MXPA97008614A - Composition of powder coating for the electrostatic coating of farmaceuti substrates - Google Patents

Abstract

A powder coating material for use in the electrostatic powder coating of pharmaceutical tablet cores has the following properties: it is pharmaceutically acceptable, it can be treated to form a film coating on the surfaces of the tablet core and includes composite particles comprising two or more components that have different physical and / or chemical properties

Description

COMPOSITION OF POWDER COATING FOR ELECTROSTATIC COATING PHARMACEUTICAL SUBSTRATES DESCRIPTION OF THE INVENTION This invention relates to the electrostatic coating of pharmaceutical substrates with a powder coating material and powder coating materials for coating pharmaceutical substrates. In particular, but not exclusively, the invention relates to the electrostatic coating of nuclei of pharmaceutical tablets with a powder coating material and powder coating materials for coating the nuclei of pharmaceutical tablets. While reference is made, throughout the specification, to pharmaceutical tablets and the invention is of particular application to pharmaceutical tablets in a conventional manner, it should be understood that the term is to be interpreted in a broad sense to also cover other products that are taken in oral form such as pellets, capsules or spherules. Electrostatic coating of electrically conductive substrates such as metal objects is well known. For example, in certain paint spray procedures, the paint is electrically charged and paint droplets are sprayed onto a grounded metal object. Such methods have been successful in obtaining a uniform coating on the substrate.

The electrostatic coating of electrically non-conductive substrates, and the nuclei of pharmaceutical tablets in particular, is more difficult. Proposals have been submitted for the electrostatic coating of tablets for many years. For example, GB 1 075 404 proposes an apparatus for coating tablets in which an atomizer is used to spray finely divided particles of a coating solution onto tablets in a high potential field. The coating is dried using, for example, an infrared heater. Such proposals, however, have not been practiced on any commercial scale and the coating of pharmaceutical tablet cores is more commonly performed as an intermittent process by applying a liquid coating on a stirring drum. The liquid coating material, of course, can be supplied in some cases in powder form but, if so, then it dissolves or disperses in a liquid before application. Therefore, it does not apply to the core of the tablet in powder form. In many ways it is easier to apply a liquid coating instead of a powder coating to the core of a pharmaceutical tablet. It is very difficult to obtain adhesion of the powder to the tablet and in order to ensure the coating to the core, the powder must be transformed to a film without damaging the core of the tablet, which will usually include organic materials. In addition, a uniform coating is required and it is difficult to obtain a uniform coating of the powder on the core of a tablet.

When a liquid coating is used, the coating must be dried. Theoretically, said drying, in some circumstances, can be carried out at room temperature, but in commercial practice it is important, for example, due to the speed at which the procedure must be performed, to heat the tablets and that it is expensive due to the large input of energy required to vaporize the solvent used in the liquid coating. Another disadvantage of the liquid coating is that it can not be used to coat materials that are not soluble or suitably dispersible in a usable liquid, preferably water. WO 92/14451 relates to the electrostatic powder coating of pharmaceutical tablets and describes and illustrates a process in which the nuclei of pharmaceutical tablets are transported on a grounded conveyor belt and an electrostatically charged powder is sprayed to the cores to form a powder coating attached to the surfaces of the cores. The powder coating is then fused to give a fused film coating secured to the core. A disadvantage of said method is that most of the powder sprayed on the cores is not charged and is not deposited on the cores. This leads to overspray and to waste the powder material and it becomes difficult to obtain a uniform coating. In a first aspect, the present invention seeks to provide a powder coating material suitable for use in the electrostatic powder coating of a pharmaceutical tablet core and to provide a method for the electrostatic coating of a pharmaceutical tablet core in which a coating material is used. in special powder to facilitate the electrostatic coating. The first aspect of the invention provides a powder coating material for use in the electrostatic powder coating of a core of a tablet, especially for use in a method for coating as defined below, and which has special properties to make it it is suitable for use in said method. The special properties, which the powder coating material advantageously has, are further defined below and wherein the advantages provided by those properties depend on the coating method employed, said method is also further defined. According to a first aspect of the invention, a suitable powder coating material is provided for use in the electrostatic powder coating of a pharmaceutical tablet core, wherein the material is pharmaceutically acceptable, it can be treated to form a coating of film and includes composite particles, the composite particles comprising two or more components having different physical and / or chemical properties. It is important that the powder coating material is a pharmaceutically acceptable material. That by itself imposes severe restrictions on the powder coating material, since at least most of the powder coating materials that are commercially available for use in electrostatic powder coating processes, are not physiologically tolerable or pharmaceutically acceptable, and materials that are commercially available for use as coating materials for pharmaceutical tablet cores are not in a form suitable for the electrostatic application of powder, since other properties of the material are not suitable. The powder coating material of the invention includes at least two different compounds, each different compound having different physical and / or chemical properties. It is much simpler to provide a powder material having the desired properties presented above, and anywhere in the specification by providing a composite material of more than one component that provides only one component material. For powder materials, including two or more different components, it has been found that improved coatings can be obtained when the powder includes particles composed of the components. It is particularly important for the particles of the coating material to include more than one of the components, wherein one or more of the components does not have the necessary electrical properties to be able to be placed as a coating on the core when, for example, the coating method used is as described in the example below. When the particles are not composite particles, those particles of components that do not have the necessary electrical properties can simply remain in the power source and will not remain as a coating on the core of the tablet. The inclusion of the composite particles is believed to improve the coating efficiency of the substrate as well as the uniformity of the applied coating. The improved efficiency of the coating can help reduce the time required for the coating of each substrate.

The term "composite particles", as used in this specification, refers to particles, which have been formed of two or more different components. The composite particles are not homogeneous, that is, they have two or more regions, each comprising different components of the particle. The composite particles can have the form of a discrete composite particle or they can be in the form of agglomerates or aggregates of discrete particles of the different components, the agglomerates or aggregates behaving as discrete composite particles. Advantageously at least 50% by weight of the powder particles are composite particles. Ideally, substantially all of the particles are composite particles, but they may not be acceptable, particularly when the particle size of the composite particle is small. When the powder includes more than two components having different physical and / or chemical properties, advantageously the composite particle also includes those other components. Ideally, substantially all of the composite particles could comprise discrete particles including each of the different components. However, in practice, satisfactory coatings can be achieved when the individual component particles are formed to the composite particle as aggregates or agglomerates. Advantageously, the two or more components have to be co-processed. The co-processing may comprise granulation, freezing, spray drying, or co-grinding. When the co-processing method results in particles of a relatively large size, for example, in the case of granulation, in some cases it may be advantageous to perform a subsequent milling step to reduce the particle size. Alternatively, a micronization step can be performed. As will be understood, mixing the powder components will usually form an orderly mixture of the components. However, in special cases, by careful selection of the mixing conditions, for example, the initial particle sizes of the components and the mixing method, composite particles can be obtained by a mixing method. According to the first aspect of the invention, the powder coating material is one which, after it has been placed as a coating on the surface of the tablet core, can be treated to form a film coating secured to the core. In this manner, the method for advantageously coating includes the step that, after the surface of the tablet core has been coated with the powder, the powder is treated to form a film coating secured to the core of a tablet. The film coating is advantageously continuous, since it is not divided into separate parts, but there may be many small holes, not visible to the naked eye, for example, between coating particles which have been secured to each other during the treatment step. In this way, the coating can be concreted. For certain applications, it is preferred that the film coating be free of voids and / or be substantially homogeneous. When the powder material is first deposited on the core of the tablet, in most cases, it is only weakly adhered to the surface of the substrate and is easily dislodged. The treatment for forming a film coating is especially advantageous when coating a pharmaceutical tablet core, since the same core is likely to be of low mechanical strength and the film coating can be used to impart strength and make the Coated tablets are more resistant to subsequent processing, such as packing and opening packages. The film coating, while being able to impart extra strength to the tablet core, will usually be very weak when insulated from the core surface.

