EP3986805A1

EP3986805A1 - Packaging for pharmaceutical products

Info

Publication number: EP3986805A1
Application number: EP20743327.7A
Authority: EP
Inventors: Nico Ros
Original assignee: REP IP AG
Current assignee: REP IP AG
Priority date: 2019-06-24
Filing date: 2020-06-23
Publication date: 2022-04-27
Also published as: AT522703A1; CA3144865A1; WO2020261104A1; AT522703B1; US20220242651A1; CN114340578A

Abstract

The invention relates to a packaging for pharmaceutical products, comprising a primary packaging (3) for receiving one dose or several doses of a pharmaceutical product, and a secondary packaging designed as a cardboard box (1), in which the primary packaging (3) is housed. The primary packaging (3) is arranged in an insulating sleeve (2) comprising a latent heat storage material and the insulating sleeve (2) is held in the secondary packaging (1) at a distance from the latter on all sides to form an insulating gap (7).

Description

Packaging for pharmaceutical products

The invention relates to a packaging for pharmaceutical products, comprising a primary packaging for receiving one dose or several doses of a pharmaceutical product, and a secondary packaging designed as a cardboard box in which the primary packaging is received.

Ready-to-use pharmaceutical products are usually first packed or filled in blisters, vials, syringes or injectors in a first step. Those provided in this way with primary packaging

In many cases pharmaceutical products are then packaged in small cardboard boxes, which are called

Secondary packaging serve and on which the for the

Marketing information required is printed.

A large number of such products, which are secondary-packaged by the manufacturer, are combined into larger units for transport and these units are combined with a

Provide transport or freight packaging. In the case of temperature-sensitive pharmaceutical products, the transport or freight packaging can include

temperature-stabilizing properties be provided, with in the transport or freight packaging

For example, temperature control modules from one

Phase change material can be inserted and the transport or cargo packaging with a thermal

Insulation layer is provided. The transport or

Freight packaging can contain temperature sensors with which compliance with a specified

Temperature window can be controlled. The transport or cargo packaging can also be designed to protect the secondary packaged products from mechanical

To protect impacts.

When transporting pharmaceuticals over periods of

several hours or days must be given

Temperature ranges during storage and transport are maintained in order to ensure the usability and the

To ensure the safety of the transported goods. For

various pharmaceuticals, temperature ranges from 2 to 25 ° C, in particular 2 to 8 ° C or 15 to 25 ° C, are specified as storage and transport conditions.

The problem here is that the pharmaceutical

Products can only be stored and transported in a temperature-controlled manner if they are in the

Transport or freight packaging, such as in one

temperature-controlled freight containers are located. It cannot therefore be determined whether a

secondary packaged pharmaceutical product before

Placing it in the transport or freight packaging or after removing it from the transport or freight packaging was outside the specified temperature window. For example, an end user at a

temperature-sensitive pharmaceutical product that he buys in a pharmacy cannot determine whether that

The product has become too warm or too cold in transit from the pharmacy home. Just as little can be done in the course of storage in the secondary packaging

End users at home, but also in a hospital or in the pharmacy, can determine whether the product has become too warm or too cold. Another disadvantage of conventional packaging systems can be mentioned that you cannot be sure

can determine whether the secondary packaging has been opened and the pharmaceutical product has been replaced by a counterfeit.

Furthermore, it is not possible to follow the path of each

track secondary packaged products. With the appropriate equipment of customary logistics systems, this is only the case with the transport or freight packaging

Dispatch unit, e.g. Transport pallet, possible, but this does not allow any differentiation with regard to each individual secondary packaging.

It follows from the problems outlined above that the

End users cannot be sure whether they have taken a medically or pharmaceutically functional drug or whether the effectiveness is due to

Temperature effects is already affected. Furthermore, the consumer cannot guarantee whether he has actually taken the original drug or one

Counterfeit.

Because of these uncertainties, it is in most

Countries are not allowed to send medication from the manufacturer or an intermediary directly to the end user, as the end user is not able to check the authenticity and functionality of the medication.

The invention is therefore aimed at developing a packaging for pharmaceutical products of the type mentioned at the outset in such a way that the effectiveness of temperature-sensitive pharmaceutical products End user ensured and compliance with a prescribed temperature window over the entire

The transport chain to the end user can be checked.

