Devices and methods for drug administration and mixing, and training of proper techniques therefor

Abstract

To provide a device for training users in a proper mixing of pharmaceutical components, or for aiding in the mixing, or for performing the mixing and administration of pharmaceutical components.SOLUTION: A device comprises a housing 202 for receiving a pharmaceutical delivery device containing pharmaceutical components. There is also a microcontroller 154 disposed in the housing 202, and a motion / orientation detection device disposed within or on the housing 202 and in communication with the microcontroller 154. A method for use of the device is also disclosed, along with a substance for use as one of the pharmaceutical components.SELECTED DRAWING: Figure 1A

Description

[Background technology]

[0001] Pharmaceutical products for injection delivery can be stored in vials or prefilled syringes. In either case, when such products consist of two or more liquid and / or solid phases, they need to be agitated before administration, usually by manual shaking, to obtain optimal results. Healthcare professionals (HCPs) and in some cases patients or caregivers are unable to provide uniform agitation for many reasons. They may not be familiar with the pharmaceutical product, may be accustomed to similar pharmaceutical products that may have the same or similar preparation process, or may mistime the shaking duration or the shaking vigor required, and may inadvertently underestimate the time or vigor required for proper agitation of the device and adequate mixing of the product. Summary of the Invention

[0002] The present disclosure aims to provide a device that provides HCPs with knowledge and experience of the minimum duration and shaking vigor required for dispensing various pharmaceutical products, such as, for example, INVEGA TRINZA™, which consists of particles in a suspension. It also aims to provide another device that alerts the user when, for example, too much time has passed since mixing and the mixing step needs to be repeated. It also aims to disclose yet another device that only works with syringes designated for a particular product, and not with syringes of competing products. This device can also be used as a means to ensure that the device is not misused with the wrong pharmaceutical product and to differentiate one product from its competitors.

[0003] Accordingly, various embodiments of apparatus and methods of operation of such apparatus are disclosed that satisfy the need and / or alleviate the shortcomings.The present invention is defined by the appended claims.

[0004] For example, in one aspect of the present invention, a device is provided for training a user on how to properly mix pharmaceutical ingredients. In another aspect, a device is provided for mixing pharmaceutical ingredients and assisting in the administration of properly mixed pharmaceutical ingredients. In another aspect, a device is disclosed for mixing and administering properly mixed pharmaceutical ingredients. In another aspect, a device is disclosed for attaching to a pharmaceutical delivery device and assisting in the administration of properly mixed pharmaceutical ingredients. All of these devices are referred to herein (both in the description and claims) as a "device." The device can include a housing, e.g., a housing extending along a longitudinal axis, e.g., having a power source disposed within the housing. A microcontroller can also be disposed within the housing and powered by the power source, and a user notification device and a motion or orientation detection device (motion / orientation detection device), e.g., an accelerometer, can also be disposed within the housing and electrically connected to the microcontroller. In this device, the microcontroller is configured to detect movement and / or orientation of the housing and indicate via a user notification device whether the movement and / or orientation of the housing during drug administration or during a training event (e.g., when shaken) is sufficient with respect to predefined thresholds, including the magnitude of force applied during shaking, the acceleration of the housing during shaking, the orientation of the housing and / or the duration of shaking.

[0005] Another aspect of the invention includes a method of operating such a device, which may be accomplished by a motion / or orientation detection device, such as an accelerometer, determining whether the magnitude and / or orientation of the housing movement is sufficient with respect to predefined thresholds including the magnitude of force applied during shaking, the acceleration, the orientation of the housing, and the duration of said shaking, and announcing with a user notification device whether the movement or orientation of the housing shaken during drug administration or a training event meets the predefined thresholds.

[0006] In addition to the various aspects described above, other features described below may be utilized in conjunction therewith to arrive at different alternative forms of the invention. For example, the device may include a start switch electrically connected to the microcontroller, the accelerometer may include a three-axis accelerometer configured to wake the microcontroller upon detecting movement of the housing during drug administration or during a training event, the microcontroller configured to detect when shaking of the housing is terminated prematurely or when the level of shaking momentum drops below a preset threshold and enter a pause mode to prompt the user to resume shaking during drug administration or during a training event, the microcontroller configured to set a timer and determine when a maximum allowable time has elapsed after shaking of the housing to alert the user to shake the device again during drug administration or during a training event, and the housing may include a finger flange at one end and a pair of finger flanges spaced apart along a longitudinal axis. the housing can include a syringe barrel element having a barrel tip and a barrel tip, the housing can include a body having a slot sized to receive the syringe barrel, the housing can include a housing provided with a compartment and a lid that receives the entire syringe, the housing can include an elongated body approximately the same length as the syringe barrel, such that the syringe is inserted into a syringe receiving hole in the body and held between the syringe finger flange and the body base by compressive force applied by the finger members, the housing can include a body having a syringe receiving slot sized to receive the syringe barrel, the housing can include a disc-shaped body having a syringe receiving hole such that during use, a syringe is inserted into the syringe receiving hole and held in place by a user's thumb at the lower thumb grip.

[0007] These and other embodiments, features and advantages will become apparent to those skilled in the art upon review of the following more detailed description of illustrative embodiments of the invention in conjunction with the accompanying drawings, which are first briefly described.

[0008] The above and other features and advantages of the present invention will be understood from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings. [Brief description of the drawings]

[0009] [Figure 1A] FIG. 1 is a block schematic diagram of an electronic system / device of the present disclosure. [Figure 1B] 1 illustrates an overview of a stand-alone simulated trainer embodiment. [Diagram 2] 1 illustrates an orthogonal view of a stand-alone simulated trainer embodiment. [Diagram 3] 1 illustrates a syringe barrel attachment embodiment showing the device separate from and attached to the syringe. [Figure 4] 1A-1D illustrate front, left and right side views of an embodiment of a syringe barrel attachment. [Diagram 5] 1A-1D illustrate front, top and bottom views of a syringe barrel attachment embodiment. [Figure 6] 1 illustrates a perspective view of a syringe housing embodiment showing a syringe next to an open housing. [Figure 7] 1 illustrates a general view of a syringe housing embodiment showing a syringe within an open housing. [Figure 8] 1 illustrates a general view of a syringe housing embodiment showing the housing closed. [Figure 9] 1 illustrates an overall view of a syringe housing embodiment showing front, top and side views. [Figure 10] 1 illustrates a syringe pot embodiment with a syringe inside, showing front and side views. [Figure 11] 1 illustrates a syringe pot embodiment without a syringe, showing front and side views. [Figure 12] 1 illustrates the syringe finger hook attachment embodiment without a syringe. [Figure 13]1 illustrates, in side view, an embodiment of a syringe with and without syringe finger hook attachment. [Figure 14] 1 illustrates an embodiment of a syringe with and without a syringe finger hook attachment in front view. [Figure 15] 1 illustrates a syringe disc embodiment with a syringe. [Figure 16] 1 illustrates a syringe disc embodiment without a syringe. [Figure 17] 1 illustrates a trainer-induced embodiment. [Figure 18] 1 illustrates packaging attachment embodiment A in a tray and attached to a syringe. [Figure 19] 1 illustrates packaging attachment embodiment A removed from a syringe. [Figure 20] 1 illustrates packaging attachment embodiment B attached to a syringe tray. [Figure 21] 1 illustrates packaging attachment embodiment B removed from a syringe tray. [Figure 22] FIG. 1 illustrates threshold requirements for a device to contain sediment. [Diagram 23] FIG. 13 illustrates how a percentage of users, without assistance, do not provide enough momentum to thoroughly mix the product. [Figure 24] FIG. 13 illustrates the role of a device or aid to modify a user's behavior so that all shaking with sufficient force exceeds a required threshold. [Diagram 25] 13 illustrates a syringe housing embodiment with an LCD display - mixing of the precipitate as represented by the display. [Figure 26] Illustrates the state of the LCD screen showing the mixing stages from precipitation on the left to mixing on the right. [Figure 27] FIG. 1 is a diagram of a method for mixing and administering pharmaceutical ingredients or drugs according to the present disclosure. [Figure 28] FIG. 2 illustrates a method of operation of an implementation system / apparatus of the present disclosure.

[0010] The accompanying drawings, in which like references represent like elements and which are incorporated in and constitute a part of this specification, illustrate presently preferred embodiments of the invention and, together with the general description above and the detailed description below, serve to explain the features of the invention. [Explanation of symbols]

[0011] Below is a list of reference numbers based on the figures: 100 Simulated trainer embodiment, plunger alternative 101 Finger flange 102 Light Emitting Feedback Window 103 barrels 104 Barrel Tip 105 Syringe plunger rod 106 Syringe back stopper 107 Syringe Barrel 108 Rubber stopper 109 Body of barrel mounted embodiment 110 Light Emitting Feedback Window 111 Syringe clamp slot 112 Syringe retention spring clip 113 Case cover 114 Main unit 115 Housing Liner 116 Housing hinge 117 Syringe 118 Spring Clip 119 Illuminating Panel 120 Lid fastener 121 Long and thin body 122 Luminous Band 123 Syringe receiving hole 124 Base of the main body 125 Syringe Receiving Slot 126 Light Panel 127 Main Unit 128 Syringe receiving hole 129 Luminous Band 130 Thumb Grip 131 Finger Grip 132 Thumb Grip 133 Luminous window 134 Main Unit 135 Main Unit 136 Blister Tray Packaging 137 Syringe 138 Side Interference Clip 139 Syringe Slot 140 Luminous Bands 141 Equipment attached to blister tray 142 Blister Tray 143 Blister Tray Film 144 Syringe 145 Return Clip 146 Illuminated Strips 147 Device body 148 Housing base 149 Top of the case 150 triaxial accelerometer 151 Battery 152 Battery Latch 153 Start switch 154 Microcontroller 155 User Notifications 200 equipment 202 Housing 301 LCD 302 First state 303 Second State 304 The Third State 305 Final State Step 401: The user applies a shaking motion 402 Step: Detecting movement and / or orientation 403 Step: Comparing the magnitude and / or direction of the movement to one or more thresholds. 404 Step: Does the movement and / or orientation meet the threshold(s)? Yes / No 405 Step: Notifying a user that the movement and / or orientation meets a threshold(s). 406 Step: Notifying the user that the movement and / or orientation does not meet the threshold(s). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The following detailed disclosure should be read with reference to the drawings, in which like elements in different drawings are numbered the same. The drawings, which are not necessarily to scale, depict selected embodiments, and are not intended to limit the scope of the invention. This detailed disclosure illustrates the principles of the invention by way of example, not by way of limitation. This disclosure clearly enables one skilled in the art to make and use the invention, and describes several embodiments, adaptations, variations, alternatives, and uses of the invention, including what are currently contemplated as the best modes of carrying out the invention.

[0013] As used herein, the terms "about," "approximately," or "substantially" in reference to any numerical value or range indicate an appropriate tolerance that allows the portion or collection of components to function for the intended purpose as described herein. More specifically, "about," "approximately," or "substantially" can refer to values ​​in a range of ±10% of the stated value, e.g., "about 90%" can refer to values ​​in a range of 81% to 99%. Additionally, as used herein, the terms "patient," "host," "user," and "subject" refer to any human or animal subject, and while use of the subject invention in human patients represents a preferred embodiment, it is not intended to limit the systems or methods to human, animal, or medical uses. References to "g" in reference to acceleration are within the range of 9.81 ms -2 , about 10ms -2 means...

[0014] The exemplary embodiments shown and described herein may utilize an electronic system, such as electronic circuitry mounted on a printed circuit board (PCB), that may include means for supplying and controlling power, means for measuring spatial acceleration, means for timing the duration of shaking, and means for communicating device status to a user, as shown in FIG. 1A.

[0015] 1A shows components of a device 200 for training or assisting a user for proper mixing of pharmaceutical ingredients. The device includes a housing 202, a microcontroller 154 disposed in or on the housing 202, and an accelerometer 150 disposed in or on the housing 202 and electrically connected to the microcontroller 154 such that the microcontroller 154 is configured to detect the movement and / or orientation of the housing 202. The microcontroller 154 can be disposed in the housing 202 so as to be housed in the housing 202. Alternatively, the microcontroller 154 can be disposed on the housing 202 so as to be attached to the housing 202. Similarly, the accelerometer 150 can be disposed in the housing 202 so as to be housed in the housing 202, or alternatively, can be disposed on the housing 202. The movement of the housing 202 can include shaking the housing 202 by the user. The shaking can include reciprocating motion, e.g., up and down, or reciprocating motion side to side, or a combination of both, of the housing 202 relative to the ground. The orientation of the housing 202 can be measured with respect to an acceleration of approximately 1 g in the direction of gravity. The orientation can also be determined based on the time integral of the acceleration force experienced by the accelerometer 150.

