Printed circuit on-in the lidding film of drug blisters, and not only, made with conductive ink, to detect the withdrawal of the product from the blister itself.

Description

Definitions

Blister : the cavity enclosing each one unit of medication or the entire blister body, included the lidding film that closes all cavities

Lidding film: the sheet of paper, aluminum, PVC or other material that closes the blister

Conductive Ink : the ink used to reproduce the printed circuit board. It has features that allow electrical conduction

Linear connector, terminals contacts made in conductive ink, printed on the lidding film of the blister that detect, through a service device, the opening of a circuit in the circuit board printed on the lidding film.

Service device: a battery-powered object to link to the linear connector and can detect and process interruptions of circuits.

1 . I NTRODUCTION

Adherence to the prescribed therapy is crucial to getting the therapeutic outcome expected. Often therapy is not followed as prescribed, therefore the expected outcome is less, generating waste of time and resources, and not acting adequately on the patient' care. Adherence to therapy means compliance with the drug doses and times and in some cases the sequence of administration units arranged in a blister pack.

Of course the therapy compliance takes a priority both in the administration of drugs where an error of intake can bring health consequences; or during clinical research treatments made with drugs under development.

The patient receiving a therapy prescription by the doctor, usually takes the drug at his own convenience; sometimes is administered by an health care professional or lay people, the caregiver.

It is therefore important to remember the patient the time of administration of the drug, and keep a journal of withdrawals from the primary package and made it available to both the patient, and the medical personnel than the caregiver. Purpose of the invention is to use as source of the data, the most common type of container for drugs, the blister that, specially modified by means of a printed circuit board, it will be able to give information to a service device allowing to obtain so the monitoring of therapy more accessible than it is today, and maintaining production costs at current levels.

2. MONITORING THE THERAPY

To met this need there are devices designed to remind the patient and health care personnel punctuality in taking any therapy: obviously gets picked up the pick up of the drug by the container, but you cannot have witness some of the intake, neither of the sequence of the administration.

In order to monitor adherence to a therapy already many devices are able to remember to take the drug by an alarm, others to collect the time data in which the drug was withdrawn and show to healthcare personnel if the patient has taken the therapy through appropriate communication systems such as websites, or app. Studies show that adherence to therapy can rise from 78% to 95%.

All existing devices to control the withdrawal of the drug require you to remove the drug from its original package and place it in the device' container.

This practice is also applied in hospitals, till the point that there are de blistering machines; the drug thus removed, is then collected in containers, which in turn can also be packed back into baggies or other blister for the daily treatment of each patient.

These devices also have considerable dimensions and some of the more sophisticated must be connected to the electric power. Not all of them are transportable.

2.1. The unmet need

It seems clear that it would be much easier to leave the medication in its primary packaging, blister, avoiding contact, contamination, possible transformations, pollution, and errors that might occur when transferring the medication in device' container. Furthermore, the products currently in use are not able to detect the correct sequence of taking in case of medicines at differentiated dosage as - for example - for the prescribed medications for the control of pregnancy.

The applications designed

In the past someone has already set himself the goal of using the blister to draw information from the emptying of blister, but in any case the projects implied to significantly alter the blister' structure, the growth of production' costs, or clashes with the good manufacturing practices - GMP - or other regulatory issues.

As example some patents identified on ESPACENET:

Patent US2017165151 (Al) DEVICE FOR DETECTING THE REMOVAL OF DRUGS https://worldwide spacenet om/publicationD^^

2017165151A1&KOA1

Patent WO2016135306 (Al) ELECTRONIC DRUG PACKAGING FOR IMPROVED COMPLIANCE httpsV/worldwide spacenet om/publicationDetatf^

R=2016135306A1&KOA1

Patent US5072430 (A) COMPLIANCE METER FOR CLINICAL EVALUATION OF DRUGS https://worldwide.espacenet.com/publicationD^

R=5072430A&KOA

The industry point of view

We need to underline that the pharmaceutical industry cannot easily change the blisters, or the number of units per box. Regulatory compliance costs would be too costly and time consuming.