The tensile strength of the film coating as a free film can be, for example, 8MN m "2 or even lower, and it was found that the tensile strength is reduced with the increase in the amount of TiO2 in the film. In the cases where the tensile strength of the free film is low, it is especially important that the film be a coherent coating on the surface of the core of the tablet with good adhesion to the core. powder is transformed to a liquid phase during the formation of the film coating, it is preferable that the viscosity of the powder material, when in the liquid phase, is less than 500 Pas, most preferably 75 Pas. powder can be treated at a temperature of less than 250 ° C, most preferably less than 200 ° C, to form a film coating Advantageously, the coating material The powder is fused at atmospheric pressure at a temperature of less than 250 ° C, most preferably less than 200 ° C. It is important that the powder can be treated to form a coating around the core of the tablet without damaging the tablet core and imposing a demand on the material, due to the sensitivity to heat the majority of the tablet cores, which contain organic materials Preferably, the powder coating material has a melting point in the range of 50 ° C to 180 ° C, most preferably in the range of 60 ° C to 100 ° C. For a material exhibiting a glass transition, the powder coating material preferably has a softening point in the range of 30 ° C to 180 ° C. The above requirements place more restrictions on the powder coating material. Many materials are not fusible and could be carbonized after the application of heat. Other materials, although they may be fusible, require a long exposure to the heat source for melting to occur, so the risk of damage to the core is significantly increased and the time taken to form the film in the core is unacceptable For economical reasons. The desired temperature at which the powder coating material can be treated, of course, will depend on the material forming the tablet core and for some materials it may be possible for the treatment step to involve temperatures above 250 ° C. In such cases, the duration of exposure to such high temperatures will be short. The treatment of the powder to form a film coating preferably involves a heating step, preferably using infrared radiation, but other forms of radiation or conduction or electromagnetic induction may be used. Also the treatment of the powder material can be achieved partially or totally by reducing the pressure of the environment of the tablet core. The change in the powder material during the treatment may simply be a physical change from a solid to a liquid and then, under cooling, to a solid continuous film. Alternatively, the powder material may include a polymer, which is cured during the treatment, for example, by irradiation with energy in the gamma, ultraviolet or radio frequency bands, to form an interlaced polymer film. It has been found that the particle size of the powder coating material also has an especially important effect on the behavior of the material in an electrostatic powder coating method. Advantageously the material has a small particle size. Preferably, at least 95% by number and preferably at least 90% by volume of the particles of the powder material have a particle size of less than 50 μm. The term "particle size" refers to the equivalent particle diameter of the particles and can be measured using, for example, laser light diffraction. When the relevant particle is a composite particle comprising an agglomerate or aggregate of particles, the particle size is that of the composite particle and not of the individual particles in the agglomerate or aggregate. Such a particle size is surprisingly small for a coating material for a pharmaceutical tablet core and in fact said small particle sizes are recognized to have disadvantages such as making the material more difficult to produce and handle by virtue of its adhesion . However, it has been found that for coating pharmaceutical tablet cores in an electrostatic process there are special benefits to adopting a small particle size and the benefits rather than to find the disadvantages. For example, the high surface-to-mass ratio provided by a small particle size increases the electrostatic forces in the particle, compared to the forces of inertia. The increase in electrostatic forces has the benefit of increasing the force in a particle that causes it to move and contact the core of the tablet, while a reduction in inertia reduces the force needed to accelerate a particle and reduces the probability that a particle reaches the core of the tablet by reacting the core. It has been found to be essentially advantageous if at least 90% by volume of the particles of the powder material have a particle size of less than 20 μm. Preferably, at least 95% by number of the particles of the powder material have a particle size of less than 30 μm. Especially in the case where for a selected powder material it has been found that there is a tendency for the particle reactions on a surface of the tablet core, a pretreatment composition can be applied to a surface of the tablet core, before of the core being supported adjacent to the source of the powder material. The pretreatment composition can improve the capture of particles by the surface of the core and can allow larger particles, even as large as 75 μm, to be used as the coating material. The pre-treatment composition can be a liquid and can increase the forces acting on the particles to maintain them in the core. When a pretreatment is used, preferably 90% by number of the particles have a size smaller than 300 μm, and preferably at least 50% by number of the particles have a size smaller than 200 μm. If the particle size is reduced too much, the difficulties associated with dust handling become severe. Accordingly, it is advantageous that at least 50%, preferably at least 75%, most preferably 90%, by volume of the powder, have a particle size of at least 5 μm. In a preferred powder coating material, the average particle diameter is about 10 μm, substantially no particle having a diameter greater than 100 μm. Preferably, at least 30% by volume of the powder particles have a particle size in the range of 5 μm to 25 μm. It has been found that it is also particularly important for the powder particles to have a narrow scale of particle size. Preferably at least 30%, most preferably at least 75% by weight of the particles have a particle size, which lies on the scale from x to 2x, most preferably on a scale from x to 1.5x, preferably at a scale of x to 1.25x, where x represents a particle size in the powder. For example, for a powder having particles of a relatively small size, preferably at least 30% by weight of the particles have a particle size, which lies on a scale from 10 μm to 20 μm, preferably in a scale of 10 μm to 15 μm, and most preferably on a scale of 10 μm to 12.5 μm. When the particles are of a relatively large size, for example, when a pretreatment is to be used as described above, the preferred relative variation in particle size will generally be less for particles of a relatively small size. It has been found that, with respect to obtaining a good uniform application of the powder to the tablet cores, and from core to core, powders in which there is a large scale of particle size, are advantageous in relation to those powders. where the particle size scale is small. That is, this is believed to be because the particles having a certain particle size are preferentially placed as a coating on the tablet core, compared to particles of smaller or larger size. This can lead to the inhomogeneity of the core coating and variations in the quality of the coating of a coated core placed as a coating from a newly introduced batch of coating material to another core coated with a subsequent coating of the same batch. Advantageously, the powder coating material has a moisture content (measured through moisture loss after drying) of more than 10%, preferably less than 5%, most preferably not more than 3% by weight, based on in the weight of the powder coating material. There are several different electrostatic effects, which