WO2017158398A1 - Automatic compounding system - Google Patents

Abstract

The present invention relates to an automatic compounding system (100) for pharmaceutical preparations of drugs, comprising: a first robotic arm (101) configured for handling and holding at least one drug container (300) containing liquid drug, wherein the drug container (300) comprises a pierceable element (500); a second robotic arm (102) configured for holding and operating at least one syringe (103), the syringe (103) comprising a needle (503), a plunger and a respective barrel for suctioning a fluid, wherein the second robotic arm (102) further comprises at least one actuator (303; 303b) for driving the plunger of the syringe (103). The first robotic arm (101) is configured for cooperating with the second robotic arm (102) so as to insert the needle (503) in the drug container (300) through the pierceable element (500), and the second robotic arm (102) is configured for operating the plunger so as to suction the liquid drug from the drug container (300).

Description

AUTOMATIC COMPOUNDING SYSTEM

DESCRIPTION

Technical Field

The present invention relates to an automatic compounding system, for compounding drugs to form pharmacy products and medicines.

In general, the present invention relates to automatic/robotic handling of compounding devices and containers, especially in aseptic conditions, for pharmacy applications.

Background art

In order to compound drugs in pharmacy applications, aseptic and sterile conditions are paramount. While drugs are typically in liquid form and held in bottles or vials, the final products which are made by suitably compounding the drugs are typically held in containers such as syringes, bags, bottles and the like. During compounding, a series of auxiliary accessories are used, such as needles and caps.

Therefore, in order to avoid contamination and improve quality of the final compound products, it is desirable to substitute human operation with automatic compounding and preparation of drugs.

In order to provide automated compounding of drugs, several systems have been proposed according to the prior art.

For example, document US2015250678A1 relates to an "Automated Pharmacy Admixture System" which includes a manipulator system to transport medical containers in a compounding chamber, whose pressure is regulated below atmospheric pressure. Such manipulator system is configured to grasp and convey syringes, IV bags, and vials, to bring a fill port into register with a filling port at a fluid transfer station in the chamber.

Document WO2015067855A1 relates to a method for using a medical syringe by at least one industrial robot, either for drawing liquid into the medical syringe or for injecting the liquid out of the medical syringe. The apparatus is used for dissolving a pharmaceutical substance in a liquid. Document US2009223592A1 relates to a system for filling containers with a product, wherein a filling arm is disposed within a chamber and an optical sensor is configured to sense openings of containers within the chamber; the location of the sensed openings are used to guide the filling arm to fill the containers with a product.

Although these automated compounding systems provide a substitute for human operation in drug preparation, the known solutions still lack effectiveness and present some disadvantages.

For example, in known systems during automated handling of containers by means of robotic arms, drug spilling and leakages may be increased due to imprecise or poorly controlled handling and movements. During common manual operation by a human user, the syringe and the vial are inverted in position, so as to extract the needle "from above". In automated process, such solution is not commonly pursued because it would complicate handling (which must allow the rotation of the complex vial-syringe system in a rigid way) and it would lead to an increase in the cycle time of compounding. In certain cases for highly toxic drugs, even leakage of gaseous components of drugs may represent a danger, so that not even extracting the needle "from above" would be sufficient to eliminate potentially harmful leakages.

Moreover, for example, in known systems during automated suctioning of drugs from the bottles/vials, it might happen that a certain amount of drug remains in the container. In fact, the manufacturers of bottles containing liquid medications have to declare a nominal volume of the contents, and in order to ensure that the volume of the actual drug content is at least equal to the nominal volume, the producer will often insert an amount of drug in excess, which can oscillate between +5% and +10% of the total. If the withdrawal of the drug from the container is only based on the nominal amount of drug, some content will be lost, with safety risks or economic loss.

Moreover, for example, during insertion in the rubber cap of vials, the needle could penetrate too much and therefore, in the final stage of suction, it could draw air instead of liquid, with the consequent creation of bubbles and mistakes in the volume of drug withdrawn. In general, the state of the art lacks a solution for an automatic compounding system of improved performances, especially for the crucial task of withdrawing the drugs from their vials, by means of a syringe.

More in general, the state of the art lacks a solution for an automatic compounding system which is more effective in handling syringes for drug withdrawal.

Summary of the invention

It is an object of the present invention to provide an automatic compounding system which is alternative to known solutions.

In particular, it is an object of the present invention to provide an automatic compounding system which is more effective in suctioning of drugs by means of a syringe, so as to optimize drug withdrawal from containers.

It is also an object of the present invention to provide an automatic compounding system which exploits a plurality of robotic arms in synergic manner.

It is also an object of the present invention to provide an automatic compounding system which decreases the incidence of spilling of drugs during withdrawal.