The invention also aims to make counterfeits of pharmaceutical products of any kind identifiable.

To achieve these objects, the invention essentially consists in a packaging of the type mentioned at the outset in that the primary packaging is in a

Latent heat storage material having insulation sleeve is arranged and that the insulation sleeve to form an insulation gap at all sides from the

Secondary packaging is held in this.

The invention is thus based on the idea that

temperature stabilizing elements inside a

To arrange secondary packaging so that compliance with the prescribed temperature window does not depend on the

temporary transport or freight packaging, such as a refrigerated freight container, a refrigerated truck or the like. depends.

The secondary packaging is that cardboard packaging that is intended for handling by the end user and the primary packaging for receiving one dose or several doses of the

pharmaceutical product contains. The

Secondary packaging is used to sell the contained

Product, which is why it is also used as sales packaging

referred to as. It can be designed for advertising purposes in order to encourage the end customer to purchase the respective content. Compared to primary packaging such as glass bottles or In blisters, the secondary packaging has no direct contact with the actual product. Nevertheless, the

Process steps in the production of secondary packaging usually comply with GMP (Good Manufacturing Practice) or FDA compliance. Furthermore, the secondary packaging must comply with the relevant pharmaceutical law

Provisions make initial information for consumers recognizable, such as the name of the pharmaceutical

Product, the active ingredient, the dosage form, the strength of the dosage form, the batch number, the expiry date and the like.

The cardboard box forming the secondary packaging is preferably designed as a folding box. The

Cardboard box, in particular cardboard folding box, is preferably constructed from single or multi-layer cardboard and has a wall thickness of a maximum of 1 mm, preferably a maximum of 0.5 mm.

The primary packaging is preferably designed as a blister pack, ampoule, injection ampoule or vial.

When equipping the secondary packaging with the

The temperature stabilization function exists

Challenge in the very limited space and the high cost pressure, as each individual packaging must be equipped with the technology. The invention retains the conventional concept of a

Cardboard box as secondary packaging and integrates a temperature stabilization element in the form of a

Latent heat storage material that wraps the inner packaging as an insulating cover. It is preferably provided within the scope of the invention that the temperature stabilization function is implemented by elements that are located within the secondary packaging, so that the external appearance of the secondary packaging remains unchanged.

Latent heat storage materials belong to the group of passive temperature control elements, which are characterized by the fact that they do not require an external energy supply during use, but instead use their heat storage capacity, whereby depending on the temperature level there is a release or absorption of heat to or from the

temperature-controlled primary packaging including the pharmaceutical product. Such passive temperature control elements are exhausted as soon as the temperature equalization with the

Primary packaging or its interior is complete. Latent heat accumulators are a special form of passive temperature control elements that can store thermal energy in phase change materials, the latent heat of fusion, heat of solution or heat of absorption is much greater than the heat that they can store due to their normal specific heat capacity.

A particularly efficient temperature stabilization is preferably achieved in that the insulating sleeve

Primary packaging surrounds on all sides.

As an additional barrier against temperature changes of the pharmaceutical product, the invention provides that the latent heat storage material includes

Insulation sleeve to form an insulation gap is held in this at a distance on all sides from the secondary packaging. The isolation gap is preferred air-filled so that the heat transfer between

Primary packaging and secondary packaging is significantly reduced at low cost.

The latent heat storage material preferably contains one

Phase change material or is formed from it.

Phase change materials have a latent heat of fusion that is significantly greater than the heat they generate due to their normal specific heat capacity

can save. Phase change materials therefore lose their effect as soon as all of the material has completely passed through the phase change. By running the

however, the latent heat storage device can be recharged with an opposite phase change.

Depending on the type of pharmaceutical product, it must be kept in a temperature range of 2 to 20 ° C, e.g. in a temperature range from 2 to 8 ° C or in a temperature range from 15 ° C to 25 ° C. The

Phase change material here has one on the

prescribed temperature range

Phase transition temperature.

The phase change material preferably has a

Phase transition temperature of 3-10 ° C, in particular about 5 ° C.

