MXPA98007532A - Components for inhalac devices - Google Patents

Abstract

The present invention relates to a component for use in an inhalation apparatus, the 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 nm. Little Ohm

Description

COMPONENTS PARR INHALATION DEVICES Field of the Invention The present invention relates to components for inhalation devices, for inhaling a medicament, especially those components which can affect particles carried by air or which come into contact with the medicament.

Background of the Invention Inhalation devices include dry powder inhalers, proposed to deliver the drug, which is in the form of a dry powder, and pressurized metered-dose inhalers, which generally contain a drug dissolved or suspended in a propellant gas liquefied, optionally together with surfactants or other excipients. The mechanism for distributing the medication varies between inhalers, but in general the medication must leave the body of the inhaler and pass through a channel to a mouthpiece. The nozzle can be connected with a spacer, that is, a dispersion chamber designed to facilitate inhalation. Ref.028314 Inhaled metered dose inhalers release a metered dose of medication during each actuation, and for maximum benefit with direct inhalation, a degree of coordination between actuation and inhalation is required. Powdered inhalers are powered by the flow of air generated in the inhalation and for a maximum benefit a certain air flow is required. With a spacer, the medication is distributed to the spacer chamber from where it can be inhaled by simply breathing normally. The residence time of the medicine in the spacer can be from a few seconds to several minutes, for example. An example of a dry powder inhaler is the Turbuhaler® inhaler. Examples of the spacers include the NebuhalerR and NebuchamberR spacers. In the course of inhalation, the medicament will come into contact with various parts of an inhalation device, including for example the body, channel and mouthpiece of an inhaler, and a spacer. Such components are generally made (but not essentially) of a polymeric material, for example, a polypropylene or a polyethylene, which is molded in the required shape.

Not all of a nominal dose of the medication from an inhaler will reach its intended target, which may be, for example, the lungs. The medication which does not reach the target is lost, for example, in the inhaler, mouth and respiratory tract. Clearly, the amount of waste should be as low as possible. WO-A-91/19524 discloses an inhaler for inhaling the sprayed medicament from inside a capsule, including a capsule chamber which can be formed of the components made of a polymeric material with a low surface resistivity to minimize the degree to which the sprayed medication released can agglomerate on the surface of the air passage through the inhaler. The desired surface resistivity is preferably less than 1012 Ohms and more preferably less than 108 Ohms. The polymeric material may incorporate a carbon or steel filler, for example, in the form of fibers or non-fibrous chemical additives. As examples of the polymeric material are mentioned, a polyether block amide product with chemical additives and a range of polypropylenes with chemical additives. The inhaler also includes a nozzle, which can be integral with the chamber, preferably having at least its inner wall formed of such a polymeric material of low surface resistivity. WO-A-95/20414 discloses a spacer for children, proposed mainly for use in conjunction with an inhaler of a pressurized metered dose. The spacer is made of stainless steel, which has a surface resistivity such that the electrostatic attraction between the respirable particles and the spacer walls is minimized. The surface resistivity is less than 109 Ohms, preferably less than 106 Ohms and more preferably less than 1 Ohm. The present invention relates to polymeric materials in components for inhalation devices. It has been found that the amount of the drug which is retained in a device comprising the components made of a polymeric material can be significantly reduced by incorporating carbon black into the polymeric material. The components according to the present invention have anti-static properties which minimize the amount of drug retained on the surfaces of the component. Carbon blacks are obtainable, for exe, from Degussa AG, Frankfurt, Germany. They are chemically and physically well defined products, which are manufactured by the incomplete combustion of oils or gases, and are composed of more than 96 percent by weight finely dispersed coal with small amounts of oxygen, hydrogen, nitrogen and sulfur. They can be produced, for exe, as dispersions, pastes, chips or pills. Until now, the most important method for the manufacture of carbon blacks is the so-called "kiln black" process. This process can produce a large variety of carbon blacks, for exe, with particular particle sizes and specific surface areas. It also allows control of the aggregation of particles, that is, the structure of carbon black. Carbon blacks consist of branched chain aggregates of approximately "spherical" primary particles. The extensive branching or interlacing produces carbon black which has a "high structure", while a less extensive interlacing produces a "low structure" carbon black. One method for determining the structure is the "DBP absorption" test, which is described in ISO 4656 and ASTN D-2414. In this method, dibutyl phthalate (DBP) is added by dripping to a certain amount of carbon black that has been placed in a calibrated kneading machine and the torque exerted by the kneading machine is measured. A change in torque indicates that all the gaps between the carbon black aggregates have been filled with DBP and the surface has been moistened. The consumption of DBP thus allows the determination of the degree of aggregation of carbon black. In general, the higher the DBP uptake in ml / 100 g (the "DBP number"), the higher the carbon black structure. Carbon blacks with a lower structure have a DBP number of less than 70 ml / 100 g of carbon black, those with a medium structure have a DBP number between 70 and 100 ml / 100 g of carbon black, and those with a high structure have a DBP number of above 110 ml / 100 g of carbon black. Carbon blacks so-called "extra-conductors" typically have a DBP number in excess of 300 ml / 100 g of carbon black. The primary use of carbon blacks is in rubber reinforcement, for pigmentation, UV stabilization and as conductive blacks.

