SK129298A3 - Components for inhalation devices - Google Patents

Abstract

A component for use in an inhalation apparatus is described, said component being made of or coated with a polymeric material loaded with carbon black in an amount sufficient to impart to the polymeric material a specific volume resistivity of less than 10<9> Ohmcm.

Description

Technical field

The invention relates to a component of an inhalation device intended for inhalation of medicaments, in particular to a part or element of an inhalation device which is capable of influencing particles of a powdered medicament entrained in an air stream or which comes into direct contact with the medicament.

BACKGROUND OF THE INVENTION

Inhalation devices include dry powder inhalers intended to deliver a dry powder medicament, and pressurized metered dose inhalers containing medicaments typically dissolved or suspended in a liquefied propellant, preferably together with surfactants and other excipients. The drug delivery mechanism varies with different types of inhalers, but generally the drug must leave the body or housing of the inhaler and pass through the duct into the mouthpiece. The mouthpiece may be connected to an inhalation hand piece forming a substantially dispersion chamber to facilitate inhalation.

Pressurized metered dose inhalers release a metered dose of substance each time the actuator is actuated and relatively precise coordination between inhaler control and inhalation during inhalation is required to ensure maximum effect in direct inhalation. Powder inhalers are controlled by the air flow generated by inhalation and a minimum air flow is required to achieve maximum effect. When using the attachment, the medicament is delivered to the spray chamber from where it can be inhaled normally. The residence time of the medicament in the spray chamber may be, for example, from a few seconds to a few minutes.

An example of an inhaler for inhaling a powdered medicament is the Turbuhaler ¹ * inhaler, examples of suitable extensions being Nebuhaler ^R and Nebuchamber ¹¹ .

During inhalation, the medicament comes into contact with various parts of the inhalation device, including, for example, an inhaler case or housing, a canal and a mouthpiece of the inhaler or adapter. These components or components, devices, are generally, but not exclusively, made of a polymeric material, for example polypropylene or polyethylene, shaped to the desired shape.

Upon inhalation, the full amount of the nominal dose of medicament from the inhaler will not achieve the intended target, which may be the patient's lungs. A drug that does not reach the target is lost, for example, in the inhaler, mouth and upper airways of the patient. Obviously, the amount of these losses should be kept as low as possible.

WO-A-91/19524 discloses an inhaler for inhaling a powdered medicament from the interior of a housing comprising a medicament housing receiving chamber formed of low surface resistivity polymeric material parts to reduce the formation of powder particles on the passageway surface air flow through the inhaler. The surface resistivity, or surface resistivity, is required in particular less than 10 ¹² Q per unit area and in particular less than 10 ^θ Ω per unit area. The polymeric material may comprise a carbon or steel filler, for example in the form of fibers or non-fibrous chemical additives. Examples of such materials include a polyether block of an amide product with chemical additives and a series of polypropylenes with chemical additives. The inhaler also comprises a mouthpiece which can be formed integrally with the chamber and in particular has at least an inner wall formed of a polymeric material with low surface resistivity.

WO-A-95/20414 discloses an inhaler extension which is intended to facilitate inhalation especially by children and which is used in particular with pressurized inhalers to deliver metered doses of medicament. The attachment is made of stainless steel and has a surface resistivity such that electrostatic attraction between the inhalable particles and the attachment walls is minimized. The surface resistivity is less than 10 ⁹ Q per unit area, in particular it is less than 10 ⁶ Q and most preferably less than 1 Q per unit area.

The invention relates to a polymeric material of a component of an inhalation device. It has been found that the amount of medicament retained in the inhalation device made of polymeric materials can be significantly reduced by adding soot made of petroleum products or natural gas to the polymeric material. The components of the invention have antistatic properties that minimize the amount of drug retained on the surfaces of the components of the inhalation device.

