BRPI0713265A2 - pharmaceutical tablets, compression tool for tablet production, tablet press, method for producing microstructures on the surface of a tool - Google Patents

Abstract

TABLETS FOR PHARMACEUTICAL USE, COMPRESSION TOOL FOR TABLET PRODUCTION, TABLET PRESS, METHOD FOR PRODUCING MICROSTRUCTURES ON THE SURFACE OF A TOOL. A tablet (4) for pharmaceutical use has at least part of its surface a diffractive microstructure (11) which generates diffraction effects that can be discernible in the visible spectrum range and which serves as a visual safety feature. The tablet (4) consists of a plurality of individual powder particles, the diffractive microstructures (11) being embedded in the surface of the individual powder particles. A compression tool (1,1a, 1b, 3) for producing such tablets (4) has microstructures (11) on a pressing surface of the compression tool (1, 1a, 1b, 3), such microstructures ( 11) have dimensions that are smaller than the dimensions of the individual crystallites (30) of the compression tool pressure surface material (1,1a, 1b, 3). The microstructures 11 of the compression tool may be produced for example by ion erosion or embossing.

Description

TABLETS FOR PHARMACEUTICAL USE, COMPRESSION TOOL FOR TABLET PRODUCTION, TABLET PRESS, METHOD FOR PRODUCING MICROSTRUCTURES ON THE SURFACE OF A TOOL.

Technical Field

The invention relates to a tablet having an optical safety feature in the form of a diffractive microstructure, a compression tool for producing such tablets and method for producing such tablets.

State of the Art

Counterfeit and parallel market products, and illegal re-importation are a major problem for pharmaceutical drugs. Drugs and medicines are increasingly being counterfeited, a problem not only for developing countries where counterfeit supply chain products often reach more than 50%, but such a problem also exists in industrialized countries where pharmaceutical drug prices are often higher. Drug or AIDS drug prices are often lower in developing countries, for example for social reasons, but this increases the risk of abusive re-importation of such drugs to industrialized nations.

To prevent abuse, pharmaceutical drug packaging is provided with anti-counterfeiting features. Holograms, optically variable inks, fluorescent dyes, special printing techniques such as micro-printing, and other safety features are either attached to the package or applied directly to the package. The major disadvantage of such labeling is that it can be removed from the product or packaging and then reused or analyzed. Some companies apply safety features to the blister pack sealing film, but they have the same disadvantages.

Methods of applying counterfeit-proof signatures, for example, known sequence DNA (US 5,451,505), molecules with characteristic isotopic composition, or micro particles with a characteristic color layer sequence (US 6,455,157) are extremely critical because such Signatures are ingested along with the drug. For this reason, control authorities such as the U.S. Food and Drug Administration (FDA) have not yet given permission for such methods.

Some attempts to apply a hologram to edible products have been published. WO 01/10464 discloses a coating of edible products with an embossable moldable layer. However, the application of such ... layers alters the composition and production process of pharmaceutical pills, which then require further official approval. Additionally, heating during the thermal forming steps is problematic for many chemical ingredients.

US 4,667,523 describes another approach in which a polymer solution is brought into contact with a mold having a diffractive relief. The polymer is then hardened by drying. This step can be accelerated with heating. In the end, the hardened edible polymer product is provided with the diffractive relief. This method is limited to polymeric solutions and is very slow. Additionally, it is also problematic here to heat the active ingredients used for the production of pharmaceutical tablets. These disadvantages have prevented the introduction of such techniques in the market. Description of the Invention

The object of the present invention is to provide a tablet having an integrated safety feature, such a tablet having essentially the same composition as a traditional tablet that can be produced without elevated temperatures during the manufacturing process, and which does not require an extension of the manufacturing process. compared to traditional processes. Another object of the present invention is to provide a compression tool with which such tablets may be manufactured as well as methods of producing such molds.

The term "tablet" in this context is understood to refer not only to swallow, suck, chew or dissolve tablets and pills in the mouth, but also to other forms of medicinal doses such as suppositories or products which are dissolved in liquids before being taken. In addition to pharmaceutical tablets, this is also meant as filled candies or sweetening tablets.

These and other objects are achieved with a tablet, a compression tool and methods for manufacturing such compression tools according to independent patent claims. Preferred variations are described in the dependent claims.

A tablet according to the invention has a diffractive structure on its surface, which creates noticeable diffraction effects in the optical spectrum range and then functions as a safety feature. The microstructured surface may also be macroscopically structured to form, for example, logos, trade names, etc. The safety feature cannot be removed from the tablet and cannot subsequently be transferred to counterfeit goods. To produce such tablets, a compression tool according to the invention consisting of a compression mold and two punches is used. The surface of the compression mold and / or one or both punches in contact with the powder mixture to be compressed is / are provided with a diffractive microstructure which is formed during the compression operation, more precisely during the compression and compaction process. , on the surface of the powder particles, thus forming a permanent diffractive microstructure on the surface of the finished tablet.

