy source for needle insertion; and an actuation means, wherein the drug container has an outlet through which the drug is expelled in use, the outlet being sealed prior to movement of the needle from the pre-needle-insertion position; [Section 2] Item 1. The drug delivery device of item 1, wherein the drug container assembly applies the force to the drug after the needle has moved from the pre-needle insertion position. [Section 3] The drug delivery device of claim 1 or 2, wherein movement of the actuating means from the first position to the second position causes the first stored energy source to move the plunger rod toward the drug container assembly, causing the plunger rod or collision part to collide with a collision surface of the drug container assembly, thereby causing the drug container assembly to apply the force to the drug. [Section 4] Item 4. The drug delivery device of item 3, wherein the plunger rod or the collision component is at least 1, 2, 3, 5, 7, or 10 mm away from the collision surface prior to movement of the needle from the pre-needle insertion position. [Section 5] Item 5. The drug delivery device of item 3 or 4, wherein following movement of the actuation means from the first position to the second position, the plunger rod or the impacting part impacts the impact surface with a momentum difference between the plunger rod or the impacting part and the impact surface of at least 0.005, 0.001, or 0.02 kg m / s. [Section 6] 6. The drug delivery device according to any one of claims 3 to 5, wherein following movement of the actuation means from the first position to the second position, the plunger rod or the collision part collides with the collision surface at a speed of at least 5, 10 or 13 m / s relative to the collision surface. [Section 7] 7. A drug delivery device according to any one of claims 1 to 6, wherein the drug container assembly includes a piston, and in use, the piston moves relative to the drug container to expel the drug through the needle. [Section 8] A drug delivery device described in any one of items 3 to 6, wherein the drug container assembly includes a piston, the collision surface is a surface of the piston, and in use, the piston moves relative to the drug container to eject the drug through the needle. [Section 9] Item 9. The drug delivery device of item 7 or 8, wherein the first stored energy source is configured to move the piston relative to the drug container to eject the drug through the needle after the needle moves from the pre-needle insertion position to the needle insertion position. [Section 10] Item 10. The drug delivery device according to any one of items 1 to 9, wherein the drug container has, in addition to the outlet, an opening that is sealed with an opening seal before the needle is moved from the pre-needle insertion position. [Section 11] Item 10. The drug delivery device according to any one of items 7 to 9, wherein the drug container has, in addition to the outlet, an opening that is sealed by an opening seal before the needle is moved from the pre-needle insertion position, and before the needle is moved from the pre-needle insertion position, the piston is positioned within the drug container and between the drug and the opening seal. [Section 12] Item 12. The drug delivery device of item 11, wherein movement of the actuating means from the first position to the second position causes the first stored energy source to move the plunger rod toward the piston so as to penetrate the opening seal. [Section 13] Item 13. The drug delivery device according to any one of items 1 to 12, wherein the drug container comprises a polymer. [Section 14] Item 14. The drug delivery device of item 13, wherein the drug container comprises one or more of a polypropylene polymer and a cyclic olefin polymer. [Section 15] Item 15. The drug delivery device according to any one of items 1 to 14, wherein the drug container contains gas bubbles in addition to the drug. [Section 16] Prior to movement of the actuation means from the first position to the second position, the gas bubble has a volume of at least 120 mm at room temperature. 3 Item 16. The drug delivery device according to item 15, having a volume of [Section 17] Item 17. The drug delivery device according to any one of items 1 to 16, wherein the device is provided with an opening mechanism for opening the outlet. [Section 18] Item 18. The drug delivery device of item 17, wherein the opening mechanism is configured to open the outlet after the needle has moved from the pre-needle insertion position. [Section 19] Item 19. The drug delivery device of item 17 or 18, wherein the opening mechanism is configured to open the outlet after the drug container assembly applies the force to the drug. [Section 20] 20. A drug delivery device according to any one of claims 17 to 19, wherein the opening mechanism is configured to open the outlet after the needle has advanced at least 50%, 75% or 90% of the distance from the pre-needle insertion position to the needle insertion position, for example, the opening mechanism is configured to open the outlet after the needle has reached the needle insertion position. [Section 21] 21. A drug delivery device according to any one of paragraphs 17 to 20, wherein the opening mechanism is configured to open the outlet at least 5, 10 or 12 ms after the drug container assembly applies the force to the drug. [Section 22] 22. A drug delivery device according to any one of claims 17 to 21, wherein the opening mechanism is configured to open the outlet at least 10 ms or 20 ms after the actuation means moves from the first position to the second position. [Section 23] 23. The drug delivery device