The phase change material is preferably selected from the group consisting of paraffin, for example n-tetradecane or n-hexadecane, esters, for example methyl esters, linear alcohols, ethers, organic anhydrides, salt hydrates, water-salt mixtures, salt solutions and / or water-based solutions, or mixtures thereof. Conventional phase change materials undergo a phase change from the solid state to the liquid state and vice versa. The phase change material must therefore be arranged in a suitable container so that it also remains in its intended location in the liquid state. A preferred embodiment of the invention provides in this context that the phase change material is present in a dimensionally stable envelope, in particular a plastic envelope. The dimensionally stable envelope together with its contents preferably forms the insulating envelope and therefore completely surrounds the primary packaging.

The arrangement of the phase change material in a

appropriately suitable covering is, however, associated with a high level of effort and also carries the risk that the phase change material through the covering

diffuses through or emerges from the envelope due to a leak and the primary packaging

contaminated. Furthermore, one is restricted in the shape of the envelope, which in turn makes handling more difficult when arranging the insulating envelope in the secondary packaging and requires more space and weight.

In order to avoid these disadvantages, a preferred development of the invention provides that the

Latent heat storage material comprises a support material which is dimensionally stable at use temperature, in which the

Phase change material is distributed or arranged so that the latent heat storage material is dimensionally stable in a temperature range both below and above the melting point of the phase change material. Under the

The usage temperature is that temperature understood where an end user applies, transports or stores the pharmaceutical product. The

Use temperature therefore preferably includes one

Temperature range from -25 ° C to + 60 ° C. This avoids the problems with handling the phase change material. In particular, it is not necessary

To arrange latent heat storage of this type in separate containers.

The carrier material forms a matrix in which the phase change material is distributed. The matrix consisting of the carrier material gives the

Latent heat storage at the service temperature

required mechanical stability and shows no phase change within the usage temperature itself.

The latent heat storage element includes in addition to

Phase change material preferably one or more copolymers, in particular styrene block copolymers, and / or ethylene-bytylene copolymers as carrier material in order to maintain the dimensional stability of the latent heat storage element above the

Ensure the melting point of the phase change material.

Nanoporous carbon, into which the phase change material is incorporated, can also be used as the carrier material. Furthermore, small-pore can be used as a carrier material

Lattice structures made from a polymer or open-pored

Foams such as Synthetic resin foams based on crude oil or the like. be used.

It is preferably provided that the

Latent heat storage material up to a temperature of 10 ° C, preferably 20 ° C, particularly preferably 40 ° C above Phase transition temperature of the phase change material is dimensionally stable. This ensures that the

Latent heat storage element is still dimensionally stable even at higher temperatures.

It can preferably be provided that the

Latent heat storage material with appropriate

Design of the carrier material when heated to a temperature well above the usage temperature

Temperature can be converted into the molten state. The transition to the molten state can take place in particular from a temperature which

is at least 60-100 ° C above the use temperature or room temperature (20 ° C). This enables the production of the insulation cover by means of a forming process,

in particular casting process allows.

A preferred embodiment provides that the insulation sleeve by injection molding of the

Latent heat storage material is made.

Injection molding processes have long been known and can therefore be used easily and safely. In particular, injection molding processes can also be used to produce complex shapes in a simple and inexpensive manner.

According to a preferred embodiment, the insulation sleeve is adapted in shape to the primary packaging and lies

preferably flat, in particular on all sides, on this. This allows a particularly efficient

Temperature stabilization of the primarily packaged product. The areal concern of the insulation sleeve on the

Primary packaging also includes embodiments in which between the form-matched insulating sleeve and the Primary packaging a separating layer, for example in the form of a plastic film, is arranged. The form-adapted

Training of the insulation jacket is particularly successful

simply by using a casting or

Injection molding process.

In particular, the insulation sleeve can be attached to the

Primary packaging be molded. This is particularly the case when the primary packaging is designed as an ampoule or

Vials advantageous. The application of the insulation sleeve then takes place in that the ampoule or the vial is used as a carrier for the injection molding process, the latent heat storage material is therefore directly on the

Primary packaging is sprayed on or the primary packaging is encapsulated with latent heat storage material.