The traditional temperatures, pressures and process speed of known tablet press machines can be maintained in the manufacture of the tablets of the invention. In particular, a compression time of much less than 100ms per tablet is sufficient. The molds of the invention may be used in traditional tablet machines. The production of the tablets of the invention is therefore compatible with existing and qualified production methods, and has no high value.

Embodiments of the invention

The invention will be explained below in more detail with the aid of the drawings.

Fig. 1 shows a simplified schematic diagram of the tablet compression operation.

Fig. 2 shows a schematic cross-section through diffractive microstructures on the tablet surface produced with the method of the invention having (a) rectangular, (b) sinusoidal and (c) triangular mesh lines.

Fig. 3 shows a photograph of a compressed diffractive microstructure tablet produced by the method of the invention.

Fig. 3a shows a schematic diagram of tablets of the invention with recessed microstructures.

Fig. 3b shows a schematic diagram of a reading device for tablet authentication of the invention.

Fig. 4 shows (a) a photograph of a micro-structured compression tool for use in the method of the invention and (b) an MVE micrograph (MVE = scanning electron microscopy) of a tablet produced by the method of the invention.

Fig. 5 schematically shows the steps of the ion erosion method for producing the compression tool of the invention: (a) holographic illumination (b) chrome oblique erosion, (c) dry erosion, (d) finished microstructured surface of the compression tool.

Fig. 6 shows an example of a stress-strain curve.

Fig. 7 shows a photograph of a cold structured micro structured aluminum plate.

Fig. 8 shows a schematic diagram of the punching process to illustrate a diffractive microstructure on the surface of a compression tool.

Powder blends for pharmaceutical tablets

Most tablets are produced by compressing a mixture of powders into a compression mold. If active and excipient powders are merely mixed and pressed directly to form tablets, direct compression is meant. This process is primarily a high pressure molding process.

The mixture to be compressed comprises particles of different sizes, and particle size distribution is critical for the tablet compression process. Table 1 shows an example of a typical blend, including excipients, for the manufacture of a pharmaceutical tablet. Table 2 shows the typical corresponding particle size distribution.

Table 1

<table> table see original document page 7 </column> </row> <table>

Table 2

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Lactose and cellulose are the binders and excipients most commonly used in direct compression processes. These substances are especially suitable because they have a diffractive microstructure.

The powder is gravity conveyed in a tablet compression machine. Thus, a good flowability property is mandatory. Aerosil improves the flowability of the powder.

Magnesium stearate is used as a lubricant. Lubricants act by being distributed on the surface of the dust. They reduce the friction forces between dust and compression tools, thus preventing the tablet from adhering to the compression tool.

Disintegrating ingredients may be added to the powder mixture to improve disintegration, such as dissolution in water. Tablet disintegration time is typically evaluated in water at 37 ° C.

Sometimes a dye is added, but only a few dyes are allowed in medicines. Therefore, practically almost all pharmaceutical tablets are neutral white in color. Some are bright red or light blue.

Thus, all tablets produced by direct compression process have luminous or light scattering surface.

Particles larger than 500 μπι and / or less than 75pm are critical for compression operation. The former reduces the mechanical stability of the pressed tablet while the latter is problematic for particle flow during filling of the compression mold cavity. The amount of these particles should therefore be kept as low as possible. In general, it can be concluded that virtually all powder particles used in tablet compression processes are much larger than diffractive microstructures, which are typically structures smaller than 5μπ \ and will be created on the surface.

To prevent undesirable chemical changes in ingredients during tableting, the temperature should advantageously be 50 ° C, even better than 40 ° C. The temperature is preferably between 15 ° C and 35 ° C, for example at room temperature.

PARAMETERS OF DIFFRACTIVE MICROSTRUCTURES

It is difficult to reliably and permanently create typical diffractive microstructures with a period t of about 1-2 μπι and a depth t of the order of 200-300 nm on the surface of a tablet, as illustrated for example in FIG. 2, and keep them reliably during the direct compression process. These powder mixtures are not, of course, microstructural and the size of the microstructures is much smaller than the particle size. For this reason, the surface itself of the particles must be microstructured. Finally, the compression process itself is not so fast, and the microstructuring process time is extremely fast. To be able to do this, some parameters of the diffractive microstructure must be optimized, in particular the diffractive microstructure on the surface of the compression tool, which acts as an embossing pattern. Parameter ranges for the microstructures of the tablets of the invention found to be especially suitable are summarized in Table 2a.