It is also an object of the present invention to provide an automatic compounding system which reduces leakages from drug containers during withdrawal.

It is also an object of the present invention to provide an automatic compounding system which minimizes non-withdrawn drug content, which would otherwise remain unused in the drug containers.

These and further objects of the present invention are achieved by an automatic compounding system which comprises the features of the appended claims which are an integral part of the present description.

An idea at the basis of the present invention is to provide an automatic compounding system for pharmaceutical preparations of drugs, which comprises: a first robotic arm configured for handling and holding at least one drug container containing liquid drug, which has a pierceable element such as a rubber cap; and a second robotic arm configured for holding and operating at least one syringe, which comprises a needle, a plunger and a respective barrel for suctioning a fluid. The second robotic arm comprises at least one actuator for driving the plunger of the syringe. The first robotic arm is configured for cooperating with the second robotic arm, so as to insert the needle in the drug container through the pierceable element. The second robotic arm is configured for operating the plunger, so as to suction the liquid drug from the drug container.

The automatic compounding system provides a robotized support system to pharmacists and hospitals, for the preparation of personalized medicines by drug compounding. The automatic compounding system is meant to operate with consumables and elements which are commonly used in pharmacies and designed for use by human operators, which generally are not meant to be used in automated systems. The automatic compounding system is meant to operate in environments wherein users are not technically skilled in mechanics and electricity, electronics and software for the management of automation systems, such as common users in hospital pharmacies. Thus the automatic compounding system is meant to preserve typical operating procedures of pharmacies, in order to simplify the "acceptance" of the automatic machine by the hospital staff.

According to an aspect, the automatic compounding system has an actuator which is configured for at least partially pulling the syringe's plunger before the needle is inserted in the pierceable element, so as to suction a first controlled volume of ambient air. The actuator is further configured for pushing the plunger after said needle is inserted in the pierceable element, so as to release the same controlled volume of ambient air inside the drug container, thus increasing the pressure inside the drug container. Preferably, the first controlled volume of ambient air is at least equal to the volume of the liquid drug to be suctioned from the drug container.

Preferably, the second robotic arm is configured for bringing the point of the needle in a top zone of the drug container, after the liquid drug has been suctioned in the syringe. The top zone is empty of liquid drug, and the actuator is further configured for further pulling the plunger so as to suction a second controlled volume of inside air from the inside of the drug container, thus decreasing the pressure inside the container before extracting the needle from the pierceable element.

Advantageously, the functioning of the automatic compounding system is improved by exploiting the seal effects between pierceable cap and needle. In fact, by increasing the pressure inside the drug container, it becomes easier to withdraw the liquid drug from the container, and controlling the extracted volume thereof. In turn, by decreasing the pressure inside the container before extracting the needle, spilling of liquid drugs is prevented and, by placing the internal environment of the container in the depression, even when the two environments across the pierceable element are in contact, leakage of aerial compounds from the will be reduced as well.

An advantage of the invention consists in the reduction of drug leakage, both in liquid and aerial form.

According to a further aspect, the automatic compounding system further comprises a force sensor configured for sensing a force between the needle and the pierceable element. Such information concerning the sensed force value over time is used to control the relative movement of the robotic arms, so as to establish the final position after insertion of the needle in the drug container. Preferably, the robotic arms are configured for arresting the needle in a final position, after a predetermined distance has been covered starting from the point of maximum force detected between the needle and the pierceable element, which corresponds to the exact location of piercing.

Preferably, the automatic compounding system comprises a frontal image acquisition device which is configured for acquiring a frontal image of the pierceable element and of the needle. The image is used by the electronic controllers of the system to control and correct the penetration point of the needle on the pierceable element, which is imposed by the relative position of the robotic arms.

Preferably, the automatic compounding system comprises a lateral image acquisition system which has a first lateral acquisition device, for acquiring a first side image of the needle, and a second lateral acquisition device, for acquiring a second side image of the needle. The first and second side images are acquired from different points of view, so as determine the direction of the needle's axis. The information concerning the needle's orientation is used by the electronic controllers of the system to control and correct the relative alignment of the needle with the drug container, by controlling the relative position of the robotic arms. Preferably, the first and second side images are acquired on orthogonal planes.

Preferably, the automatic compounding system comprises a container image acquisition device, configured for acquiring an image of the syringe, so as to monitor air bubbles in the liquid drug. Therefore, in the final stage of suction creation of bubbles can be monitored so as to avoid drawing air instead of liquid out of the drug container.

Advantageously, each and all of the above features concur to maximizing and effectively withdrawing the amount of liquid drug which is withdrawn by suctioning into the syringe. All sensor means contribute to assure that piercing of the cap element is optimally executed, for example assuring that the needle's penetration stops immediately just after the pierceable cap and that the aspiration is stopped only after a full dose of required drug has been suctioned.