[0016] 1A , the device 200 includes a power source 151 disposed within the housing 202 and electrically connected to the microcontroller 154. The power source 151 may be disposed or contained within the housing 202 and may include, for example, a battery 151 or any other suitable power source, such as a capacitor. The power source 151 may be connected to the microcontroller 154 to power the microcontroller 154. It will be appreciated that various types of power sources may be provided.

[0017] In particular, the microcontroller 154 may be powered by the power source 151. The microcontroller 154 may optionally be powered by the power source 151, for example a battery, which may be useful when the device 200 is in transit or is not going to be used for an extended period of time.

[0018] The microcontroller 154 can be configured to detect when the power source 151 is low on available power. In this case, the microcontroller 154 can detect when the power source 151 is insufficient to realize all the functions of the device 200, or when the power source 151 will soon be insufficient to power, for example, the microcontroller 154 or the accelerometer 150 so that they can function as intended or in a normal manner. This can be done by monitoring the voltage provided by the power source 151, how the voltage changes under different loads, what power is available, or how stable the supply is. If a rechargeable battery is used, the microcontroller 154 can additionally be able to monitor the health of the battery.

[0019] 1A , the microcontroller 154 can be configured to detect anomalies or failures in the functioning of the device 200. For example, the failure can be a failure of one or more of the movement / orientation device 150, the housing 202, or the attachment or housing of the medication delivery device. As an example, in the case of the accelerometer 150 or any other movement / orientation device, the microcontroller 154 may receive an unexpected signal or may not receive a signal at all. If this is detected by the microcontroller 154, the unexpected signal or lack of signal can be detected as an anomaly in the device 200. Similarly, the microcontroller 154 can be capable of detecting the state of the housing 202 or the contained medication delivery device, for example, whether the housing 202 is closed and / or whether the delivery device is properly or sufficiently inserted into the housing 202. Similarly, the microcontroller 154 can detect an unexpected signal or lack of a signal that should be present, for example, from the microcontroller 154 or the accelerometer 150, and record this as an anomaly or failure.

[0020] As described above, when the microcontroller 154 detects low available power or detects a fault or anomaly in the power source 151, the device 200 can one or more of: issue a warning to the user (e.g., via the user notification device 155) indicating low available power and / or prevent activation of the medication delivery device to deliver the pharmaceutical ingredient to the user. The device 200 can issue a warning to the user that the available power is low. This allows the user to take corrective action or to know that the device 200 may not be usable now or in the future. If the power drops to a certain level, the circuit, the microcontroller 154, or any other components may become unreliable. For example, an unstable power supply to the microcontroller 154 may cause unexpected results by the microcontroller 154. In this case, the device 200 may encourage incorrect user behavior, such as not requesting completion of a shaking event or not detecting a threshold correctly. This may lead to the use of pharmaceutical ingredients that are not properly mixed. In this case, the microcontroller 154 can prevent activation of the pharmaceutical delivery device for delivery of the pharmaceutical ingredient to the user. Prevention of activation of the delivery device can be achieved in a number of ways. If the shaking device 200 is also a drug delivery device, the microcontroller 154 can be connected to an actuatable lock that resists the delivery mechanism or activator of the delivery device to prevent the expression of the pharmaceutical ingredient, for example by a stopper that can be moved from an unlocked position to a locked position and vice versa. The lock can be a device, such as a valve, that prevents the flow of the pharmaceutical ingredient out of the device through the nozzle. Alternatively, if the drug delivery device comprises an actuator for actuating the delivery of the pharmaceutical ingredient, the lock can be a component that prevents the actuator from expressing the ingredient. If the actuator is automatically driven by a spring, the lock can also be a component that disengages the spring from the actuator so that the actuator cannot express the ingredient from the drug delivery device.When the shaking device of the present invention engages a separate drug delivery device, such as by clipping or housing the device, the shaking device can prevent activation of the drug delivery device by other means. In one example, the drug delivery device includes circuitry that can communicate with the microcontroller 154 of the shaking device. Communication can be achieved by an electrical connection when the two devices are connected, or alternatively by wireless communication. The circuitry of the drug delivery device can be active or passive, and can include its own power source or share the power source 151 of the shaking device. In this embodiment, the drug delivery device can achieve prevention of activation of the medicine delivery device by the same means as described above. Alternatively, the shaking device can include an actuatable lock that interacts with a corresponding lock of the drug delivery device. The actuatable lock of the shaking device 200 can mechanically couple with the corresponding lock of the drug delivery device to prevent activation of the drug delivery device. Alternatively, the actuatable lock of the shaking device 200 can be a movable magnet. When the drug delivery device is engaged with the shaking device 200, the movable magnet can be movable between a first position in which the delivery device cannot be activated and a second position in which the delivery device can be activated. For example, to prevent activation of the delivery device, the movable magnet can be moved such that a magnetic ball in the delivery device prevents the expression of the pharmaceutical ingredient. Instead of a movable magnet, the shaking device 200 can include an electromagnet that can be activated or deactivated to provide a moving magnetic field that can selectively prevent activation of the delivery device.

[0021] The device 200 may comprise a delivery device identification unit in communication with the microcontroller 154. In this case, the device 200 may have a means for identifying the delivery device. The device 200 may be capable of reading an RFID tag, a barcode or a text on the delivery device. In this case, the device 200 may be capable of detecting whether the correct delivery device is being used. The delivery device identification unit may be configured to read data of a data storage means of a delivery device housed in the housing 202 during use, the read data being indicative of the properties of the pharmaceutical ingredient housed in the device 200 and / or the delivery device itself. In this case, the microcontroller 154 may identify the pharmaceutical ingredient in the delivery device. The data may include one or more of: an expiration date of the pharmaceutical ingredient, whereby the microcontroller 154 is configured to alert the user by the user notification device 155 of the device 200 if a current date determined by the microcontroller 154 is past the expiration date; an expiration date; and / or data identifying the pharmaceutical ingredient contained within the delivery device, for example data indicating the manufacturer or composition of the pharmaceutical ingredient, whereby the microcontroller 154 is configured to alert the user by the user notification device 155 of the device 200 if the data identifying the pharmaceutical ingredient does not match or does not sufficiently correspond to an authorized pharmaceutical ingredient stored in the microcontroller 154 or a memory connected to the microcontroller. The microcontroller 154 may include a clock that keeps track of the current date and / or time, or may be configured to receive the current date and / or time from an external source, such as a radio signal. In either case, the current date may be compared to the expiration date of the pharmaceutical ingredient. The data read from the storage means may include a specific expiration date, or information that allows the expiration date to be calculated. For example, the data read from the storage may include a manufacturing date and an indication of the period for which the pharmaceutical ingredient can be stored. The data may include data that identifies the component itself, which may be the name of the component, which may or may not be codable.The coded names of the ingredients can be associated with the actual ingredients. The data identifying the pharmaceutical ingredients can also be used to identify the correct level of shaking vigor and / or time for mixing the ingredients before shaking. The user notification device 155 can provide instructions to the user for properly mixing the pharmaceutical ingredients. The microcontroller 154 can further warn the user if the data identifying the ingredients does not match or does not fully correspond to an authorized pharmaceutical ingredient. Advantageously, this warns the user in the event that an incorrect pharmaceutical ingredient is about to be used. The correct ingredients to use can be stored in the microcontroller 154 or memory prior to use of the device 200.

[0022] The data may include one or more of: an expiration date of the pharmaceutical ingredient, whereby the microcontroller 154 is configured to prevent activation of the pharmaceutical delivery device to deliver the pharmaceutical ingredient to the user if a current date determined by the microcontroller 154 is past the expiration date; an expiration date; and / or data identifying the pharmaceutical ingredient contained within the delivery device, such as data indicating the manufacturer or composition of the pharmaceutical ingredient, whereby the microcontroller 154 is configured to prevent activation of the pharmaceutical delivery device to deliver the pharmaceutical ingredient to the user if the data identifying the pharmaceutical ingredient does not match or does not sufficiently correspond to an authorized pharmaceutical ingredient stored in the microcontroller 154 or a memory connected to the microcontroller. In these examples, the microcontroller 154 may prevent use of the delivery device if the pharmaceutical ingredient is expired or not intended for use. This may be achieved by the mechanisms described above.

[0023] 1B, which illustrates a specific embodiment of the present disclosure, the housing 202 can extend along a longitudinal axis LL. The housing 202 can be elongated to mimic or have a shape suitable for supporting a container for a pharmaceutical ingredient.

[0024] The housing 202 has a major longitudinal axis LL. A drug delivery device may be elongated or have a major longitudinal axis, for example as shown in FIG. 1B. Such a device 200 may also be elongated or have a major longitudinal axis. This may be to mimic or accommodate a drug delivery device or other container for a pharmaceutical ingredient, such as a vial.

[0025] The housing 202 can be configured to receive a drug delivery device having a major longitudinal axis, for example as shown in Fig. 3, and further align the major longitudinal axis along the major longitudinal axis of the drug delivery device. Advantageously, such a device 200 can be capable of receiving a drug delivery device in a particular orientation. Because the axes of the device 200 and the drug delivery device are aligned, the alignment of the drug delivery device with respect to any other components that may be secured to the housing 202 is known. For example, the orientation of the microcontroller 154 with respect to the housing 202 is known, and the major longitudinal axes of the two devices are aligned, and the orientation of the microcontroller 154 with respect to the drug delivery device is known.

[0026] The microcontroller 154 may be configured to detect movement and / or orientation of the housing 202 with respect to movement along or around a longitudinal axis, in which case the accelerometer 150 may distinguish between acceleration forces along and around the longitudinal axis of the housing 202. An axis of the accelerometer 150 may be aligned with the longitudinal axis of the housing 202 such that measurements along that axis correspond to movement along the longitudinal axis of the housing 202. Alternatively, the accelerometer 150 may have at least two axes that are not aligned with the longitudinal axis of the housing 202, and forces may be resolved to determine movement along the longitudinal axis. The accelerometer 150 may also detect movement in any other direction or rotation around any other axis. The accelerometer 150 may also detect the orientation of the housing 202 with respect to movement applied to the housing. A method of operation of the device 200 controlled by the microcontroller 154, e.g., by executable instructions executing therein, is shown in FIG. 28.

[0027] 28, in a shaking event, a user applies a shaking motion to a device (401). The device detects the device's motion and / or orientation (402). The device compares the magnitude and / or orientation of the device's motion to one or more thresholds (403). At 404, if the device's motion and / or orientation meets the one or more thresholds, the process proceeds to notify the user that the motion and / or orientation meets the one or more thresholds (405). At 404, if the device's motion and / or orientation does not meet the one or more thresholds, the process proceeds to notify the user that the motion and / or orientation does not meet the one or more thresholds (406).

[0028] As shown in FIG. 1A, the device 200 may include a user notification device 155 in communication with the microcontroller 154. The user notification device 155 may provide user notifications as commanded by the microcontroller 154. The user notification device 155 may include one or more of a display, a haptic feedback unit, a light emitting device, and / or a vibration alert unit. The user notifications may include one or many of the following notifications: the device 200 is running, the device 200 is not running, shaking has started, shaking has been paused, shaking has stopped, an incorrect frequency of shaking has been applied, a correct frequency has been applied, sufficient shaking has occurred, or too much time has passed after completion of shaking. The user notification device 155 may show the notification to the user by visual means such as a light emitting element or an LCD screen. For example, an LCD display with many pixels or other elements may be used. The display may be of the light reflective type, the backlight transmitting type, or the light emitting type. The light emitting device may include a light emitting diode. The light emitting diodes can be configured to emit light of a particular color or colors. The light emitting device can also include a light bulb. Optionally, the user notification device 155 can indicate to the user by audible means, such as a buzzer or speaker. Optionally, the user notification device 155 can be tactile, using vibrations or physical movement of components by a motor. Beneficially, the user feedback allows the user to change behavior in response to feedback from the device 200. In one example, during use, if the user begins to shake the device 200 with an appropriate level of vigor, as determined by the accelerometer 150, but stops maintaining a sufficient level of vigor, the device notifies the user to increase the vigor. This can be by an audible alarm, a visual cue, or a haptic vibration. Alternatively, the device 200 can provide positive feedback while a sufficient level of vigor is reached and release the feedback when the user falls below this level.For example, haptic feedback can confirm that shaking is sufficient and cease when the user no longer reaches this level. Alternatively, a light can be turned on when the user has shaken sufficiently and turned off when the level of shaking is insufficient. The user notification device 155 can be mounted on an exterior surface of the housing 202 to notify the user of its status. This can be particularly useful if the user notification device provides visual feedback, as this places the device in a position that is easily seen by the user. However, any user notification device can benefit from being located in close proximity to the user in this manner.