Carbon blacks of this kind are supplied, for example, by Degussa AG of Frankfurt, Germany. These carbon blacks are chemically and physically well-defined products, are produced by incomplete combustion of petroleum products or gases, and consist of 96% by weight finely divided carbon and a small amount of oxygen, hydrogen, nitrogen and sulfur. These carbon blacks can be produced, for example, in the form of dispersions, pastes, flakes or pellets. At present, the most important way of producing this kind of soot is the so-called retort process for producing soot from petroleum products or natural gas. This process can produce a wide variety of soot with, for example, particular particle sizes or different surface areas. In this process it is also possible to control the bonding of the particles and thus the structure of this kind of soot. The carbon black consists of branched chains of clusters of approximately spherical primary particles. Extensive branching and interconnection of particles produce carbon black having a high structure, while less extensive particle transfer produces low structure carbon black. One method for determining the structure is based on the dibutyl phthalate (DBP) absorption test, which is described in ISO 4656 and ASTM D-2414. In this test, dibutyl phthalate is added dropwise to a certain amount of carbon black loaded into a calibrated mixer, and the torque generated by the mixer is measured. The change in torque indicates that all gaps between the particle clusters have already been filled with dibutyl phthalate (DBP) and their surface has already been wetted. The amount of dibutyl phthalate (DBP) consumed thus makes it possible to determine the degree of soot aggregation. In general, the greater the absorption of DBP in ml / 100 g of carbon black (DBP number), the higher the structure of the carbon black. Low structure carbon blacks have a DBP number of less than 70 ml / 100 g of carbon black, medium structure carbon blacks have a DBP number of between 70 and 100 ml / 100 g of carbon black, and high structure carbon blacks have a DBP number of greater than 110 ml / 100 g of carbon black. The so-called highly conductive carbon black from petroleum products or natural gas has a DBP number greater than 300 ml / 100 g of carbon black.

The primary use of carbon blacks of this type occurs in rubber reinforcement, pigmentation, UV stabilization, and can serve as conductive carbon black.

SUMMARY OF THE INVENTION

SUMMARY OF THE INVENTION The present invention provides a component according to the invention for an inhalation device, wherein the component is made of or coated with a polymeric material filled with carbon black prepared from petroleum products or natural gas, the carbon black having a DBP number greater than 300 ml / 100 carbon black and are contained in the polymeric material in an amount of between 3 and 15% by weight of the polymeric material so that the polymeric material has an intrinsic resistivity of less than 10 ⁹ Q.cm.

The invention also relates to an inhalation device, in particular to an adapter thereof, comprising a component as described above.

In a preferred embodiment, the internal resistivity of the polymeric composition is less than about 10 ® Q.cm, preferably less than 10 ⁴ Q.cm. In a particularly preferred embodiment of the invention, the intrinsic resistivity of the polymeric material is less than about 10 ²

Q. cm.

The intrinsic resistivity can be measured using commercially available conductivity meters.

The use of carbon black produced from petroleum products or natural gas is particularly advantageous since good dispersion of the carbon black in the polymeric material can be achieved. The polymeric material filled with these carbon blacks contains homogeneously dispersed carbon black.

The very low intrinsic resistivity values that can be achieved with the solution according to the invention are particularly advantageous if the part of the inhalation device made of this material is part of the extension of the inhalation device. In fact, it is necessary to ensure a relatively long residence time of the sprayed medicament in the nozzle, and the longer the medicament-air mixture stays inside the nozzle, the greater the possibility of the medicament settling on the walls of the nozzle.

It will be understood that the component of the inhaler manufactured according to the invention may also be other than the extension of the inhalation device, for example it may be in the form of a housing, channel or mouthpiece of the inhaler.

The carbon black is preferably contained in the component material of the inhalation device in amounts of from 6 to 10% by weight, in particular between 8 and 10% by weight of the carbon black-filled polymer material.

In an even more preferred embodiment of the invention, the carbon black content is about 10% or about 9% or about 8% or about 7% or about 6% or about 5% or about 4% by weight of the carbon black-filled polymer material.