Another advantage of the above features, is the possibility of completely emptying drug containers, maximizing the use of the drug contained in them, effectively exploiting not only the nominal volume of drug contained, but the effective volume which usually is slightly larger.

Further aspects and advantageous technical features of the present invention, are set out in the dependent claims.

Brief description of the drawings

Further features and advantages of the present invention will become apparent in the detailed description of preferred non-exclusive embodiments, which are described as non-limiting examples with the help of the annexed drawings, wherein:

- Figure 1 represents a first view of a preferred embodiment of an automatic compounding system according to the invention.

- Figure 2 represents a second view of a preferred embodiment of an automatic compounding system according to the invention.

- Figure 3 (a) to (h) exemplifies drug withdrawal using a syringe hold in a robotic arm, from a drug container hold in a further robotic arm, for an automatic compounding system according to the invention. - Figure 4 represents a schematic view of an automatic compounding system according to the invention.

- Figure 5 represents a detailed view of a syringe's needle penetrating in a container's cap.

- Figure 6 represents a schematic view of a frontal camera, acquiring the image of a container's cap.

- Figure 7 represents a schematic view of lateral cameras, acquiring orthogonal images of a syringe's needle.

- Figure 8 illustrates the correction of the syringe's position, performed by an automatic compounding system according to the invention.

- Figure 9 (a) and (b) illustrates the needle's insertion in a container, performed by an automatic compounding system according to the invention.

In general, the drawings may illustrate different aspects and embodiments of the present invention and, where appropriate, like elements or components or materials or actions in different figures are indicated by analogous reference numbers.

Detailed description of embodiments

Figure 1 represents an automatic compounding system 100 which comprises a first robotic arm 101 and a second robotic arm 102. The first robotic arm 101 is configured handling and holding one drug containers which contain liquid drug. The second robotic arm 102 is configured for holding and operating a syringe 103.

The automatic compounding system 101 accepts the drugs (held in containers, such as bottles or vials) and the final containers (syringes, bags, bottles and the like) in addition to a series of auxiliary accessories for the syringe (i.e. needles and caps). The output product, made by suitably combining the input drug products, is constituted according to a compounded formulation with appropriate dosage. Each element mentioned above will be briefly described.

The syringe 103 comprises of two parts: a barrel (a cylindrical hollow body); a plunger (whose relative motion with respect of the barrel allows to suck and inject a fluid) and a needle or a stopper which may be mounted at the end of the syringe 103, preferably using a "Luer lock" mechanism. The syringe 103 may be approximated to a cylinder of variable diameter as a function of the capacity, which can vary from 1 ml to 50 ml.

The vials are containers which contain the drug in liquid form; these have a capacity typically ranging from a few milliliters up to 150 ml.

The bags are containers made of soft plastic, having a capacity ranging typically from a minimum of 50 ml to a maximum of 1000 ml.

The bottles are containers made of rigid plastic, having a capacity ranging typically from a minimum of 50 ml to a maximum of 1000 ml.

The infusers are containers made of rigid plastic which contain an elastomer, which allows the continuous delivery at a known and constant dosage of the drug infused therein.

The elements mentioned above must be handled by the automatic compounding system 100: each of them must be grabbed in a certain and repeatable manner, by means of the mechanical clamps of the robotic arms 101 and 102, which, for simplicity of construction, allow the simple parallel movement of two "finger" like elements. Preferably, each of the first robotic arm 101 and second robotic arm 102 comprise an anthropomorphous robot having six degrees of freedom.

The first robotic arm 101 and/or second robotic arm 102 are configured for carrying out several other operations, especially on the syringe, such as: needle capping, needle de-capping, needle installation, needle removal. These operation may be carried out in manners according to the art.

Preferably, the first robotic arm 101 is configured for retrieving the drug container from a shelved deposit 104.

The drug containers containing the liquid drug which is used as input for compounding, comprise each a pierceable element, such as a rubber cap, or in case of the bag a pierceable portion, which can be penetrated by the syringe's needle. The vials may be assimilated to cylinders having variable diameter: body, neck and cap have in fact different diameters; in a preferred embodiment (not shown) the first robotic arm 101 is configured for holding the bottle or vial by mechanically grabbing the ring portion of the cap; this limits the variations of the grabbed diameter and consequently simplifies the gripping and robots' fingers.

The bags, bottles and infusers are much more complex to handle, as they are meant primarily for human operation, and therefore do not have a point of repeatable grabbing, and may also be deformable (especially for bags). The automatic compounding system 100 provides for a bottle or bag or infuser being placed in a predetermined position over a tray, so as to define a point of for accurate and repeatable hold, and wherein the first robotic arm 102 is configured for holding the tray from such predetermined grabbing portion.