according to any one of claims 1 to 22, wherein the drug container assembly applies the force to the drug at least 5, 10, or 12 ms before the needle reaches the needle insertion position. [Section 24] 24. A drug delivery device according to any one of claims 1 to 23, wherein the drug container assembly applies the force to the drug before the needle advances 25% or 50% of the distance from the pre-needle insertion position to the needle insertion position. [Section 25] 25. The drug delivery device of any one of claims 1 to 24, wherein the first stored energy source is released to move the plunger rod toward and relative to the drug container assembly after movement of the needle from the pre-needle insertion position and before the needle reaches the needle insertion position. [Section 26] 26. A drug delivery device according to any one of claims 1 to 25, wherein the device comprises a housing, the actuation means comprises a skin sensor element that is movable relative to the housing, and movement of the actuation means from the first position to the second position comprises distal movement of the skin sensor element relative to the housing. [Section 27] prior to movement of the needle from the pre-needle insertion position, the skin sensor element is biased to a proximal position relative to the housing. [Section 28] 28. The drug delivery device of claim 26 or 27, wherein the actuation means is configured to press the skin sensor element against the injection site, thereby moving the skin sensor element distally relative to the housing. [Section 29] Item 29. The drug delivery device according to any one of items 1 to 28, wherein the drug comprises a non-Newtonian fluid or a gel. [Section 30] Item 30. The drug delivery device of any one of items 1 to 29, wherein the drug comprises a shear-thinning fluid or gel. [Section 31] Item 31. The drug delivery device of any one of items 1 to 30, wherein the drug comprises a thixotropic fluid or gel. [Section 32] Item 32. The drug delivery device according to any one of items 1 to 31, wherein the drug comprises a solute dispersed in a solvent. [Section 33] Item 33. The drug delivery device according to any one of items 1 to 32, wherein the drug is not homogeneous in its lowest energy state. [Section 34] Item 34. The drug delivery device according to any one of items 1 to 33, wherein the force applied to the drug reduces the dynamic viscosity of the drug. [Section 35] Item 35. The drug delivery device of item 34, wherein the force applied to the drug reduces the dynamic viscosity of the drug to less than 10 cP (mPa·s) at room temperature, more preferably less than 8 or 4 cP (mPa·s) at room temperature. [Section 36] Item 36. The drug delivery device of Item 35, wherein the force applied to the drug reduces the dynamic viscosity of the drug from more than 10 cP (mPa·s) to less than 8 or 4 cP (mPa·s) at room temperature. [Section 37] Item 37. The drug delivery device according to any one of items 1 to 36, wherein the device is an autoinjector. [Section 38] A method of mixing a drug in a drug delivery device, the device comprising a drug ejection mechanism including a stored energy source and a drug container containing a drug, the method comprising using the stored energy source to apply a force to the drug to mix the drug, increase the homogeneity of the drug in the drug container, and / or reduce the kinematic viscosity of the drug in the drug container. [Section 39] Item 39. The method of claim 38, wherein applying the force to the drug comprises impacting a plunger rod or an impacting component against an impact surface. [Section 40] 40. The method of claim 39, wherein the plunger rod or the impact component is spaced at least 1, 2, 3, 5, 7, or 10 mm from the impact surface before applying the force to the drug. [Section 41] 41. The method of any one of claims 38 to 40, wherein the device comprises an actuation means, and the method comprises moving the actuation means from a first position to a second position to release the stored energy source and apply the force to the drug. [Section 42] Item 42. The method of claim 41, wherein the drug container has an outlet through which the drug is expelled in use and which is initially sealed, and the method includes opening the outlet. [Section 43] Item 43. The method according to Item 42, wherein opening the outlet is performed after applying the force to the drug. [Section 44] 44. The method of claim 42 or 43, wherein the outlet is automatically opened after moving the actuation means from the first position to the second position. [Section 45] 45. The method of any one of paragraphs 38 to 44, wherein the device includes a needle, and the method includes moving the needle from a first needle position to a second needle position. [Section 46] 45. The method of any one of clauses 41 to 44, wherein the device comprises a needle, and the method includes moving the needle from a first needle position to a second needle position, and movement of the actuation means from the first position to the second position causes movement of the needle from the first needle position to the second needle position. [Section 47] 47. The method of claim 45 or 46, wherein the application of the force to the drug occurs before the needle reaches the second needle position. [Section 48] Item 48. The method according to any one of items 45 to 47, wherein the force is applied to the drug after the needle has moved from the first needle position. [Section 49] The method according to any one of Items 38 to 48, wherein the method is a method of mixing drugs in the drug delivery device according to any one of Items 1 to 37. [Brief explanation of the drawings]