can be used in an electrostatic process for coating a pharmaceutical tablet core with a powder, according to the first aspect of the invention, and various electrical properties different from the powder which are especially well suited for the use of different effects. Now, three different effects and associated properties of the powder will be described, and it should be appreciated that each can be employed independently of or together with one or more of the others. A first possibility is to induce a temporary dipole in a powder particle, the particle then being directed towards the tablet core by interaction and the electric field in the region between the powder source and the tablet core. The coating material preferably has a resistance in the range of 108 to 1016 Om. A second possibility is to apply a net charge to a particle of dust. The net charge can be introduced triboelectrically or by corona charging. The coating material is therefore preferably receptive to said net charge and is capable of retaining the charge (sufficiently long for the material to be directed to the core of the tablet). A third possibility is to provide a permanent dipole, or an almost permanent dipole, in a powder particle. Said "electret" is then capable of being directed towards the core of the tablet by interacting with the electric field in the region between the powder source and the tablet core. In this way, the coating material may comprise an electret. A fourth possibility is to provide a magnetic dipole in a powder particle using iron or other magnetic or paramagnetic material. It is preferred that the powder material be directed towards the tablet core without relying on any complete net charge that is applied to the powder material and without relying on any permanently implemented load on the powder material. Thus, it is preferred that the powder material is susceptible to movement under the action of electrostatic forces, the susceptibility being determined by the test defined below. To determine whether or not a powdered material is susceptible to movement under the action of electrostatic forces, the following test must be conducted: A sample of 0.5 g of the powder was taken and placed on a horizontal electrically conducting metal plate, maintained at a potential to ground in an environment that has a relative humidity of no more than 65%. The powder material is extended to a thickness that approaches a monolayer. After leaving the powder in the environment for 30 minutes, an electrically conductive spherical metal probe with a diameter of 5 mm, was placed 10 mm above the center of the powder material and then a high voltage potential was applied first of + 10 kV and after -10 kV (with limited current to approximately 5 μA) to the probe for approximately 10 s. If the particles of the powder material, representative of the material as a whole, are expelled upwards in contact with the probe during the application of either a high voltage potential, then the result of the test is that the powder material is susceptible of movement under the action of electrostatic forces; if the dust particles are not ejected upward to contact the probe, or if only certain types of particles are ejected, so that the ejected particles are not representative of the material as a whole, then the result of the test is that the powder material is not susceptible to movement under the action of electrostatic forces. The susceptibility of the powder material will depend, of course, on a combination of the electrical properties of the powder and other physical properties such as the size of the particles in the powder. As the particles of coating material are charged (eg, triboelectrically) before joining the surfaces of the cores, it is particularly advantageous that the particles are substantially all of the same charge sign. It has been found that when a particle cloud contains a mixture of positive and negative charges, a less satisfactory coating is produced on the surface of the core. In that way, it is advantageous if the powder is of a composition such that, if the powder is charged, substantially all the particles are of the same charge sign. In addition, if the particles are not of the same charge sign, there is more over-spraying of the powder material, thus reducing the efficiency of the coating process. Preferably, most of the particles will also have substantially the same magnitude of charge. Since the material comprises more than one component, the properties of the powder material can be altered by adjusting the relative proportions of the components. In general, when reference is made to a property of the powder material, this is the property exhibited by the material as a whole, which is being referred to and it may be that one or more components of the material by themselves exhibit that property. It can also be satisfactory, however, if only one or some of the components of the powder coating material, and not the ma'ep ??! As a whole, exhibit the property referred to: for example, the benefit of the material forming a film coating at a low temperature can be achieved by only one of two or more components of the material exhibiting that property; the components can remain as solid particles and can represent a greater proportion by weight than the particles that are transformed to the film coating; in such a case, there may be a substantial variation in the particle sizes of the two components; for example, the particles that are transformed to the film coating can have a particle size in the range of 5 to 20 μm, while the particles that remain as solid particles can be substantially larger. One of the different components can serve to impart the electrostatic properties necessary for the powder material. For example, a different component may be triboelectrically charged and / or by corona charging, and / or may be an electret and / or may be susceptible to movement under the action of electrostatic forces, as defined by the test described herein. The chemical properties of the powder material are also of importance in determining the effectiveness of the formation and appearance of the coating. In discussing the chemical properties of the material, it is convenient to treat the material as composed of a plurality of components but, as will be apparent from the following description, the same chemical compound can be used as more than one components and, therefore, the reference in the description, which is presented below, to the powder material being composed of more than two components, should not be considered as requiring that more than two different components are necessarily present, except where the components are specifically referred to as being different Preferably, the powder material includes a first component, which is fusible to form a continuous film on the surface of the core, preferably at a temperature of less than 250 ° C, preferably less than 200 ° C. As discussed above, the fusion can have the form of fusing, softening, or interlacing the first component within the temperature ranges indicated above. Preferably, the first component is substantially soluble in aqueous media. Usually, the first component will be soluble in neutral aqueous media, but can be soluble only at a selected pH scale, for example pH 3 at pH 6, or pH 8 at pH 14. The first component preferably comprises one or more polyoxyethylenes, alcohols of sugar and unsaturated or saturated fatty acids or esters. The first component may comprise a fusible cellulose derivative at a temperature below 250 ° C, for example, hydroxy propyl cellulose. Not all cellulose derivatives are suitable for use as the first component, for example, hydroxypropyl methyl cellulose does not have the required melting properties and slags by heating. The first component can comprise polyethylene glycol, which has good fusibility properties, after the treatment, it can form a good continuous coating on the surface of the substrate. The preferred sugar alcohol is xylitol, since that material has both suitable electrical properties and is fusible at a suitable temperature to be used as the coating material in the coating of pharmaceutical tablet cores.