The syringes may be assimilated to cylinders, and are effectively manipulated using the caliper parallel fingers of the second robotic arm 102. In particular, the syringe comprises a needle, a plunger and a respective barrel for suctioning the fluid.

The second robotic arm 102 comprises at least one actuator for driving the plunger of the syringe.

The first robotic arm 101 is configured for cooperating with the second robotic arm 102, so as to insert the needle in the drug container through the pierceable element thereof. The second robotic arm 102 is configured for operating the plunger, so as to suction the liquid drug from the drug container, as it will be also further described. In a variant, not shown, more drug containers could be hold simultaneously by the first robotic arm, and/or more syringes could be operated in parallel by the second robotic arm. In a variant, more actuators could be provided, if more syringes are used in parallel.

Figure 2 represents a further view of the automatic compounding system 100. The analysis of the elements to be handled by the system, and the operating procedures required for the compounding, have led to the conclusion that any task can be performed by the system if it provides for simultaneously manipulating a maximum of three rigid bodies.

Specifically, an operations that requires such capability is the one in which the system must restrain in a position a container, and withdraw the liquid content thereof with a relative movement between a syringe body and a syringe's plunger.

Preferably, the automatic compounding system 100 comprises a locking system (specifically for retaining the plunger) and two robot arms 101 and 102 which are configured respectively for handling the container and the syringe. This choice has allowed to reduce the complexity of the machine, while maintaining practically unchanged its operational capability.

The two robotic arms are configured for cooperating with each other, that is, these must have the ability to move in a completely synchronized manner with each other. This is achieved for example by using the "alter" mode, which is typical for the anthropomorphic robot arms made by company Staubli; this function makes it possible, as the name suggests, to change (alter) in real-time the motion parameters of one of the two robots (slave) by using the commands from the other robot (master). This generates synchronous movements of two robots where the slave exactly replicates the movements of the master. This technique is not exclusive for Staubli robots, but applies for any cooperative movement between two robots.

The introduction in the system of two robotic arms which are capable of cooperating requires a specific software programming, while allowing operations (such as the withdrawal of liquid from a vial) which would not be executable using a single robotic arm. This greater flexibility of the automatic compounding system has enabled the execution of complex operations (such as: liquid removal from a bottle/vial, assembly and disassembly of the needle from the syringe, fitting the cap on the syringe ...) using only two robotic arms. The resulting automatic compounding system 100 becomes very simple in structure, and eliminates some of the equipment which would be otherwise exclusively dedicated to perform the operations described above. In addition, the use of two cooperating robotic arms improves effectiveness of spillage reduction and force control.

Preferably, the two robotic arms 101 and 102 have different sizes, in an "asymmetric configuration" which allows to use the larger robot as a system for loading and unloading of a large stock of consumables, allowing the operating autonomy of the machine to exceed sixty minutes, without any external intervention.

Figure 3 (a) to (h) represents a syringe 103 and a vial 300 which contains liquid drug. The vial 300 is hold in a robotic hand 301 associated to the first robotic arm 101 (not shown). The syringe is hold and operated by a robotic hand 302, associated to the second robotic arm 102 (not shown). The system comprises an actuator 303 for operating the plunger of syringe 103; such actuator is simplified and schematized in Figure 3 (a) to (h), to improve intelligibility, but the drawings have no limiting purpose for determining the features of the actuator.

In an embodiment, the actuator 303 is mounted on the robotic hand 302 and is dedicated to pulling and pushing the plunger with respect of the syringe's body hold by the same robotic hand 302. A further preferred embodiment will be described and illustrated with reference to Figure 4.

In order to perform drug withdrawal from the container 300, a liquid drug is needed; if the bottle contains powdered drug, the system will perform a recovery process, including all the operations which serve to dissolve the powder in a liquid solvent, according to the art.

The cooperation of robotic arms and movable robotic hands 301 and 302 provides for controlling the displacements of the syringe 103, including its plunger and its needle. The system operation is described in detail in the following, with reference to subfigures (a) to (h).

Figure 3(a) illustrates the needle approaching the pierceable element of the container 300 from the bottom; the needle of the syringe 103 is ready for piercing the rubber seal. At this stage, the air pressure inside the container 300 is coinciding with good approximation to the atmospheric pressure.

Figure 3(b) illustrates that the actuator 303 opens the syringe plunger by an amount slightly greater than the amount of liquid drug that will be removed from the container 300. This allows to load in the syringe 103 a volume of air at atmospheric pressure which is slightly larger than the volume of liquid drug to be suctioned.

Figure 3(c) illustrates that the needle mounted on the syringe 103 is inserted into the container 300, while maintaining the plunger pulled in the previous position.