Table 2a

<table> table see original document page 9 </column> </row> <table>

It is a challenge in the compression process to avoid breaking the diffractive microstructures protruding from the tablet surface of the invention. Microstructures with network lines (network 1d) are more suitable than network points (network 2d) because lines have more mechanical stability than points. Network-shaped crossover lines are equally suitable, thanks to the stability of the connected network lines.

Microstructuring increases the surface area of the compression tool, thereby increasing the contact area between the compression tool and the compressed tablet. This results in greater adhesion and may interfere with the removal of the finished tablet from the mold. To minimize this effect, the microstructure advantageously has a round or trigonal shape, for example a sinusoidal network (Fig. 2 (b), (c)). Additionally, the depth t of the microstructure should be as small as possible. However, a minimum depth t of about 80nm is required for a visible diffractive effect. The diffractive efficiency of a sine grid reaches its maximum for example when the depth of the grid corresponds to 0.3-0.4 grid periods. Additionally, the microstructure should be deeper than the lubricant layer between the surface and the compression tool or the compression mold wall and the tablet mass. Most lubricants have a sliding plane laminar structure moving slightly parallel to the surface of the compression tool or compression mold. For this reason, microstructures introduced only in this lubricant layer are easily broken.

Production of diffractive microstructure tablets

Fig. 1 schematically shows the process for producing a tablet. The powder 2 to be pressed is a mixture of powdery constituents placed in the press mold 3. Two axially aligned punches 1a, 1b exert axially mechanical forces, thereby forming a tablet.

The diffractive microstructure to be created in the tablet is provided on the punch surface la, 1b and / or on the inner wall of the compression mold 3. If the compression mold wall 3 is provided with a diffractive linear lattice as a microstructure, then for supporting ejection of the finished tablet 4, the mesh lines are preferably arranged parallel to the axial direction of movement of the punches. However, it is simpler, in relation to the mechanical stresses that occur in the compression process, to apply the microstructure to the punches 1a, 1b.

The powder fills the cavity in the compression mold 3, which is sealed by the lower punch Ib (see fig. 1 (a)). The volume of the compression mold defines the amount of powder that is pressed to define the tablet. This volume can be adjusted by the position of the lower puncture Ib during cavity filling. The compression force is typically between 5 and 25 kN. Modern rotary compressing machines allow maximum compression forces of up to 160 kN. During the compression process, two interrelated phenomena happen simultaneously: compression and consolidation (K. Marshall, "Tablet Press Fundaments," Tablets & Capsules 2005, pp. 6-11).

The former leads to a reduction in mass volume, while the latter causes an increase in the mechanical strength of the mass. Thus, when force is applied to the dust, its volume is first reduced because the air between the particles is displaced (see fig.

1 (b)). This step is known as the "repacking step" and is limited in achieving the maximum possible packing and / or friction density at the contact points of the dust particles. Most materials then undergo elastic deformation to the limit of plasticity (see Fig. 1 (c)). This step is known as the "tightening step". Particles may also experience brittle fractures due to volume reduction. Then the components may undergo plastic and / or viscoelastic deformation.

The diffractive microstructure is introduced to the tablet surface mainly by such plastic and / or viscoelastic deformation. Many tableting materials, for example some polymers used as binders, have viscoelastic properties. If the surface of the particles is coated with a plastic material, the plasticity of a powder can be improved. Particles may be partially coated with a binder such as polyvinyl pyrrolidone (PVP), for example via wet granulation, thereby improving particle compressibility. Because of particle-particle interactions, the mechanical strength of the compression mass becomes progressively greater as the applied compression force increases. In particle-particle interactions, bonds are formed on particle surfaces because they increase the number of contact points. Depending on the chemical composition, the bonds are ionic or covalent, dipole-dipole interactions and van de Waals forces. Often a mixture of these forces occurs.

Additionally, liquid films may solidify. Solidification of liquid films can occur in two ways - first, when frictional heat at the contact points results in the softening or melting of an ingredient that has a low melting point, so that the mechanical stress at that point is dissipated. The ingredient then hardens via a fused bond. Second, an ingredient at high voltage contact points can dissolve in the liquid film on the surface of a particle. Here again the mechanical stress is dissipated and the material recrystallizes to form a bond. If hardening occurs near the surface of the microstructured compression mold, then the softened, molten or dissolved ingredient supports replication of the diffractive microstructure.

At the end of the tablet pressing process, the pressure is removed (Fig. 1 (d)) and the finished tablet 4 is ejected (Fig. 1 (e)). Subsequent elastic recoil should be minimized to achieve high mechanical stability of the tablet. The composition is optimized in this regard as needed.

