United States Patent:  6,054,082

Assignee:  GGU Gesellschaft fur Gesundheits- und Umweltforschung mbH & Co. (Frankfurt, DE)

Filed:  April 14, 1997

A solidified drug supply for generating inhalable drug particles with the aid of a metering device includes a removal unit, with the drug supply being brittle and textureless. The density and the mechanical strength of the drug supply is abraded everywhere in such a way that the structure of the material removed from one side of the drug supply by the metering device is uniform across the entire usage region in the direction of the removal.

SUMMARY OF THE INVENTION

It is the object of the invention to provide a solidified drug supply which can be removed reproducibly over the entire usage region and which produces the desired particle uniformity.

The object of the invention is solved by a drug supply including a solidified body of medicament having a texture formed by applying a pressing force from outside in a direction toward a core positioned centrally in the solidified body. In particular, the solidified body has a density and a mechanical strength is and so defined as to enable an abrasion everywhere in such a way that the structure of the material removed from one side of the drug supply by the metering device is uniform across the entire usage region in the direction of the removal.

The drug supply provided according to the invention may be disposed in an aerosol generator, like aerosol generator known from WO 93/24165 by the present applicant. The device described in this publication is explicitly referenced herein, and is incorporated into the present application by reference. When the aerosol dose is removed by the face cutter operating in an axial direction, the drug supply of the invention provides a very small, but particularly coaxial density distribution which does not affect the generated amount of aerosol and the quantity of the aerosol.

In a preferred embodiment of the invention, the structure of the drug supply may be generated by applying a pressing force in a direction essentially perpendicular to the direction of the subsequent removal. Surprisingly, this method of applying pressure--which is different from isostatic pressing--results in excellent properties of the solidified drug supply. Since in this embodiment the pressing force is applied exclusively in one direction, for example, radially, the density gradient in the drug supply which is generated in this fashion, is also directed strictly radially due to the internal friction described above, i.e. the zones of equal density extend parallel and concentrically to the longitudinal axis of the drug supply.

According to another embodiment of the invention, the drug supply may have a circular cross section and may be fabricated by applying the pressing.

The invention is particularly advantageous with ring-shaped tablets. Here too, a pressing force is essentially directed radially against a stationary core.

As a result of this geometrical shape, a particularly advantageous structure with minimum density gradients in radial and axial direction is attained when only the radial pressing force is applied. According to another preferred embodiment of the invention, the density gradient perpendicular to the removal direction may be no larger than 0.3% and 0.05% in the removal direction. It has not been possible until now to realize such small density gradients with drug supplies adapted for generating inhalable drug particles with a metering device. The drug supply may be fabricated from a granulated carrier material-active ingredient mixture, wherein the pressing forces for the drug supply of the invention are between 50 and 500 MPa.

Another feature of the invention relates to a method for fabricating a solidified drug supply for generating inhalable drug particles with a metering device comprising removal means wherein a pressing force is applied to the drug material. According to the invention, the pressing force is here applied essentially in the direction perpendicular to the direction of the subsequent removal wherein, according to a preferred embodiment, the pressing force in every direction perpendicular to the subsequent removal direction is identical. With this fabrication method, the advantageous properties of an abovedescribed drug supply used for generating drug particles are attained.

Depending on the shape desired for the solidified drug supply, the drug supply is pre-shaped when subjected to the pressing force. For a ring tablet, the drug material--either in powder form or pre-densified--is placed around a stationary core and subsequently pressed against the core by radial pressing force. The core is preferably removed after the pressing step and the ring tablet is taken out.

According to another preferred embodiment of the method, the drug supply is initially formed as a rod-shaped body with, for example, a length of 200 mm, and is subsequently separated perpendicular to its long axis. This method enables a particularly efficient fabrication of the plurality of drug supplies with the desired properties for use in a cooperating aerosol generator.

Another feature of the invention relates to an apparatus for fabricating a solidified drug supply by applying a pressing force to a drug material. The apparatus of the invention comprises a press space formed by at least two parallel stationary plates separated in space and a flexible ram, wherein the faces of the plates and the ram facing the press space are arranged perpendicular with respect to each other. Such apparatus enables the fabrication of a drug supply with the desired properties in an easy and convenient manner.

According to a preferred embodiment, the press space may be a ring space formed about a cylindrical core, the ring space surrounded by the flexible ram, wherein the extrusion die, when subjected to pressure, is moveable towards the core, thereby providing the exclusively radial pressing force.

Claim 1 of 15 Claims

1. A solidified drug supply for making inhalable drug particles through a metering device including a removal means for abrading the solidified drug supply, said drug supply comprising a solidified body of medicament having a substantially uniform radial density formed by applying a radial pressing force from outside in a direction toward a core positioned centrally in the solidified body.

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