Patent Application
20220313895
This invention relates to a nozzle for a container for the intranasal administration of a liquid formulation, in particular for the intranasal administration of a nasal spray or nasal wash, to a packaging comprising such nozzle, and to a product comprising such packaging.
Intranasal administration of a liquid formulation, for example a drug formulation or a medicinal product formulation frequently employs a primary packaging for such formulation that comprises a container and a nozzle that is suitable to be introduced to a user's nostril and from which such liquid formulation is dispensed into the nostril.
Numerous packaging solutions comprising nozzles suitable for intranasal administration of a liquid formulation are known. For example, EP2335759 (B1) discloses an apparatus and method for preparing a pH balanced saline solution and using the saline solution for rinsing a nasal passage wherein the apparatus comprises a container having flexible sidewalls and an opening for a removable cap, that cap being pressed against a nostril and having an opening from which the saline solution is dispensed into a user's nasal passage.
CN203885832U discloses a nasal irrigation device that comprises a flexible container bottle, a flexible nozzle, a bottle cap and a flow guide tube wherein the flexible nozzle is connected with the top of the bottle cap and wherein the nasal irrigation fluid is ejected out of the flexible nozzle.
When adjusting nozzles to suit the intranasal administration of a liquid formulation, there are several difficulties that one is likely to encounter.
Packaging materials must suffice various requirements before they can be used in the field of health care, pharmaceuticals or cosmetics. A Packaging for liquid formulations is considered particularly critical, and therefore regulatory authorities have established quality criteria for packaging materials that must be met to guarantee patient and consumer safety. Examples of such criteria are migration studies and interaction studies and limits for leachable and extractable compounds. The qualification of any packaging material that is in contact with a liquid formulation is costly and time-consuming and thus limiting the range of possible materials for the innovator in the field.
Dimension and shape of the nozzle must be adjusted to reflect the anatomy of the nostril and the nasal cavity and the intranasal region that is targeted. For example, a nozzle that is aimed to topically and locally administer a liquid formulation onto the mucosa of the sinuses will have a different shape than a nozzle that is designed to administer a liquid formulation into the systemic pathway via the respiratory mucosa.
The anatomy of the nostril and the nasal cavity also present challenges. The skin around the nostril as well as the intranasal mucosa are very sensitive. Especially when a patient suffers conditions including nasal symptoms such as runny nose, the skin and mucosa in the nasal region can be painfully irritated and inflamed. Therefore, it is a desirable feature of a nozzle for the intranasal administration of a liquid formulation to provide a soft surface feel that is gentle to the nostril skin, the intranasal skin and the intranasal mucosa, and that is not causing further irritation of the skin in the nasal region.
The small size of the nasal vestibule makes it difficult to introduce a nozzle. This especially applies for users with impaired motor skills or when one person aims to administer a liquid formulation to another person. Flexible nozzles made from a rubber or an elastic plastic material may be more suitable for such purposes, as they may prick and hurt less than rigid nozzles when the administering person tangents the surroundings of the nostril, for example the ala of the nose, the nasal septum or columella, the philtrum or the outer parts of the nostril. However, when the administering person does not introduce the nozzle directly into the nostril with the nozzle being well centered, such flexible nozzles may bend over instead of gliding into the nostril. Multiple attempts may be necessary for a successful introduction into the nostril. Additionally, rubber and elastic plastics need to fulfill regulatory requirements for plastic immediate packaging materials, which results in the disadvantages set out above.
Therefore, the problem underlying the present invention is to provide a nozzle and a packaging for the intranasal administration of a liquid formulation which has enough stability to glide into the nostril instead of bending over, even if the administering person tangents the surroundings of the nostril thus making the introduction into the nostril easier, but still provides a soft surface feel and a gentle contact to the anatomy of the nose, the nostril and the surroundings of the nostril, while still being cost-effective.
This problem is solved by the subject matter of the invention.
According to the invention there is provided a nozzle for a container for intranasal administration of a liquid formulation, comprising a nozzle body with an upper end and a lower end, a channel traversing the nozzle body and ending with an orifice in the upper end, and a nozzle cover covering an area of the outer surface of the nozzle body which is designed to be introduced into a user's nostril, wherein the nozzle body is made out of a first material, and the nozzle cover is made out of a second material, said first material being a rigid plastic material, and said second material being an elastic plastic material, and wherein the nozzle cover is not in contact with the orifice.
In one embodiment, the nozzle is produced by bi-injection moulding.
In one embodiment, the first material is a thermoplastic material.