[0029] If the user notification device 155 is a display, the microcontroller 154 can be configured to indicate the status of the mixing or simulated mixing of the pharmaceutical ingredients in real time via the display. In this way, the user is provided with feedback that allows them to understand how much progress has been made in the shaking event. This can be an indication of how long the user has shaken satisfactorily. This can also be an indication of how well the ingredients have been mixed. For example, shaking with greater intensity can promote mixing of the ingredients, in which case the display can be configured to indicate that mixing has progressed further after shaking for the same duration with less intensity. As a further indication, the microcontroller 154 can be configured to gradually change the color and / or pattern of one or more display elements on the display as shaking occurs until sufficient shaking has occurred for satisfactory mixing or simulated mixing of the pharmaceutical ingredients for delivery. This can alert the user to the progress of the shaking event or mixing of the pharmaceutical ingredients by changing the color of one or more display elements. For example, the display elements can change from red to green, green to red, or any other color change to indicate that mixing has progressed. The display may also vary the pattern of display elements. For example, this may be a bar graph of progress, or an arrangement of display elements that shows a sparser arrangement as mixing progresses. The display may also use any combination of these variations in display elements to indicate to the user that satisfactory mixing or simulated satisfactory mixing is occurring.

[0030] Further, in the case where the device 200 includes a display 301, referring to FIG. 26, the microcontroller 154 may be configured to display at least two types of display elements on the display 301, which are separated into at least two separate parts on the display 301 before the start of shaking, and gradually blend into each other on the display 301 as long as the shaking continues with sufficient or a predetermined force and / or sufficient or a predetermined duration until it is determined that sufficient shaking has occurred for satisfactory mixing or simulated satisfactory mixing of the pharmaceutical ingredients for delivery, and when so determined, completely merge into each other in a regular pattern across the display 301. In this way, the user is provided with an intuitive indication of the progress of the mixing. In a training event, there may be no pharmaceutical ingredients for the user to see. In this case, the display 301 provides visual feedback that may represent how well the ingredients have been mixed. In either the case of a training event or a real mixing event where pharmaceutical ingredients are present, the user may not be able to see the pharmaceutical ingredients in situ, or the visual characteristics of the pharmaceutical ingredients may make it difficult to see the extent of mixing. In either case, the display 301 provides easily identifiable feedback to the user that the ingredients are mixed. There may be more than two display elements that can achieve a similar effect as two display elements.

[0031] In a device 200 where there are only two types of pharmaceutical ingredients to be mixed or to be simulated mixed and there are only two types of display elements, one of the types of display elements can correspond to one of the pharmaceutical ingredients and the other of the types of display elements can correspond to the other of the types of display elements. The display elements corresponding to the pharmaceutical ingredients thus provide the user with an intuitive display of the mixing state or progress of the mixing event. This can be extended to other compositions that include more than two ingredients, each of which corresponds to a different type of display element. In addition to this, two types of display elements can be used to represent more than two pharmaceutical ingredients. Alternatively, more than two types of display elements can be used to represent two pharmaceutical ingredients.

[0032] The microcontroller 154 can be configured to detect in a shaking event whether the movement and / or orientation of the housing 202 being shaken during a pharmaceutical administration or training event is sufficient for one or more predefined thresholds, including one or more of the magnitude of force applied to the device 200 during shaking, the orientation of the housing 202, the acceleration of the device 200, and the duration of said shaking. Many factors can affect the effectiveness of shaking in achieving mixing of pharmaceutical ingredients. For example, a user who shakes the device 200 "harder" can accelerate the device 200 more at both ends of the rocking motion. Greater acceleration and more vigorous shaking can mix the ingredients faster and disperse them better, since the ingredients are subjected to more force. While "more vigorous" shaking can result in better mixing, for certain compositions of pharmaceutical products, the additional benefit of "more vigorous" shaking above a certain threshold can be diminished. Thus, the device 200 can only require a certain threshold to be met and record the shaking behavior from that threshold. In some cases, the orientation of the housing 202 may affect the mixing of the pharmaceutical ingredients, in which case the device 200 detects in which direction the shaking motion is applied by the accelerometer 150 and provides feedback accordingly. For example, the user may shake the device 200 across the vertical axis instead of along the vertical axis. In this case, the device 200 may ignore this shaking motion as it does not contribute to mixing the pharmaceuticals. Instead, it is known that shaking across the vertical axis can also contribute to mixing the pharmaceuticals, and the device 200 may include this shaking in monitoring the shaking behavior. Shaking across the vertical axis of the device 200 may contribute less, the same, or more to recording the shaking behavior than shaking along the vertical axis. In a further aspect, if the device 200 includes a user notification device 155, the microcontroller 154 may indicate to the user whether the movement or orientation of the shaking housing 202 is sufficient for one or more of the predetermined thresholds.

[0033] The sufficient threshold applicable for mixing two pharmaceutical ingredients can be in one of the following ranges: 2g-15g, 5g-12g, and 7g-10g or thresholds of 3g, 4g, 5g, 6g, 7g, 8g, 9g, or 9.3g. Meanwhile, the suitable orientation of the movement along the longitudinal axis for mixing can be substantially along the longitudinal axis, perpendicular to the ground, or in the range of + / - 2 degrees on either side of the longitudinal axis, + / - 2 degrees on either side of the longitudinal axis, + / - 10 degrees on either side of the longitudinal axis, + / - 20 degrees on either side of the longitudinal axis, + / - 30 degrees on either side of the longitudinal axis. These thresholds are suitable for mixing the ingredients of INVEGA TRINZA™ as described in more detail below.

[0034] Referring again to FIG. 1A, the device 200 includes an initiation device 153 in communication with the microcontroller 154. The initiation device 153 can be configured to initiate detection of a shaking event by the microcontroller 154. Advantageously, the initiation device 153 can provide an input to the device 200 to indicate exactly when the device 200 is to be used. This allows the device 200 to conserve power because the microcontroller 154 and / or other components of the device 200 can enter a low power mode configured to consume less power from the power source 151. The initiation device 153 can be one of a start switch in communication with the microcontroller 154, a start button of a user interface displayed by a touch-sensitive display screen of the device, or the initiation device 153 can be a motion-sensing device that, when the housing 202 is moved, can indicate that detection of a shaking event should be initiated. By using the initiation device 153, a user can choose when the device 200 is ready for detection of a shaking event. This can be useful, for example, when the device 200 is carried around or transported to another location, helping to preserve the power source 151 for actual use rather than accidental triggering of the device 200.

[0035] If the initiation device 153 is a start switch, the start switch can be configured to wake up the microcontroller 154 from a power saving mode to an active mode upon detecting movement of the housing 202 during a drug mixing and administration event or during a training event. This allows the device 200 to conserve power when it is not in use or is not scheduled to be used. The start switch 153 can be configured to wake up the microcontroller 154 at one of many threshold levels of movement of the housing 202. For example, the start switch 153 can be configured to wake up the microcontroller 154 when the user lifts the device 200. Alternatively, the start switch 153 can be configured to require the user to give a sharp jolt to the device 200 to wake up the microcontroller 154. Alternatively, the start switch 153 can be configured to require the user to shake the device 200 more than once to wake up the microcontroller 154.

[0036] During such a power saving mode, the microcontroller 154 can be configured to consume less power, or no power at all, from the power source 151 during the power saving mode than in the active mode. In this way, the device 200 can conserve power when not in use. This advantageously saves use of the power source 151 for when it is needed. If the power source 151 is a battery, the battery charge can be conserved during periods of inactivity to extend the battery life of the device 200. Other power sources can also benefit from the conservation of their use.

[0037] Instead of or in addition to the start switch, the accelerometer 150 can be configured to start detecting a shaking event upon detecting movement of the housing 202 above a predetermined level during a medication administration or training event. Beneficially, in this embodiment, the user simply needs to start shaking the device 200, and the device 200 will automatically start recording the shaking. Advantageously, such a device does not require physical components such as switches or touch screens on the outside of the device 200. This allows the device 200 to have no physical external components or to have a reduced number of physical external components. This can improve the ease of use of the device 200 or make operation more simple.

[0038] The microcontroller 154 can be configured to detect, by the accelerometer 150, when the shaking of the housing 202 is prematurely terminated. The microcontroller 154 receives a signal from the accelerometer 150 and measures how long the shaking has occurred. If the shaking is stopped, the microcontroller 154 can receive a signal from the accelerometer 150 indicating that the shaking has stopped and compare the actual duration of the shaking with the required shaking time. The microcontroller 154 can also be configured to detect, by the accelerometer 150, when the level of shaking momentum drops to a level below one or more preset thresholds. Even if the user does not stop shaking the device 200, the degree of shaking may not be sufficient to meet the mixing requirements of the pharmaceutical ingredients. In this case, the microcontroller 154 is configured to detect when the force is not large enough to meet the thresholds. The microcontroller 154 can also be configured to detect when the average level of shaking momentum over a predetermined time of the shaking event drops to a level below one or more predetermined thresholds. In this embodiment, more versatility is achieved with the shaking measurement. More than one threshold can be set to more accurately determine if the correct degree of shaking has occurred. One threshold can be set requiring less shaking intensity for a longer time, while another threshold can be set requiring more shaking intensity for a shorter time, or vice versa. This allows the device 200 to more accurately determine how well it has been shaken. The microcontroller 154 can also be configured to detect, via the accelerometer 150, when the shaking component in a given direction is insufficient for a given level. Advantageously, in such a device, the microcontroller 154 can distinguish between many shaking directions, either along the vertical axis or in any other direction. The microcontroller 154 can also determine if a rotation in any direction has been applied to the device 200. The microcontroller 154 can give a certain weight to different components of the shaking action and / or combine all the indications of the different directions to determine if overall mixing has occurred.

[0039] The microcontroller 154 can be configured to notify the user of the unsatisfactory shaking when one or more of the events are detected. Notification to the user can be achieved using a user notification device 155. This can be positive feedback such as a light such as a lit or flashing LED, a message displayed on a screen, vibration as haptic feedback, a sound emitted from a sound emitting device, or alternatively negative feedback such as the dismissal of any of the notifications.

[0040] The microcontroller 154 can be configured to notify the user of a satisfactory shaking after or when the shaking event has elapsed a given time, such that satisfactory shaking is indicated by the absence of detection of one or more of the events. The notification can be given to the user by lighting or flashing an LED, changing the color of an LED, displaying a message on a screen, providing tactile feedback such as vibration, emitting a sound from a speaker or buzzer, or ceasing to provide any of the notifications as positive feedback. In addition, the given time can be upon completion of the shaking event, such that ingredients are mixed or ingredients are simulated to be mixed.

[0041] The microcontroller 154 can be configured to enter a pause mode to pause detection by the microcontroller 154, and then allow the user to resume shaking and continue detection during the shaking event. The user may need to momentarily stop shaking the device 200, for example, to adjust their grip or to pause for a while. In either case, the device 200 is configured such that a short enough interruption in shaking does not mean that shaking cannot continue. If the user stops shaking to readjust their grip, they can then continue shaking the device 200, and the microcontroller 154 will exit the pause mode and continue measuring the elapsed time and shaking.

[0042] The microcontroller 154 can be configured to start a timer and determine when the maximum allowable time after shaking the housing 202 has elapsed and alert the user via the user notification device 155 to shake the device 200 again during drug administration or during a training event. After the act of mixing the pharmaceutical composition, the ingredients may begin to separate. After a sufficient amount of time has elapsed after mixing, the composition is no longer in a state in which the user should administer the ingredients, for example, a suspension of particles may have formed a precipitate. Advantageously, with a device 200 in which the microcontroller 154 determines the maximum allowable time, the user is notified that too much time has elapsed and should shake the device 200 again before administering the drug. In the case of a drug administration device or assistance, the user is notified and needs to shake the device again to mix the ingredients. In the case of a training event, the user is notified of the time the drug should have been administered and the training assistance.

[0043] As shown in the embodiment of FIG. 1A, the accelerometer 150 may comprise a three-axis accelerometer 150 configured to detect each of three tangential components of the shaking acceleration and provide data indicative of the components to the microcontroller 154. Advantageously, the device does not require the accelerometer 150 to be placed in a particular orientation within the device 200 to enable detection of vertical shaking of the device 200 or shaking in any other direction. Furthermore, the microcontroller 154 may indicate to the user that shaking is not occurring in the correct direction for mixing the pharmaceutical ingredients. In addition to this, the microcontroller 154 may also consider shaking motions in many directions and use each of them to determine whether the shaking event was successful.

[0044] 1B and 2, the housing 202 includes syringe-shaped components located on or formed by the housing 202. Advantageously, these components provide the training device with components that mimic those present in an actual syringe, in which the housing 202 provides the user with haptic feedback similar to that experienced by using an actual syringe, aiding in the ability to train the user.