[0081] [Figure 1] FIG. 1 is a cross-sectional view of a drug delivery device with a cap covering the proximal end of the device. [Figure 2] 2 is a cross-sectional view of the drug delivery device of FIG. 1 in a pre-actuated position with the cap and needle shield removed. [Figure 3] 3 is a cross-sectional view of the drug delivery device of FIG. 1 with the actuation means in a distal position relative to the housing and front chassis. [Figure 4a] 4a is an alternative cross-sectional view of the distal end of the drug delivery device of FIG. 1 in a pre-actuated position. [Figure 4b]FIG. 4b is an alternative cross-sectional view of the distal end of the drug delivery device of FIG. 1 in operation, showing the drug container holder displaced proximally relative to the release pin. [Figure 4c] 4c is an alternative cross-sectional view of the distal end of the drug delivery device of FIG. 1 in operation, showing the plunger rod decoupled from the release pin. [Figure 4d] FIG. 4d is an alternative cross-sectional view of the distal end of the drug delivery device in operation, showing the plunger rod displaced proximally relative to the drug container holder. [Figure 5] Figure 5 is a cross-sectional view of the drug delivery device of Figure 1 in operation, showing the needle moving proximally from the pre-needle insertion position and the plunger rod disengaging from the release pin but remaining distanced from the opening / sealing foil of the drug container. [Figure 6] FIG. 6 is a cross-sectional view of the drug delivery device of FIG. 1 showing the plunger rod in contact with the impact surface. [Figure 7] FIG. 7 is a cross-sectional view of the drug delivery device of FIG. 1, showing the needle reaching the needle insertion position. [Figure 8] 8 is a cross-sectional view of the drug delivery device of FIG. 1 after opening the outlet of the drug container. [Figure 9] FIG. 9 is a cross-sectional view of the drug delivery device of FIG. 1 upon completion of drug delivery through the needle. DETAILED DESCRIPTION OF THE INVENTION