In one embodiment, the first material is a polyolefin.
In one embodiment, the first material is a low-density polyethylene.
In one embodiment, the first material has a Shore A hardness of 80-100.
In one embodiment, the second material is an elastomer, a thermoplastic elastomer or a thermoplastic rubber.
In one embodiment, the second material is a thermoplastic elastomer.
In one embodiment, the second material has a Shore A hardness of 20-40.
In one embodiment, the outer surface of the nozzle body and the nozzle cover have an approximately semi-spherical shape.
In one embodiment, the nozzle, when introduced into a nostril, seals the nostril.
In one embodiment, the nozzle cover has an orifice which flushes with the upper end of the nozzle body.
In one embodiment, the nozzle cover has a flat rim surrounding an orifice of the nozzle cover and the flat rim flushes with the upper end of the nozzle body.
In one embodiment, a flow channel for the liquid formulation is formed in the nozzle, and the flow channel is lined by the first material only.
In one embodiment, an orifice of the nozzle cover is aligned with the orifice of the nozzle body, and the orifice of the nozzle cover has a larger diameter than the orifice of the nozzle body.
In one embodiment, the nozzle is designed such that the liquid formulation is not in contact with the second material when dispensed from the nozzle.
According to the invention, there is provided a packaging for a liquid formulation for intranasal administration comprising a container and such nozzle.
In one embodiment, the container is a squeeze bottle.
According to the invention, there is provided a product comprising such a packaging and a liquid formulation in said packaging.
In one embodiment, the liquid formulation is a nasal wash formulation. In one embodiment, the liquid formulation is a nasal spray formulation.
The nozzle and the packaging of the present invention are suitable for the intranasal administration of liquid formulations, for example drug product formulations or medicinal product formulations. These include for example medicated or non-medicated nasal sprays, rinses or washes. The teachings of the present invention can be applied to all nozzles for the intranasal administration of liquid formulations and therefore to all packagings comprising such nozzles and to all products comprising such packagings. The nozzle and the packaging of the present disclosure are especially beneficial for nasal wash formulations.
The channel traversing the nozzle body allows a liquid formulation to flow through it and to be dispensed through the orifice in the upper end of the nozzle body.
The rigid plastic material of the nozzle body ensures that the nozzle has enough stability to be introduced into or to glide into the nostril of the user without bending over, even if the administering person tangents the surroundings of the nostril, thus facilitating the introduction into the nostril. It also allows the nozzle body to be easily mounted on or connected to other parts, for example to a container or to a connecting piece connecting the nozzle and an actual container. The material of the nozzle body is in contact with the liquid formulation and therefore needs to fulfill regulatory requirements for plastic immediate packaging materials for liquid dosage forms. Rigid plastic materials meet these requirements more often than rubber or elastic plastic materials, namely because they do in general not contain plasticizers that could migrate into the liquid formulation. This is one of the reasons why rigid plastic materials are preferred packaging materials in the field of health care, pharmaceuticals or cosmetics, and the manufacturer may choose from a broad spectrum of suitable rigid plastic materials commercially available.
The elastic plastic material of the nozzle cover provides a soft surface feel that is gentle to the nostril skin, the intranasal skin and the intranasal mucosa and is not causing further irritation of the skin in the nasal region. Additionally, the elastic plastic material reduces the risk of pricking, hurting and injury. This ensures an easier and safer introduction into the nostril, especially for users with impaired motor skills or when a person such as a caretaker or a parent aims to administer a liquid formulation to another person. In comparison with nozzles having a rigid plastic material surface, the elastic plastic material of the nozzle cover also provides a better sealing of the nostril and ensures that the liquid formulation does not immediately flow back out of the nose.
Using a first, rigid plastic material for the nozzle body and a second, elastic plastic material for the nozzle cover combines the advantages of both materials as set out above.
According to the present invention, the elastic plastic material of the nozzle cover is not in contact with the orifice.
This eliminates the risk of an interaction between the liquid formulation and the elastic plastic material, such as migration of plasticizers or other ingredients of the elastic plastic material into the liquid formulation. Therefore, a qualification of the elastic plastic material as plastic immediate packaging material for medicinal products is not necessary, making the qualification of the total packaging less costly and less time consuming and making it possible to choose from a broader range of materials for the elastic plastic material.
In a preferred embodiment, the nozzle cover has an orifice which flushes with the upper end of the nozzle body. The nozzle cover only covers an area of the outer surface of the nozzle body and not an upper area or inner area of the nozzle body. The nozzle cover does not project above the upper end of the nozzle body.