[0045] In particular, the syringe-shaped components can include a syringe-like barrel element 103 having a finger flange 101 at one end and a barrel tip 104 spaced apart along a longitudinal axis. These components mimic the key features of a syringe that a user may experience handling for mixing pharmaceutical ingredients.

[0046] The housing 202 can be configured to receive a pharmaceutical delivery device that contains a pharmaceutical ingredient. The pharmaceutical delivery device can be a syringe that can be manually activated by a user by depressing a plunger, or it can be an automatic injector. In either case, the housing has a configuration that can at least partially receive the delivery device. Further examples are provided in the remainder of this disclosure.

[0047] 3, the housing 202 comprises a body 109 sized and / or shaped to receive a syringe barrel 107 or vial. The housing 202 cooperates with the syringe barrel 107 or vial to allow the user to shake and mix the actual pharmaceutical ingredient while receiving feedback from the device. Alternatively, the device 200 can be used to train a user on proper technique before applying the device to the actual pharmaceutical ingredient prior to administration. When the device 200 is coupled to a syringe barrel 107 or vial, the shaking of the syringe barrel 107 or vial can be measured instead.

[0048] 6, the housing 202 includes a compartment that receives the entirety of the syringe 117 or vial. In this case, the device 200 can fully accommodate the syringe 117 or vial. This can assist users who find the size or shape of the syringe 117 or vial difficult to hold. Alternatively or additionally, the device 200 can provide some protection for the syringe 117. By fully receiving the syringe 117 or vial, the syringe 117 or vial can also be covered so that the contents are not easily seen by people other than the user. This can be a benefit to the user if there is a perceived social stigma associated with syringes.

[0049] Additionally, the housing may include a movable cover or lid 113 that is movable from a closed position that fully or partially covers the compartment, as shown in Figure 7, to an open position that allows a syringe 117 or vial to be inserted into the compartment, as shown in Figure 8. By providing a lid 113 for the housing, a user may selectively seal a syringe 117 or vial within the housing so that it can be sealed during transport or shaking events and released when drug delivery is intended.

[0050] Additionally, the compartment can be sized to snugly receive the entire syringe 117 or vial and securely retain it within the housing, where the compartment conforms to the configuration of the syringe 117 or vial to a degree that securely retains the syringe 117 or vial within the housing, allowing the syringe 117 or vial to fit precisely within the housing such that the orientation of the syringe 117 or vial relative to the housing is known.

[0051] 10, the housing includes an elongated body 121 approximately the same length as the syringe barrel such that a syringe can be inserted into a syringe receiving aperture 123 in the body 121 and held between a syringe finger flange and a body base 124 by compressive force applied by the finger members. In such a device, the housing body 121 is capable of receiving a syringe therein by aperture 123. The syringe can be inserted to a stop position, where a user can hold the syringe in the housing by holding the finger flange against the body base 124. This can be done by holding the finger flange between two fingers and holding the body base with the thumb.

[0052] The housing 202 may have an opening through which the discharge nozzle of the syringe or vial can extend, or may have an opening through which at least a portion of the syringe barrel near the discharge nozzle of the syringe can extend. In this embodiment, only a portion of the syringe or vial is housed in the housing 202. The syringe or vial can be inserted into one end of the housing 202, which can provide a form that is easy for a user to grasp.

[0053] 4, 6, and 12, the housing 202 comprises a body having a syringe receiving slot 125 sized to receive a syringe barrel or vial containing a pharmaceutical ingredient. In such a case, the slot 125 may extend through the body of the device 200 such that both ends of the syringe barrel or vial may protrude from both ends of the slot 125. The slot may allow the longitudinal axis of the syringe or vial to be aligned with the device 200 in a known relative orientation, such that the orientation of the syringe barrel 107 or vial relative to the ground or relative to the shaking direction during a shaking event may be known.

[0054] Continuing with reference to the embodiment of Figures 4, 6, and 12, the device may further comprise a releasable clip 112, 118 configured to hold the syringe in the slot. The clip 112, 118 may be biased such that the syringe barrel 107 can pass past the clip, but a threshold force on the syringe is required to again bias the clip 112, 118 to remove the syringe. This allows the device 200 to be kept together with the syringe for storage. This may also assist the user in keeping the device 200 securely attached to the syringe 117 during a shaking event. The releasable clip 112, 118 may be biased by a resilient member such as a spring, or may be biased by a movable component such as a user-operated switch or lever, allowing the user to selectively lock the syringe in the slot of the device 200.

[0055] 15, housing 202 includes a disk-shaped body 127 having a syringe receiving aperture 128 such that, during use, a syringe is inserted into the syringe receiving aperture and held in place by a user's thumb at lower thumb grip 130. In this manner, a user can hold the device in a grip with their thumb at disk-shaped body 127. Some users may find this grip easier to maintain while shaking device 200 during a shaking event.

[0056] Referring now to a syringe as shown in Figure 3, the syringe may include an ejection member adapted to eject the contents of the syringe upon application of force. Such an ejection member may be a bung housed within the body of the syringe and providing a seal within the syringe for containing the pharmaceutical component. Application of pressure to the ejection member or bung increases pressure on the pharmaceutical component, expelling it through an opening.

[0057] The device 200 may comprise an activator adapted to act on the discharge member of the syringe to expel its contents through the discharge nozzle. Such an activator may be a plunger 105 that can be manually depressed by a user to act on the discharge member to expel the pharmaceutical ingredient. Alternatively, the activator may be a plunger acted on by an automatically actuated member such as a spring.

[0058] 3 and 12, the housing 202 may further include an activator opening through which a syringe's discharge member may penetrate for a user to apply force directly from outside the housing. In this embodiment, the housing may accommodate a majority of the syringe, but the syringe does not necessarily need to be removed from the housing for the user to administer the pharmaceutical ingredient. This may reduce the time it takes for a user to administer the pharmaceutical ingredient after successfully completing a mixing event.

[0059] The device 200 can be an attachment for a syringe, with the housing 202 adapted to fit against the barrel of the syringe. In this embodiment, the device can be attached to the syringe and positioned against the barrel. Such a device can have a small size and can simplify attachment to the syringe.

[0060] Alternatively, device 200 can be an attachment for a syringe, with housing 202 adapted to fit around syringe barrel 107. Similarly, device 200 can have a small size, simplifying attachment to a syringe, but can at least partially surround syringe barrel 107 for a tighter fit. Housing 202 can be adapted to fit only partially around syringe barrel 107, or can be adapted to fit entirely around syringe barrel 107.

[0061] Alternatively, the housing 202 can be formed of two hinged parts that rotate relative to each other in a hinged manner, such that the hinged parts close around and latch to the barrel. The hinged parts can be connected to each other by a rotatable hinge or a living hinge. At least one of the two parts can include a slot to receive the barrel of the syringe. The two parts can be held together by a user applying force or can be held together by a mechanical latch, such as a latch member.

[0062] Instead of requiring a syringe employing an ejection nozzle, the housing 202 may be provided with an ejection nozzle adapted to be in fluid communication with the contents of a vial when such a vial is inserted into the housing 202. In such a device, the vial may be received by the housing 202 such that the housing 202 provides an ejection nozzle for expelling the pharmaceutical ingredient. In addition, the device 200 may further comprise an activator 105 adapted to act on the ejection member to expel the contents of the vial through the ejection nozzle. In this embodiment, the vial may be replaced while components of the device may be reused.

[0063] Referring now to the device shown in Figures 18 to 21, a device 200 is configured to be attached to a packaging 136, 142 containing a syringe 144. The syringe 144 may be supplied in a packaging 136, 142 which may be removed before the pharmaceutical component is administered. A mixing event may be performed using the device 200 before the packaging is removed. Using such a device 200, the syringe 144 does not need to be removed from its packaging 136, 142 until the pharmaceutical component is actually administered.

[0064] 18-21, the device 200 may further comprise at least one retaining member 138, 145 configured to hold the device 200 against the packaging 136, 142 containing the syringe 144. The device 200 may include an element, such as a latch, a side interference clip 138, or a return clip 145, configured to engage with a corresponding portion of the packaging 136, 142 of the syringe 144, such as a recess or edge of the packaging 136, 142. Alternatively or additionally, the device 200 may comprise an adhesive to hold the device 200 against the packaging 136, 142. Additionally, the device 200 may be held against the packaging 136, 142 by the application of force by a user.

[0065] The pharmaceutical ingredients for mixing include at least two phases. The at least two phases may separate after a period of inactivity. The ingredients may include more than two phases. For example, if there are two phases, both phases may be liquid phases, or one phase may be a liquid phase and the other a solid phase. In either case, the ingredients may be mixed by shaking the container enclosing the ingredients. If there are three phases, there may be two liquid phases and one solid phase, one liquid phase and two solid phases, or a combination of three liquid phases. The liquid phase may include ingredients for a suspension of solid phase, the solid phase including the pharmaceutical active ingredient. Alternatively or in addition, any liquid phase may include the pharmaceutical active ingredient.

[0066] Further disclosure of various features will now be described with reference to the figures. In particular, FIG. 1A illustrates a simplified schematic diagram of an electronic system that can be used with various embodiments described and illustrated herein. It is noted that in these embodiments, the force is measured, preferably using a three-axis accelerometer 150. This is because a user's shaking motion will often be in more than one direction, and sufficient acceleration can be a factor of acceleration in multiple directions. Thus, the threshold can be determined to be a function of one or more acceleration directions.

[0067] In addition, the system may include a start switch 153, which may be a manually activated switch or, preferably, an acceleration activated switch to power up the circuit, thus conserving battery power when the device is not in use. The advantage of an acceleration activated switch is that the user only needs to initiate shaking of the device to turn it on. In some embodiments, it may be preferable to require the user to make a conscious decision to turn the device on and take a specific, well-defined action to turn the device on, and thus a manual switch may be preferred. Once the device is powered up, the battery latch 152 ensures that power is provided from the battery 151 for a sufficient time to complete the shaking cycle and provide feedback to the user.

[0068] Further developments of this embodiment are described below. The time is measured from the moment shaking is first detected using a microcontroller 154, microprocessor or timer. The electronic system is programmed with an algorithm that compares the measured shaking acceleration and duration with preset thresholds. The electronic system compares the recorded elapsed time and force measurements and returns a communication signal corresponding to the device status 155. The device status is communicated using one or preferably a combination of the following: visual feedback such as a light emitting diode (LED), a graphic display such as a liquid crystal display (LCD), audible feedback such as an audible buzzer or a polyphonic speaker, tactile feedback such as a vibration motor. Such electronic circuits require a power source such as a battery, which may or may not be rechargeable. If rechargeable, the battery may or may not be replaceable, in which case the device must be discarded in its entirety at the end of its life, which is defined by the end of the battery life. If the battery is rechargeable, it may or may not be replaceable, in which case the device must be disposed of in its entirety at the end of its life, defined by the end of the battery life when it can no longer hold a sufficient charge to effectively power the device, which may be defined by the number of charging cycles.

[0069] The electronic circuitry is housed inside the device, along with a visual feedback means viewable by the user through a window or light-transmitting element.The electronic circuitry provides an additional design feature.

[0070] Pause feature. The program may enable the system to detect, using an accelerometer or acceleration-activated switch, when shaking is terminated prematurely or when the shaking momentum level drops below a preset threshold. If such an event is detected, the device may enter a pause mode, pausing the timing process and indicating to the user that the device has entered pause mode. The indication to the user may be a pause in the feedback being provided, such as pausing an audible sound or pausing a haptic vibration, or other means such as a change in the state of a light or screen. Upon receiving the indication of the pause, the user may correct the action by restarting the shaking action or increasing the momentum of the shaking action, at which point the device will switch out of pause mode and resume the timing and force monitoring process from the time count when it was paused. If the device has been in pause mode for such a significant amount of time that particles may have begun to reform a precipitate, the timer is reset. The reset of the timer may or may not be indicated to the user by a user notification device. This may be communicated to the user, for example, by a message on the display, an audible sound emission, a haptic vibration, or as a change in the state of a light or screen.

[0071] Syringe Dosing Timer. A timer can be used to warn the user that too much time has passed since the device has been shaken. After shaking, the particles slowly return to a settled state. Thus, there is a maximum time limit between shaking the device and administering the injection. In some circumstances, the user may shake the device correctly but be distracted long enough that the particles in the syringe resediment. Once the maximum allowable time has elapsed after shaking the housing, a timer can be set to warn the user to shake the device again before administering. This warning can be communicated using several methods. By way of example, an audible buzzer can be sounded once the maximum time has elapsed, or a green light emitted to indicate that shaking is complete can be turned off.