[0082] Detailed Description Figure 1 is a cross-sectional view of a drug delivery device in an initial, pre-actuation position prior to use. The device shown in Figure 1 is a drug delivery device comprising a drug container assembly including a drug container 17 containing a drug 18 and an air bubble 30. The drug delivery device is an auto-injector and comprises a housing 28 that houses the drug container assembly. The drug delivery device comprises a needle 4 through which the drug 18 is expelled in use, the needle 4 being movable relative to the device housing 28 from a pre-needle insertion position (shown in Figure 1) to a needle insertion position (shown in Figure 7), a plunger rod 8 that is spaced apart from the drug container assembly prior to movement of the needle 4 from the pre-needle insertion position, a first stored energy source 5 that is a helical spring, a needle insertion stored energy source 10 that is another helical spring, and an actuation means including a skin-contacting element, referred to herein as skin sensor element 2.

[0083] The medication container 17 comprises an outlet through which the medication 18 is expelled in use, the outlet being sealed by a sealing element 22 prior to movement of the needle 4 from the pre-needle insertion position.

[0084] The device is configured such that movement of the actuation means from the first position to the second position releases the needle insertion stored energy source 10 to move the needle 4 from the pre-needle insertion position to the needle insertion position, and releases the first stored energy source 5 to move the plunger rod 8 towards and relative to the drug container assembly to apply a force to the drug container 17, which in turn applies a force to the drug 18 before the needle 4 reaches the needle insertion position.

[0085] The drug container 17 has a generally tubular shape and forms an internal space for containing the drug 18. An outlet is provided at the proximal end, and a distal opening is provided at the distal end.

[0086] In this embodiment, the drug is a non-Newtonian fluid. Specifically, the drug is a thixotropic fluid, which tends to increase in viscosity if left standing for a sufficient period of time. This can make the drug difficult to dispense and can result in the drug clogging the needle. The drug also tends to separate into layers if left standing for a sufficient period of time, with the drug's component concentrations differing between the layers. Applying force to the drug helps to reduce the viscosity and mix the drug to increase homogeneity before delivery to the patient.

[0087] The piston 21 is disposed between the drug 18 and the distal opening. In this embodiment, the drug container 17 is formed from a cyclic olefin polymer. The piston 21 has an impact surface on its distal surface. During use, the piston 21 forms a seal with the inner wall of the drug container 17, thereby preventing the drug 18 from passing from one side of the piston 21 to the other. The piston 21 is movable proximally relative to the drug container 17 to deliver the drug 18 through the outlet of the drug container 17 and through the needle 4.

[0088] An opening seal 19, such as a sealing foil, seals the distal opening of the medication container 17 in the pre-actuated position and is arranged to be penetrated by the plunger rod 8 in use.

[0089] A fluid sealing element in the form of a rubber stopper 22 is provided between the drug container 17 and a seal retainer 23. The seal retainer 23 is coupled to the drug container 17, and the rubber stopper 22 is coupled to a proximal opening of the drug container 17. In use, the rubber stopper 22 is configured to be penetrated by a needle 4. The needle 4 is secured to a needle holder 26 that is slidably coupled to the proximal end of the drug container 17. During use, the drug container assembly is moved proximally relative to the needle holder 26, causing the distal end of the needle 4 to penetrate the rubber stopper 22 and creating a fluid pathway for the drug 18 through the needle 4.

[0090] The medication container 17 is coupled to a medication container holder 16. The medication container holder 16 houses a plunger rod 8, which has a proximal face configured to penetrate a sealing foil 19 and abut against a piston 21. In the pre-actuated position, the plunger rod is located approximately 5 mm from the sealing foil 19. At its distal end, the plunger rod 8 has two opposing distal plunger rod arms 81. A first stored energy source 5 is mounted around the plunger rod 8 and configured such that its proximal end is located on the face of the plunger rod 8. The distal end of the first stored energy source 5 is positioned against a spring retainer 6. The spring retainer 6 is coupled to the medication container holder 16 and has a central opening large enough to allow the distal plunger rod arms 81 to advance therethrough.

[0091] As shown in FIG. 1, in the pre-actuated position, the distal plunger rod arm 81 is configured to reside through the central opening of the spring retainer 6, such that the first stored energy source 5 is in a first compressed state and the proximal face of the plunger rod 8 is spaced apart from the drug container 17 and the sealing foil 19.

[0092] A release pin 15 is located at the distal end of the device and is coupled to a rear chassis 29, which is fixed to the housing. The release pin 15 includes a proximally extending protrusion 152 that is configured to reside between two opposing distal plunger rod arms 81 in the first, stored position.

[0093] The needle insertion stored energy source 10 is disposed along the spring shaft 11. In this embodiment, the needle insertion stored energy source 10 is a spring, and therefore may be referred to as a needle insertion spring 10. The needle insertion spring 10 has a distal end abutting the proximal surface of the rear chassis 29 and a proximal end abutting a spring boss 12. The spring boss 12 is configured to be slidably disposed relative to the spring shaft 11. The spring boss 12 houses the needle insertion spring 10 and is coupled to a spring holder 13 slidably disposed relative to the spring shaft 11. The spring holder 13 is coupled to the drug container holder 16 such that proximal movement of the spring holder 13 under the biasing force of the needle insertion spring 10 is equal to proximal displacement of the drug container assembly. A locking member (not shown) of the spring holder 13 prohibits movement of the spring holder 13 relative to the rear chassis 29. The locking member of the spring holder 13 comprises a locking member latch (not shown) and is associated with an actuating means in the first position.