In another preferred embodiment, the nozzle cover has a flat rim surrounding an orifice of the nozzle cover and the flat rim flushes with the upper end of the nozzle body. The rim is the uppermost part of the nozzle cover and does not project beyond or over the upper end of the nozzle body. The nozzle cover ending in the flat rim, rather than for example pointy, aids prevention of stripping of the two layers.
In a preferred embodiment, a flow channel for the liquid formulation is formed in the nozzle. The flow channel is lined by the first material only. When the nozzle is used to expel a liquid formulation from a container, the liquid formulation flows from the container, optionally through a dip tube, through the channel traversing the nozzle body and out of the orifice of the nozzle body, without any contact to the nozzle cover.
In a preferred embodiment, and as shown in the figures, an orifice of the nozzle cover is aligned with the orifice of the nozzle body and has a larger diameter than the orifice of the nozzle body. Thereby, a distance between the two orifices is created which separates the nozzle cover from the orifice of the nozzle body. The distance is filled by the nozzle body, i.e. the first material. Thereby, the liquid formulation is not in contact with the second material, even after expulsion from the orifice of the nozzle body.
Preferably, the orifice of the nozzle cover is arranged concentric with the orifice of the nozzle body. Concentric arrangement of the two orifices provides that the difference in diameters, i.e. the distance between, the two orifices is consistent throughout the circumferences of the orifices.
Preferably, the orifice of the nozzle cover and the orifice of the nozzle body are on the same height of a lengths of the nozzle in direction of a flow channel of the liquid formulation. Preferably, the orifice of the nozzle body and the orifice of the nozzle cover are aligned with the upper end of the nozzle body. This arrangement avoids edges, protrusions or depressions where material or dirt could accumulate.
In a preferred embodiment, the nozzle is designed such that the liquid formulation is not in contact with the second material when dispensed from the nozzle. A flow channel of the liquid formulation as well as a flow direction of the liquid formulation after expulsion are free from the second material of the nozzle cover. The nozzle cover is recessed from the orifice of the nozzle body such that a liquid formulation, when expelled from the orifice of the nozzle body, scatters without contact to the nozzle cover.
These preferred constructions all increase the security that the liquid formulation that is dispensed from the orifice of the nozzle body is not in contact with the nozzle cover, but only with the nozzle body, i.e. the first material.
Preferably, the nozzle is produced by bi-injection moulding. This method allows to produce in a single production step both the nozzle body and the nozzle cover and to provide a permanent bond between the rigid plastic material of the nozzle body and the elastic plastic material of the nozzle cover. Bi-injection moulding is a well-established method for the processing of plastic materials and therefore a wealth of materials suitable for this injection-moulding, and in particular for bi-injection moulding, has been developed and is commercially available.
In one preferred embodiment, the first material is a thermoplastic material. Thermoplastic materials are preferred because they can be processed by injection moulding and bi-injection moulding, are recyclable, sufficiently rigid, stable and lightweight. Their characteristics such as colour, hardness and flexibility can easily be adjusted by mixture of different plastics and/ or by the addition of additives.
In a more preferred embodiment, the first material is a polyolefin, most preferred a low-density polyethylene. Polyolefins show desirable chemical and mechanical stability and can conveniently be processed by standard methods in the art, for example injection moulding and bi-injection moulding. Low-density polyethylene is preferred because containers made from this material show excellent containment of liquids and impermeability, thus providing the desired protection for the contained product. It is a well-established plastic material in the fields of food, cosmetics and pharmaceutics and a wealth of low-density polyethylene raw materials are commercially available, including pharmaceutical grade quality.
In one preferred embodiment, the second material is an elastomer, a thermoplastic elastomer or a thermoplastic rubber. Typically, elastomers and thermoplastic elastomers are elastic and flexible materials that show the desired characteristic of the soft surface feel as described above. Elastomer and thermoplastic elastomer raw materials that may be processed by injection moulding and bi-injection moulding are available.
In a more preferred embodiment, the second material is a thermoplastic elastomer, most preferred injection-moulding grade of thermoplastic elastomer. Thermoplastic elastomers are a class of copolymers or a physical mix of polymers, such as a plastic and a rubber, that have thermoplastic as well as elastomeric properties. They can be processed with the same methods as thermoplastic materials, for example in the same production step, for example by bi-injection moulding. Thermoplastic materials and thermoplastic elastomers, when injected into a mould subsequently, may mix to a certain degree on the interface between the two materials, forming a permanent bond between the two materials upon cooling. Additionally, moulding of thermoplastic elastomers does not require an additional step of cross-linking that would be required for elastomers, what makes thermoplastic elastomers recyclable.