Other possible materials for the first component include waxes and oils or alcohols of waxes or oils, polaxamers, alkyl phthalates, for example, diethyl phthalate, citric acid or esters. When a component of the powder is a liquid, the component can simply be added to other components in liquid form or it can be present with, for example, a carrier material in powder form. Clearly there are other compounds that have suitable fusion properties and the foregoing are given merely as examples. The first component may consist of only one compound, or may include two or more compounds. In many cases, the component that has the most desirable melting properties will not have the most preferred electrical properties and / or will not be suitable to provide the finish, coverage or appearance of the desired coating. Accordingly, a second component having the required electrical properties is preferably provided, as described above.

It will be understood that the first component can also have the desired electrical properties of the second component and that the second component can have the desired melting properties of the first component. The second component may comprise, for example, one or more of acrylic acid, polymers and copolymers of acrylic acid and their derivatives, for example, polymethyl acrylate, polyalkuenes and their derivatives, including esters and aryl esters and their derivatives, polyvinyl alcohols. and esters, cellulose and its derivatives, for example, cellulose ethers and cellulose esters (either entangled or non-interlaced) for example, ethyl cellulose, and one or more enteric polymers, for example, cellulose acetate-phthalate and phthalate. hydroxyproyl methyl cellulose. The second component may include one or more of the biodegradable polymers, for example, one or more of polylactides, polyglycolides, polyhydroxybutyrates, polyhydroxy-valirate, ethylene-vinyl acetate copolymers, and polyanhydrides (homo and hetero polymers). The second component can be polyethylene oxide. As already described, it is possible that the first component and the second component include the same compound or compounds, but in most cases the first and second components are different compounds. For example, the first and second components each may include xilitotl, but in such a case, viscosity modifiers and crystalline inhibitors must be added to provide the desired fusion properties for the second component. The coating material that includes two or more different components, preferably also includes a dispersion component, which improves the dispersion of the different components. The dispersion component is preferably a surface active agent which may be anionic, cationic or non-ionic, but may be another compound which can not be termed a "surface-active agent", but which has a similar effect. The dispersion component can be a cosolvent. The dispersion component may be one or more of, for example, sodium lauryl sulfate, sodium docusate, Tweens (sorbitan fatty acid esters), poloxamers, and cetostearyl alcohol. The dispersion component can comprise the same compound or compounds as those of the first and / or second components. As described above, both the third and the first components may comprise poloxamers. Preferably, the material includes at least 1%, preferably 2% to 5% by weight of the dispersion component, based on the weight of the material. Advantageously, the powder coating material includes a component against friction to reduce the frictional forces and / or other forces between the particles of the powder coating material to improve the flowability of the powder. The anti-friction component can be titanium dioxide, colloidal silicon dioxide, talc or starch or a combination of these. When the coating material is used for "immediate" release tablets, the powder coating material advantageously includes a disintegrator, which can break the coating. In the case of a coating on a tablet core, the inclusion of a disintegrator in the coating facilitates the disintegration of the coating once the tablet has been ingested. The disintegrator can be one which rapidly swells and is extensively in contact with moisture, thus breaking the coating. Some blasters can swell to make 40 times their original volume in seconds. Examples of suitable disintegrants include sodium glycolate and starch (interlaced) and sodium carboxymethylcellulose (interlaced). Alternatively, or in addition, the disintegrator may be of a wicking type, which allows the penetration of moisture through the coating to the core of the tablet, but which prevents moisture from moving from the core of the tablet. tablet through the coating, thus causing the coating to break. Examples of suitable disintegrators of the wicking type include native starch, interlaced polyvinylpyrrolidone (crospovidone). The disintegrator may be a type of gas production, for example, sodium carbonate, sodium bicarbonate and sodium glycinate. Preferably, the powder coating material contains 10% by volume hands of the disintegrator. Preferably, the powder contains less than 5%, preferably less than 2%, preferably less than 1%, and most preferably around 0. 5% by weight of the disintegrator. Preferably, the powder coating material further includes one or more opacifiers, for example, titanium dioxide and talc. Preferably the material comprises less than 50%, preferably less than 40%, most preferably less than 30% or less than 10% by weight opacifiers based on the weight of the material. Preferably, the powder coating material further includes one or more colorants, for example, metal oxides or lacquers, for example aluminum lacquers, iron oxide, colorants and may include one or more flavor modifiers, for example, aspartame, acelsulfame k, cyclamates, saccharin, sugars and sugar alcohols or flavorings. Preferably, the material comprises less than 10%, preferably 1 to 5% by weight of the colorants based on the weight of the material and preferably less than 5%, most preferably less than 1% of the flavor based on the weight of the material . When the flavor is a sweetener, the material preferably comprises less than 0.5% by weight of the sweetener. Preferably the material comprises less than 5% by weight of colorants and flavors based on the weight of the material. It will be appreciated that the anti-friction component, the opacifier, the colorant and the taste modifier may comprise the same compound or compounds as those of the other component of the powder coating material. The powder coating material can include a biologically active material, i.e. a material which increases or reduces the speed of a process in a biological environment. The biologically active material can be one which is physiologically active. The coating material comprising an active material can be applied to, for example, a tablet core containing the same or a different active material, or it can be applied to a core containing a non-active material. The active material may include one or more compounds. The active material may include peptic acid and mobility influencing agents, laxatives, antidiarrheals, colorectal agents, pancreatic enzymes and bile acids, antiarrhythmic, antianginal, diuretic, anti-hypertensive, anti-coagulant, anti-thrombotic, fibrinolytic, haemostatics, hypolipidaemic agents, agents against anemia and neuropenia, hypnotics, anxiolytics, anti-psychotics, anti-depressants, anti-emetics, anti-convulsants, CNS stimulants, analgesics, anti-pyretics, anti-migraine agents, formerly anti-inflammatory steroids, anti-gout agents, muscle relaxants, neuro-muscular agents, steroids, hypoglycemic agents, hyperglycemic agents, diagnostic agents, antibiotics, anti-fungal agents, anti-malarial agents, antivirals, immunosuppressants, nutritional agents, vitamins, electrolytes, anorectic agents , appetite suppressants, bronchodilators, expectorants, antitussives, mucoli ticos, decongestants, glaucoma agents, oral contraceptive agents, diagnostic and / or anti-neoplastic agents.

The tablet core to which the powder coating material is applied will usually comprise one or more inactive agents. The inactive agent may include diluents, for example, including lactose, sucrose, dextrose, starch, cellulose, microcrystalline cellulose; binders, for example, polyvinyl pyrrolidone, starch mucilage, gelatin, acacia, disintegrants, for example, interlaced sodium carboxymethyl cellulose, sodium starch glycolate, interlaced polyvinyl pyrrolidone; lubricants, for example, magnesium stearate, sodium stearyl fumarate; glidants, for example, colloidal silica, talc; surfactants, for example, wetting agents; sodium lauryl sulfate, docusate sodium; colorants; flavors and / or gas producers, for example, sodium bicarbonate and citric acid. The tablet core may also comprise one or more of the active materials listed above. Preferably, the powder coating material includes at least 0.5% by weight, most preferably 1% by weight, of the active material based on the weight of the powder coating material. For example, a 10 mg coating on a tablet may contain approximately at least 0.05 mg of the active material. The proportions in which the components of the powder coating material are mixed depend greatly on the materials comprising the powder coating material and on the nature of the substrate to be coated. The proportions will be adjusted so as to obtain the desired electrical and melting properties of the powder coating material. Usually, the powder coating material will contain at least 10%, preferably at least 15%, preferably about 20% by weight of the first component. Usually, the powder coating material will contain at least 10%, preferably at least 20%, and most preferably at least 40% by weight of the second component, in each case based on the weight of the coating material in dust. Preferably, the ratio, by weight, of the second component to the first component is about 3: 1. The ratio of the components depends on the material comprising the first and second components. The ratio can be 2: 1 or 1: 1. The invention also provides a coating material for the electrostatic coating of a pharmaceutical substrate, the coating material including an active material. As indicated above, the coating material comprising the active material can be applied to, for example, a core of a tablet containing the same or a different active material, or it can be applied to a core that does not contain any material active. When very small doses of the active material are administered in the form of a tablet, the active material is mixed with a large volume of a non-active "filler" material in order to produce a tablet of manageable size. Until now, the active material and the filler material have simply been mixed together and the doses of the resulting mixture have been formed into tablets. It has been found that it is very difficult to accurately control the amount of active material contained in each tablet, leading to a poor dose uniformity. This is especially the case where the required amount of the active material in each tablet is very low. It has been found that application of the active material to a surface of the tablet is possible to accurately apply very small amounts of the active material to the tablet, leading to improved dose-reproducibility. The amount of the active material contained in the coating material will depend, of course, on the size of the dose of the active material that will be applied to the substrate and the thickness of the coating that will be formed. Usually, the material includes at least 0.5% by weight of the active material based on the weight of the coating material. Advantageously, the coating material is a powder coating material. The coating material can therefore be advantageously applied using a method similar to that described above, in this way the coating material can be applied to the substrate with accuracy and as little over-expression. Preferably, the coating material including the active material has at least 90% by number of particles having a particle size not greater than 50 μm. Preferably, at least 90% by number of the particles of the powder have a particle size of less than 30 μm, more preferably less than 20 μm. The invention also provides the use of a coating material comprising the active material in the electrostatic coating of a substrate, especially in the electrostatic coating of a core of a pharmaceutical tablet. The first aspect of the invention also provides a method for electrostatically coating a pharmaceutical tablet core, the powder material being as defined above. The first aspect of the invention further provides a powder coating material for use in the electrostatic coating of a substrate, the powder obtained by a method as described above. The first aspect of the invention further provides a pharmaceutical tablet comprising a tablet core and a powder coating material, as defined above. The first aspect of the invention further provides a method for coating a pharmaceutical tablet core with a powder, the method comprising maintaining the tablet core adjacent to a source of powder coating material in an electric field and with at least a part of the core maintained at said electrical potential different from that of the coating material that the application of the electric potential difference causes the energy to be directed from the energy source towards the tablet core and a surface of the core to be coated with the powder coating material.