[0094] The actuation means comprises a skin sensor 2 provided at the proximal end of the drug delivery device. The skin sensor 2 is slidably disposed relative to a housing 28 and a front chassis 14, which is fixed to the housing 28. The skin sensor 2 is biased to a first proximal position (seen in FIG. 1 ) relative to the housing 28 by a skin sensor spring 9. When the skin sensor 2 is in the first proximal position, a locking member latch of a spring holder 13 is coupled to the front chassis 14.

[0095] The sequence of operation of the device shown in Figure 1 will now be described, with the same reference numerals being used to denote the same features in all figures.

[0096] In the pre-actuation position shown in Figure 1, cap 1 covers the proximal end of the drug delivery device. Cap 1 is slidably removable from the housing 28 of the device. Cap 1 includes a distally extending protrusion 101 that resides within the housing 28 in the pre-actuation position. Cap 1 also includes a removal arm 102 that is positioned around a proximal feature of the needle shield 3. The needle 4 is positioned to fit within the needle shield 3 when cap 1 is on the device, which thereby provides a sealed, sterile environment.

[0097] The skin sensor 2 includes a flexible member 201 that resides in a recess on the front chassis 14 when the skin sensor 2 is in the extended position. With the cap 1 covering the proximal end of the device, the extension protrusion 101 prevents the flexible member 201 of the skin sensor 2 from moving from its first position within the front chassis 14, thereby preventing premature movement of the skin sensor 2 and premature actuation of the device.

[0098] In a first step, the user removes the cap 1 together with the needle shield 3 from the housing 28 of the drug delivery device. The device with the cap removed is shown in Figure 2. Removing the cap 1 from the drug delivery device removes the distal protrusion 101 from within the housing 28, thus allowing the flexible member 201 of the skin sensor 2 to disengage from the front chassis 14. The proximal end of the needle 4 is exposed. The skin sensor 2 is biased to a first proximal position by the skin sensor spring 9.

[0099] A user operates the drug delivery device by placing the proximal end of the device at an injection site while holding the housing 28. When the user presses the housing 28 toward the injection site, the skin sensor 2 is slidably displaced distally within and relative to the housing 28, as shown in FIG. 3 . As the skin sensor 2 is displaced distally, the elastic arm 201 of the skin sensor 2 is urged to move out of the recess on the front chassis 14 and deflect to a second position. The skin sensor spring 9 is compressed between the skin sensor 2 and the front chassis 14.

[0100] As the skin sensor 2 is further displaced relative to the housing 28 to a retracted, distal position, the locking member latch of the spring holder 13 is released from its first, locked position into the opening in the skin sensor 2. The latch disengages from its locked position to a second, unlocked position that allows the spring holder 13 to be moved from its first position.

[0101] Figures 4a-4d are cross-sectional views of the distal end of the device showing how, in this embodiment, there is a time delay between the actuation of the needle insertion spring 10 to move the needle 4 from the pre-needle insertion position and the release of the plunger rod 8 to contact the drug container assembly.

[0102] FIG. 4a shows the distal end of the drug delivery device of FIG. 1 in a pre-actuation position. In the pre-actuation position of the device, the first stored energy source 5 is held between the plunger rod 8 and the spring retainer 6, as described above. The biasing force of the first stored energy source 5 urges proximal movement of the plunger rod 8 relative to the drug container holder 16. This biasing force urges the two distal plunger rod arms 81 to deflect inward, but is prevented from doing so by the protrusion 152 of the release pin 15 located between the two distal plunger rod arms 81. The drug container holder 16 and the associated spring retainer 6 are held in position relative to the rear chassis 29 by the locking member latch of the spring holder 13. Because the release pin 15 is coupled to the rear chassis 29, relative movement between the spring retainer 6 and the release pin 15 is prohibited in the pre-actuation position.