Detailed description of the invention Accordingly, the present invention provides a component for use in an inhalation device, the component is made of, or coated with, a polymeric material loaded with carbon black having a DBP number of greater than 300 ml / 100 g of carbon black and in an amount of between 3 and 15 percent by weight of the polymeric material to impart to the polymeric material a specific volume resistivity of less than 109 Ohmcm. The present invention also extends to an inhalation device, in particular a spacer, incorporating the component described above. Preferably, the specific volume resistivity of the polymeric material is less than about 106 Ohmcm, more preferably less than about 104 Ohmcm. In a particularly preferred embodiment, the specific volume resistivity of the polymeric material is less than about 102 Ohmc. The specific volume resistivity can be measured using commercially available apparatus for conductivity measurement. The use of a carbon black dispersion is particularly advantageous because good dispersion of the carbon black in the polymeric material can be achieved. Preferably, the polymeric material charged with carbon black comprises a homogeneous distribution of the carbon black. The very low specific volume resistivity values, which can be achieved in accordance with the present invention, are particularly valuable when the component is incorporated in a spacer. In a spacer, a comparatively long medication residence time is necessary, and the longer the residence time, the greater the opportunity for the drug to "attack" the walls of the spacer. It will be understood that the component of the present invention may be different from that incorporated in a spacer. For example, the component may comprise the body, a channel, or the mouthpiece of an inhaler. Preferably, the carbon black is included in an amount of between 6 and 10 percent and especially between 8 and 10 percent by weight of the polymeric material loaded with carbon black. More preferably, carbon black is included in an amount of about 10 percent, or about 9 percent, or about 8 percent, or about 7 percent, or about 6 percent, or about 5 percent, or about 4 percent by weight of the polymeric material loaded with carbon black. Suitable carbon blacks are commercially available, for example, from Degussa AG, or from Cabot Plastics, Belgium. Examples of carbon blacks from Degussa AG are in the range of carbon blacks known as Printex®, for example "Printex L", "Printex L 6", and the extra-conductor "Printex XE 2". The polymeric material can be any which can be molded into the desired shape. For example, the polymeric material may be a polypropylene, a polyethylene, a polyester, a polycarbonate, a polystyrene, a polyoxyethylene, a fluoropolymer, or a copolymer thereof. Suitable polymeric materials can be obtained, for example, from Hoechst AG, Frankfurt, Germany. As specific examples of the polymeric materials there may be mentioned the polyethylenes Hostalen® and Hostalen GUR®; and the Hostalen PPR and Hostacen® polypropylenes; as well as TopasR, Hostaform®, Kemetal®, Celanex®, Vandar®, Impet®, Celstra®, Fortron®, Vectra® and Hostaflon®, all available from Hoechst AG. Preferably, the polymeric material is a polypropylene or a polyethylene. The polymeric material charged with carbon black, and the homogeneous mixture, can be manufactured by conventional methods, for example, by extrusion of the polymeric material together with the carbon black. Mixing parameters, flow conditions and cooling conditions can be easily optimized by methods well known to a person skilled in the art., according to the particular polymeric material and the carbon black used. Polymeric materials loaded with carbon black are also commercially available, for example, from Premix Oy, Rajamáki, Finland. The components according to the present invention can be made by conventional molding techniques, for example, by injection molding or by blow molding. The molding parameters can be easily optimized by a person skilled in the art, according to the particular materials used. The preferred method of manufacture is injection molding. Typical injection molding parameters can be for example a cylinder nozzle temperature from 200 to 250 ° C, a mold temperature from 30 to 80 ° C, an injection pressure from 600 to 1800 bar and an injection speed moderate Preferably, a low molding speed is used initially and increases slowly during the molding process. Preferably, the counter pressure is as low as technically possible. Preferably, the material for injection molding is pre-dried, for example, from 75 to 80 ° C for up to 4 hours, typically from 2 to 4 hours. The present invention also provides a method for forming the component for use in an inhalation device as described above, comprising the step of molding the component at least in part from a polymeric material loaded with carbon black. When the polymeric material loaded with carbon black is a coating or other polymeric material, it can be co-molded with the other polymeric material, for example, using two extruders, to produce a molded component in which the polymeric material loaded with black carbon is surrounded by the other material, i.e., the "inner" surface of the component is of the polymeric material loaded with carbon black and the "outer" surface of the component is of the other polymeric material. The external material can be provided with any desired pigmentation to hide or mask the black color of the carbon black in the circumstances where it could be considered undesirable.

The thickness of the component or the polymer layer loaded with carbon black can vary according to the nature of the molded component. Where the component is incorporated in a spacer, for example, the thickness of the polymeric material loaded with carbon black can be, for example, up to about 10 mm, preferably between 1 and 5 mm thick. The present invention will be further described with reference to the following non-limiting Examples.