Since the coating of the tablet core involves the direction of the powder material towards the tablet core as a result of the application of an electric field and an electrical potential difference between at least part of the tablet core and the powder material, the The destination of the powder material can be confined, at least mainly, to the surface of the core of the tablet, if it is arranged to be the only exposed surface that is close to the powder material and to a potential difference suitable for the material in question. dust. A particular advantage of the method is that it can be realized as a continuous process. Advantageously, the tablet core is transported on conveyor means through a region adjacent to the source of the powder coating material. The transportation of the tablet core is possible to ensure that the tablet core is delicately handled throughout the coating process, so that a still fragile tablet core is not damaged. The method can be employed to coat cores of tablets that may be too fragile to withstand conventional tablet coating processes. In this way, the invention allows the production of tablets in a conventional manner, but on a larger scale of compositions; Also, tablets of non-conventional shapes, for example, having opposite flat faces instead of conventional convex faces can be produced by the invention. Said flat-faced tablets are generally too fragile to be coated using conventional methods. In addition, the flat faces of the tablets are usually joined together to form twin tablets or groups of tablets, which then can not be properly coated when using conventional coating method. The tablet core can be supported from above adjacent to the source of the powder coating material and the powder can be raised from the source up to and on a lower surface of the substrate. The tablet core produced by the coating method defined above can only be partially coated and advantageously the coating method includes the additional step of keeping the coated tablet core adjacent to a source of powder coating material in said electric field and with at least a part of the core maintained at an electrical potential different from that of the coating material, that the application of the electrical potential difference causes the energy to be directed from the energy source to the tablet core and a surface not Coated from the core that will be coated with the powder coating material. In that form, a coating can be easily provided on the entire surface of the tablet core, and different coating materials can be used to coat different parts of the core. For example, a coating of different colors can be formed on each of the opposite faces of the tablet. The first aspect of the invention further provides a pharmaceutical tablet that has been electrostatically coated through a method as defined above. The powder coating material and the coating method according to the first aspect of the invention have been developed to coat pharmaceutical cores and to meet the severe conditions imposed on the material, due to that application. Having developed a suitable material and method for use in the coating of pharmaceutical tablet cores, other applications have also been considered where the material and the method can be usefully employed. For example, within the pharmaceutical industry, the material and method can be used to coat other pharmaceutical products that are not taken orally, for example, a pessary, candelilla or suppository, or other pharmaceutical substrates. Thus, according to a second aspect of the invention, a powder coating material is provided for use in the electrostatic powder coating of a pharmaceutical substrate, the material having one or more of the following properties: a) are ingestible by humans and / or animals, b) they are made of at least two different components, the particles preferably being composite particles, c) they are fusible in a film coating at a temperature of less than 250 ° C at atmospheric pressure, d) at least 30% by volume of the particles having a particle size in the range of 5 μm to 20 μm, e) are susceptible to movement under the action of electrostatic forces, the susceptibility being determined by the test defined herein. It is particularly advantageous that the powder coating material is a physiologically tolerable material and preferably a pharmaceutically acceptable material. As indicated above, it imposes severe restrictions on the powder coating materials used. The material can also have any of the other properties named above when describing materials for coating pharmaceutical tablet cores. The invention also provides a method for producing a powder coating material comprising at least two different components for use in the electrostatic coating of a substrate, the method including the step of co-processing at least the two different components. The second aspect of the invention further provides a method for electrostatically coating a pharmaceutical substrate with a powder coating material as defined above. When referring to% in number of particles, for example,% in number of particles having a particular size, the particles will preferably also have a volume% of particles of that size. Further, when referring to% by volume of particles, the particles will preferably also have that% by weight of particles. By way of example, a method for coating a core of a pharmaceutical tablet and certain powder coating materials suitable for use in coating pharmaceutical tablet cores, will now be described with reference to the accompanying drawings, in which: Figure 1 schematically shows a side view of an apparatus for coating a core of a tablet; and Figure 2 schematically shows a cross section of a drum of the apparatus of Figure 1. The apparatus shown schematically in Figure 1 is for coating both sides of pharmaceutical tablet cores. The apparatus comprises a tablet core 10 feeding gutter, inclined, leading to a first rotary drum 12. The drum 12 is made of steel and has circular depressions 14 (FIG. 2) on its external surface, in each of which a The core can be maintained by suction, as will be explained later. The drum 12 can rotate in the direction shown by the arrow.