Suitable carbon blacks are, for example, supplied by Degussa AG or Cabot Plastics from Belgium. Exemplary types of carbon black produced by Degussa AG are known under the designation

Printex®, for example Printex L, Printex L6 and especially conductive Printex XE 2.

The polymeric material can be any material that can be formed into desired articles in a mold. The polymeric material may be, for example, polypropylene, polyethylene, polyester, polycarbonate, polystyrene, polyoxyethylene, a fluoropolymer or a copolymer thereof. Suitable polymeric materials can be obtained from Hoechst AG of Frankfurt, Germany. Specific examples of suitable polymeric materials include polyethylenes Hostalen ^R , Hostalen GUR ^R , polypropylenes Hostalen PP ^R and Hostacen ^{R as} well as Topas ^R , Hostaform ^R , Kemetal ^R , Celanex ¹¹ , Vandar ^R , Impet ^R , Celstram ^R , Fortron ^R , vectra ^R and Hostaflon ^R , all products of Hoechst AG.

The polymeric material is preferably polypropylene or polyethylene.

The polymeric material with a carbon black filler of the above type and a homogeneous mixture of these components can be produced by conventional techniques, for example by extruding the polymeric material together with the carbon black. The mixing parameters, flow conditions and cooling conditions can be easily optimized by methods well known to those skilled in the art and determined according to the particular polymeric material used and the type of carbon black.

The polymeric materials with the carbon black filler can also be obtained in a finished state, for example from Premix OY of Rajamäki, Finland.

The components of the inhalation device according to the invention can be manufactured by conventional molding techniques, for example by injection molding or blow molding. The parameters of the molding techniques can be readily determined by those skilled in the art depending on the particular material used. Injection into molds is considered to be the preferred manufacturing method. Typical injection parameters may be a roller injection nozzle temperature of 200 to 250 ° C, a mold temperature of 30 to 80 ° C, an injection pressure of 760 to 180 MPa and a moderate injection rate, preferably lower injection rates that slowly increase over time the forming process. The back pressure should be as low as possible. The injection molding material is preferably pre-dried, for example at temperatures of from 75 to 80 ° C for 4 hours, in particular for 2 to 4 hours.

SUMMARY OF THE INVENTION In the process for producing components for an inhalation device as described in the preceding section, the component is formed in the form of at least partially a polymeric material with added carbon black obtained by combustion of petroleum products or natural gas.

If the polymeric carbon black additive material forms a coating layer on another polymeric material, it may be molded together with another polymeric material by, for example, two extruders to produce a shaped component of an inhalation device in which the polymeric carbon black additive material is surrounded by another material, that is, the inner surface of the component is formed of a polymeric material with added carbon black, and the outer surface of the component is formed of another polymeric material. The outer layer of the other material may have any pigmentation to cover the black carbon black in those cases where it would be undesirable.

The wall thickness of the carbon black component or polymer layer is selected according to the nature of the molded component. If the component is part of the inhaler extension, the layer thickness of the polymeric material with the addition of carbon black may be, for example, up to 10 mm, in particular between 1 mm and 5 mm.

The invention will be further elucidated by means of the exemplary embodiments set forth below.

Example i

Pre-Elec TP 4474 PP1381 (formerly Pre-Elec TP 4474), containing carbon black added by incomplete combustion of petroleum products or natural gas, containing polypropylene Hostalen PPU 1734S1, Hoechst AG, and 9% Printex XE 2 carbon black from Degussa AG, used to manufacture a nozzle for use with an inhaler for inhaling dry powder by means of a Ferromatic injection molding machine having a manufacturing temperature of 240 ° C, while maintaining a temperature of 30 ° C inside the mold, an injection pressure of 170 MPa, a back pressure of 160 MPa and injection was at a low speed.

The internal resistivity of the manufactured part was 100 O.cm and the surface resistivity was 1300 Q per unit area.