For tablets with diffractive microstructures on their surfaces, a composition that meets all tableting requirements and yet has sufficiently high plastic deformability to be able to create the microstructure is required. As already mentioned, the powder to be compressed consists of a mixture of various substances having distinct functions. The amount of plastic deformable materials in the composition should be as large as possible, but the end product conditions as well as FDA standards must be respected. For example, the amount of microcrystalline cellulose or plastic binders such as PVP may be increased, or such materials used rather than excipients which are equivalent except for having less plastic deformability.

Modern industrial tableting machines are high performance machines capable of producing tablets at very high speeds. The production speed of ultra-modern unitary rotary presses is approximately 30,000 to 300,000 tablets per hour.

In addition, they must be extremely reliable and accurate because all tablets must meet strict specifications regarding thickness, weight, hardness and shape. Machines as well as their components must comply with GMP (Good Manufacturing Practice) and FDA conditions.

Table 3 shows examples of speed specific data for various tablet presses. Additional information can be obtained from N. A. Armstrong, "Considerations of Compression Speed in Tablet Manufacture," Pharmaceutical Technology, September 1990, pp. 106-114. The short compression time is sufficient to compress the powdered raw material into a hard tablet. Table 3

<table> table see original document page 14 </column> </row> <table>

Together, downtime and downtime are approximately equal to or slightly longer than the time required in roll-to-roll (R2R) processes to embed hot diffractive microstructures in polymeric films.

Such R2R processes are used to produce cash security holograms and work with polymer feed rates of about 100m / min. The polymeric substrate, process parameters and temperature are optimized for good microstructure replication.

Similarly, the compression process of the invention is adapted to the requirements of microstructuring. Most pharmaceutical pills are round in shape. This facilitates the production process because the rotary compressing machine is rotationally symmetrical and can rotate freely during the compression process. For creating the diffractive microstructure, however, it is advantageous if punch rotation is avoided to reduce the resulting shear forces, particularly when the punch is moving away from the tablet surface, the tablet and mold surfaces remain in contact. for a short time due to elastic recoil.

Protecting microstructured tablet surface from mechanical damage

To protect the microstructure from mechanical damage throughout the product life cycle, in particular abrasive forces, contact between the microstructured surface and other surfaces can be minimized, for example by arranging the diffractive microstructure 11 in a macroscopic recess 12 on the surface of the product. tablet 4 (see Fig. 3a).

Such macroscopic recesses are common with the conventional direct compression process. They are mainly used for marketing purposes to display, for example, the company logo, etc. If the recess 12 is deep enough and small enough that the sharp edge of another tablet cannot touch the microstructures surface (see Fig. 3a), then the diffractive microstructure is well protected against mechanical damage. No abrasion may occur in collection containers, sorting machines or storage bottles, but are occasionally unavoidable due to design requirements.

Alternatively or additionally, the microstructured tablets may also be coated with an additional protective layer without destroying the diffractive effect, assuming that the protective layer is transparent in the visible spectrum range and has a refractive index that does not correspond to that of the material bearing the coating. structure. Such a coating likewise protects the diffractive microstructure. If the refractive index of this coating is higher, the thickness less than 1 μm and the microstructure grating period less than 500 nm, then zero-order color diffractive effects can be obtained. These color diffractive effects are extremely effective against counterfeiting and are easy to recognize.

Example of a pharmaceutical tablet according to the invention with a diffractive microstructure

A powder mixture formulated according to Table 1 was compressed into a German company Fette type 1200i single rotary press with 24 pairs of punches to form tablets. The punches were 11.8mm in diameter with hard chrome plated surface. The diffractive microstructure with a period of 1.4 μπι and depth of about 500 nm was subjected to ionic erosion on the hard chromium coated surface (see fig. 4 (a)). Visible diffractive effects on tablets weighing 540 mg were obtained with a compressive strength of 25kN and a production speed of 30,000 tablets per hour. Fig. 3 shows one of the tablets produced in this manner. The diffractive microstructure produces a clearly visible "CSEM" inscription. The diffraction effects produced cannot logically be reproduced in the black and white photograph of Fig. 3. The hardness of the tablet is 154 N, which is a satisfactory value with respect to tablet dissolubility. Fig. 4b shows an MVE micrograph of the microstructured surface of such a tablet. The diffractive microstructure is clearly visible.

Authentication of the Tablets of the Invention If the tablets of the invention have a strong and / or bright color, such a background may make it difficult to recognize the rainbow effect on the diffractive microstructure. Since the usual dust components have a refractive index of about 1.5 in the visible spectrum range, only a small percentage of the incident light in the tablet will be reflected at the first or highest diffraction orders. The angular distribution of the diffracted light is given by <formula> formula see original document page 17 </formula>

where Bra is the reflection angle of the mth diffraction order, Bi is the angle of incidence and λ is the wavelength of light (see Fig. 2 (a)).