Adjacent the circumference of the drum 12 downstream of the tablet feed gutter 10, there is a pre-conditioning station comprising an electrostatic spray gun 16, which causes the exposed surfaces of the cores to be covered with charged droplets of the gun 16. Downstream of the pre-conditioning station, there is a coating station B comprising a powder vibration tray 18, to maintain, fluidize and recirculate, in the coating zone D, the powder with which they are going to coat the nuclei. Downstream of the coating station, there is a melting station C comprising a heater 20. After the melting station C, the coated core passes to a cooling station, not shown, where cold air is directed on or around the core to cool the fused coating. A second drum 12 'is adjacent to the first drum 12, the clamping line between the drums being downstream of the melting station C. The second drum 12' rotates in an opposite direction to the first drum 12, as indicated by the arrow . The second drum 12 'is provided with a pre-conditioning station A' which comprises a gun 16 ', a coating station B' comprising a tray 18 'for powder, a melting station C comprising a heater 20' and a cooling station (not shown). A core collection gutter 22 is tilted down away from the second drum 12 'downstream of the fusion station C, taking the coated cores to be further processed and packaged. The first drum 12 will be described in more detail with reference to Figure 2. This comprises a rotating shell 24, the outer surface of which carries the depressions 14. In Figure 2, only five illustrative depressions are shown; it will be appreciated that in practice more depressions will be uniformly spaced apart in a circumferential row around the shell 24, and that there are several circumferential rows across the width of the drum, either formed by a continuous shell or several collaterally secured cuirasses. The depressions 14 in the drums are configured and sized to ensure that the entire face of the core and half the depth of the side wall are exposed, while the core is on the drum. In the case of a circular tablet core, a depression diameter close to that of the core diameter is preferred. In some applications, the depth of the depression must be such that it allows at least 50% of the core thickness to be exposed to the particles of the coating material so that it exposes the first face of the core and then the other leads to the complete core coverage. Each depression 14 is electrically isolated from the other depressions in the drum and is provided with a respective pick-up arm 26 extending radially inwardly, toward but ending reduced at the center of the drum. The pick-up arms 26 are attached to the inner surface of the shell 24 and rotate with it. Each associated pick-up arm 26 and depression 14 together cause an electrode to move to load a core in the depression. Each depression 14 has means to maintain the core against forces such as gravity, for example, a passage 28 through its wall, which may be in communication with said suction manifold 30, which does not rotate with the shell and extends around of a portion of the periphery of the interior of the drum from immediately upstream of the core feed gutter 10 adjacent to the clamping line between the first drum 12 and the second drum 12 '. A first arcuate, fixed, grounded electrode 32 is located within the drum at an angular position corresponding to the pre-conditioning station A. A second arched electrode, fixed, 34, to a potential earth difference is located inside the drum at an angular position corresponding to coating station B. The outer arcuate surfaces of the fixed electrodes are at the same radial distance from the center of the drum as the ends free of the collecting arms 26 of the moving electrodes. Since the shell 24 rotates, the moving electrodes are brought into contact with the first and second electrodes sequentially. The drum 12 is maintained at the same potential difference to ground as the coating powder, preferably to the ground potential, preferably being connected to the dust tray 18. The second drum 12 'is constructed similar to the first drum, comprising a rotating shell with depressions, pick-up arms and first and second fixed electrodes and a suction manifold. The angular locations of the first and second fixed electrodes correspond to the second pre-conditioning station A 'and the second coating station B', and the suction manifold extends from upstream of the clamping line between the two adjacent drums to the core collection gutter 22. During use, the cores are continuously fed to the core feed gutter 10. A core passes below the core feed gutter 10 to a depression 14 in the rotation shell 24 of the first drum 12 In an angular position, the depression covers the suction manifold 30, and thus the core is maintained in the depression through the suction through the passage 28 in the shell. The shell 24 continues to rotate leading to the core to the pre-conditioning station A, where the collecting arm 26, attached to the depression 14, comes into contact with the first fixed electrode 32, connecting the moving electrode to earth and thus the nucleus remains in depression. Since the grounded tablet core passes to the electrostatic spray gun 16, its exposed surface is sprayed with the charged droplets of a capture enhancing liquid, for example, polyethylene glycol. The shell 24 continues to rotate, leading the moving electrode 26 out of contact with the first fixed electrode 32 and bringing it into contact with the second fixed electrode 34, as the tablet approaches the coating station B. The core surface of exposed tablet, treated with polyethylene glycol, is now at a potential difference to ground, and the powder coating material is directed towards it from the tray 18 for powder by virtue of the electrostatic forces. The potential well generated by keeping the surface of the drum and the dust at the same potential difference to ground as each other, and the core to a potential other than ground, ensures that dust is attracted to the core but that the surface of the drum remains substantially free of dust.

The shell 24 continues to rotate, leading the moving electrode 26 out of contact with the second fixed electrode 34, and carries the core to the fusion station C, where the heater 20 fuses the powder on the coated surface of the core to form a continuous movie. Since the shell 24 continues to rotate, the core leaves the fusion station C, passes through the cooling station (not shown), and the depression leading to the core no longer covers the suction manifold 30. The core falls from the first drum 12 towards a depression on the outer surface of the second drum 12 ', with its uncoated surface further out on the drum 12'; the depression is in communication with the suction manifold 30 of the second drum. The core liner is finished as it travels through the second pre-conditioning stations A ', coating B', fusion C and cooling. The powder coating material in the second coating station may be the same as the first, or different. In this way, tablets having differently coated surfaces can be produced. Since the coated tablet is ejected adjacent to the collection gutter 22, the depression that carries it ceases to cover the suction manifold, and the coated tablet falls into the gutter and is further processed and packaged. The drums by themselves preferably have a diameter of at least 60 mm and not less than the diameter of the smallest tablet in width that rotates at least? A r. p. m .. The suction pressure in the suction manifolds is sufficient to maintain the tablets against gravity, preferably between 0.2 and 0.6 bar below atmospheric pressure. In the electrostatic spray guns 16, 16 ', in the pre-conditioning stations A, A', a non-volatile semiconductor fluid, such as polyethylene glycol or an aqueous solution thereof is fed at a rate of 0.1 to 1 ml / min. , towards a steel capillary with an internal diameter of 0.05 to 2 mm. The capillary is connected to a potential high voltage difference limited to current (up to 50 kV from 30 to 100 μA) to ground, as each core in a drum passes to the gun, and a mist of charged droplets from the capillary is discharged towards the core of the drum; since the cores in the drums are connected to ground in the pre-conditioning stations, the charged droplets are guided by the electric field between the capillary and the core to the exposed surface of the core, where they are captured. The cores can be kept at a potential difference to ground in the pre-conditioning stations, provided that they are also at a potential difference to the capillaries. In this case, the first fixed arcuate electrode 32 is at a potential difference to ground. The supply of drops from each capillary is controlled by switching the voltage and grounding the capillary through a resistor (1 to 10 MO) as each core leaves the pre-conditioning station; this ensures a sharp cut of the drops between the tablet cores. In the coating stations B, B ', powder coating material is supplied through vibration feeders to the vibration trays 18, 18'. The level of dust in the trays is determined by a leveling knife above each tray. The powder can be fluidized by vibration and continuously recirculated. The trays may be made of a plastic material having a strip of metal grounded under the arc swept by the tablet cores in the respective drums or they may be metal trays. An alternative to charge the particles is the triboelectric charge. The trays preferably have a length of 50 to 150 mm and a width of 3 to 40 mm. If more than one tray is used, to provide a face of two colors or multiple colors, or a face that carries more than one polymer composition, the dimensions of the tray will be appropriately different. The tablet cores are charged by a voltage of one current from -3 to -15 kV limited to 5 μA. In the fusion or drying stations C, C, the energy is imparted to the surfaces of the core to fuse the powder and provide a uniform coating on the exposed surfaces of the core. The energy is provided by focused radiation, preferably in the infrared region; The power requirement of energy will be determined enormously by the coating material. After melting or drying, the coating is fixed by cooling, using an air blower. The preferred coating apparatus according to the invention can coat up to 300,000 tablet cores per hour.

Now, examples of powder coating materials suitable for use in the method for coating tablet cores described above will be given with reference to Figures 1 and 2.