For this reason, the changes that you can make the blisters are limited and must allow both normal use, and both the medication management tracking device without having to differentiate packaging.

Thanks to these conditions the blister, as result of the invention, may be adopted in an industrially convenient manner both objectively offering a convenient plus for the industry, both for the patient and for the medical staff, or caregivers.

3. THE PACKAGING OF THE MEDICATION IN A BLISTER

The blister can perform a function of primary packaging if it is made to hold, for example, and not only, tablets, pills, capsules, tablets, or secondary packaging, if contains ampoules, vials, pre-filled syringes, etc.

The drug, then, typically one tablet, pill, capsule, is distributed through a primary package, that in some countries it is a container box, carrying the patient' name and the therapy to accomplish, but in many countries the drug is distributed by blister.

The Blister

The blisters are made up of two main parts: a part where they obtained the individual cavities (which we call as blister, too), obtained by hot or cold procedure, and that once filled with the drug to be packed are sealed with a multilayer lidding material, that we call as a lidding film.

The hot formed blister

The blister is a container, consisting of a sheet of PVC (or similar material) thermoformed to form many cavities in size that it can receive one unit of medication whether any Tablet, pill, capsule, or vial. This multiple container, once filled, is closed with a lidding film . To extract the drug from the blister, the patient, or health professionals, must break the lidding film. See Figure 1 attached For a better understanding of manufacturing procedures, we invite you to watch the video that walks you through the process at: https://www.youtube. com/watch ?v=S-N3Mr03HtI

Especially note the section of tube 2.30 - 2.54 where explains how the lidding film is customized and positioned to coincide with each blister cavities.

Cold formed blisters

It is a multilayer with aluminum base rolled differently with PVC and other materials that enable it to be robust. It is a cold working which forms the cavities for the drug through under pressure modeling.

Even in this case there is a lidding film.

• In grey on the top of Figure 2

• just below the blister depicted in Figure 3.

The lidding film

The lidding film is always an integral part of the entire blister' body. Consists of a multi -layered film, often on paper, PVC, or composed of aluminum foil for about 20 microns laminated with other materials.

From contact with the blister until the outer surface you can find many different layers; for example: temperature-sensitive lacquer for sealing, primer, aluminum, printing, glossy finish.

The purpose of the invention, the glossy finish can be obtained by a non-conductive paint.

4. DESCRIPTION OF THE INVENTION

The invention aims to use the lidding film of the "blister" as print media for a "printed circuit board", PCB.

The circuit board is designed using a "conductive ink" .

The lidding film consists of several layers of different materials, the PCB will be affixed to one layer or in between of several non-conductive layers.

This printed circuit will pass through the surface of the lidding film at each cavity of the blister in order to create an independent circuit for each cavity. All circuits will have one end connected to a first "input" contact common to all the circuits and will terminate "output" independently.

The printed circuit board will start and end on one side of the blister, forming an aligned series of terminal contacts defined as " linear connector ". Each "output" contact is relative to a single cavity containing the unit.

By coupling the blister to a service device able to connect to the " linear connector ", it makes "closed" the circuits and independent for each cavity. When the lidding film is broken to allow the exit of product from the cavity that houses it, it also breaks down the corresponding circuit making it as "open", and through its terminals allows the service device to detect the opening and the occurred withdraw, the timing and sequence of the pick of each unit contained in blister.

(The description refers to figure 4.)

5. RECOMMENDATIONS FOR THE IMPLEMENTATION BLISTER PACK WITH PRINTED CIRCUIT BOARD.

The present invention is made possible by market availability of inks with conductive capacity, and by lidding films without electrical conduction capacity.

The ink

Printing is accomplished by a conductive ink with electrical capacity. This ink is defined as "conductive ink" in this text.