Since the higher order diffraction effects are weaker, detection of the typical diffraction pattern may not be entirely simple for the layman. The deep reflected intensity is not a disadvantage, however, because the strong diffractive color effects could irritate the end consumer.

Many patients are afraid of strong colored tablets. On the other hand, the visibility of the diffractive effect can easily be increased by adequate lighting with an optimized angle of incidence. This makes the effect what is called the second level security feature. In the pharmaceutical industry, second or third tier security aspects are widely used because corporations do not necessarily want to reveal to their end consumers that counterfeiting is a problem. Under exposure to a white LED, for example, the rainbow effect of the diffractive microstructure appears under a certain angle of observation. With some practice, one can verify the presence of diffractive microstructure in less than one second with the aid of such a verification device.

Checking for the presence of a diffractive microstructure is a qualitative authentication. A simple and fast method of quantitative verification of diffractive microstructures is to expose the structures to the beam of a laser diode (eg λ = 650 nm) under a fixed angle of incidence. The laser beam is diffracted in several diffraction orders according to the formula given above. Since the laser wavelength λ and the incidence angle B1 are known, the microstructure period Λ can be determined by measuring the diffraction angle in at least one order. This is done, for example, with the aid of a portable reading device, which has a recess where the tablet is arranged, ensuring a fixed angle of incidence for the laser beam (see Fig. 3 (b)). The diffracted laser beams are intercepted by a row of photo diodes and the microstructure period is calculated based on the positions of the diffracted rays. Such portable reading devices may be used in pharmacies or by customs inspectors, for example.

Producing a compression tool according to the invention

To ensure a long life, the tool material containing the microstructure must be very hard. At the same time, however, it must be possible to create the microstructure on its surface. Suitable materials include, for example, hard steel, hard chrome plated steel, tungsten carbide or molybdenum carbide. All of these materials are FDA approved and can be used in punch or compression molds. However, these materials are not compatible with traditional holography and lithography techniques, but can be microstructured using other methods described below.

Ion erosion

Hard steel, hard chrome plated steel, tungsten carbide or molybdenum carbide can be microstructured with a special ion erosion technique. This technique comprises the following steps, which are schematically illustrated in Figures 5 (a) to 5 (d):

1. A thin light-sensitive layer 20, called a photo-resistant, is applied to the microstructured surface of the compression tool. In Fig. 5 (a), this is the puncture 1. The coating is done in a special room without blue or UV radiation. Photoresist materials include, for example ma-N440 (R) Microposit S1800 (Rohm & Haas) and AZ1500 (Clariant). The optimum thickness of layer 20 is between 300 nm and 2,000 nm. If the tool is properly clamped, the coating can be applied by high speed rotating coating (Convac 100ls) or spray coating (EFD MicroCoat MC780S). The latter should be optimized for good homogeneity in the desired thickness range. After coating, the layer is hardened for 1-60 minutes (depending on the layer thickness and material at 100 ° C or 120 ° C, called "soft baking").

2. As a next step, the photoresist layer 20 is exposed using two interfering laser beams 21 in a holographic exposure (see Fig. 5 (a)). Cross networks are implemented by two orthogonal exposures. Integrated performance is controlled by a photodiode and depends on the photoresist material and desired network parameters. The laser is, for example, a HeCd laser with wavelength λ = 441.6 nm.

Depending on the incidence angle Θ of the two beams as well as the optical components of the holographic arrangement used, lattice periods Λ of 270 nm to 16,000 nm are possible, Λ = λ / (2n sin Θ), where η is the refractive index of the material through which laser beams expose the photoresist surface. If exposure takes place in the air, then η = 1. Shadow masks can be used to define the shape of the net surface. This makes it possible, for example, to implement logos, trademarks, etc.

3. After exposure, the photoresist layer is developed with a suitable developer solution. For example, the basic developer S303 (Microposit) or concentrate (Microposit) may be used for this purpose. Developing time depends on the network parameters to be set. Immediately after development, the tool is placed in an interruption bath with pure water. The temperatures of both baths are 30 ° C and are monitored at ± 0.2 ° C. At the end of the developing step, the photoresist layer of the tablet compression tool has the mesh of desired time and depth (see Fig. 5 (b)). The shape may be sinusoidal, as already shown, or it may be more complex.