EXAMPLE 1 A dry powder coating material was prepared by the following method. (a) a sample containing by weight: 55.5% Eudragit RS (trademark) (fine powder ammonium methacrylate copolymer) 18.5% polyethylene glycol (high molecular weight: approximately 20,000) 15.0% titanium dioxide 5.0% aluminum lacquer 5.0% of sodium lauryl sulfate 0.5% of Explotab (trademark) (sodium glycolate-starch) 0.5% of Aerosil 200 (trademark) (colloidal silicon dioxide) was combined in a high shear mixer. Before mixing, the particle sizes of the components of the sample were: TiO2 50% by volume less than 5 μm Aluminum slurry 50% by volume less than 1 μm Sodium lauryl sulphate 50% by volume less than 100 μm Euuddrraaggiitt 50% by volume less than 40 μm Polyethylene glycol 50% by volume from 60 to 70 μm b) The premixed mixture was wet granulated by the following method. Water was slowly added to the mixture obtained in (a) above in a high shear mixer for a few minutes until a granular mixture was obtained. The weight of the water added was between 10 and 15% of the weight of the premixed mixture. c) The granulated mixture obtained in step b) above was dried in a fluid bed dryer at a temperature of about 45 ° C for about 20 to 30 minutes to give a material having a moisture content (measured as loss) in drying) below 3% by weight. d) The granules obtained in step (c) were ground by impact and then micronized using a fluid energy mill to a powder containing particles having a size distribution so that 50% by volume of particles were of one size less than 20 μm, and almost 100% by volume were smaller than 60 μm. The peak in the size distribution of the particles was seen at approximately 10 μm. It was found that the powder is susceptible to movement under the action of electrostatic forces as defined above. e) The powder was coated on the tablet core using the method and apparatus described above. No pre-treatment of capture enhancer fluid was used. The powder coating on the surface of the tablet core was then fused using an infrared source to heat the coating material on the tablet core at a temperature of about 130 ° C and for about 5 seconds. The resulting coating has good opacity, was smooth, bright and bright colors. It was found that the thickness of the coating was less than 100 μm. The particle size distribution of the particles of the powder produced in step (d) above was measured. The particle size distribution was measured in% by volume. 100% less than 57.25 μm 70.29% less than 22.04 μm 5.58% less than 1.52 μm Approximately 50% of the particles had a size of 15.05 μm to 32.29 μm. Approximately 35% of the particles had a size of 18.21 μm to 32.29 μm. The average particle size was 19.17 μm (calculated as a mode).

EXAMPLE 2 A sample containing, by weight, 59.6% Eudragit RS (ammonium methacrylate copolymer) 19.9% Klucel (trademark) (hydroxy propyl cellulose) 15.0% titanium dioxide 5.0% aluminum lacquer 0.5% croscarmellose sodium ( interlaced sodium carboxymethyl cellulose) was used to make a powder coating material through the method described in steps (a) to (d) of Example 1. The powder was coated on and melted onto the surface of the powder. a tablet core as described in step (e) of Example 1. The resulting coating was smooth and highly glossy with strong color and good opacity. It was judged that the coating exhibits a higher brightness than would be expected for a tablet coated with the conventional film.

EXAMPLE 3 A sample containing, by weight, 39.75% Eudragit RS (ammonium methacrylate copolymer) 39.75% Klucel (trademark) (hydroxy propyl cellulose) 15.0% titanium dioxide 5.0% aluminum lacquer 0.5% Aerosil 200 (dioxide of colloidal silicon) was used to make a powder coating material by the method described in steps (a) to (d) of Example 1. The powder coating material was coated and fused on the surface of a tablet core as described in step (e) of Example 1. The resulting coating was smooth and shiny with a strong color and good opacity.

EXAMPLE 4 A sample containing, by weight, 60.0% of Eudragit RS (ammonium methacrylate copolymer) 20.0% of glyceryl monostearate 15.0% of titanium dioxide 5.0% of aluminum lacquer was used to make a powder coating material by the method described in steps (a) to (d) of Example 1. The powder material was coated and fused on the surface of a tablet core as described in step (e) of Example 1. The resulting coating was smooth and tinted with a strong color and good opacity.

EXAMPLE 5 A sample containing, by weight, 60.0% of Eudragit RS (ammonium methacrylate copolymer) 20.0% xylitol 15.0% titanium dioxide 5.0% aluminum lacquer was used to make a powder coating material by the method described in US Pat. Steps (a) to (d) of Example 1. The powder material was coated and fused on the surface of a tablet core as described in step (e) of Example 1. The resulting coating was semi- Shiny with a strong color and good opacity.

EXAMPLE 6 A sample containing, by weight, 46.5% of Eudragit RS (ammonium methacrylate copolymer) 28.0% of Klucel (hydroxy propyl cellulose) 15.0% of titanium dioxide 5.0% of aluminum lacquer 5.0% polyethylene glycol 6000 0.5% of Aerosil 200 (colloidal silicon dioxide) was used to make a powder coating material by the method described in steps (a) to (d) of Example 1. The powder material was placed as a coating and fused onto the surface of a tablet core as described in step (e) of Example 1. The resulting coating was smooth with strong color and good opacity.

EXAMPLE 7 a) A sample containing, by weight, 56.25% polyethylene glycol 20.0% titanium dioxide 18.75% Eudragit RS (ammonium methacrylate copolymer) 5.0% aluminum lacquer was mixed using a high shear mixer. Before mixing, the polyethylene glycol and the Eudragit were of a similar particle size with at least 50% by volume of the particles having a size of between 100 μm and 200 μm and at least 50% by volume of the particles of titanium dioxide and the aluminum lacquer had a particle size less than 1 μm. b) The dry combined mixture was then milled to give a powder material having a particle size of less than 300 μm with at least 50% by volume of the particles having a size between 100 μm and 200 μm. c) The material was coated on the tablet cores using the method and apparatus described above, including a pre-treatment spray of polyethylene glycol. The powder coating on the surface of the tablet core was then fused using an infrared source to heat the coating material on the tablet core at a temperature of about 130 ° C for about 5 seconds. The resulting coating was smooth and highly glossy with strong color and good opacity. It was judged that the coating exhibited a higher brightness than would be expected from a tablet coated with a conventional film.

EXAMPLE 8 A sample containing, by weight, 56.25% polyoxyethylene glycol 20.0% titanium dioxide 18.75% Eudragit RS (ammonium methacrylate copolymer) 5.0% aluminum lacquer the components having a particle size similar to that of Example 7 before mixing (the polyoxyethylene having a particle size similar to that of the Eudragit), dry mixed using a high stress mixer and the blended mixture was milled as described in step (b) of Example 7. The material obtained was coated on the tablet cores as described in step ( c) of Example 7 and the resulting coating was smooth and highly glossy with a strong color and good opacity. The coating was judged to exhibit a higher brightness than would be expected for a tablet coated with a conventional film. Since in the examples described above, all components are in the form of a solid particulate material, it should be understood that the powder coating material may include components, which are in liquid form.