The use of a dimensionally stable

Latent heat storage material offers the further advantage that the insulation sleeve can serve as additional protection for the primary packaging against mechanical effects. Depending on the rigidity, this can

Latent heat storage material also used as shock absorbers

are used and the e.g. made of glass

Protect primary packaging when packing

for example falls to the ground. The rigidity of the

Latent heat storage material can be optimally adapted to the product, since dimensionally stable

Latent heat storage materials with a high

Modulus of elasticity of up to 3000 N / mm2 or with a very low modulus of elasticity of up to 1 N / mm2

have it manufactured. In the variant where a

Liquid phase change material in a plastic cover is cast, the additional mechanical protection can take place via the rigidity of the plastic shell.

The insulation sleeve can preferably consist of at least two

Layers exist which are particularly preferred

Phase change materials with different

Have phase transition temperatures. This allows the desired temperature range to be easily and efficiently

be determined.

The insulation sheath can be formed from two half parts or from a plurality of parts, which the

Wrap the primary packaging together.

The isolation gap is preferably on the outside through the

Cardboard box and inside through the insulation sleeve

limited. In order to obtain particularly good thermal insulation of the pharmaceutical product, it is preferably provided that the insulation gap is filled with a gas, e.g. with air, CO2, krypton, xenon or a mixture of these gases, or evacuated.

The insulation gap preferably has a thickness of <16 mm, in particular 5-10 mm. With a 10 mm thick

Insulation gap, the heat conduction of the air in the gap is around 2.6 W / m ² K. As measurements have shown, the heat transfer coefficient is at the interface between the outer packaging and the air of the insulation gap or between the insulation sleeve and the air of the

Isolation gap at approx. 3-5 W / m ² K. With a gap width of less than 5 mm, the decisive insulation effect arises due to the two heat transfer coefficients

adjacent surfaces to the air gap no longer over the Air. The insulation gap can preferably also have a thickness of <5 mm, in particular 1-3 mm.

The insulation performance of the insulation gap can go further

be improved by the two surfaces delimiting the gap or only one of the surface

is coated with a heat reflective coating.

A preferred training therefore provides that the

Insulation sleeve on its outside

heat reflective coating, e.g. a metallic coating or a metal foil.

Alternatively or additionally it can be provided that the cardboard box has a

heat reflective coating, e.g. a metallic coating or a metal foil.

The heat-reflecting coating of a metallic, in particular gas-tight coating, preferably a coating with an emissivity of <0.5, preferably <0.2, particularly preferably <0.04, such as e.g. a coating of aluminum.

The coating allows the energy transfer due to thermal radiation to be significantly reduced and the

Insulation performance is thereby without an essential

Increased cost increases.

The insulation performance can be further increased by adding further layers to the insulation gap

reflect foils being filled, or by adding the

Isolation gap the gas is withdrawn (vacuum). Alternatively the insulation gap can be filled with a highly insulating material such as an airgel.

To improve the insulation effect of a gas-filled

To further improve the insulation gap, it is preferably provided that the insulation gap is subdivided by at least one intermediate layer, preferably a film, arranged in the insulation gap. At least one

The intermediate layer is preferably essentially parallel to the outer and outer layers delimiting the insulation gap

Arranged inside surfaces. If the thickness of the

Isolation gap is too large, can be inside the

Insulating layer an unwanted convection take place. To prevent this from happening, the at least one divides

Intermediate layer, the isolation gap in at least two areas, each with a smaller thickness. The intermediate layer can preferably be one or both sides

heat reflective properties, in particular be provided with a heat reflective coating. The heat-reflecting coating is preferably a metallic, in particular gas-tight coating, preferably a coating with an emissivity of <0.5, preferably <0.2, particularly preferably <0.04, such as e.g. a coating of aluminum.

At least one layer, in particular a plurality of superimposed layers, is particularly preferred in the insulation gap

Layers, a heat-reflecting film, in particular metal foil, arranged.

According to a preferred embodiment, the isolation gap is created in that spacer elements are arranged, in order to keep the insulation sleeve at a distance from the secondary packaging on all sides.

The spacer elements can be formed by separate parts that are distributed around the insulation cover and are arranged between the insulation cover and the secondary packaging, the contact surfaces of the

Spacer elements on the insulation sleeve and the

Cardboard boxes are minimized in order to reduce the heat transfer through thermal conduction.

The spacer elements preferably consist of the

Phase change material of the insulation sleeve or are of cardboard elements, in particular cardboard elements of the

Secondary packing, formed.

