WO2001015547A2 - Active agent preparation for veterinary use and method for the production thereof - Google Patents

Abstract

The invention relates to an active agent preparation for veterinary use. Said preparation comprises at least one first active agent that is poorly accepted by the animal and that is enclosed as a component in active cores. The active cores are covered by a coating at least to such an extent that the first active agent can no longer be sensorically perceived by the animal and thus prevent medication. The inventive preparation makes sure that the effect of the active agent is guaranteed even if, for example, it has an unpleasant taste.

Description

 Active ingredient preparation for veterinary application and method for its

manufacturing

Technical field of the invention

The invention relates to the field of veterinary medicine and here to the production and use of an anthelmintic.

State of the art

A large number of active substance combinations are known from WO 95/23590, in which a benzimidazole, for example fenbendazole, is used as the active substance. From this publication compositions are also known in which praziquantel is used as an active ingredient. The compositions described in this publication are intended exclusively for transdermal use.

When designing such a preparation, it is also known to provide a mixture of praziquantel as the first active ingredient and fenbendazole as the second active ingredient, the production leading to a homogeneous preparation in tablet form (Chemical and pharmaceutical documentation / European Pharmacopoera Commission 1995).

In the oral application of a preparation in tablet form, however, it is very disadvantageous that some of the active ingredients from the spectrum available here for the formation of anthelmika have a very unpleasant taste for animals, which leads to the oral application sought here the preparation is not accepted by the animal and therefore the medication effect is not achieved. In the example mentioned above, praziquantel is the active ingredient with this disadvantageous property. Presentation of the invention

The object of the invention is a formulation and a production method of an active substance preparation which contains an active substance of low acceptance by the animal while ensuring the medication effect of the preparation.

According to the invention the object is achieved according to the characterizing part of patent claim 1.

The basic idea of the invention is to be seen in the fact that the component with low acceptance is “hidden” in a core, in the casing of which only an active ingredient is contained which does not have this unpleasant property, which is therefore essentially tasteless. Fenbendazole is such a water-insoluble, taste-free active ingredient, so that the active ingredient preparation presents itself tasteless when administered orally to the animal and the first active ingredient with low acceptance is only perceived by the animal late or not at all anymore.

A two-component active substance preparation of this form can preferably be realized in that the active cores are produced in the form of spheronized granules (for example by means of a process as described in DE 36 23 321 A1) and in that the coating in the form of a water Active ingredient suspension is sprayed onto the granules thus produced.

Another particularly preferred measure provides that a strongly swellable additive is added to the coating; this measure has the effect that, when the animal takes in the preparation, there is a delay in the taste perception of the first active ingredient incorporated into the core, which is little or not accepted, since the taste is perceived only in the dissolved form of the active ingredient A. The pharmaceutical and other administration properties can be modified in the usual way according to the medical or technological requirements during manufacture, without departing from the basic idea of the invention, namely the introduction of the little-accepted first active ingredient exclusively in the active core for its sensory neutralization when the Preparation by the animal.

Further advantageous refinements of the inventive concept can be found in further subclaims.

Brief description of the drawings

A preferred embodiment of the two-component preparation according to the invention and the method for its production is now explained in more detail with reference to figures, in which:

Figure 1: A schematic representation of the drug preparation in its dosage form,

FIG. 2: a schematic flow diagram for the production of the active core as spheronized granules with a preferred formulation of the starting materials,

FIG. 3: a schematic flow diagram for applying the coating to the active core with a preferred formulation of the starting materials, and

Figure 4: schematic representations of the equipment used for the production. Description of the preferred embodiment

Figure 1 shows schematically the structure of the active ingredient preparation from the active core 10 and the casing 20, the active core 10 containing the entirety of the first active ingredient A, which is not accepted by the animal, and part of a second active ingredient which is tasteless and therefore to a certain percentage can also be provided in the envelope 20. In the following, the first active ingredient A is praziquantel, the second active ingredient B is fenbendazole.