Figure 3(d) illustrates that syringe plunger is pushed, so as to expel air which enters into the container 300, thereby putting the latter in slight overpressure. This facilitates withdrawal of the drug, as the volume of air inserted into the bottle (at atmospheric pressure) is slightly greater than the volume of liquid that will be withdrawn.

In summary, the actuator 303 is configured for at least partially pulling the plunger before the needle is inserted in the pierceable element of the container 300, so as to suction a first controlled volume of ambient air, and is further configured for pushing the plunger after the needle is inserted in the pierceable element, so as to release the controlled volume of ambient air inside the drug container 300 and increase the pressure therein.

Figure 3(e) illustrates that the syringe plunger is opened of a sufficient quantity to suction the required volume of drug; in practice, the required volume of drug is sucked by the syringe, helped by the overpressure in the container 300.

Figure 3(f) illustrates that the needle is further inserted into the container 300, so that its tip emerges from the "free surface" of the liquid drug and its opening is within the air volume contained in the container 300, which is now close to atmospheric pressure.

Figure 3(g) illustrates that the plunger is further pulled by the actuator 303, thereby sucking air from the container 300, so that the inside of the container 300 will have a pressure which is lower than atmospheric pressure. This allows, in the process of extraction of the needle, that when the external and internal environments are put in contact, a flow of air from the outside towards the inside of the bottle will be established; such flow of air prevents the release of potentially harmful drug aerosols contained in the bottle. Preferably, in the phase of extracting the needle, a further slight pulling of the plunger is applied by actuator 303, so as to draw any drug remained in the needle.

Figure 3(h) illustrates that the needle is extracted from the container 300. Subsequently (not shown) the needle is inserted in the needle guard, and the plunger is positioned at a volume corresponding to the final volume to be suctioned, in order to eliminate any air present in the syringe 103, which becomes ready for subsequent use.

In summary, the first robotic arm 101 and the second robotic arm 102 are configured for bringing the point of the needle in a top zone of the drug container 300 which is empty of liquid drug, after suctioning the desired volume of liquid drug. The actuator 303 is further configured for further pulling the plunger so as to suction a second controlled volume of inside air from the inside of the drug container 300, thereby decreasing the pressure therein, before extracting the needle from the pierceable element (cap) of the container 300.

The above summarized configuration improves the functioning of the system, by increasing/decreasing the pressure in the drug container by means of the same syringe. In fact, this arrangement makes it possible to prevent spillage of liquid drug which would take place, in other operating conditions, when the needle is extracted from the rubber seal that closes the vial, putting in communication the internal environment with the external environment. Even more important, by placing the internal environment of the container in slight depression, when the two environments become in contact, there will be no leakage of drug aerosol and air. As mentioned and depicted, the needle is extracted "from below" of the container, in order to reduce the complexity of the movement of the robotic arms.

Figure 4 represents a schematic view of an automatic compounding system according to the invention, which is illustrated in exemplificative manner highlighting its key elements.

Before proceeding with the description of the system, it is useful to emphasize that it is important to use as much as possible of the drug contained in the bottles, without leaving residues which may become harmful and represent a rather expensive waste of drug.

For improving the system and completely withdraw the drug from the container, it is important to monitor in a functional way exactly when and where the needle has penetrated the pierceable element (rubber cap), so as to stop the needle in the appropriate location.

The automatic compounding system 100 is configured for handling a syringe 103 and a drug container 300, as described.

The automatic compounding system 100 is able to implement a controlled displacement of the plunge, barrel and needle of the syringe 103; in the specific, two robotic arms 101 and 102 ensure a comprehensive flexibility and programmability of displacements and kinematics with which the movements are executed: in a preferred embodiment, the system comprises a first TX60L robotic arm and a second TX40 robotic arm.

In a preferred embodiment the actuator 303b for driving the plunger comprises a fixed element configured for holding the operable end of the plunge. Therefore, when the second robotic arm 102 moves away or nearer the barrel of the syringe 103, it respectively pulls or pushes the plunge, considering the relative motion of the same with respect of the barrel.

The automatic compounding system 100 further comprises a force sensor 401 configured for sensing a force between the needle and the pierceable element of the container 300, so that the final position after insertion of the needle may be controlled by the cooperative movement of the first and second robotic arms 101 and 102, according to the force sensed.

In particular, in a preferred embodiment the device for the measurement of the force exchanged between the needle and the pierceable element (rubber closure cap) of the container, is represented by a Force/Torque sensor.

In an embodiment, the Force/Torque sensor can be fully virtualized, so as to obtain the vector for force and torque, by measuring the current supplied by the drives of the motors of the robot joints and therefore, indirectly, also the torque at those joints. This method, is very simple from the operational point of view, because it does not require a dedicated sensor, but is characterized by a high uncertainty of measurement (due to the uncertainty with which it is possible to estimate the friction of the various moving parts) and complexity (a dynamic model of the robot devoid of gravitational component must be available).