• Example 1 A polymeric material loaded with carbon black, "PP 1381" (formerly "Pre-Elec TP 4474"), Premix Oy, comprising polypropylene "Hostalen PPU 1734S1", Hoechst AG, and 9 percent by weight of carbon black" Printex XE 2", Degussa AG, was used to make a spacer for use with a dry powder inhaler, by injection molding using a molder by "Ferromatic" injection, with a cylinder nozzle temperature of 240 ° C, a mold cavity temperature of 30 ° C, an injection pressure of 1700 bars, a back pressure of 1600 bars and a moderate injection speed .

The specific volume resistivity obtained was 100 Ohmcm. (Surface Resistivity 1300 Ohms).

Example 2 A polymeric material loaded with carbon black, "Pre-Elec TP4479", Premix Oy, comprising polypropylene "Hostalen PPU 1734S1", Hoechst AG, and 22 weight percent of "Black Pearls 4750", Cabot Plastics, was used for fabricating a spacer for use with a dry powder inhaler, by injection molding as in Example 1. The specific volume resistivity obtained was 30 Ohmcm. (Surface resistivity of 800 Ohms).

Example 3 A polymeric material loaded with carbon black, "Pre-Elec TP 4480", Premix Oy, comprising polypropylene "Hostalen PPU 1734S1", Hoechst AG, and 37 percent by weight of carbon black "Channel Black MPC", Cabot Plastics , was used to manufacture a spacer for use with a dry powder inhaler, by injection molding as in Example 1.

The specific volume resistivity obtained was 10000 Ohmcm. (Surface resistivity 100000 Ohms).

Example 4 The budesonide doses of a dry powder inhaler (Pulmicort Turbuhaler®) containing 200 unit doses each comprising 400 μg of budesonide were expelled by means of a suction flow in a spacer according to Example 1 above. After a delay of 2 seconds, the suction flow medium was used to eject the dose of the spacer on a filter. The experiment was repeated using a spacer constructed only of polypropylene. The means for manufacturing the polypropylene spacer only were as in Example 1, but with an injection pressure of 900 bar and a counter pressure of 600 bar. The amount of budesonide on the filter after ejection of the polypropylene spacer charged with carbon black of Example 1 was 2.4 times larger than the amount resulting from the ejection of the conventional polypropylene spacer.

This was taken as an indication of the greatly reduced amount of the drug which has been retained in the spacer according to the present invention, when compared to a conventional spacer.

Example 5 The budesonide doses of a dry powder inhaler (Pulmicort Turbuhaler®) containing 200 unit doses each comprising 400 μg of budesonide are expelled by means of a suction flow to a spacer according to Example 1 above. After a delay of 30 seconds, the suction flow means were used to eject the dose from the spacer onto a filter. The experiment was repeated using a spacer constructed only of polypropylene. The means for manufacturing the polypropylene spacer only were as in Example 1, but with an injection pressure of 900 bar and a counter pressure of 600 bar. The amount of budesonide on the filter after ejection of the polypropylene spacer charged with carbon black of Example 1 was 2.8 times larger than the amount resulting from the ejection of the conventional polypropylene spacer. This was taken as an indication of the greatly reduced amount of medicament which has been retained in the spacer according to the present invention., when compared to a conventional spacer.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, property is claimed as contained in the following

Claims (12)

1. A component for use in an inhalation device, the component is characterized in that it is made of, or is coated with, a polymeric material loaded with carbon black having a DBP number of more than 300 ml / 100 g of carbon black and in an amount of between 3 and 15 weight percent of the polymeric material to impart to the polymeric material a specific volume resistivity of less than 109 Ohmcm.

2. The component according to claim 1, characterized in that the specific volume resistivity is less than 106 Ohmcm.

3. The component according to claim 2, characterized in that the specific volume resistivity is less than 102 Ohmcm.

4. The component according to any of claims 1 to 3, characterized in that the carbon black is a carbon black dispersion.

5. The component according to any of claims 1 to 4, characterized in that the polymeric material charged with carbon black comprises a homogeneous mixture of carbon black and polymeric material.

6. The component according to any of claims 1 to 5, characterized in that the polymeric material charged with carbon black comprises carbon black in an amount between 8 and 10 weight percent of the polymeric material.

7. The component according to any of claims 1 to 6, characterized in that the polymeric material is a polypropylene, a polyethylene, a polyester, a polycarbonate, a polystyrene, or a copolymer thereof.

8. The component according to any of claims 1 to 6, characterized in that the polymeric material is a polypropylene or a polyethylene.

9. The component according to any of claims 1 to 8, characterized by 19 because the component is one of the body of an inhaler, the mouthpiece of an inhaler or a channel of an inhaler.

10. An installation device, characterized in that it incorporates the component according to any of claims 1 to 8.

11. A spacer, characterized in that it incorporates the component in accordance with any of 10 claims 1 to 8.

12. A method for forming the component according to any of claims 1 to 8, characterized in that it comprises the step of molding the 15 component at least in part from a polymeric material loaded with carbon black. twenty 25