The production of the active core as spheronized granules can be seen in FIGS. 2 and 4: in a compulsory mixer (FIG. 4A), praziquantel, 80% of the total amount of fenbendazole, lactose, 60% of xantane, 50% of Na lauryl sulfate, PEG 10,000, maltodextrin and microcrystalline cellulose weighed and premixed dry. Distilled water is added gradually until the mixture has become a moist, crumbly mass. This mass is taken from the mixer and placed in an extruder (FIG. 4B). This can be a commercial extruder for this purpose with a 0.5 mm perforated plate, for example a twin-screw extruder type DE 40 / 10D from the company WLS (address?). The strands produced in the extruder are shaped into pellets of 500 μ in the subsequent spheronizer (FIG. 4C); A commercially available spheronizer, for example a type 602 spheronizer from the company WLS mentioned, can also be used for this purpose, which breaks the strands formed by the extruder at a speed of 300 to 400 rpm and accomplishes the formation into the pellets at 700 revolutions per minute ,

This creates moist, spherical microstructures in the fluidized bed, which are then dried to form active cores 10. Subsequent screening to active cores with diameters between 200 and 500 μm can be carried out, for example, with machines from the Fuchs company of the "SIFTOMAT" type; Active cores that are outside of this range are fed back to the kneader.

To coat these Gutkorn-Aktivkeme with a suitable coating 20 (Figure 3), a dispersion of 1% xanthan solution is first produced, the PVP K25 component is added until their solution is complete and finally the Na lauryl sulfate and the remaining 20% of the total amount of fenbendazole are added. When a homogeneous, sediment-free dispersion of this mixture is achieved, it is sprayed onto the dried, spherical, active active core by means of a multi-component nozzle, as a result of which the casing 20 is formed. Such a coating can be done, for example, with a machine from the Huttier company of the "ball coater" type. Then there is a ready-to-use preparation that is packaged in sachets.

The homogeneous distribution of the fenbendazole dispersion in the sense of a layering together with the other components results in the desired taste coverage of the first active ingredient A (praziquantel) which is accommodated in the active core 10 and is not accepted by the animal.

The fillers in the active core 10 (maltodextrin or microcrystalline cellulose) reduce the percentage of active ingredients A and B in the active ingredient preparation, so that the pellets each represent only a small dose in each case. A larger number of such pellets can be distributed well in the chyme, for example; their total surface area is significantly larger than the surface area of a tablet according to the prior art, so that the active substances can be absorbed over a larger area of the mucous membrane and distributed more quickly through the bloodstream. Damage to the mucous membranes, such as can occur with local, occasionally high drug deliveries, is avoided.

Claims

claims 1. A process for the preparation of an active ingredient preparation for veterinary application with at least one first active ingredient (A) of low acceptance by the animal, characterized in that the first active ingredient (A) is incorporated at least as far as a component in active cores, which are covered by a covering be enclosed at least to such an extent that the first active ingredient (A) is no longer perceptible to the animal from the senses of medication. 2. The method according to claim 1, characterized in that at least a first portion (B1) of a second active ingredient (B) is added to the active core, the second portion (B2) of which is added to the coating. 3. The method according to claim 1, characterized in that at least one first additive is added to the active core. 4. The method according to claim 3, characterized in that an additive is a filler. 5. The method according to claim 1, characterized in that at least a second additive is added to the covering. 6. The method according to claim 5, characterized in that the second additive is a swelling agent. 7. The method according to claim 1, characterized by the use of praziquantel as the first active ingredient (A). 8. The method according to claim 1, characterized by the use of fenbendazole as the second active ingredient (B). 9. The method according to claim 4, characterized by the use of maltodextrin as a filler. 10. The method according to claim 1, characterized in that the active cores are produced in the form of spheronized granules with a predetermined diameter range. 11. The method according to claim 1, characterized in that mainly distilled water is used as the coating, which is sprayed onto the active cores as a suspension. 12. The method according to claim 11, characterized in that the spraying is carried out using larger amounts of air with increased air temperature. 13. The method according to claim 3, characterized by the use of a pharmaceutically neutral additive in the active core to avoid underdosing.