[0072] Low Battery Warning. Such electronic systems require a power source, preferably a battery cell. When the battery power drops to a level where the functionality of the device may be impaired in due course, the device may indicate to the user that battery failure is imminent and that the battery needs to be replaced. The device may shut down in such an event, such that the device cannot be used until the battery is replaced. This prevents potential malfunction of the device. The battery condition may be measured as the charge or power remaining in the battery, the voltage supplied to the circuit, the current supplied to the circuit, or the stability of the battery under load variations. Alternatively, in the case of a rechargeable battery, the health of the battery may be monitored to indicate when the functionality of the device may be impaired. If the device notifies the user of an impending power failure, the user may take steps to replace the battery or the entire device. If the battery is not replaceable, the finite life of the battery may be shorter than the life of the other components, and may beneficially indicate to the user that the device should be replaced before any other components reach their end of life.

[0073] Abnormality warning. Such electronic systems can perform self-diagnosis of the system and major components so that the user can be alerted if an abnormality is detected. The system can perform such self-diagnosis whenever the device is booted up for a shake cycle and immediately communicate that an abnormal mode has been entered. This prevents the user from using the faulty device and prompts the user to take corrective action, such as returning the device to the manufacturer and using an alternative device.

[0074] Information that distinguishes between force and time. In a first instance, the invention is described as providing a single piece of information to the user regarding the success of the shaking action when both sufficient time and sufficient momentum are achieved. An alternative configuration of such an electronic system can provide feedback to the user regarding the component, providing two pieces of information: the elapsed time and the level of momentum over that time. Thus, if the user does not achieve a sufficient combination of time and momentum, the information provided can be examined to determine the reason for the lack of success, determining if they did not shake for a sufficient time or did not shake with enough momentum.

[0075] Drug Expiry Alert. A development of such an electronic system employs a means to read the expiration data on the syringe and alert the user if the expiration date has been passed. When the user is informed that the expiration date has been passed, the expired syringe can be discarded and another unexpired syringe can be used. Such a system may use a scanning component that reads a bar code or text on the syringe to collect the expiration date, or may communicate with a chip on the syringe that contains the lot and expiration information, compare the date to an internal clock and calendar programmed into the processor, and provide an alert if the collected date is prior to the date on the internal clock and calendar.

[0076] The features described and exemplified above can be embodied in the following embodiments 1 to 8, which have important variations and differences between the respective embodiments described with reference to the drawings shown below.

[0077] Embodiment 1. Mimicry. The trainer embodiment (FIGS. 1B and 2) uses a housing form factor that mimics that of a syringe. The embodiment can include a syringe barrel element 103 with a finger flange 100 on one end and a barrel tip 104 on the other end. The distance between the finger flange 100 and the barrel tip 104 is similar to that of a syringe so that the barrel element can be held in a similar manner. At the top of the form is a cylindrical section 100 that represents the syringe plunger rod. The barrel 103 includes a light emitting feedback window 102 through which light is emitted to communicate the status of the device. In a preferred embodiment, an amber light is used to indicate that the device is operating in a shaking cycle and monitoring the level of agitation imparted to the device, and a green light is used to indicate that the shaking cycle is complete and sufficient shaking has occurred. When not in use, the light is turned off to conserve battery power and to indicate that the shaking cycle has not yet begun.

[0078] Embodiment 2 - Mounting. The embodiment shown in Figures 3-5 is mounted on a syringe and provides feedback to the user while the user is shaking the syringe. The device housing can include a body 109 having a slot 111 sized to receive the syringe barrel 107. A clip 112 (Figure 4) in the slot 111 holds the syringe. Once the device housing is mounted on the syringe, the shaking motion is measured using an internal electronic system and the device status is communicated in two simultaneous ways. The first communication method is with light emitted from the light emitting feedback window 110. An amber light indicates that a shaking cycle is in progress and a green light indicates that the shaking cycle is complete. The second simultaneous feedback method is audible. An intermittent audible buzzer tone indicates that a shaking cycle is in progress and changes to a continuous tone when the shaking cycle is complete. Additionally, the intermittent sound emitted during the shaking cycle is set at a frequency of approximately 3 Hz to increase the shaking frequency and speed required for optimal mixing, taking advantage of the human tendency to conform repetitive movements to an audible vibrational sound.

[0079] EMBODIMENT 3 - Housing. The embodiment shown in Figures 6-9 houses a syringe and provides feedback to the user while the user is shaking the syringe. The device housing is opened by pressing the lid catch 120 and the syringe 117 is placed in the housing liner 115 where it is held by the spring clip 118 as shown in Figure 7. Alternatively, the syringe can be held by the housing lid 113 when the device housing is closed. The housing lid 113 pivots around the housing syringe 116 and encloses the syringe as shown in Figure 8. The housing includes flat surfaces on the housing base 148 and housing top 149 (Figure 9) to prevent rolling when resting on a desk or tabletop. The housing is closed and held in the closed position by the lid catch 120. The housing profile is designed to allow the user to hold the housing comfortably and securely during shaking. The shaking motion is measured using an internal electronic system and the device status is communicated in two simultaneous ways. The first communication method is using light emitted from the light emitting panel 119, where an amber light indicates that a shaking cycle is in progress and a green light indicates that the shaking cycle is complete. The second simultaneous feedback method is tactile. Intermittent vibrations transmitted to the holding hand indicate that a shaking cycle is in progress and change to continuous vibrations when the shaking cycle is complete. Additionally, the intermittent vibrations emitted during the shaking cycle are set at a frequency of approximately 3 Hz to increase the frequency and speed of shaking required for optimal mixing, taking advantage of the human tendency to match repetitive behavior to vibration stimuli. The light emitting panel turning green indicates the user to remove the syringe and continue the drug administration process. This embodiment can be further developed with a syringe lockout mechanism. This feature detects the presence of an internal syringe and locks the housing in a closed state, unlocking the housing only when sufficient time and shaking momentum have been achieved. Additionally, if the user does not open the housing and remove the syringe to inject within the specified time, the housing may relock on itself and / or the light may change back to amber, indicating that the device housing must be shaken again to resuspend the particles before the syringe can be used.

[0080] EMBODIMENT 4 - POT. The embodiment shown in Figures 10 and 11 includes an elongated body housing approximately the same length as the syringe barrel. The syringe is inserted into a syringe receiving hole 123 in the body housing and is held between the syringe finger flange 101 and the device body housing base 124 by compressive force applied by the finger. When the combined device and syringe are shaken, the movement is measured using an internal electronic system and the device status is communicated in two simultaneous ways. The first communication method is using light emitted from the light emitting band 122, with an amber light indicating that a shaking cycle is in progress and a green light indicating that the shaking cycle is complete. The second simultaneous feedback method is tactile. Intermittent vibrations transmitted to the holding hand indicate that a shaking cycle is in progress and change to a continuous sound when the shaking cycle is complete. Additionally, the intermittent vibrations emitted during the shaking cycle are set to a frequency of approximately 3 Hz to increase the frequency and speed of shaking required for optimal mixing, taking advantage of the human tendency to match repetitive behavior to vibration stimuli. The light-emitting panel turns green to indicate to the user to remove the syringe and continue the drug administration process. As with other embodiments, additional auxiliary communication means such as audible or tactile vibration feedback can be included, and a timing function can be used to inform the user if the syringe has not been removed from the device before a specified time, indicating that the device should be shaken again to resuspend the particles before injection can be performed. A switch inside the receiving hold 123 is used to detect when the syringe is attached to the device.

[0081] EMBODIMENT 5 - Finger Hook Attachment. The embodiment shown in Figures 12, 13 and 14 is similar to embodiment 2 in that it is attached to a syringe. This embodiment is shown on the syringe in Figures 13 and 14. The syringe fits into and is held in the syringe receiving slot 125. The electronic system is housed on the front and interacts with the user via a light panel 126 on the front. Orange indicates the device is sensing and turns green once the device has been sufficiently shaken. As with the other embodiments, additional auxiliary communication means can be included such as audible or tactile vibration feedback.

[0082] 15 and 16 is similar to embodiment 4 in that it fits under a syringe, but is a much more compact design. The embodiment can include a body housing 127 having a syringe receiving hole 128. The interface is provided by a peripheral luminous band 129 around the diameter of the base of the form. In use, a syringe is inserted into the syringe receiving hole 128 and held in place by the user's thumb at the lower thumb grip 130. As with the other embodiments, additional auxiliary communication means can be included, such as audible or tactile vibration feedback.

[0083] EMBODIMENT 7-INDUCTION. The embodiment shown in FIG. 17 is similar to embodiment 1 in FIG. 1B and FIG. 2. The embodiment is a stand-alone device, does not interact with a syringe, and is intended for use prior to administration procedures. The user can practice shaking before shaking a real syringe. The device can include a device body housing 134 with finger grips 131 and thumb grips 132 at either end. The distance between the finger grips and thumb grips is similar to the distance between the syringe finger grips and the rubber stopper to ensure that the feel of the device is similar. When the user shakes the device, the device detects the applied force and emits amber light from the light emitting window 133. The light changes to green when shaking occurs with sufficient force and for a sufficient period of time. As with the other embodiments, additional auxiliary communication means can be included, such as audible or tactile vibration feedback.

[0084] Embodiment 8 - Packaging B 20 and 21, this embodiment is similar to embodiment 8 in that the device 141 is attached to a syringe blister package 142 while a syringe 144 is housed inside. In this embodiment, the protective film 143 is still in place on top of the blister tray 142. Referring to FIG. 21, the device is attached to the blister tray by sliding the device along the length of the blister tray and is held against the blister tray using a return clip 145 on the underside of the device. The main housing of the device 147 contains a transmission means, namely, a light emitting strip 146. As with the other embodiments, an electronic system within the device detects the onset of shaking and begins monitoring the shaking momentum and duration. While doing so, the light emitting strip 146 emits an amber light. Once sufficient momentum and duration are achieved, the light changes to green. After shaking is complete, the device is removed from the blister tray 142, the blister tray film 143 is peeled off, and the device is used normally according to the syringe administration instructions. As with other embodiments, additional auxiliary communication means may be included, such as audible or tactile vibration feedback.

[0085] During formulation development of Invega Sustenna Three Month, the required duration and vigor was identified and quantified as 15 seconds of vigorous shaking. Vigorous shaking was initially defined using a training video in which a skilled practitioner experienced in the correct dispensing of pharmaceutical products shook a syringe for the required 15 seconds at the required level of vigor. Video analysis was used to estimate the amplitude and frequency of shaking demonstrated and it was found that a shaking amplitude of approximately 40 cm was used at a frequency of 3.4 Hertz. Assuming simple harmonic motion, it was calculated that the syringe experienced a maximum acceleration of 9.3 g. This provides an indication of the required acceleration to be imparted to the fluid to achieve sufficient mixing as recommended by skilled practitioners in the dispensing of such formulations.

[0086] A failure mode associated with not mixing the syringe sufficiently is not dispensing the full dose from the syringe. This occurs because an insufficiently shaken syringe contains residual sediment that may block or partially block the syringe or needle during administration. Thus, syringes containing fluids with different sediment properties such as mass, density, and concentration can quantify the required mixing momentum by applying (by experimental means) a controlled and known level of acceleration that measures the force required to expel the fluid from the syringe. Using such methods, different shaking momentum thresholds can be determined for different fluids with different properties. Figure 22 illustrates the device requirements for thresholds that exceed the inherent variability of the device population.

[0087] Once the required threshold is determined, the user's behavior should also be understood. Different users have different abilities, strengths, habits and likelihoods, and therefore there is inherent variability in how each interprets the instruction to "shake vigorously", some of which will necessarily not meet the required threshold, as illustrated in the diagram of FIG. 23. Different users also utilize different shaking techniques, some of which are more vigorous than others. While acknowledging this variability, the conclusion is drawn that a need exists for the device described in this disclosure, since a minimum shaking time and vigor is required. The device can communicate the required time and vigor to the user, modifying their behavior and increasing the likelihood that the user will achieve the required minimum level of mixing. The subsequent effect of the device on the behavior of an entire population of users is illustrated in FIG. 24.

[0088] Once the threshold requirements and the goal of the behavior change are understood, various embodiments of form and functionality that can elicit the desired behavior change can be considered. Such embodiments can be used as either stand-alone devices or in-process devices.

[0089] A standalone device is used separate from the dosing process, providing the user with an opportunity to shake the device and learn what level of vigor is required when shaking a real device. Such a standalone device may have a form factor that is close to that of a syringe, thereby representing as close an experience as possible to shaking a real syringe. Other form factors may also be used. For example, if the drug is sold in vials, a vial-shaped device may be more appropriate.