[0103] The cross section of FIG. 4b shows the device after the skin sensor 2 of the actuation means has moved from the first position to the second position. This movement of the skin sensor 2 releases the locking member latch of the spring holder 13 from its first locked position into the opening of the skin sensor 2, as previously described. This releases the latch from its locked position to its second unlocked position, allowing the spring holder 13 to move from the first position. The needle insertion spring 10 biases the spring holder 13 proximally relative to the housing 28. Because the spring holder 13 is coupled to the drug container holder 16, the needle insertion spring 10 also moves the drug container assembly proximally relative to the housing 29 and relative to the release pin protrusion 152. Thus, the drug container holder 16 slides within the rear chassis 29. The spring retainer 6 and plunger rod arm 81 also displace relative to the release pin protrusion 152. The first stored energy source 5 remains compressed.

[0104] 4c and 4d are further cross-sectional views illustrating the relative movement between the plunger rod 8 and release pin protrusion 152 and the medication container holder 16. When the medication container holder 16 moves proximally a sufficient distance, the distal plunger rod arm 81 disengages from the release pin protrusion 152, allowing it to deflect inward under the biasing force of the first stored energy source 5. This inward deflection is shown in FIG. 4c. A chamfered edge 82 on the distal plunger rod arm 81 is configured to aid inward deflection of the distal plunger rod arm 81 and aid in the proximal movement of the plunger rod 8 through the inner bore of the spring retainer 6. An opposing chamfered ledge 62 is found on the spring retainer 6 to further encourage inward deflection of the distal plunger rod arm 81. This inward deflection allows the distal plunger rod arm 81 to move through the internal bore of the spring retainer 6 relative to the drug container holder 16 under the action of the first stored energy source 5, as shown in Figure 4d.

[0105] Figure 5 is a cross-sectional view of the drug delivery device of Figure 1, in which the spring boss 12 has been displaced proximally under the biasing force of the needle insertion spring 10 along the spring shaft 11. The proximal displacement of the drug container holder 16 removes the release pin protrusion 152 of the release pin 15 from the vicinity of the distal plunger rod arm 81, as described above in connection with Figures 4c and 4d.

[0106] The distal plunger rod arm 81 and release pin protrusion 152 may be designed so that the first stored energy source 5 is released at a desired time, for example, a predetermined time after the actuation means is moved to the second position or after the plunger rod 8 has moved a predetermined distance relative to the release pin protrusion 152. For example, the proximal length of the release pin protrusion 152 may be shortened to release the plunger rod 8 sooner.

[0107] In the embodiment shown in FIG. 5, the first stored energy source 5 is released so that a force is applied to the drug 18 approximately 12 ms (milliseconds) before the needle 4 reaches the needle insertion position and when the needle 4 has traveled approximately 10% of the distance between the pre-needle insertion position and the needle insertion position.

[0108] FIG. 6 is a cross-sectional view of the device of FIG. 1 , showing the first stored energy source 5 expanding to move the plunger rod 8 proximally relative to the drug container assembly. The plunger rod 8 is displaced to penetrate and open the opening seal 19 of the distal opening of the drug container 17. After penetrating the opening seal 19, the plunger rod 8 abuts against the impact surface of the piston 21, which is located between the drug 18 and the distal opening of the drug container 17. At the time of impact, the difference in momentum between the plunger rod 8 and the piston 21 is approximately 0.02 kg·m / s. This momentum difference can be attributed to the impacting components colliding at a relative velocity of approximately 13 m / s. The abutment or collision between the proximal face of the plunger rod 8 and the impact surface of the piston 21 results in a force being applied to the drug 18. This force can mix the drug 18. Without being bound by theory, it is believed that air within the drug container 17 aids in mixing under certain circumstances. In the pre-actuated position, the medication container 17 has a length of approximately 120 mm (at about atmospheric pressure and a temperature of about 20° C.). 3 17. Mixing can be aided by rapid compression of the air located at the distal end of the drug container 17. After rapid compression, this air can "explode" into multiple bubbles that can travel within the drug container 18 and aid in mixing of the drug 18. The rubber stopper 22 remains attached to the drug container 17 and continues to seal the proximal outlet at this stage.