In order to be able to monitor compliance with the prescribed temperature range and / or in order to be able to detect impermissible opening of the secondary or primary packaging for the purpose of introducing a forgery, a preferred development provides that a

Temperature sensor or a temperature control strip is arranged in the insulation gap, in the latent heat storage material, between the latent heat storage material and the primary packaging or in the primary packaging.

Temperature control strips are a type of chemical

Paper thermometer in which a measuring strip changes its color irreversibly when it reaches a predetermined temperature.

Furthermore, in this context, an electronic memory can be used to store temperature measurements recorded at regular intervals or continuously Packaging be provided, the electronic

Memory is preferably connected to an electronic circuit for wireless reading of the stored temperature measurement values. For example, the stored temperature measurement values can be fed to an antenna for wireless inductive transmission of the values to a reading device. The data transfer can e.g. via the RFID or NFC standard.

The temperature sensor is preferred between the

Primary packaging and the secondary packaging arranged or within the insulating sleeve. When it is arranged within the insulation sleeve, the

Temperature measurement determine whether this has been opened.

Without opening the insulation cover, it cannot happen

sudden rise in temperature. At a

Opening the insulation cover inevitably leads to a jump in temperature, as the outside temperature does not rise to e.g. 0.1K of the internal temperature can be adjusted as the internal temperature is not known for a third party. It can thus be ensured that an exchange of the pharmaceutical product is automatically recognized by a system.

The invention is explained in more detail below with reference to exemplary embodiments shown schematically in the drawing. 1 shows a perspective view of the packaging according to the invention and FIG. 2 shows a cross section of the packaging according to FIG. 1.

In Fig. 1 and 2, a cardboard box is denoted by 1, which represents the secondary packaging. Inside the cardboard box 1, an insulating sleeve 2 is arranged, which consists of a latent heat storage material or contains one. The insulation cover encloses a

Primary packaging 3, which e.g. is designed as a glass ampoule, which receives a pharmaceutical product in its interior 4. The insulating cover 2 can e.g. from two

There are half-shells which can be separated from one another along a separation plane 5 in order to make the primary packaging 3 accessible. As can be seen in FIG. 2, the insulating sleeve is adapted to the outer shape of the primary packaging 3 so that the insulating sleeve 2 is flat, in the

In the present case along a cylindrical surface on which the primary packaging 3 rests.

Between the insulating sleeve 2 and the cardboard box 1 are on all sides, i.e. on all six sides of the cuboid, spacer elements 6 are arranged, which ensure that an insulation gap 7 is provided between the insulation sleeve 2 and the cardboard box 1. The isolation gap 7 is filled with a gas, e.g. Air filled. To improve the thermal insulation can be on the outside of the

Insulation sleeve 2 and / or on the inside of the

Cardboard box 1 has a heat reflective coating 8 or 9 e.g. be attached in the form of a metal foil. A heat reflective sheet, e.g. a

Metal foil can also be arranged in the insulation gap 7, as is indicated by way of example with the dashed line 10 in the area between the two right-hand spacer elements 6.

To control the temperature of the pharmaceutical

The product is also a temperature sensor 11

provided, which in the case of the formation of the insulating sleeve 2 from two half-shells directed towards the parting plane 5 is. The temperature sensor 11 can not only monitor the temperature of the pharmaceutical product, but also any unauthorized opening of the packaging

detect. If the two half-shells of the insulation cover are separated from one another, the one from the changes

Temperature sensor 11 recorded temperature namely abruptly.

Claims

Patent claims:

1. A packaging for pharmaceutical products, comprising a primary packaging (3) for receiving one dose or several doses of a pharmaceutical product, and one designed as a cardboard box (1)

Secondary packaging in which the primary packaging (3)

is included, characterized in that the

Primary packaging (3) in a one

The insulating sheath (2) having latent heat storage material is arranged and that the insulating sheath (2) is arranged on all sides to form an insulating gap (7)

Distance from the secondary packaging (1) is kept in this.

2. Packaging according to claim 1, characterized in that the insulating sleeve (2) surrounds the primary packaging (3) on all sides.

3. Packaging according to claim 1 or 2, characterized

marked that the primary packaging (3) as

Blister pack, ampoule, injection ampoule or

Vial is formed.