4. To be able to dry erode the mesh on the tool surface, a contrast of at least 2: 1 must be obtained in the erosion ratio. This is achieved by applying a metal coating, preferably an apparent chrome coating of 10 nm to 200 nm to the protruding portions of the mesh to which the photoresist layer 20 is applied. The optimum thickness depends on the depth and length of the net. The tablet compression tool with the photoresist layer revealed is placed in a vacuum chamber (Balzers BAK550) so that vaporized atoms are unable to reach the recesses of the mesh. This oblique erosion is in the schematic diagram of Fig. 5 (b). The angle of incidence α of the metal atoms here is from 3 ° to 45 °, depending on the depth and period of the lattice. If required, oblique erosion is performed on two or more sides to form symmetrical metal roofs.

5. Then the photoresist layer 20 is opened, thus forming the mask 22. As shown in Fig. 5 (c), the portions of the resistant polymeric layer are then eroded with O2 plasma (Oxford RIE) without chrome coatings. The kinetic energy of reactive oxygen ions is in the range of 500 eV. The erosion rate also depends on the pressure in the vacuum chamber. The end of this opening step is defined by an end point detection system which is based on laser interferometry.

6. The open mask 22 is then used to transfer the mesh structure 11 to the tool surface by another dry erosion step. This erosion on the hard surface of the tablet compression tool is accomplished by bombarding it with argon ions (Veeco RF 350) with a kinetic energy of the order of 500 eV. At 500 eV, the energy is low enough to avoid a large penetration depth of source ions into the sample but without reducing the speed of erosion. Table 4 shows typical erosion rates r for such argon bombardment under an ion density current of 1 mA / cm2, a kinetic energy of 500 eV ions and perpendicular bombardment, for various elements and compounds.

Table 4

<table> table see original document page 21 </column> </row> <table>

If the desired mesh depth has been reached, the remaining photoresist and chromium are removed, leaving behind the finished microstructured surface of the compression tool according to the invention (see Fig. (C)).

For low cost production of the diffractive microstructures of the compression tools of the invention, several of such tools are used in parallel in the most time consuming steps, namely oblique erosion and dry erosion.

With the mentioned ion erosion method, coated compression tools can be microstructured, eg hard chrome plating. Fig. 4 (a) shows an illustration of a punch of the invention 1 (a) with a hard chrome plated surface. According to the method described above, the diffractive microstructure 11 was created on the surface.

Fig. 4 (b) shows an MVE micrograph of the microstructured surface of a pressed tablet using this compression tool.

Embossamento

Another method of creating a diffractive microstructure in a punch of the invention is to punch the desired microstructure on the surface of the compression tool of the invention by a tapping method using a main tool. This main tool can be microstructured with the ion erosion method described above.

It is known that macroscopic structures, for example chassis numbers or trade names, can be punctured in metal. In the smallest case, such structures are only a few millimeters in size. The accuracy required in structuring is small because the only requirement is that the numbers and letters are legible. Puncturing diffractive microstructures with periods of the order of 1 μm in compression tools of the invention is obviously more complicated. The required accuracy is too high to obtain the interference effect on the microstructures.

Additionally, the microstructures are smaller than the internal structures of the metals (grain size) and the tools are made of very hard metal alloys.

To facilitate the understanding of this method, some characteristic mechanical properties of metals are summarized below. Metals tend to have a high melting point in view of the strength of the metal bond. The binding force varies from one metal to another and depends, among other things, on the number of electrons each atom emits in said free electron gas. Additionally it depends on the packing density. Each metal consists of a plurality of individual grains and / or crystallites, i.e. perfectly ordered microcrystalline regions. The typical average diameter of such grains is between 10 pm and 100 μιη. Atoms in the grain peripheries, also known as displacements, are also inappropriately aligned. Special treatments provide larger grain sizes, therefore harder metals.

If a small mechanical strain acts on a metal, individual metal layers begin to slide over each other. Once the mechanical stress is removed, atoms return to their original positions (elastic deformation). If the effort is greater, the atoms slide to new positions and the metal permanently deforms (plastic deformation). The movement of displacements causes disruption of a limited number of atomic bonds. The force required to break the bonds of all atoms in a crystalline plane simultaneously is very high. The movement of displacements, however, allows atoms in crystalline planes to slide together with much less effort. The energy required for such movement is the smallest among the densest of crystalline planes, so displacements within a metal grain have a preferred direction of movement. This leads to sliding displacements along parallel planes within the grain. The diameter of such sliding lines is typically on the order of 10 nm to 1000 nm. Sliding lines are grouped and form sliding line bands. The latter are visible with an optical microscope. As described below, sliding lines and sliding line bands support microstructure replication. The displacement of atomic layers on top of each other is hampered by grain boundaries, which can be attributed to an inadequate constellation of rows of atoms. This means that the more boundaries there is in a piece of metal, the smaller the individual crystalline grains, the harder the metal. Grain boundaries are regions where atoms do not have good contact with each other, so metals tend to break at grain boundaries. Thus, the metal is not only harder due to the increase in the number of grain boundaries, but also becomes more brittle.