[0109] FIG. 7 shows the device after the needle insertion spring 10 has further expanded, displacing the spring boss 12 further along the spring shaft 11 and placing the needle 4 in the needle insertion position. In this position, the proximal face of the needle holder 26 abuts the surface of the front chassis 14. When the needle holder 26 abuts the front chassis 14, the needle 4 is in the needle insertion position, and the abutment of the needle holder 26 against the front chassis 14 prevents the needle 4 from moving proximally beyond the needle insertion position. However, the spring boss 12 is configured such that when the needle 4 is in the needle insertion position, further movement of the spring boss 12 along the spring shaft 11 is permitted under the action of further expansion of the needle insertion spring 10. As the spring boss 12 advances this distance, the drug container assembly moves proximally relative to the needle 4 and needle holder 26, as shown in FIG. 8.

[0110] As shown in FIG. 8 , the needle holder 26 advances within the internal cavity of the seal retainer 23 until the distal face of the needle holder 26 abuts the inner surface of the seal retainer 23. During this movement, the distal end of the needle 4 penetrates the rubber stopper 22. Thus, after the needle 4 reaches the needle insertion position, the proximal outlet of the drug container 17 is opened to allow the drug 18 to be delivered therethrough. In this embodiment, the proximal outlet of the drug container 17 is opened approximately 20 ms after the actuation means moves from the first position to the second position and approximately 12 ms after a force is applied to the drug. Once this outlet is opened, the piston 21 is permitted to advance relative to the drug container 17 under the biasing force of the first stored energy source 5 to deliver the drug 18 through the needle 4. In this embodiment, the outlet is opened after the needle 4 reaches the needle insertion position.

[0111] 9 shows the device after the piston 21 has moved proximally through the drug reservoir 17 to deliver the drug through the needle 4. The needle 4 can then be removed from the injection site by pulling the device away from the injection site. Alternatively, a needle retraction mechanism can be incorporated into the device to retract the needle into the device following completion of drug delivery.

[0112] Thus, through the description of the sequence of operations of the drug delivery device, it is apparent that a method of mixing a drug within a drug delivery device is provided. The device includes a drug ejection mechanism comprising a first stored energy source 5 and a piston 21. The method of mixing the drug includes applying a force to the drug using the first stored energy source 5, which mixes the drug 18 within the drug reservoir 17 to increase homogeneity and reduce the kinematic viscosity of the drug 18.

Claims

1. 1. A drug delivery device comprising: The housing part, a medication container assembly including a medication container containing a medication; a needle through which the medicament is dispensed in use, the needle being movable relative to the housing portion from a pre-needle insertion position to a needle insertion position; a plunger rod spaced from the medication container assembly prior to movement of the needle from the pre-needle insertion position; a first stored energy source; a stored energy source for needle insertion; and actuation means, the medication container having an outlet through which the medication is expelled in use, the outlet being sealed prior to movement of the needle from the pre-needle insertion position; the device is configured such that movement of the actuation means from a first position to a second position releases the needle insertion stored energy source to move the needle from the pre-needle insertion position to the needle insertion position, and releases the first stored energy source to move the plunger rod toward and relative to the drug container assembly, whereby the drug container assembly applies a force to the drug before the needle reaches the needle insertion position. Drug delivery devices.

2. The drug delivery device of claim 1 , wherein the drug container assembly applies a force to the drug after the needle has moved from the pre-needle insertion position.

3. 3. The drug delivery device of claim 1, wherein movement of the actuating means from the first position to the second position causes the first stored energy source to move the plunger rod toward the drug container assembly, causing the plunger rod or a collision part to collide with a collision surface of the drug container assembly, thereby causing the drug container assembly to apply the force to the drug.

4. 4. The drug delivery device of claim 3, wherein the plunger rod or the impacting piece is spaced at least 1 mm from the impact surface prior to movement of the needle from the pre-needle insertion position.