4. Packaging according to claim 1, 2 or 3, characterized

characterized in that the latent heat storage material contains or is formed by a phase change material.

5. Packaging according to claim 4, characterized in that the phase change material is selected from

Group consisting of paraffin, for example n-tetradecane or n-hexadecane, esters, for example methyl esters, linear alcohols, ethers, organic anhydrides, salt hydrates, water-salt Mixtures, salt solutions and / or water-based solutions, or mixtures thereof.

6. Packaging according to claim 4 or 5, characterized

characterized in that the phase change material is a

Phase transition temperature of 3-10 ° C, in particular about 5 ° C, has.

7. Packaging according to claim 4, 5 or 6, characterized

characterized in that the phase change material is present in a dimensionally stable envelope, in particular a plastic envelope.

8. Packaging according to one of claims 4 to 7, characterized in that the latent heat storage material is a carrier material which is dimensionally stable at the use temperature

comprises, in which the phase change material is distributed or arranged so that the latent heat storage material is dimensionally stable in a temperature range both below and above the melting point of the phase change material.

9. Packaging according to claim 8, characterized in that the latent heat storage material up to one

Temperature of 5 ° C, preferably 10 ° C, particularly preferably 15 ° C above the phase transition temperature of the

Phase change material is dimensionally stable.

10. Packaging according to claim 8 or 9, characterized

characterized in that the insulating sleeve (2) through

Injection molding of the latent heat storage material is made.

11. Packaging according to one of claims 1 to 10, characterized in that the insulating sleeve (2) to the

Primary packaging (3) is adapted in shape and lies flat against it, in particular on all sides.

12. Packaging according to one of claims 1 to 11, characterized in that the insulating sleeve (2) to the

Primary packaging (3) is formed.

13. Packaging according to one of claims 1 to 12, characterized in that the insulating sleeve (2) has a

Has a modulus of elasticity of 1 - 3,000 N / mm ² .

14. Packing according to one of Claims 1 to 13, characterized in that the insulating sleeve (2) has a heat-reflecting coating (8) on its outside, e.g. a metallic coating or a metal foil.

A package according to any one of claims 1 to 14, characterized in that the cardboard box (1) has a heat-reflective coating (9), e.g. a metallic coating or a

Metal foil, wears.

16. Packaging according to claim 14 or 15, characterized

characterized in that the heat-reflecting coating (8, 9) consists of a metallic, in particular gas-tight coating, preferably a coating with an emissivity of <0.5, preferably <0.2, particularly preferably <0.04, such as e.g. a coating

Aluminum.

A package according to any one of claims 1 to 16, characterized in that the insulation gap (7) is filled with a gas, e.g. with air, CO2, krypton, xenon or a mixture of these gases, or evacuated.

18. Packaging according to one of claims 1 to 17, characterized in that at least one layer (10), in particular several superimposed layers, of a heat-reflecting foil, in particular metal foil, is arranged in the insulation gap (7).

19. Packing according to one of claims 1 to 18, characterized in that the insulation gap (7) has a thickness of <16 mm, in particular 5-10 mm.

20. Packaging according to one of claims 1 to 19, characterized in that spacer elements (6) are arranged in order to hold the insulating sleeve (2) in this at a distance on all sides from the secondary packaging (1).

21. Packaging according to claim 20, characterized in that the spacer elements (6) consist of the phase change material of the insulating sleeve (2) or are formed by cardboard elements, in particular cardboard elements of the secondary packaging (1).

22. Packaging according to one of claims 1 to 21, characterized in that a temperature sensor (11) or a temperature control strip in the insulation gap (7), in the

Latent heat storage material, between

Latent heat storage material and primary packaging (3) or in the primary packaging (3) is arranged.

23. Packaging for pharmaceutical products, comprising a cardboard box (1)

Secondary packaging in which a primary packaging (3) for receiving one dose or several doses of one

pharmaceutical product can be received, characterized in that the cardboard box is a

Contains insulation sleeve (2) having latent heat storage material which encloses an interior space in which the

Primary packaging (3) can be arranged, and that the

Insulation sleeve (2) for forming an insulation gap (7) is held in the cardboard box (1) at a distance on all sides.