The harder a metal, the harder it is to shape it. Table 5 lists the Vickers hardness (HV), material density ρ and Young's modulus of elasticity for various materials (not only metals and alloys).

Table 5

<table> table see original document page 24 </column> </row> <table> <table> table see original document page 25 </column> </row> <table> <table> table see original document page 26 < / column> </row> <table>

The modulus of elasticity does not depend on the degree of hardness. Hardness is a measure in which plastic deformation begins

due to mechanical stress. Young E = do / ds modulus is the slope of the linear portion of the stress / strain curve σ (ε). Fig. 6 shows an example of such a curve for a ductile material such as steel. The greater the resistance of the material to elastic deformation, the greater the value of Young's modulus. Plastic deformation happens above the elastic limit (40). The yield point oy measures the resistance to plastic deformation. In this zone called the flow zone, the deformation is relatively large even with a slight increase in stress. This process, which is often characterized by a very small slope / strain curve, is commonly referred to as "perfect plasticity". After flow, this effort is increased to the breaking force or maximum tensile force oy at which the material breaks (41). In the case of breakable materials, the flow zone practically does not exist. Breakable materials compared to ductile materials often have relatively high Young modulus and maximum tensile strength. Table 5 lists the maximum values of oy and or. All values in table 5 are merely reference values. Suitable sample data may differ substantially from this. Coating values of such materials depend on process parameters and growth mechanism, among others.

In order to punch a diffractive microstructure with a main tool in the compression tool of the invention, the following prerequisites must be fulfilled:

1. The hardness of the main tool must be greater than that of the compression tool.

2. Young's modulus should be as high as possible for both of them to minimize elastic deformation.

3. The applied force shall be greater than the yield point but less than the maximum pulling force of the compression tool. Moreover, it must be less than the yield point (if any) and the maximum pulling force of the main tool.

If necessary, the compression mold or its surface may be hardened after puncturing the microstructure by subsequent heat treatment or ion implantation.

Fig. 8 schematically shows how the main tool microstructures in the embossing step are replicated by filling the cavities through the sliding planes of the metal grains in the compression tool.

To microstructure a compression tool with a hard chromium galvanized surface, a tungsten carbide main tool is required, for example, and an embossing force of about 400-500 Mpa is required. Alternatively, the main tool may also be made of hardened steel with a tungsten carbide, SisNa or ZrO2 coating, for example, which carries the microstructure. This latter variant is less expensive because only the coating needs to be made of very hard and fracture resistant material.

Fig. 7 shows an example of microstructure produced by such method of embossing on a metal surface. An aluminum block 61 approximately 4mm thick was microstructured using a round nickel shim 60 about 12mm in diameter. Nickel shim 60 is on metal block 61 in Fig. 7. The shim has a refractive lattice with a period of 1400 nm and a depth of about 300 nm showing the 4 letters CSEM in the mirror image. This shim was pressed onto the aluminum block about 0.5 seconds under pressure of 3 tons at room temperature. As shown in fig. 7, the diffractive microstructure was well reproduced in the aluminum block.

NUMBER LIST OF REFERENCES

1, la, Ib puncture

2 powder mix

3 compression mold

4 tablet

10 network line

11 network microstructure

12 recess

20 photoresist layer

21 laser interference radiation

22 mask

30 grains, crystallites

40 elastic limit

41 fracture

50 laser

51 photo diodes

60 nickel shim

61 metal block

The period

t depth

0m reflection angle of m-th diffraction order

Ok angle of incidence

m diffraction order

Claims (32)