In a preferred embodiment, a sensor 401 is used, which is capable of measuring the force vector and the torque vector. There are commercially available dedicated sensors to provide this information; such sensor is preferably a cylinder with a radius greater than its height, to be interposed between the end flange of a robot arm and its operating end (or robot hand). These sensors, in the majority of cases, have deformable elements inside of them whose deformation is detected by means of strain gauge sensors. A conditioning and a suitable processing of the electronic measurements allow to estimate in real time the force and the torque that the robot is applying (and receiving) from the environment.

The automatic compounding system 100 further comprises a frontal image acquisition device 402, configured for acquiring a frontal image of the pierceable element of the container 300, and of the needle of the syringe 103, so as to control and correct the penetration point of the needle on the pierceable element, which is imposed by the first and second robotic arms 101 and 102 moving cooperatively. Such acquisition device 402 is able to accurately determine the exact location in which the needle will penetrate the cap; and guide the system to the target point. In a preferred embodiment, the acquisition device comprises a matrix TV camera capable of acquiring a two-dimensional image from the scene, which is appropriately calibrated so as to allow the estimate in metric units (millimeters) of the corrections to be made to the movement of the robotic arms, so as to allow the needle to target the center of the pierceable element. It is sufficient to use a two-dimensional camera, since in the machine reference system, the equation of the plane in which the correction movements take place is known.

The use of such correction system to control and correct the penetration point of the needle on the pierceable element, allows to perform multiple operations in the same pierceable element, for example at different points, thus reducing the risk of damage to the pierceable element and the consequent generation of spillage.

Preferably, the acquisition device 402 is positioned with its optical axis perpendicular to the plane that contains the correction movements.

In an embodiment, the system has been designed as acquisition device 402 a camera type IDS UI-3060 CP, in the version with a Bayer filter, having a Sony IMX174 CMOS technology sensor, with a resolution of 1936 x 1216 pixels, with great sensitivity which allows the system to work even in scarce light.

The automatic compounding system 400 further comprises a lateral image acquisition system, comprising a first lateral acquisition device 403 configured for acquiring a first side image of the needle, and a second lateral acquisition device 404 configured for acquiring a second side image of said needle.

The first side image and the second side image are acquired from different points of view by the acquisition devices 403 and 404, so as determine the direction of the needle of the syringe. According to the determined needle's direction, the relative alignment of the needle with the drug container is controlled and corrected by the second robotic arm 102 and/or the first robotic arm 101 , moving cooperatively.

In a preferred embodiment, the two acquisition devices 403 and 404 are placed on orthogonal planes, so as to capture images which in turn are taken from orthogonal planes.

Preferably, to be able to determine accurately the needle's direction, the vision system comprising acquisition devices 403 and 404 is used for calculating the real direction or deviations from the axis of the syringe (which is coincident with the direction of movement of the plunge). The direction of the needle is typically a three- dimensional information (vector in space), which is obtained from a stereoscopic imaging which requires the use of two images, taken from two different points of view - in a manner similar to human visual perception. Such a pair of images is obtainable using two cameras 403 and 404, whose relative positions are either known. Alternatively, such pair of images is equivalently calculated exploiting the robotic arms to impose a known needle displacement, and recovering both images with a same camera.

The system works by identifying in both stereoscopic images the stem base and the tip of the needle; these two points are then triangulated knowing the displacement imposed to the needle by the robotic arms, and the calibration of the cameras so as to obtain in the machine reference system the three-dimensional coordinates of both points. From these three-dimensional coordinates of two points, it becomes straightforward to calculate the actual direction of the needle.

This system is advantageous, since the needle of the syringe 103 is designed for manual use, and would otherwise require no special construction accuracy.

The system has been designed using for the acquisition devices 403 and 404, the camera IDS UI-3060 CP in the version with Bayer filter. To improve detection of the two points for which the needle passes, a front lighting is provided. In order to make a robust imaging, it is preferred to put the needle behind a green (or other suitable color, such as blue) background so that, by analyzing the image in the HSL space, it would be simple to reliably extract the needle direction, for any condition of light.

The robotic arms 101 and 102 are configured for changing the needle's penetration direction, as a function of the information coming from the vision system; the system is thus able to change the needle penetration direction, by imparting commands to the robotic arm 101 , for example, which manipulates the container 300, in its movement of approach towards the needle.

In fact, once the direction in space of the needle of the syringe 103 hold by the second robotic arm 102 is known, it is easier to command the first robotic arm 101 to align the container 300 as shown in Figure 8. The needle penetration movement will then take place with a movement of the robotic arm 102, holding the container 300, along the rotation axis of the sixth joint which coincides with the direction of the needle in space.