Softness and hardness of different plastic materials may suitably be assessed with a Shore durometer and applying the American Society for Testing and Materials' standard ASTM D2240 (“Standard Test Method for Rubber Property-Durometer Hardness”). Results are expressed in values on the Shore hardness scale. An indentor is forced into a material under specified conditions. The indentation hardness negatively correlates to the penetration and is dependent on different material properties. Low values indicate softer materials and less resistance. For soft materials, suitably the Shore durometer A with a truncated indentor is used to determine the hardness on the Shore scale A, which herein is referred to as Shore A hardness.
In one preferred embodiment, the nozzle body may have a Shore A hardness of 80-100. Nozzle bodies of this hardness exhibit the stability that is required for the introduction into the nostril and the connecting to a container as set out above, exhibit desired containment and still are elastic enough to not break.
In one preferred embodiment the nozzle cover may have a Shore A hardness of 20-40, more preferred a Shore A hardness of 25-35, even more preferred a Shore A hardness of 28-32. Nozzle covers of this hardness exhibit the soft surface feel and the benefits as set out above and still are sufficiently resistant to mechanical forces. Additionally, they exhibit advantageous conjunction when processed with a thermoplastic material by bi-injection moulding.
In one preferred embodiment the outer surface of the nozzle body and the nozzle cover have an approximately semi-spherical shape. A semi-spherical shape avoids sharp edges that could provoke lesions of the nostril skin, the intranasal skin and the intranasal mucosa. Additionally, such a shape is easy to introduce into the nostril because the nostril also has an approximately round cross-section. Typically, the cross-section of the nozzle may be circular, and the nozzle may be rotationally symmetric around a central axis. The dimension of the nozzle, i.e. its diameter, length, and tapering, may suitably be designed in such way to partially fit into the nostril and to seal the nostril when introduced, thereby avoiding that the nasal wash immediately flows back out of the nose.
The nozzle, when introduced into a nostril, thus seals the nostril. This is especially beneficial for nozzles for nasal wash formulations, because a backflow of the wash through the same nostril is thereby prevented. Furthermore, sealing of the nostril facilitates building up of the pressure that is needed to direct the nasal wash formulation through the nasal cavities and out through the opposite nostril.
In another aspect of the invention there is disclosed a packaging for the intranasal administration of a liquid formulation comprising a container and a nozzle as described above. Said packaging may include a removable closure cap.
In one preferred embodiment, the container is a squeeze bottle. The nozzle can be mounted directly on the squeeze bottle, without a need for any further dosing or dispensing mechanism. Alternatively, the container can be a conventional bottle, and the nozzle can then be mounted on a dispensing or dosing mechanism, or the dispensing or dosing mechanism can be accommodated inside the nozzle. The nozzle is suitable for use in combination with metered-dose spray pumps, continuous spray pumps or any other pump, dosing mechanism and dispensing mechanism that is suitable for intranasal administration of liquid formulations.
Typically, the design and the dimensions of the container may be adjusted to address the requirements that come along with different liquid formulations for intranasal administration. Typically, the container can contain a volume of 10 ml to 150 ml. For example, the container may contain a volume of around 100 ml of a liquid formulation of a nasal wash and a volume of around 10m1 for a nasal spray.
In another aspect of the invention there is disclosed a product comprising a packaging as described above.
For nasal wash products, a relatively large dose of liquid formulation has to be introduced into the nostril and exact dosing is not needed. Therefore, said products are often sold in squeeze bottles. For nasal spray products, for example non-medicated nasal spray products, a smaller dose and controlled droplet size of the spray are required. Therefore, these products typically are contained in solid bottles and dispensed with a spraying mechanism, for example a continuous spray pump. For medicinal products and medicated nasal sprays, exact dosing and a controlled droplet size are required. Therefore, these products are typically contained in solid bottles and dispensed with a spray mechanism and a dosing mechanism, for example a metered-dose spray pump.
A preferred embodiment of the invention will now be described by way of example only with reference to the accompanying drawings.
Referring to
These plastic materials are preferred as they offer suitable Shore A hardness and allow efficient manufacture by bi-injection moulding.
| Number | Date | Country | Kind |
|---|---|---|---|
| 19191644.4 | Aug 2019 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/072664 | 8/12/2020 | WO |