Example 2

Pre-Elec TP 4479 carbon black polymer material, Premix OY, containing polypropylene Hostalen PPU 1734S1, Hoechst AG, and 22% by weight of Black Pearls 4750 carbon black, Cabot Plastics, was used to manufacture an inhaler adapter for inhalation to dry powder by inhalation. the forms of Example 1.

The intrinsic resistivity of the manufactured part was 30 Q.cm and the surface resistivity was 800 Q / cm.

Example 3

Pre-Elec TP 4480 carbon black additive material, Premix OY, containing polypropylene Hostalen PPU 1734S1, Hoechst AG, and 37% by weight Channel Black MPC carbon black, Cabot Plastics, was used to manufacture an adapter for use on an inhaler for dry powder inhalation the forms of Example 1.

The intrinsic resistivity of the manufactured part was 10000 Q. cm and the surface resistivity was 10000 Q / m.

Example 4

Batches of budesonide from a dry powder inhaler (Pulmicort Turbuhaler ¹ *) containing 200 unit doses, each containing 400 gg of budesonide, were blown with a suction air stream into the adapter according to the example.

1. After 2 seconds of rest, a suction device was used to create a jet of intake air and blow a dose of medicament from the adapter onto the filter surface.

This experiment was repeated using an extension made of polypropylene only. The polypropylene-only extension device was the same as in Example 1 except that an injection pressure of 90 MPa and a back pressure of 60 MPa was used.

The amount of budesonide retained on the filter after blowing from the polypropylene adapter with the carbon black additive of Example 1 was

2.4 times the amount captured from a batch blown from a conventional polypropylene adapter. This shows that the amount of drug retained on the handpiece of the invention is significantly reduced compared to conventional handpieces.

Example 5

Batches of budesonide from a dry powder inhaler (Pulmicort Turbuhaler ^R ) containing 200 unit doses, each containing 400 gg of budesonide, were blown with a suction air stream into the lance of Example 1. After 30 seconds of rest, a suction device was used to generate a suction stream. air and blowing out the dose of medicine from the filter attachment.

This experiment was repeated using an extension made of polypropylene only. The device for producing a polypropylene only extension was the same as in Example 1 except that an injection pressure of 90 MPa and a back pressure of 60 MPa was used.

Bar.

The amount of budesonide retained on the filter after blowing from the polypropylene soot additive attachment of Example 1 was 2.8 times greater than the amount collected from the blown blown from a conventional polypropylene attachment. This shows that the amount of drug retained on the handpiece of the invention is significantly reduced compared to conventional handpieces.

Claims (12)

A component of an inhalation device, characterized in that it is made of or coated with a carbon black additive polymer material having a DBP number greater than 300 ml / 100 g of carbon black in a quantity of between 3 and 15% by weight of the polymer material per weight. providing an internal resistivity of the polymer material of less than 10 ⁹ O.cm. Component according to claim 1, characterized in that its intrinsic resistivity is less than 10 ⁶ Q.cm. Component according to claim 2, characterized in that its intrinsic resistivity is less than 10 ² n.cm. Component according to claims 1 to 3, characterized in that the carbon black is present in the component in the form of a dispersion. Component according to claims 1 to 4, characterized in that the polymeric material with added carbon black comprises a homogeneous mixture of carbon black and polymeric material. Component according to claims 1 to 5, characterized in that the polymeric material with added carbon black contains carbon black in an amount of between 8 and 10% by weight of the polymeric material. Component according to claims 1 to 6, characterized in that the polymeric material is polypropylene, polyethylene, polyester, polycarbonate, polystyrene or copolymers thereof. Component according to claims 1 to 6, characterized in that the polymer material is polypropylene or polyethylene. Component according to claims 1 to 8, characterized in that it is in the form of an inhaler housing, an inhaler mouthpiece or an inhaler duct. An inhalation device comprising a component according to claims 1 to 8. An inhalation device extension comprising a component according to claims 1 to 8. Method for producing a component according to claims 1 to 8, characterized in that the component is formed at least partially from a polymeric material containing a carbon black additive.