Claims (3)

1. CLAIMS 1 .- A method for electrostatically coating a pharmaceutical tablet core with a powder material, the powder material including composite particles, each composite particle comprising two or more components having different physical and / or chemical properties.
2. 2. A method according to claim 1, wherein at least 50% by weight of the powder particles are composite particles.
3. 3. A method according to claim 1 or claim 2, wherein at least 30% by volume of the powder particles have a particle size in the range of 5 μm to 25 μm. 4 - A powder coating material suitable for use in the electrostatic powder coating of a pharmaceutical tablet core, wherein the material is pharmaceutically acceptable, can be treated to form a film coating and includes composite particles, the composite particles comprising two or more components having different physical and / or chemical properties and wherein at least 30% by volume of the powder particles have a particle size in the range of 5μm to 25μm. 5. A powder coating material suitable for use in the electrostatic powder coating of a pharmaceutical tablet core, wherein the pharmaceutically acceptable material can be treated to form a film coating and includes composite particles, the composite particles comprising two or more components having different chemical and / or physical properties. 6. A material according to claim 5, wherein at least 50% by weight of the powder particles are composite particles. 7. - A material according to claim 5 or claim 6, wherein at least 30% by volume of the powder particles have a particle size in the range of 5 μm to 25 μm. 8. A material according to any of the preceding claims, wherein at least 95% by number of the particles of the material have a particle size of less than 50 μm. 9 - A material according to any of the preceding claims, wherein at least 90% by number of the particles of the material have a particle size of less than 5 μm. 10. A material according to any of the preceding claims, wherein the material has a resistivity in the range of 108 to 1016Om. 1 1 - A material according to any of the preceding claims, which is capable of being triboelectrically loaded and / or charged by corona. 12. A material according to any of the preceding claims, which is an electret or a magnet or a paramagnetic. 13. A material according to any of the preceding claims, which is susceptible to movement under the action of electrostatic forces, the susceptibility being determined by the test defined herein. 14. A material according to any of the preceding claims, wherein the material can be treated at a temperature of less than 250 ° C to form a film coating. 15. A material according to any one of claim 14, wherein the material is capable of being fused to form a film coating at a temperature of less than 250 ° C at atmospheric pressure. 16. A material according to any of the preceding claims, wherein the material has a melting point in the range of 50 ° C to 180 ° C. 17.- A material according to any claim 16, where the material has a melting point on the scale of 60 ° C to 100 ° C. 18. A material according to any of the preceding claims, wherein the material exhibits a glass transition and the softening point of the material is in the range of 30 ° C to 180 ° C. 19. A material according to any of the preceding claims, wherein the material comprises a polymer that is curable to form an interlaced polymer film. 20. A material according to any of the preceding claims, which has a moisture content (measured by moisture loss) of not more than 3% by weight, based on the weight of the powder coating material. 21. A material according to any of the preceding claims, which includes a first component, which is fusible to form a continuous film on the surface of the substrate. 22. A material according to any one of claim 21, wherein the first component is fusible to a film coating at a temperature of less than 250 ° C. 23. A material according to any one of claim 21 or claim 22, wherein the material includes at least 10% by weight of the first component based on the weight of the material. 24 - A material according to any of claims 21 to 23, including a second component, which is capable of being triboelectrically charged. 25. A material according to any of claims 21 to 24, which includes a second component, which is an electret, or a magnet or a paramagnetic. 26. A material according to any of claims 21 to 25, which includes a second component, which is susceptible to movement under the action of electrostatic forces, the susceptibility being determined by the test defined herein. 27. A material according to any of claims 24 to 26, wherein the second component comprises one or more of the materials in the group comprising polymers of acrylic acid and its derivatives, polyalkenes and their derivatives, polyvinyl alcohols and esters and cellulose and its derivatives. 28. A material according to any of claims 24 to 27, wherein the material includes at least 20% by weight of the second component based on the weight of the material. 29. A material according to any of claims 21 to 28, which includes a dispersion component for improving the dispersion of the first component and the second component. 30. A material according to claim 29, wherein the dispersion component comprises a surfactant. 31. A material according to claim 29 or claim 30, wherein the material includes at least 1% by weight of the dispersion component based on the weight of the material. 32. - A material according to any of the preceding claims, which includes an anti-friction agent. 33. A material according to any of the preceding claims, wherein the material includes a disintegrator. 34. A material according to any of the preceding claims, which includes selected components of opacifiers, colorants and flavorings. 35. - A material according to any of the preceding claims, wherein the material includes a biologically active material. 36.- A material according to claim 35, wherein the material includes at least 0.5% by weight of the active material based on the weight of the material. 37. - A coating material for the electrostatic coating of a pharmaceutical substrate, the coating material includes an active material. 38.- A coating material according to claim 37, wherein the coating material includes at least 0.5% by weight of the active material based on the weight of the coating material. 39 - A coating material according to claim 37 or claim 38, wherein the coating material is a powder coating material. 40. - A coating material according to any of claims 37 to 39, wherein at least 90% by number of the particles of the powder have a particle size of not more than 50 μm. 41 .- The use of a coating material comprising an active material in the electrostatic coating of a substrate. 42. A method for electrostatically coating a pharmaceutical tablet core with a powder material, the powder material according to any of the preceding claims. 43.- A method according to claim 42, the method comprising maintaining the substrate adjacent to a source of energy coating material with a surface of the substrate maintained at said electrical potential different from that of the coating material that the application of the potential electrical causes the energy to move from the source of the powder to the substrate and the surface of the substrate is coated with the powder coating material. 44.- A coating material according to claim 43, wherein the method is carried out as a continuous process. 45.- A coating material according to claim 43 or claim 44, wherein the substrate is transported on conveyor means through a region adjacent to the source of powder coating material. 46. - A coating material according to any of claims 43 to 45, wherein the substrate is loaded when the substrate is adjacent to the source of powder coating material. 47 - A coating material according to claim 46, wherein the energy source of the powder coating material is connected to ground. 48. A coating material according to any of claims 43 to 47, wherein the substrate is maintained from above and the powder moves from the source upwards to a lower surface of the substrate. 49 - A coating material according to any of claims 43 to 48, wherein, before the substrate is held adjacent to the source of powder coating material, a pretreatment composition is applied to a surface of the substrate 50.- A coating material according to claim 49, wherein the pre-treatment composition is a liquid. 51 - A coating material according to claim 50, wherein the liquid is polyethylene glycol. 52. A coating material according to any of claims 43 to 51, wherein the method further includes the step of which after the surface of the substrate has been coated with the powder, the powder is treated to form a continuous film coating secured to the substrate. 53. A coating material according to any of claims 43 to 52, wherein the method further includes the steps of maintaining the coated substrate adjacent a source of powder coating material with an uncoated surface of the exposed substrate and with a surface of the substrate maintained at an electrical potential different from that of the coating material, whereby the application of the electric potential causes the powder to move from the source of the powder towards the substrate so that the exposed surface is coated with the powder coating material. 54. A method for producing a powder coating material comprising at least two different components for use in the electrostatic coating of a substrate, the method involving the step of co-processing at least the two different ones. components. 55.- A coating material for use in the electrostatic coating of a substrate thereof, the powder can be obtained by a method according to claim 54. 56. - A pharmaceutical tablet comprising a core. of tablet and a powder coating material according to any of claims 5 to 40. 57.- A pharmaceutical tablet that has been electrostatically coated by a method according to any of claims 43 to 53. 58. - A coating material for use in an electrostatic process, the material having one or more of the following properties: a) are ingestible by humans and / or animals, b) are made of at least two different components, preferably processed, c) are fuses in a film coating at a temperature of less than 250 ° C at atmospheric pressure, d) at least 30% by volume of the particles having a particle size in the range of 5 μm to 20 μm, e) are susceptible to movement under the action of electrostatic forces, the susceptibility being determined by the test defined herein. 59. A method for electrostatically coating a substrate with a powder coating material according to any of claims 5 to 40 or claim 58.