Typically, but just an example cites the "bare conductive ink" produced by the company Bare Conductive to London: https://www.bareconductive.com .

This ink is no different from any other water-based inks, except that conducts electricity. Can be used to draw any contact or switch directly to each material. It is non -toxic, organic solvent-free electrical conductor, and water soluble. Can be used with different printing techniques. It is adequate for low voltages.

The print media (Lidding film)

The lidding film material always consists of several layers. The lidding film useful for carrying out the invention must ensure that the circuit it can be printed on a layer without conductive characteristics.

One of the aims of the present invention is to intervene as little as possible about methods of manufacture; from this perspective, if the material of the lidding film does not include conductors, (such as when you use PVC, paper), you don't need the extra measures; will suffice to affix circuit printing on the outside of the lidding film, that is the opposite side to the cavity of the blister.

If in the stratification of the lidding film materials there is a conductor, such as aluminum, this layer must be adjusted so that the layer on which it is applied and painted, the circuit printed is not conductive. This varies at the discretion of the materials used and the supplier will be responsible to verify and assure no conductivity, as well as the adhesion of conductive ink .

Nothing prevents the circuit board can be placed between two layers of material not conductive among many layers add the lidding film, provided that the parts of the linear connector remain connected to the service. Printed circuit board Design.

The rules

Printed circuit design to appear on the lidding film must respect certain rules:

• must be a "semi closed circuit" independent for each unit contained in blister through the surface of the lidding film at the blister cavity. Semi closed loop system is the link between a contact - "input"- (red in figure 4 and 5 of exemplification) of the linear connector and that - "output"-corresponds to the cavity of each unit (in black in figures of exemplification 4 and 5). The circuit will be closed once connected to a service device.

• should possibly show the QR code, or other optical coding graphics of the drug/product.

Standard-setting of connection to the service

Keep these recommendations will enable manufacturers of the service device to access a standardized system.

• On the side on which is placed the linear connector, the distance between the edge of the blister and the cavity containing the nearest drug unit should allow a "grip" enough for the attachment of the service device. We recommend a distance of not less than 5 mm.

• Contact terminations of linear connector, made of the same conductive ink, must be sized so that they can be connected and activated by a metal contact on the service device.

Approximately 1.5 mm wide interposed between them a space of 1.5 mm, similar to a USB port.

• The contact of the linear connector, assigned to supply all closed circuits, it is recommended that's posted at 10 mm from the edge of the proximal side. In the space between the edge of the blister and the first contact will be placed the first coupling pin to grip the service device.

Complexity and extra touches

Normally in addition to the printed circuit board can be printed both the drug name, manufacturer's name and always with conductive ink.

In the case when by current good manufacturing practice is provided for a widespread drug name and stamp of the manufacturer on the lidding film, so dense as to interrupt or adversely affect the characteristics of the circuit, this marking will be printed in a first step of printing using paint without electrical conductivity. While the printed circuit board will be affixed above it in a second step of printing.

Opening of the circuit When the blister is connected to service device, circuits become closed and when the lidding film is broken to allow the release of the drug in correspondence from the cavity that houses it, the circuit is "open", enabling the service device to detect a successful withdrawal.

Description

The PCB will begin will end on one side of the blister forming a series of contacts here defined herein as " linear connector " .

In Figure 4 - example - represents the flat side of the blister. On the surface (grey) of the lidding film are traced solid black lines representing the printed circuit board, and ellipsoidal forms dashed blue representing the surface of lidding film at the blister cavities. The white areas dotted are reserved:

• the embossed seal as required by some manufacturers and some regulations to indicate the lot and expiration date.

• a QR code or other electronically optical readable code to identify of the product.

In the lower-left corner shows the contacts, printed using conductive ink, which constitute the linear connector.

In Figure 4 is exemplified a typical blister to treat a week; the arrangement of the blister cavity, and accordingly printed circuit paths, will be adapted to the needs of the packaging without size limit or number.