The automatic compounding system 400 further comprises a syringe image acquisition device 405, which is configured for acquiring an image of the syringe 103, so as to monitor the conditions of the liquid drug therein and the insurgency of air bubbles suctioned from the container 300 or from the outside.

In particular, the syringe image acquisition device 405 is provided for establishing the appearance of air "bubbles" in the syringe, and then to verify that a complete withdrawal of the desired quantity of liquid drug has been performed.

The syringe image acquisition device 405 is preferably associated to a light illumination system, which is configured to aid in highlighting the outline of bubbles which may be present in the liquid. In fact, bubbles are characterized by an abrupt change in light intensity, which can be detected by a suitable image algorithm. The analysis of the appearance and the dimensional variation of the bubbles edge allows to understand also when the desired quantity of liquid drug has been completely suctioned in the syringe. The system identifies the presence of bubbles in the image, searching from to needle's stem to the end of the plunger.

The system has been designed using for the syringe image acquisition device 405, the camera IDS UI-3060 CP in the version with Bayer filter.

In an embodiment, the syringe image acquisition device 405 is configured for operating a correction in the nominal amount of liquid drug to be withdrawn, increasing the suctioned amount so as to account for possible air bubbles in the syringe.

Figure 5 represents the needle 503 of the syringe 103 penetrating in the pierceable element 500 of the container 300.

The pierceable element 500 (rubber cap) assures liquid-tightness for the container 300, in order contain the liquid drug. When the pierceable element 500 is pierced by the needle, it is important that the needle is arrested so that its opening is inside the container, but its tip remains as close as possible to the pierceable element 500, as shown in Figure 5, so as to suction as much liquid drug as possible, thus reducing waste.

Figure 6 represents the frontal view of the pierceable element 500 acquired by the frontal image acquisition device 402, which is configured for acquiring a frontal image of the pierceable element 500 as previously described. The frontal image acquisition device 402 is capable of determining, among others, the center point 601 on the exposed surface of the pierceable element 500.

Figure 7 represents images of the syringe's needle 503, acquired by the lateral image acquisition system previously described. Image 701 is acquired by the first lateral acquisition device 403, while image 702 is acquired by the second lateral acquisition device 404. As explained, the two side images 701 and 702 are acquired from different points of view, so as determine the direction of the needle of the syringe and correct the relative alignment of the needle 503 with the drug container 300, as provided by the second robotic arm 102 and/or the first robotic arm 101 , moving cooperatively. In a preferred embodiment, the images 701 and 702 are taken from orthogonal planes.

Figure 8 represents the algorithm for controlling the robotic arms 101 and 102 according to the images acquired by the lateral image acquisition system comprising devices 403 and 404 previously described. The needle's penetration direction is changed as a function of the information coming from the vision system; the system is thus able to change the needle penetration direction, by imparting commands to the robotic arm which manipulates the container 300, in its movement of approach towards the needle.

Figure 9 represents (a) the movement of the needle 503 travelling the distance which makes it penetrate the pierceable element 500, from a starting point 901 to a final point 902. Figure 9 (b) represents the force sensed by sensor 401 over the coordinate from starting point 901 to a final point 902.

The needle insertion is not performed by imposing a final destination coordinate, but by monitoring in real time the force diagram exchanged between needle 503 and pierceable element 500, so as to define first the contact point with the pierceable element and then the successful piercing; this allows to precisely stop the movement of the needle 503 as soon as it has pierced the cap (that is, in the best condition to maximize the amount of drug that can be withdrawn). In other words, the coordinate movement of the first and second robotic arms is configured for arresting the needle 503 in the final position 902 after a predetermined distance has been covered, starting from the point 903 of maximum force detected between the needle 503 and the pierceable element 500.

This features allow to maximize the amount of drug which is suctioned out of the container; together with the other image sensors they ensure that the piercing is performed in the best manner, and that the suctioning is stopped only after a complete suctioning of the liquid drug.

An advantage of the invention, compared to existing solutions, consists in the possibility of completely emptying the drug containers, thus maximizing the use of the drug. This is important for fully exploit the complete amount of drug in the container, and not just the nominal amount declared by the manufacturer.

The system according to the invention, as merely exemplified in the present description with the implementing details herein given, is susceptible to a number of changes and variants which become apparent to the skilled in the art which considers the present description.

