Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form
Reexamination Certificate
1996-08-22
2001-02-13
Clardy, S. Mark (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
C424S447000, C424S448000, C424S449000
Reexamination Certificate
active
06187322
ABSTRACT:
The present invention relates to a process and a device for the production of a flat administration form therapeutic system comprising a preparation which contains pharmaceutically active substances.
BACKGROUND OF THE INVENTION
Such a flat-shaped administration form is a dermal or transdermal therapeutic system in the form of a patch, for example, described in DE 36 29 304. There an active substance depot with textile sheet material is surrounded by a matrix on all sides; metering the active substance into the depot is particularly difficult. DE 36 30 603 and EP 0 219 762 propose to apply the active substance-containing mass by means of a roll coater. A similar proposal is made in DE 38 44 250 where the active substance is printed in flowable form on a web-shaped absorbent textile substrate. Engraved roll coating, extrusion coating, screen printing, or spray coating are mentioned as possible printing methods.
However, these methods have some shortcomings. On the one hand, the active substance is applied on the whole continuous web, although only defined sections of the web-shaped material can normally be used for the actual administration form; this results in large quantities of active substance-containing waste.
On the other hand, the skilled artisan knows that the accuracy specified for therapeutic systems can only hardly, if at all, be achieved. This also applies to the processes proposed in DE 35 31 795, such as screen printing, flexoprinting, gravure printing, and inkjetting.
A practical method avoiding active substance-containing waste is the tampon printing method described in DE 37 27 214 and DE 37 27 232. The disadvantage in this case lies in the fact that the amount of liquid filled in the printing block as well as that transferred by the tampon depends on factors that are difficult to control, such as temperature, viscosity, printing rate, pressure on the support, and surface property. For this reason the demands with respect to accuracy are also difficult to meet. Controlling the transferred amount is only possible outside the actual manufacturing process by printing preweighed patterns.
An improvement can be achieved by the process described in P 42 30 589.6; here the tampon presses the web material directly into the filled cavity of a printing block where it absorbs the liquid active substance. Again, the disadvantage is that the printing block cannot be filled exactly, and that the liquid active substance preparation must have a medium to high viscosity .
An absolutely different way is described in DE 34 23 328. Here adhesive and active substance are physically separated and printed in the form of dots by means of screen printers. However, the disadvantages of this method are that the printed area only forms a very small part of the total surface, on the one hand, and that the above-mentioned restrictive conditions with respect to accuracy are applicable in this case too.
DESCRIPTION OF THE INVENTION
It is accordingly the object of the present invention to transfer in a simple and reliable manner a flowable active substance-containing preparation of a broad viscosity range onto a defined area of a layer of a flat-shaped administration form with high accuracy and at a high rate.
This object is achieved according to the present invention by a process in which a quantity of the flowable preparation, which can be metered with high accuracy, is transferred through a distribution plate (
3
), which is provided with at least one passage (
4
), of an applicator device (
12
) on a defined area of a layer (
7
) of the flat administration form, that can be brought into contact with said applicator device (
12
). Further, process according to the characterizing part of claim
1
. Further suitable embodiments of the present invention are described in the disclosure.
The use of a precise proportioning pump known per se, for example, a piston-type dosing pump, may provide very high accuracy with very high number of cycles at the same time. The conveyed amount may be determined over a broad viscosity range of the flowable preparation. The flowable active substance-containing preparation is evenly distributed over the defined area of the administration form by passage through a distribution chamber and an adjoining distribution plate which is provided with at least one opening. The flowable active substance-containing preparation is directly transferred by short-term contact of the distribution plate with the sheet-like administration form. The dosage of the preparation and its transfer onto the administration form can be carried out isochronously or in chronological order, i.e., simultaneously or in sequence.
This process makes it possible to transfer both low-viscous active substance preparations having a viscosity of from 0.1 mPas and high-viscous active substance preparations having a viscosity of up to 10,000 mPas without any problems. The process may preferably be used for viscosity ranges of 100 to 10,000 mPas.
Advantageously, the flowable preparation, which also includes one-component systems according to the p resent invention, is transferred on an absorbent area of the administration form. In this connection, it may be advantageous to compress this area by means of the distribution plate first, to proportion the flowable active substance preparation, and then to relax the layer again. The surface area of the administration form which is to be provided with the active substance-containing preparation may also have other characteristic features, such as pressure-sensitive adhesive properties.
In large scale manufacture of flat administration forms it is advantageous to perform a rotary process. This can achieve production rates of 20 m/min. and more. To this end, several distributor chambers with associated distribution plates are arranged over the circumference of a cylinder. By means of one or several proportioning pumps the flowable preparation is transported successively into the individual distribution chambers, predosed on the distribution plates, and transferred onto the flat-shaped administration forms in a rotary manner.
A major advantage of the process according to the present invention is that the amounts conveyed by the pump may be controlled in accordance with production safety. For instance, the amount of dosed flowable preparation may be rated at each individual administration form by means of a mass or volume flowrate measuring unit—e.g., according to the Coriolis force principle—permitting a 100% in-process verification.
The process according to the present invention makes it possible to apply at the same time two or more different flowable active substance-containing preparations on adjacent surfaces of the administration form; in this case the distribution chamber is subdivided accordingly.
In general, uniform distribution of the active substance in the sheet-like administration form is desired. To this end, it is useful to distribute the passages uniformly over the area of the distribution plate and to select their inner diameter in the range of 0.1 to 1 mm. The total area of the passages should by no means exceed 10% of the distribution plate surface. For particularly high demands on accuracy a two-step distribution should be carried out i.e., behind the first distribution chamber and distribution plate there is a second distribution chamber and a second distribution plate. In order to avoid plugging of the passages, a filter may be integrated into the device. In a two-stage distribution it is particularly useful to combine the filter with the first distributor plate.
For some applications it may be useful to form the openings in the distribution plate in the shape of slots. As for the rest the distribution plate may consist of an open-cell sintered or foamed material or of a screen.
In order to adjust a processable viscosity range of the preparation it is sometimes suitable that the applicator unit is of a temperature-controlled construction.
The advantages that can be achieved with the present invention particularly lie in the fact that the flowa
Grader Ludwig
Hille Thomas
Schumann Klaus
Clardy S. Mark
LTS Lohmann Therapie-Systeme GmbH
Shelborne Kathryne E.
Wenderoth , Lind & Ponack, L.L.P.
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