5. 5. A drug delivery device as described in claim 3 or 4, wherein following movement of the actuation means from the first position to the second position, the plunger rod or the collision part collides with the collision surface with a momentum difference between the plunger rod or the collision part and the collision surface of at least 0.01 kg-m / s, preferably at least 0.02 kg-m / s.

6. A drug delivery device according to any one of claims 1 to 5, wherein the drug container assembly comprises a piston, which, in use, moves relative to the drug container to expel the drug through the needle.

7. A drug delivery device according to any one of claims 3 to 5, wherein the drug container assembly comprises a piston, the collision surface being a surface of the piston, and in use the piston moves relative to the drug container to expel the drug through the needle.

8. 8. The drug delivery device of claim 6 or 7, wherein the first stored energy source is configured to move the piston relative to the drug container to expel the drug through the needle after movement of the needle from the pre-needle insertion position to the needle insertion position.

9. The drug delivery device of any one of claims 1 to 8, wherein the drug container has, in addition to the outlet, an opening that is sealed by an opening seal before movement of the needle from the pre-needle insertion position.

10. A drug delivery device according to any one of claims 6 to 8, wherein the drug container has, in addition to the outlet, an opening sealed by an opening seal before movement of the needle from the pre-needle insertion position, and before movement of the needle from the pre-needle insertion position, the piston is positioned within the drug container and between the drug and the opening seal.

11. 11. The drug delivery device of claim 10, wherein movement of the actuation means from the first position to the second position causes the first stored energy source to move the plunger rod toward the piston so as to penetrate the opening seal.

12. A drug delivery device according to any one of claims 1 to 11, wherein the drug reservoir contains gas bubbles in addition to the drug.

13. 13. The drug delivery device of claim 12, wherein prior to movement of the actuation means from the first position to the second position, the gas bubble occupies at least 5% of the volume enclosed by the piston and the drug container at room temperature and atmospheric pressure.

14. The drug delivery device according to any one of claims 1 to 13, wherein the device comprises an opening mechanism for opening the outlet.

15. 15. The drug delivery device of claim 14, wherein the opening mechanism is configured to open the outlet after the force is applied to the drug.

16. 16. The drug delivery device of claim 14 or 15, wherein the opening mechanism is configured to open the outlet after the needle has advanced at least 50% of the distance from the pre-needle insertion position to the needle insertion position, for example, the opening mechanism is configured to open the outlet after the needle has reached the needle insertion position.

17. The drug delivery device of any one of claims 14 to 16, wherein the opening mechanism is configured to open the outlet at least 5 ms after the force is applied to the drug.

18. 18. The drug delivery device of claim 1, wherein the drug container assembly applies the force to the drug at least 5 ms before the needle reaches the needle insertion position.

19. 19. The drug delivery device of claim 1, wherein the first stored energy source is released to move the plunger rod toward and relative to the drug container assembly after movement of the needle from the pre-needle insertion position and before the needle reaches the needle insertion position.

20. 20. A drug delivery device according to any one of claims 1 to 19, wherein the device comprises a housing, the actuation means comprises a skin contact element movable relative to the housing, and movement of the actuation means from the first position to the second position comprises distal movement of the skin contact element relative to the housing.

21. 21. The drug delivery device of any one of claims 1 to 20, wherein the drug comprises one or more of a non-Newtonian fluid, a non-Newtonian gel, a solute dispersed in a solvent, and / or the drug is not homogeneous in its lowest energy state.

22. A drug delivery device according to any preceding claim, wherein in use the force applied to the drug reduces the dynamic viscosity of the drug.

23. A drug delivery device according to any one of claims 1 to 22, wherein the device is an autoinjector.

24. 1. A method of mixing drugs in a drug delivery device, comprising: The device comprises: a drug delivery mechanism including a stored energy source; and a drug container containing a drug; The method comprises: applying a force to the drug using the stored energy source to mix the drug, increase homogeneity of the drug within the drug container, and / or reduce the kinematic viscosity of the drug within the drug container.

25. 25. The method of claim 24, wherein applying the force to the medication comprises impacting a plunger rod or impacting piece against an impact surface.

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