[0090] The assistive device is required to couple, attach or house the real syringe. Thus, a coupling, attachment or housing means is required. This leads to various opportunities for several form factors, illustrated in Figures 1-21. Several means of communicating the device status to the user are possible. As previously mentioned, the means can include lights of different colors or states (flashing or steady), audible means such as buzzers and speakers, and tactile means such as vibration. As shown in Figure 25, further means are possible, such as an LCD 301 (liquid crystal display) or equivalent, which can use graphical means to communicate the device status. The LCD can be used as a segmented display, communicating the device status through words and icons, or as described in Figure 26, as a figurative representation of the mixed state of the solvent. In this case, segments or pixels of the LCD are turned on or off to form a visual representation of the particles mixing with the solvent. On the left side 302 of Figure 26, the dark pixels in the lower part of the display represent the presence of sediment at the bottom of the syringe. As shaking is detected by the electronic system, different pixels are turned on and off across the screen to indicate ongoing mixing, and once sufficient mixing is achieved the LCD may show a uniform and homogenous color across the screen, indicating that the solution is also uniform and homogenous. In turn, as the device is shaken, mixing progresses from a first state 302, indicating the presence of precipitate, turning different pixels on and off across the screen, and the state progresses to a second state 303. As shaking and mixing continues, fewer pixels are lit and the screen displays sparser pixels in a third state 304, until the entire screen is homogenous at the final state 305.

[0091] Various embodiments of the present invention, when configured as a stand-alone training device, realize certain benefits: (a) make the user aware of how much shaking time is needed, allowing the user to learn through experience; (b) allow the user to experience what level of shaking vigor is needed; (c) teach the user what duration and level of vigor is needed for a real device without slowing down the normal administration process flow; (d) allow the device to have a form factor that is very close to that of a real syringe; (e) develop the user's skill to shake the syringe sufficiently without having to rely on the assistance of an assistant; and (f) be independent of the actual injection process, and therefore do not overly complicate the process.

[0092] When the present invention is configured as an actual or "in-process" device, other benefits are also realized: (a) it makes the user aware of how much shaking time is needed, allowing the user to learn through experience; (b) it gives the user experience of what level of shaking vigor is needed; (c) when attached to a syringe, it allows for actual syringe shaking, giving the user real-time confidence that the syringe has been shaken sufficiently; and (d) when used correctly, it reduces the chances that a real syringe will be insufficiently shaken.

[0093] It is understood that these embodiments have been prototyped for testing with an injectable multi-phase pharmaceutical solution. Such testing has led to the selection of a version for commercialization with a product bearing the trademark INVEGA TRINZA™, which product is intended for sale by Janssen Pharmaceuticals, Inc., Titusville, New Jersey 08560. The proposed commercialized version of the invention is intended for use with INVEGA TRINZA™, which is described in more detail below.

[0094] In one particular embodiment, a device for training a user for proper mixing of pharmaceutical ingredients is provided, including a housing extending along a longitudinal axis and housing an electronic system, as shown in FIG. 1A. A battery is disposed within the housing to provide power to the device. The device includes a three-axis accelerometer for measuring spatial acceleration or force applied to the device. The three-axis accelerometer allows for measurement of the user's shaking motion in more than one direction. In addition, an acceleration-activated start switch is provided to power the device when the user starts shaking the device. Once the device is powered up, a battery latch is connected to the battery so that the battery provides power for a sufficient time to complete a shaking cycle and provide feedback to the user. A microcontroller is provided within the device and is connected to the acceleration-activated switch, the three-axis accelerometer, and the battery latch. Time is measured using the microcontroller from the moment shaking is first detected. The electronic system is programmed with an algorithm that compares the measured shaking acceleration and duration with preset thresholds. The electronic system compares the recorded elapsed time and force measurements and returns a communication signal corresponding to the device status. Additionally, the device is provided with at least one light emitting diode (LED) for visual feedback and a vibration motor for tactile feedback. The electronic system is housed inside the device, and the visual feedback is made visible to the user by a window or a light-transmitting element.

[0095] In use, a user activates the device by beginning to shake the device. The microcontroller measures the elapsed time. While the user is shaking the device, acceleration is measured using a three-axis accelerometer. The microcontroller algorithmically determines if the level of shaking momentum exceeds a preset threshold. An amber light emitted from an LED indicates this while a shaking cycle is in progress. Also during the shaking cycle, the vibration motor emits an intermittent audible buzzer tone. The intermittent tone is set to a frequency of approximately 3 Hz to increase the frequency and speed of shaking required for optimal mixing.

[0096] If the level of shaking momentum applied by the user is below the preset threshold, the electronic system detects this using the three-axis accelerometer. If this event is detected, the device enters a pause mode, suspends the timing process, and indicates to the user that the device has entered the pause mode. This indication to the user is brought about by interrupting the haptic vibrations by the vibration motor. Upon receiving the indication of the pause, the user can either resume the shaking action or correct the action by increasing the momentum of the shaking action so that the level of shaking momentum is above the preset threshold. At this moment, the device switches out of the pause mode and resumes the timing and acceleration monitoring process. In this case, the time count starts from the time count when the device was paused. If the device has been in the pause mode for a significant amount of time during which particles may have started to reform the sediment, the timer is reset.

[0097] Once the user achieves sufficient shaking vigor and duration, the electronic system determines that the shaking cycle is complete. Completion of the shaking cycle is indicated to the user by emitting a green light from the LED. Completion of the shaking cycle is also indicated to the user by the vibration motor emitting a continuous sound.

[0098] Once the shaking cycle is successfully completed, a timer begins counting to ensure that too much time does not elapse between shaking the device and administering the infusion. The timer is set to warn the user after the maximum allowable time has elapsed after shaking the housing to shake the device again before administering. The timer can be set, for example, to warn the user after five minutes of inactivity after shaking the housing. An indication to the user that the maximum time has elapsed is given by turning off the LED green light that previously indicated the shaking cycle was complete.

[0099] When the remaining power of the battery reaches a low enough level that the functionality of the device may eventually be impaired, the device is configured to indicate to the user that battery failure is imminent, at which point the user can replace the battery. In the event that the electronic system detects that the battery power level is too low, the device is disabled so that it cannot be used until the battery is replaced.

[0100] When initiated by the user in preparation for a shake cycle, the electronic system performs a self-diagnosis of the system and key components such as the three-axis accelerometer. If the electronic system determines that the device is faulty, it will enter an abnormal mode and communicate this to the user via an LED or vibration motor. This prevents the user from using a faulty device and prompts the user to take corrective action.

[0101] Further information regarding the mixing of pharmaceutical ingredients, which forms part of this disclosure, is provided below with reference to FIG.

[0102] 1. Indications and Usage INVEGA TRINZA™ (paliperidone palmitate), 3-month infusion, is indicated for the treatment of patients with schizophrenia after the patient has been adequately treated with INVEGA SUSTENNA® (1-month extended-release paliperidone palmitate injectable suspension) for at least 4 months [see Dosage and Administration (2.2) and Clinical Trials (14)]. 2. Dosing and Administration 2.1 Dosage Instructions INVEGA TRINZA(TM) should be administered once every three months. Each injection should only be administered by a medical professional. Parenteral products should be visually inspected for foreign matter and discoloration prior to administration. It is important to shake the syringe vigorously for at least 15 seconds to ensure a homogenous suspension. Inject INVEGA TRINZA within 5 minutes after vigorously shaking [see Dosing and Administration (2.8)]. INVEGA TRINZA(TM) is intended for intramuscular use only. Do not administer by any other route. Avoid inadvertent injection into a blood vessel. Administer the dose in a single injection. Do not divide the dose into multiple injections. Inject slowly and deeply into the deltoid or gluteal muscles. INVEGA TRINZA™ should be administered only with the thin-walled needle provided in the INVEGA TRINZA™ pack. To reduce the risk of blockage, do not use needles from 1-month extended-release paliperidone palmitate injectable suspension packs or any other needles available on the market. deltoid muscle injection The recommended needle size for administration of INVEGA TRINZA™ into the deltoid muscle is determined by the patient's weight. For patients weighing less than 90 kg, a 2.5 cm (1 inch), 22 gauge thin-walled needle is recommended. For patients weighing 90 kg or more, 4 cm (1 1 / 2 inch), 22 gauge thin wall needles are recommended. Administer into the central deltoid muscle. Deltoid injections should be alternated between the two deltoid muscles. Buttock injection The recommended needle size for administration of INVEGA TRINZA™ to the gluteal muscles is 4 cm (1 1 / 2 22 gauge thin wall needle. Administer into the upper outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles. Incomplete dosing To avoid incomplete dosing of INVEGA TRINZA, be sure to shake the prefilled syringe vigorously for at least 15 seconds within 5 minutes prior to administration to ensure a homogenous suspension and to ensure that the needle does not clog during injection [see Dosing and Administration (2.8)]. However, if an incomplete dose is administered, do not refill the syringe or administer another dose of INVEGA TRINZA(TM). Closely monitor and treat patients as medically appropriate with oral intake until the next scheduled 3-month infusion of INVEGA TRINZA(TM). 2.2 Schizophrenia adult INVEGA TRINZA™ should only be used after INVEGA SUSTENNA™ (1-month extended-release paliperidone palmitate injectable suspension) has been established as sufficient therapy for at least 4 months. To establish a consistent maintenance dose, it is recommended that the last 2 doses of INVEGA SUSTENNA™ be at the same dosing strength as was used prior to initiating INVEGA TRINZA™. When the next monthly paliperidone palmitate dose is scheduled with the INVEGA TRINZA™ dose based on the previous monthly infusion dose, initiate INVEGA TRINZA™ at the 3.5x equivalent dose as shown in Table 1. INVEGA TRINZA™ may be administered up to 7 days prior to or up to 7 days after the scheduled monthly time point of the next paliperidone palmitate monthly dose.

[0103] [Table 1] Following the initial dose of INVEGA TRINZA, INVEGA TRINZA should be administered every three months. If necessary, incremental dose adjustments within the range of 273 mg to 819 mg may be made every three months based on individual patient tolerance and / or efficacy. Due to the duration of action of INVEGA TRINZA, a patient's response to an adjusted dose may not occur for several months [see Clinical Pharmacology (12.3)]. 2.3 Forgetting to take medication Medication window Avoid missing doses of INVEGA TRINZA. If necessary, patients can receive an infusion up to 2 weeks before or after the 3-month time point. 3 days since last injection 1 / 2 Forgot to take medication for 4 months 3 days after last INVEGA TRINZA™ infusion 1 / 2 If more than three months (maximum, but less than four months) have passed, the previously administered dose of INVEGA TRINZA(TM) should be administered as soon as possible and this dose should be followed by three monthly infusions. Forgotten to take medication 4 to 9 months after the last injection If 4 months up to 9 months have passed since your last infusion of INVEGA TRINZA™, do not administer the next dose of INVEGA TRINZA™. Instead, use the reinstatement schedule shown in Table 2.

[0104] [Table 2] Missed dose for more than 9 months since last injection If more than 9 months have passed since the last infusion of INVEGA TRINZA™, resume treatment with 1-month extended-release paliperidone palmitate injectable suspension as described in the product's prescribing information. INVEGA TRINZA™ may be resumed after the patient has been fully treated with 1-month extended-release paliperidone palmitate injectable suspension for at least 4 months. 2.4 Concomitant use with risperidone or oral paliperidone Paliperidone is the primary active metabolite of risperidone, so caution is advised when coadministering INVEGA TRINZA with risperidone or oral paliperidone for extended periods of time. There are limited safety data regarding the concomitant use of INVEGA TRINZA with other medications for schizophrenia. 2.5 Dose adjustments in patients with renal impairment INVEGA TRINZA™ has not been systematically studied in patients with renal impairment [see Clinical Pharmacology (12.3)]. For patients with mild renal impairment (creatinine clearance >50 mL / min to <80 mL / min [Cockcroft-Gault]), titrate to INVEGA TRINZA™ after stabilizing the patient with a 1-month extended-release paliperidone palmitate injectable suspension [see Table 1 in Dosage and Administration (2.2)]. [See also Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)] INVEGA TRINZA® is not recommended for patients with moderate or severe renal impairment (creatinine clearance <50 mL / min) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]. 2.6 Switching from INVEGA TRINZA to 1-Month Extended-Release Paliperidone Palmitate Injectable Suspension To switch from INVEGA TRINZA™ to INVEGA SUSTENNA® (1-month paliperidone palmitate extended-release injectable suspension), the 1-month paliperidone palmitate extended-release injectable suspension should be initiated 3 months after the last dose of INVEGA TRINZA™ at 1 / 35 equivalent dose as shown in Table 3. The 1-month paliperidone palmitate extended-release injectable suspension should be continued dosed at 1-month intervals.