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Claims

1 . An automatic compounding system (100) for pharmaceutical preparations of drugs, comprising: a first robotic arm (101 ) configured for handling and holding at least one drug container (300) containing liquid drug, wherein said drug container (300) comprises a pierceable element (500); a second robotic arm (102) configured for holding and operating at least one syringe (103), said syringe (103) comprising a needle (503), a plunger and a respective barrel for suctioning a fluid, wherein said second robotic arm (102) further comprises at least one actuator (303; 303b) for driving said plunger of said syringe (103); characterized in that said first robotic arm (101 ) is configured for cooperating with said second robotic arm (102) so as to insert said needle (503) in said drug container (300) through said pierceable element (500), and in that said second robotic arm (102) is configured for operating said plunger so as to suction said liquid drug from said drug container (300).

2. The automatic compounding system according to claim 1 , wherein said actuator (303; 303b) is configured for at least partially pulling said plunger before said needle (503) is inserted in said pierceable element (500), so as to suction a first controlled volume of ambient air, and is further configured for pushing said plunger after said needle (503) is inserted in said pierceable element (500), so as to release said controlled volume of ambient air inside said drug container (300) and increase the pressure therein.

3. The automatic compounding system according to claim 2, wherein said first robotic arm (101 ) and said second robotic arm (102) are further configured for, after suctioning said liquid drug, bringing the point of said needle (503) in a top zone of said drug container (300) which is empty of liquid drug, and wherein said actuator (303; 303b) is further configured for further pulling said plunger so as to suction a second controlled volume of inside air from the inside of said drug container (300), decreasing the pressure therein, before extracting said needle (503) from said pierceable element (500).

4. The automatic compounding system according to any one of claims 2 or 3, wherein said first controlled volume of ambient air is at least equal to the volume of said liquid drug to be suctioned from said drug container (300).

5. The automatic compounding system according to any one of claims 1 to 4, further comprising a force sensor (401 ) configured for sensing a force between said needle (503) and said pierceable element (500), wherein the final position (902) after said insertion of said needle (503) in said drug container (300) is controlled by the relative movement of said first robotic arm (101 ) and said second robotic arm (102) according to said force sensed.

6. The automatic compounding system according to claim 5, wherein said first robotic arm (101 ) and said second robotic arm (102) are configured for arresting said needle (503) in said final position (902) after a predetermined distance has been covered starting from the point of maximum force (903) detected between said needle (503) and said pierceable element (500).

7. The automatic compounding system according to any one of claims 1 to 6, further comprising a frontal image acquisition device (402), configured for acquiring a frontal image of said pierceable element (500) and of said needle (503), so as to control and correct the penetration point (601 ) of said needle (503) on said pierceable element (500), imposed by the relative movement of said first robotic arm (101 ) and said second robotic arm (102).

8. The automatic compounding system according to any one of claims 1 to 7, further comprising a lateral image acquisition system (403, 404) comprising a first lateral acquisition device (403), configured for acquiring a first side image (701 ) of said needle (503), and further comprising a second lateral acquisition device (404), configured for acquiring a second side image (702) of said needle (503), said first side image (701 ) and said second side image (702) being acquired from different points of view so as determine the direction of said needle (503), for controlling and correcting the relative alignment of said needle (503) with said drug container (300) by the relative movement of said first robotic arm (101 ) and said second robotic arm (103).

9. The automatic compounding system according to claim 8, wherein said first side image (701 ) and said second side image (702) are acquired on orthogonal planes.

10. The automatic compounding system according to any one of claims 1 to 9, further comprising a syringe image acquisition device (405), configured for acquiring an image of said syringe (103), so as to monitor air bubbles in said liquid drug.

1 1 . The automatic compounding system according to any one of claims 1 to 10, wherein said first robotic arm (101 ) is further configured for retrieving said drug container (300) from a shelved deposit (104).

12. The automatic compounding system according to any one of claims 1 to 1 1 , wherein said at least one actuator (303b) for driving said plunger comprises a fixed element configured for holding the operable end of said plunge, wherein said second robotic arm (102) is configured for moving said barrel so as to pull or push said plunger which is in relative motion with respect of said barrel.

13. The automatic compounding system according to any one of claims 1 to 12, wherein said drug container (300) is a vial comprising a cap, and wherein said first robotic arm is configured for holding said bottle or vial by mechanically grabbing a ring portion of said cap.

14. The automatic compounding system according to claim any one of claims 1 to 12, wherein said drug container is a bottle or a bag, and wherein said bag or bottle is placed in a predetermined position over a tray, and wherein said first robotic arm is configured for holding said tray from a predetermined grabbing portion.

15. The automatic compounding system according to any one of claims 1 to 14, wherein each of said first robotic arm (101 ) and second robotic arm (102) comprise an anthropomorphous robot having six degrees of freedom, and wherein said first robotic arm (101 ) and/or second robotic arm (103) are further configured for carrying out at least one of the following tasks of said syringe (103): needle capping, needle de-capping, needle installation, needle removal.