1. Tablets (4) for particular pharmaceutical use, comprising a plurality of individual powder particles, wherein diffractive microstructures (11) having discernible diffraction effects in the visible spectrum range are provided on at least a portion of the tablet surface. (4), characterized by the fact that diffractive microstructures are embedded in the surface of individual dust particles. Tablets according to claim 1, characterized in that the diffractive microstructure (11) has a relief with an essentially triangular or sinusoidal profile. Tablets according to any one of the preceding claims, characterized in that the mesh microstructures (11) are linear mesh or apertured mesh. Tablets according to any one of the preceding claims, characterized in that the period length A of the network microstructure (11) is between 300 nm and -5000 nm, preferably between 800 nm and 2500 nm. Tablets according to any one of the preceding claims, characterized in that the depth t of the relief between the mesh lines (10) of the mesh microstructure (11) is at least 80 nm, preferably 300 nm, and especially preferably 400 nm. . Tablets according to any one of the preceding claims, characterized in that the depth t of the relief between the mesh lines (10) of the mesh microstructure (11) is a maximum of 1,000 nm. Tablets according to any one of the preceding claims, characterized in that the depth t of the relief between the mesh lines (10) of the mesh microstructure (11) is between 0.3 and 0.4 period lengths A of the network microstructure (11). Tablets according to any one of the preceding claims, wherein the tablets (4) are provided with a coating which is transparent in the visible spectrum range and which has a different shrinkage index than the tablet material, preferably with a difference of at least 0.2. Tablets according to claim 8, characterized in that the shrinkage index of the coating is greater than the refractive index of the tablet material, and that the coating thickness is less than 1 µm. Tablets according to any one of the preceding claims, characterized in that the tablets (4) have at least one recess (12) on their surface on which the net microstructure is arranged. Tablets according to any one of the preceding claims, characterized in that the tablets (4) are produced by direct compression. Compression tool (1, 1, 1b, 3) for tablet production (4), in particular for tablet production (4) according to any one of claims 1 to 11, compressing a mixture of powder (2), characterized in that microstructures (11) are arranged on a compression surface of the compression tool (1, 1a, 1b, 3), and such microstructures (11) have dimensions that are smaller than the dimensions of individual crystallites (30) from the compression surface material of the compression tool (1, 1a, 1b, 3). Compression tool according to Claim 12, characterized in that the microstructures (11) are present on only a portion of the compression surface. Compression tool according to claim 12 or 13, characterized in that the microstructures are diffractive mesh microstructures (11) having diffractive effects that are discernible in the visible spectrum range. Compression tool according to Claim 14, characterized in that the microstructure (11) has an essentially triangular or sinusoidal profile relief. Compression tool according to claim 14 or 15, characterized in that the mesh microstructures (11) are linear mesh or open mesh. Compression tool according to any one of claims 14 to 16, characterized in that the period length Λ of the network microstructure (11) is between 300 nm and 5,000 nm. Compression tool according to any one of claims 14 to 17, characterized in that the depth t of the relief between the mesh lines (10) of the mesh microstructure (11) is at least 80 nm, preferably 300 nm. and especially preferably 400 nm. Compression tool according to any one of claims 14 to 18, characterized in that the depth t of the profile between the mesh lines (10) of the mesh microstructure (11) is a maximum of 1,000 nm. Compression tool according to any one of claims 14 to 19, characterized in that the depth t of the profile between the mesh lines (10) of the mesh microstructure (11) is between 0.3 and 0.4. Λ period lengths of the network microstructure (11). Compression tool according to any one of Claims 14 to 19, characterized in that the compression tool is a punch (1, 1a, 1b). Tablet press having at least one compression tool (1, 1a, 1b, 3) according to any one of claims 12 to 21. Tablet press according to claim 22, characterized in that said tablet press is a rotary press. Method for producing microstructures (11) on the surface of a tool, particularly a compression tool (1,1,1a, 1b, 3) according to any one of claims 12 to 21, characterized in that it comprises the following steps: surface with a photoresist layer (20); exposing the photoresist layer (20) with a microstructure; - revealing the photoresist layer (20); transferring the microstructure in the photoresist layer (20) to the tool surface by dry erosion; and remove the photoresist layer (20) Method according to claim 24, characterized in that the photoresist layer (20) is exposed by interfering laser beams (21). Method according to Claim 24 or 25, characterized in that a macroscopic structure of the microstructure (11) is created by means of a mask. Method according to any one of claims 24 to 26, characterized in that prior to dry erosion, a metal layer is applied to the protruding parts of the microstructure of the photoresist layer (20), preferably by oblique erosion. A method according to claim 27, characterized in that prior to dry erosion, the non-metal coated photoresist portions (20) are removed by an oxygen plasma. Method for producing microstructures (11) on the surface of a tool, in particular a compression tool (1, 1, 1b, 3) according to any one of claims 12 to 21, characterized in that the microstructures (11) are embedded in the tool surface (1,1a, 1b, 3) with a main tool provided with the inverse microstructure shape (11). Method according to claim 29, characterized in that the Vickers hardness of the surface of the main tool provided with the microstructures (11) is greater than that of the tool (1,1a, 1b, 3). Method according to claim 29 or 30, characterized in that the mechanical stress applied during the microstructure (11) bending is greater than the yield point and less than the maximum tensile force of the tool material (1, la, lb, 3) and, at the same time, is less than the yield point and the maximum tensile force of the main tool material. A method according to any one of claims 29 to 31, characterized in that the microstructured surface of the tool (1, 1, 1b, 3) is hardened after the microstructure is embedded in the surface.