[0105] [Table 3] 2.7 Switching from INVEGA TRINZA™ to Extended-Release Oral Paliperidone Tablets To switch from INVEGA TRINZA™ to extended-release oral paliperidone tablets, daily dosing of extended-release paliperidone tablets should be initiated 3 months after the last INVEGA TRINZA™ dose and transitioned over the next several months following the last INVEGA TRINZA™ dose as described in Table 4. Table 4 provides a dose conversion schedule that will achieve similar paliperidone exposure with once-daily paliperidone extended-release tablets in patients previously stabilized on different doses of INVEGA TRINZA™.

[0106] [Table 4] 2.8 Usage Procedure Give every 3 months Shake the syringe vigorously for at least 15 seconds (see Figure 27). Intramuscular injection only. Do not administer by any other route. INVEGA TRINZA(TM) should be administered by a healthcare professional as a single injection. Do not divide the dose into multiple injections. INVEGA TRINZA(TM) is intended for intramuscular use only. Inject slowly and deeply into the muscle, taking care not to inject into a blood vessel. Read instructions thoroughly before use. dosage This medication should be administered once every three months. Dispensing Remove the tab label from the syringe and place it in the patient record. INVEGA TRINZA™ requires longer, more vigorous shaking than INVEGA SUSTENNA® (1-month extended-release paliperidone palmitate injectable suspension). With the syringe tip facing up, shake the syringe vigorously for at least 15 seconds (see Step 2) within 5 minutes prior to administration.

[0107] In addition to the embodiments and disclosures presented above, which may be claimed individually, separately, in part, or in any combination with the features of the overall disclosure presented herein, the following enumerated embodiments may be claimed individually, separately, in part, or in any combination with the features of the overall disclosure presented herein. 1. An apparatus for training a user for proper mixing of pharmaceutical ingredients, an apparatus for assisting in the mixing and administration of pharmaceutical ingredients, or an apparatus for mixing and administering pharmaceutical ingredients, comprising: a housing for receiving a pharmaceutical delivery device containing a pharmaceutical ingredient; a microcontroller disposed within the housing; a motion / orientation detection device disposed within or on the housing and in communication with the microcontroller; The device comprises: 2. The device of enumerated embodiment 1, wherein the motion / orientation detection device is electrically connected to a microcontroller. 3. The device of any one of enumerated embodiments 1-2, wherein the motion / orientation detection device comprises a device configured to detect one or both of motion and orientation of the housing relative to a ground. 4. The device of any one of enumerated embodiments 1-3, wherein the motion / orientation detection device is configured to detect motion of the housing and provide a signal indicative of the motion to the microcontroller. 5. The device of any one of enumerated embodiments 1-4, wherein the motion / orientation detection device is configured to detect an orientation of the housing and provide a signal indicative of the orientation to the microcontroller. 6. The device of any one of enumerated embodiments 1-5, further comprising a user notification device. 7. The device of enumerated embodiment 6, wherein the user notification device comprises one or more of a display, a haptic feedback unit, a light emitting device, and / or a vibration alert unit. 8. The device of enumerated embodiment 6 or 7, wherein a user notification device is mounted on an exterior surface of the housing to notify a user of its status. 9. The device of any one of the enumerated embodiments 1 to 8 when dependent on any one of the enumerated embodiments 6 to 8, wherein the microcontroller is configured to indicate via a user notification device whether the movement and / or orientation of the housing being shaken during mixing and administration of the medication or during a training event is sufficient for satisfactory mixing of the pharmaceutical ingredients for delivery. 10. The device of enumerated embodiment 9, wherein the user notification device is a display, and the microcontroller is configured to indicate the mixing status of the pharmaceutical ingredients in real time via the display. 11. The device of enumerated embodiment 10, wherein the microcontroller is configured to, upon shaking, gradually change the color and / or pattern of one or more display elements on the display until sufficient shaking has occurred for satisfactory mixing of the pharmaceutical ingredients for delivery. 12. The device of enumerated embodiment 10, wherein the microcontroller is configured to display two types of display elements on the display, the two types of display elements being separated into two separate parts of the display before shaking begins and gradually blending into each other on the display as long as shaking continues with sufficient or a predetermined force and / or sufficient or a predetermined duration until such time that sufficient shaking is determined to have occurred for satisfactory mixing of the pharmaceutical ingredients for delivery, and when so determined, fully integrating with each other in a regular pattern across the display. 13. The device of any one of enumerated embodiments 9-12, wherein the microcontroller is configured to determine whether there is a satisfactory mix with respect to one or more predefined thresholds, including a magnitude of force applied during shaking, an orientation of the housing, and a duration of the shaking. 14. The device of any one of enumerated embodiments 1-13, wherein the motion / orientation detection device comprises an accelerometer. 15. The apparatus of enumerated embodiment 14, wherein the accelerometer comprises a three-axis accelerometer. 16. The device of any one of enumerated embodiments 1-15, further comprising a power source disposed within the housing. 17. The apparatus of enumerated embodiment 16, wherein the microcontroller, when active, is powered by the power source. 18. The device of any one of enumerated embodiments 1-17, further comprising a start switch electrically connected to the microcontroller. 19. The device of enumerated embodiment 18, wherein the initiation switch is configured to wake up the microcontroller from a power saving mode to an active mode upon detecting movement of the housing during a drug mixing and administration event or during a training event. 20. The apparatus of enumerated embodiment 19, wherein the microcontroller is configured to consume less power, or no power at all, from the power source during the power save mode than during the active mode. 21. The device of any one of enumerated embodiments 18-20, wherein the initiation switch is a motion / orientation detection device. 22. The device of any one of enumerated embodiments 18-20, wherein the initiation switch is separate from the motion / orientation detection device. 23. The device of any one of enumerated embodiments 1-22, wherein the microcontroller is configured to detect, during mixing and administration of the medication or during a training event, when shaking of the housing ends prematurely for sufficient mixing of the components or when the level of shaking momentum of the housing drops to a level below a preset threshold for sufficient mixing of the components, and in that case, enter a pause mode to resume shaking. 24. The device of enumerated embodiment 23, wherein the pause mode is notified to a user by a user notification device. 25. The device of any one of enumerated embodiments 1-24, wherein the microcontroller is configured to set a timer during mixing and administration of the medication or during a training event to determine when a maximum allowable time has elapsed after completion of sufficient shaking of the housing, and to alert the user via a user notification device to shake the device again if the maximum allowable time has elapsed. 26. The device of any one of enumerated embodiments 1-25, wherein the housing extends along a longitudinal axis of the device. 27. The device of any one of enumerated embodiments 1-26, wherein the pharmaceutical delivery device comprises a syringe or a vial. 28. The device of enumerated embodiment 27 when dependent on enumerated embodiment 26, wherein the housing includes a syringe barrel element having a finger flange at one end and a barrel tip spaced apart along the longitudinal axis. 29. The device of enumerated embodiment 27 or 28, wherein the housing comprises a body having a slot sized to receive a syringe barrel or vial containing the pharmaceutical ingredient. 30. The device of enumerated embodiment 29, wherein the slot is aligned with the longitudinal axis of the housing and the longitudinal axis of the syringe barrel or vial. 31. The device of any one of enumerated embodiments 27-30, wherein the housing is provided with a compartment and a lid for receiving the entire syringe or vial. 32. The device of enumerated embodiment 31, wherein the compartment is dimensioned to closely receive the entire syringe or vial and securely retain it within the housing. 33. The device of any one of enumerated embodiments 27-32, wherein the housing has an elongated body that is approximately the same length as or slightly larger than the length of the syringe barrel, and the syringe is inserted into a syringe receiving hole in the body and held between the syringe finger flange and the body base by a compressive force applied by the finger members. 34. The device of any one of enumerated embodiments 27-33, wherein the housing comprises a body having a syringe receiving slot sized to receive a syringe barrel. 35. The device of any one of enumerated embodiments 27 to 34, wherein the housing comprises a disk-shaped body having a syringe receiving hole, such that during use, a syringe is inserted into the syringe receiving hole and held in place by the user's thumb at the lower thumb grip. 36. The device of any one of enumerated embodiments 27 to 35, wherein the housing has an opening therethrough through which the discharge nozzle of the syringe or vial can extend, or has an opening therethrough through which at least a portion of the syringe barrel near the discharge nozzle of the syringe can extend. 37. The device of any one of enumerated embodiments 27 to 35, wherein the housing is provided with a discharge nozzle adapted to be in fluid communication with the contents of the vial when the vial is inserted into the housing. 38. The device of any one of enumerated embodiments 27-35, wherein the syringe is provided with an ejection member adapted to eject the contents of the syringe upon application of force. 39. The device of enumerated embodiment 38, further comprising an activator adapted to act on the discharge member of the syringe or to act on the vial to expel its contents through the discharge nozzle. 40. The device of enumerated embodiment 38, wherein the housing further comprises an activator opening through which the ejection member of a syringe can penetrate to allow a user to apply a force directly from outside the housing. 41. The device of enumerated embodiment 27, wherein the device is an attachment for a syringe and the housing is adapted to fit around the barrel of the syringe. 42. The device of enumerated embodiment 41, wherein the housing is adapted to fit only partially around the barrel of the syringe. 43. The device of enumerated embodiment 41 or 42, wherein the housing is formed of two hinged parts that rotate hingedly relative to each other, and the hinged parts are adapted to close around and latch to the barrel. 44. The device of any one of the enumerated embodiments 1 to 43 when dependent on any one of the enumerated embodiments 16 to 22, wherein the microcontroller is configured to detect that the power source has low available power remaining. 45. When the microcontroller detects that the power supply is low on available power, issuing a warning to a user, for example by a user notification device, indicating that the available power is low; and Preventing activation of a medication delivery device to deliver a pharmaceutical ingredient to a user; 45. The apparatus of enumerated embodiment 44, performing one or more of the following: 46. ​​The device of any one of enumerated embodiments 1 to 45, wherein the microcontroller is configured to detect a malfunction of one or more of the devices, for example, the motion / orientation detection device, the housing, or an attachment or container of the medication delivery device. 47. When a microcontroller detects an abnormality, it: issuing a warning to a user, for example by a user notification device, indicating the anomaly; and Preventing activation of a pharmaceutical delivery device to deliver a pharmaceutical ingredient to a user 47. The apparatus of enumerated embodiment 46, performing one or more of the following: 48. The device of any one of enumerated embodiments 1 to 47, further comprising a delivery device identification unit in communication with the microcontroller. 49. The device of enumerated embodiment 48, wherein the delivery device identification unit is configured to read data on the data storage means of the delivery device indicative of characteristics of the pharmaceutical ingredients contained in the delivery device and / or the delivery device itself. 50. Data is an expiration date of the pharmaceutical ingredient, whereby the microcontroller is configured to alert a user via a user notification device of the device if a current date determined by the microcontroller is past the expiration date; data identifying a pharmaceutical ingredient contained within the delivery device, e.g., data indicative of a manufacturer or composition of the pharmaceutical ingredient, whereby the microcontroller is configured to alert a user via a user notification device of the device if the data identifying the pharmaceutical ingredient does not match or does not sufficiently correspond to an authorized pharmaceutical ingredient stored in the microcontroller or a memory connected to the microcontroller; an expiration date of the pharmaceutical ingredient, whereby the microcontroller is configured to prevent activation of the pharmaceutical ingredient in the medication delivery device to deliver to the user if a current date determined by the microcontroller is past the expiration date; and data identifying a pharmaceutical ingredient contained within the delivery device, e.g., data indicative of a manufacturer or composition of the pharmaceutical ingredient, whereby the microcontroller is configured to prevent activation for delivery of the pharmaceutical ingredient within the pharmaceutical delivery device to the user if the data identifying the pharmaceutical ingredient does not match or does not sufficiently correspond to an authorized pharmaceutical ingredient stored in the microcontroller or a memory connected to the microcontroller; 50. The apparatus of enumerated embodiment 49, comprising one or more of: 51. A method of instructing a user on proper drug mixing technique using a device according to any one of claims 1 to 50, comprising at least the step of determining the movement and / or orientation of the housing. 52. A device according to any one of claims 1 to 50, wherein one of the medicinal components comprises an active pharmaceutical substance which is INVEGA TRINZA (trademark) (see Appendix, Chapter 11). 53. A device according to any one of claims 1 to 50, wherein one of the pharmaceutical components comprises an active pharmaceutical agent comprising a racemic mixture of (+) and (-) paliperidone palmitate. 54. One of the medicinal ingredients is C 39 H 57 FN 4 O 4 51. A device according to any one of claims 1 to 50, comprising an active pharmaceutical agent which is 55. A device according to any one of claims 52 to 54, wherein the active pharmaceutical substance and / or device is for use in the treatment of schizophrenia. 56. The device of any one of claims 52-55, wherein at least one other of the pharmaceutical components comprises a fluid in which the active pharmaceutical agent is suspended. 57. A substance for use as one of the medicinal components in a device according to any one of claims 1 to 50, comprising an active pharmaceutical substance which is INVEGA TRINZA (trademark) (see Appendix, Chapter 11). 58. A substance for use as one of the pharmaceutical ingredients in a device according to any one of claims 1 to 50, the substance comprising an active pharmaceutical agent comprising a racemic mixture of (+) and (-) paliperidone palmitate. 59. A substance used as one of the medicinal ingredients in the device according to any one of claims 1 to 50, comprising C 39 H 57 FN 4 O 4 4. A substance comprising an active pharmaceutical ingredient which is 60. A substance according to any one of claims 57 to 59 for use in a device for the treatment of schizophrenia.