In Figure 5 is exemplified, a blister with contacts to 14 doses.

Inverted symmetry linear connector positioning helps avoid contacts fatigue when subjected to shock and extended actions during for two weeks, during transport of the blister when linked with the service device .

6. POSSIBLE CONSIDERATIONS INCREASES IN COSTS OF PRODUCTION

While considering all possible necessary changes to blister packaging system, cost shared is really negligible.

• The positioning of the lidding film will have to strictly align the circuit parts that will need to open the contact in correspondence of the of the blister's cavities surfaces. This technique is common, typically for birth control pills, but it is not applied in all packaging lines.

• The renewal of the stamp' matrix for printing the lidding film that includes the printed circuit board.

• Ink for circuit board printing might have another cost than that normally used.

• The insulating finish when the lidding film includes a conductive layer

• An additional printing procedure of the lidding film when it needs to print on a surface where already many characters are printed that may interfere with the circuit board. Normally there should be no changes of the thermal mold.

Normally it should not be necessary to amend the die-cutter.

Normally it should not be necessary to change the secondary packaging,

Normally it should not be necessary to amend the sheet of product characteristics regulatory adjustments.

7. SUGGESTIONS FOR THE MANUFACTURE OF A SERVICE DEVICE

This blister, coupled to a "related service device" will provide information about the opening of each circuit, and then pick up time of each unit of medication, and if applicable, the sequence of recruitment as required for hormone therapies for birth control.

With the help of a smartphone, (or other reception/transmission system), and a dedicated application, it will be possible to put this information at the disposal of both the patient and the medical personnel in order to verify adherence to therapy.

This service device, and the App are not covered by this patent application and are not part of the claims.

This service device requires some tricks for making and may offer different services. A hypothetical scheme of service device and its mating system is presented in Figure 6 and 7.

Power supply

Battery-powered, possibly rechargeable via USB Check the contact openings

Contact verification of the blister will occur with a frequency of time defined by the firmware of the service device (for example, 30 minutes, 1 hour) by sending a low -voltage pulse in the circuit.

Technique of coupling

The device must be able to physically restrain the blister. Typically with at least two points (pins) of contact that passing through the surface of the same and keeping steady in position the linear connector of the blister with the metal contacts of the service device connector. For this purpose are reserved 10 mm before the first contact with the linear connector, where its possible place the first pin.

See Figure 4 and 5.

Connection technology

This device has a " linear connector " receiving contacts and will able to accommodate at least one blister for a single therapy. Depending on the characteristics of the device it may be linked to more than a blister. It is recommended that the manufacturer of the service device to prepare a linear connector of receiving contacts for at least 14 contacts can be used for individual blister packs containing up to 28 units. Then 14 + 1 = 15 points of contact in linear connector - receiver -place on the service.

The first contact might be at 10 mm from the base of the left edge; other metal contacts, interspersed on its axis by 3 mm. Always referring to figure 4.

Communication technology

Bluetooth or similar radio system that links the service with your smartphone or other telecommunication device. The communication will be in both directions.

Minimum flow of communication between service and device smartphone

From smartphones to the device:

• the withdrawing frequency (Administration) and the date and time of first pick up

• the gap of time the unit can be taken (e.g. +/-15 minutes) without triggering the alarm.

From service device to smartphones

• The data about the opening of circuits will be the only active communication from the device to the smartphone they will be: date, time, sequence.

• The service device must be able to store contacts openings until they come into connection with your Smartphone.

• The failure to pick up at the appointed time can be managed either by the service, both from a smartphone.

Basic Services provided by App installed on smartphone or on other device by control

• Reading the QR code or other optical code made available on the backside of the blister to identify the product

• Collecting data on the time, day and pick up unit' sequence

• Access to the given by the patient, caregiver, or health personnel through an App.

• Alarm to remind to take the medication

• Alarm with push technology for healthcare professionals to report the delay and off hiring at recruitment made

• programming of verification timing of open circuits.