[0108] Although the present invention has been described with respect to certain variations and exemplary diagrams, those skilled in the art will understand that the present invention is not limited to the variations or diagrams described. In addition, where the methods and steps described above show events occurring in a particular order, those skilled in the art will recognize that the order of certain steps can be changed and that such changes are in accordance with variations of the present invention. In addition, some of the steps can be performed simultaneously in parallel processes, where possible, or sequentially as described above. Thus, to the extent that variations of the present invention are within the spirit of the present disclosure or the scope of equivalents of the present invention as found in the claims, this patent is intended to cover those variations as well.

[0109] [Embodiment] (1) An apparatus for training or assisting a user in the proper mixing of pharmaceutical ingredients, comprising: Housing and a microcontroller disposed within or on the housing; a motion / orientation detection device disposed within or on the housing and electrically connected to the microcontroller such that the microcontroller is configured to detect motion and / or orientation of the housing; The device comprises: (2) The device of embodiment 1, wherein the housing extends along a longitudinal axis. (3) The apparatus of claim 2, wherein the housing has a main longitudinal axis. (4) The device described in embodiment 3, wherein the housing is adapted to receive a drug delivery device having a main longitudinal axis and further align the main longitudinal axis of the housing along the main longitudinal axis of the drug delivery device. (5) An apparatus as described in any one of claims 2 to 4, wherein the microcontroller is configured to detect movement and / or orientation of the housing with respect to movement along or around the longitudinal axis.

[0110] (6) The apparatus of any one of claims 1 to 5, further comprising a user notification device in communication with the microcontroller and configured to generate a user notification upon instruction of the microcontroller. (7) The device of any of embodiments 1 to 6, wherein the microcontroller is configured to detect during a shaking event whether the movement and / or orientation of the housing being shaken during a pharmaceutical administration or training event is sufficient with respect to one or more predefined thresholds, including one or more of the magnitude of force applied during the shaking, the orientation of the housing, and the duration of the shaking. (8) The device described in embodiment 6 or embodiment 7 when dependent on embodiment 6, wherein the microcontroller is configured to notify a user via the user notification device whether the movement or orientation of the housing being shaken during medication administration or a training event is sufficient with respect to one or more predetermined thresholds, including one or more of the magnitude of force applied during the shaking, the orientation of the housing, and the duration of the shaking. (9) The apparatus of any one of claims 7 to 8, further comprising an initiation device in communication with the microcontroller, the initiation device configured to initiate detection of the shaking event by the microcontroller. (10) The device of embodiment 9, wherein the initiation device is one of a start switch in communication with the microcontroller and a start button on a user interface displayed by a touch-sensitive display screen of the device.

[0111] (11) A device described in any of embodiments 7 to 10, wherein the motion / orientation detection device is configured to initiate detection of the shaking event upon detecting movement of the housing above a predetermined level during medication administration or a training event. (12) The device of any of embodiments 7 to 11, wherein the microcontroller is configured to detect one or more of the following events during a shaking event using the motion / orientation detection device: when shaking of the housing is terminated prematurely; when the level of shaking momentum falls below one or more preset thresholds; when an average level of shaking momentum over a predetermined time period of the shaking event falls below one or more predetermined thresholds; or when the shaking component in a predetermined direction is insufficient relative to a predetermined level. (13) The device described in embodiment 12 when dependent on embodiment 6, wherein the microcontroller is configured to notify a user of unsatisfactory shaking when one or more of the events are detected. (14) The device of embodiment 12 or 13 when dependent on embodiment 6, wherein the microcontroller is configured to notify a user of satisfactory shaking after or when the shaking event has elapsed for a given time such that satisfactory shaking is indicated by the failure to detect one or more of the events. (15) The apparatus of claim 14, wherein the given time is the completion of the shaking event.

[0112] (16) The device described in any one of embodiments 7 to 15, wherein the microcontroller is configured to enter a pause mode to pause detection by the microcontroller, and then prompt the user to resume shaking and continue detection during the shaking event. (17) A device described in any of embodiments 7 to 16 when dependent on embodiment 6, wherein the microcontroller is configured to start a timer, determine when a maximum allowable time after shaking of the housing has elapsed, and alert the user via the user notification device to shake the device again during drug administration or a training event. (18) The apparatus of any one of claims 1 to 17, wherein the motion / orientation detection device includes a three-axis accelerometer configured to detect components of each of three tangential directions of shaking acceleration and provide data indicative of the components to the microcontroller. (19) The device of any one of the preceding claims, wherein the housing includes a syringe-shaped component located on or formed by the housing. (20) The device of claim 19, wherein the syringe-shaped component comprises a syringe-like barrel element having a finger flange at one end and a barrel tip spaced apart along the longitudinal axis.

[0113] (21) The device of any one of the preceding embodiments, wherein the housing comprises a body sized and / or shaped to receive a syringe barrel or a vial. (22) The device of embodiment 21, wherein the housing includes a compartment for receiving an entire syringe or an entire vial. (23) The device of embodiment 22, wherein the housing includes a movable cover or lid that is movable from a closed position that completely or partially covers the compartment to an open position that allows the syringe or vial to be inserted into the compartment. (24) The device of any one of claims 1 to 22, wherein the housing has an elongated body having approximately the same length as a syringe barrel, such that a syringe can be inserted into a syringe receiving hole in the body and held between a syringe finger flange and a body base by compressive force applied by the finger members. (25) The device of any one of embodiments 1 to 22, wherein the housing comprises a body having a syringe receiving slot sized to receive a syringe barrel.

[0114] (26) A device as described in any one of claims 1 to 22, wherein the housing has a disk-shaped body having a syringe receiving hole, and during use, a syringe is inserted into the syringe receiving hole and held in place by a user's thumb at a lower thumb grip. (27) The device described in any one of embodiments 1 to 26, further comprising a power source disposed within the housing and electrically connected to the microcontroller. (28) The apparatus of claim 27, wherein, during use, the microcontroller is powered by the power source. (29) The device described in any one of embodiments 1 to 28, wherein the motion / orientation detection device is an accelerometer. (30) A method for instructing a user regarding mixing of pharmaceutical ingredients using a device, the device comprising: Housing and a microcontroller disposed within or on the housing; a motion / orientation detection device disposed within or on the housing and electrically connected to the microcontroller to detect motion and / or orientation of the housing; The method comprises: determining by the motion / orientation detection device whether the magnitude and / or direction of the movement of the housing is sufficient with respect to one or more of predetermined thresholds, including the magnitude of force applied during shaking, the orientation of the housing, and the duration of the shaking.

[0115] 31. The method of claim 30, wherein the housing extends along a longitudinal axis. (32) The method of embodiment 31, further comprising determining by the motion / orientation detection device whether the magnitude and / or orientation of the movement of the housing with respect to movement along or about the longitudinal axis of the device is sufficient with respect to one or more of predetermined thresholds including the magnitude of the force applied along or about the longitudinal axis of the housing, the orientation of the housing, and the duration of the shaking. (33) A method according to any one of embodiments 30 to 32, wherein the device further comprises a user notification device. (34) The method of embodiment 33, further comprising notifying by the user notification device whether the movement or orientation of the housing being shaken during drug administration or a training event meets the predetermined threshold. (35) A method according to any of embodiments 30 to 34, wherein the apparatus further comprises an initiating device in communication with the microcontroller, the initiating device being configured to initiate detection of the shaking event by the microcontroller.

[0116] (36) The method of claim 35, wherein the initiation device is one of a start switch electrically connected to the microcontroller and a start button on a user interface displayed by a touch-sensitive display screen of the device. (37) The method of any of embodiments 30 to 36, wherein the motion / orientation detection device comprises a three-axis accelerometer. (38) A method according to any of embodiments 30 to 37, wherein the motion / orientation detection device is configured to wake up the microcontroller upon detecting movement of the housing during drug administration or a training event. (39) A method according to any of embodiments 30 to 38, wherein the microcontroller is configured to detect when shaking of the housing terminates prematurely or when the level of shaking vigor drops below the preset threshold, enter a pause mode, and allow the user to resume the shaking during drug administration or training event. (40) A method according to any of embodiments 30 to 39, wherein the microcontroller is configured to set a timer and determine when a maximum allowable time has elapsed after shaking the housing and to alert the user to shake the device again during drug administration or a training event.

[0117] (41) A method according to any of embodiments 30 to 40, wherein the microcontroller is configured to detect one or more of the following events during the shaking event using the motion / orientation detection device: when shaking of the housing is terminated prematurely; when the level of shaking momentum falls below the one or more preset thresholds; when an average level of shaking momentum over a predetermined time period of the shaking event falls below one or more predetermined thresholds; or when the shaking component in a predetermined direction is insufficient relative to a predetermined level. (42) The method according to embodiment 41 when dependent on embodiment 33, further comprising a step of notifying a user of unsatisfactory shaking when one or more of the events are detected. (43) The method of embodiment 41 or 42 when dependent on embodiment 33, further comprising the step of notifying a user of satisfactory shaking after or when the shaking events have elapsed for a given time such that satisfactory shaking is indicated by the absence of detection of one or more of the events. 44. The method of claim 43, wherein the given time is the completion of the shaking event. 45. The method of claim 44, wherein the housing comprises a syringe-shaped component located on or formed by the housing.

[0118] (46) The method of any one of claims 30 to 45, wherein the housing comprises a syringe barrel element having a finger flange at one end and a barrel tip spaced apart along the longitudinal axis. (47) The method of any one of embodiments 30 to 46, wherein the housing comprises a body having a slot sized to receive a syringe barrel or a vial. (48) The method of any one of embodiments 30 to 47, wherein the housing comprises a housing provided with a compartment and a lid that receives an entire syringe or an entire vial. (49) The method of embodiment 48, wherein the housing comprises a movable cover or lid that is movable from a closed position that completely or partially covers the compartment to an open position that allows the syringe or vial to be inserted into the compartment. (50) The method of any of embodiments 30 to 44, wherein the housing has an elongated body having approximately the same length as a syringe barrel, and a syringe is inserted into a syringe receiving hole in the body and retained between a syringe finger flange and a body base by compressive force applied by the finger members.

[0119] (51) The method of any one of embodiments 30 to 44, wherein the housing comprises a body having a syringe receiving slot sized to receive a syringe barrel. (52) A method according to any of claims 30 to 44, wherein the housing comprises a disk-shaped body having a syringe receiving hole, and during use, a syringe is inserted into the syringe receiving hole and held in place by a user's thumb at the lower thumb grip. (53) The method of any one of embodiments 30 to 52, further comprising a power source disposed within the housing and electrically connected to the microcontroller. (54) The method of embodiment 53, wherein during use, the microcontroller is powered by the power source. (55) The method of any one of embodiments 30 to 54, wherein the movement / orientation detection device is an accelerometer.

[0120] (56) The device or method of any one of embodiments 1 to 55, wherein the pharmaceutical composition comprises at least two phases. (57) The apparatus or method of embodiment 56, wherein at least one of the two phases is a solid phase and at least one of the two phases is a liquid phase. 58. The apparatus or method of embodiment 56, wherein two of the at least two phases are liquid phases.

Claims

[Claim 1] 1. A system for training or assisting a user in proper mixing of pharmaceutical ingredients, the system comprising: a housing defining a longitudinal axis; a microcontroller disposed within or on the housing; a motion / orientation detection device disposed within or on the housing and electrically connected to the microcontroller such that the microcontroller is configured to detect movement and orientation of the housing with respect to movement along or about the longitudinal axis; An apparatus comprising: the microcontroller is configured to detect, during a shaking event, whether the movement and orientation of the housing is sufficient and the direction of the shaking force applied to the housing with respect to a number of predetermined thresholds, including an orientation of the housing within a range of ±30 degrees on either side of the longitudinal axis, a magnitude of the force applied during the shaking and a duration of the shaking; The system, wherein the pharmaceutical ingredient comprises paliperidone palmitate.

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