Inkjet ink for solid preparation, solid preparation, and method for producing solid preparation

Abstract

Provided are: an inkjet ink for a solid preparation, the inkjet ink having exceptional dischargeability from a nozzle of an inkjet head when applied using an inkjet method; a solid preparation; and a method for producing a solid preparation. An inkjet ink for a solid preparation according to the present invention contains ethanol that serves as the main solvent, an active ingredient that is soluble in ethanol, and a viscosity adjuster that adjusts the viscosity of the inkjet ink for a solid preparation, the viscosity modifier being at least one selected from the group consisting of polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, lauromacrogol, polyvinylpyrrolidone having a K value of 25 or lower, and shellac.

Description

Inkjet ink for solid preparations, solid preparations, and method for producing solid preparations

[0001] The present invention relates to an inkjet ink for solid preparations, a solid preparation, and a method for producing a solid preparation, and more particularly, to an inkjet ink for solid preparations having excellent ejection properties when applied by an inkjet method, a solid preparation, and a method for producing a solid preparation.

[0002] Conventionally, in the production of solid preparations as pharmaceuticals, a method of mixing a medicinal ingredient (active ingredient) with an excipient or the like and then molding this mixture with a tableting machine has been adopted. However, in such a production method, when the amount of the medicinal ingredient is small, it cannot be uniformly mixed with the excipient or the like, and as a result, it is easy to obtain a solid preparation in which the medicinal ingredient is unevenly distributed. In addition, it is not easy to carry out multi-variety small-lot production by such a production method.

[0003] Therefore, a method has been proposed in which an ink containing a medicinal ingredient is applied to the surface of a tablet by a dispensing method and then dried, thereby retaining a trace amount of the medicinal ingredient on the tablet surface (Patent Document 1). According to this Patent Document 1, as the ink, it is also described that an organic solvent such as ethanol is contained as a solvent and a binder is further added. However, since the binder is added for the purpose of fixing the medicinal ingredient on the surface of the tablet or capsule, when the ink described in Patent Document 1 is used for coating by an inkjet method, there is a problem that nozzle chipping or the like occurs on the coating surface of the ink and the ejection property is not good.

[0004] International Publication No. 2020 / 218310

[0005] The present invention has been made in view of the above problems, and an object thereof is to provide an inkjet ink for solid preparations, a solid preparation, and a method for producing a solid preparation, which are excellent in ejection properties from the nozzles of an inkjet head when applied by an inkjet method.

[0006] The inkjet ink for solid formulations according to the present invention, in order to solve the above problems, comprises ethanol as a main solvent, an active ingredient that is soluble in ethanol, and a viscosity modifier that adjusts the viscosity of the inkjet ink for solid formulations, wherein the viscosity modifier is at least one selected from the group consisting of polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, lauromacrogol, polyvinylpyrrolidone with a K value of 25 or less, and shellac.

[0007] According to the above configuration, since ethanol is used as the main solvent, compared to, for example, when water is used as the main solvent, it is possible to reduce or suppress the penetration, dissolution, disintegration, or swelling of the solid formulation inkjet ink (hereinafter sometimes referred to as "inkjet ink") into the tablet. As a result, the abrasion resistance of the tablet after printing can be improved. Furthermore, by including a viscosity modifier such as polyoxyethylene sorbitan monolaurate, good viscosity can be imparted to the inkjet ink. This suppresses the decrease in viscosity of the solid formulation inkjet ink despite the use of ethanol as the main solvent, and stabilizes the formation of a meniscus inside the inkjet head, thereby maintaining good droplet ejection performance of the inkjet ink. In addition, since ethanol is a low-boiling point solvent compared to, for example, water, inkjet inks using ethanol as the main solvent tend to dry out easily inside the nozzle of the inkjet head. However, by increasing the viscosity of the inkjet ink through the addition of a viscosity modifier, the boiling point of the inkjet ink itself can be raised. As a result, the increase in drying within the nozzle can be suppressed, and the ejection recovery performance can be improved.

[0008] Furthermore, in the above configuration, it is preferable that the viscosity modifier is at least one selected from the group consisting of polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, polyvinylpyrrolidone with a K value of 17 or less, and shellac. By using these compounds as viscosity modifiers, the drying effect inside the nozzle can be further reduced, and the discharge recovery performance can be further improved.

[0009] Furthermore, in the above configuration, it is preferable that the viscosity modifier is at least one selected from the group consisting of polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, lauromacrogol, and polyvinylpyrrolidone with a K value of 25 or less. By using these compounds as viscosity modifiers, the abrasion resistance and discharge recovery properties can be further improved.

[0010] Furthermore, in the above configuration, it is preferable that the solvent consists solely of ethanol. When the solvent consists solely of ethanol and does not contain water, the penetration of inkjet ink into the tablet is further prevented, thereby further improving abrasion resistance.

[0011] In the above configuration, it is preferable that the viscosity of the solid formulation inkjet ink is within the range of 2.5 mPa·s or more and 10 mPa·s or less at 25°C. By setting the viscosity of the inkjet ink to 2.5 mPa·s or more, droplet separation of the liquid ejected from the nozzle of the inkjet head can be suppressed, preventing the ejection from being disrupted by contamination of the head by the separated liquid droplets or mist, and thus preventing a decrease in the accuracy of the coating amount. On the other hand, by setting the viscosity of the inkjet ink to 10 mPa·s or less, it is possible to suppress the inkjet ink from becoming difficult to push out from the nozzle, and good ejection can be maintained.

[0012] Furthermore, in order to solve the above-mentioned problems, the solid formulation of the present invention is characterized in that at least a portion of the surface of the tablet is provided with an active ingredient-containing layer consisting of a dried film of the inkjet ink for solid formulations.

[0013] According to the above configuration, the inkjet ink, which is the material for the active ingredient-containing layer, can reduce or suppress dissolution, disintegration, or swelling due to penetration into the tablet compared to, for example, an inkjet ink using water as the main solvent. As a result, a solid formulation with excellent abrasion resistance can be obtained. Furthermore, as mentioned above, the inkjet ink has excellent ejection and ejection recovery properties from the nozzles of the inkjet head, and can prevent or reduce the occurrence of nozzle chipping, etc., so, for example, an active ingredient-containing layer with uniform thickness and no film defects can be formed. As a result, even when the amount of active ingredient is small, a solid formulation with precisely controlled active ingredient content can be obtained.

[0014] In the above configuration, the tablet may be a placebo tablet.

[0015] Furthermore, in order to solve the above-mentioned problems, the present invention provides a method for manufacturing a solid formulation, comprising: a coating step of applying the inkjet ink for solid formulations to at least a part of the surface of a tablet using an inkjet method to form a coating film of the inkjet ink for solid formulations; and a drying step of drying the coating film to form an active ingredient-containing layer consisting of a dried film of the inkjet ink for solid formulations.

[0016] According to the above configuration, since the inkjet ink uses ethanol as its main solvent, compared to, for example, the case where water is used as the main solvent for inkjet ink applied to the tablet surface, the penetration of the inkjet ink into the tablet can be suppressed, reducing or preventing the dissolution, collapse, or swelling of the tablet. As a result, solid formulations with good abrasion resistance can be manufactured. Furthermore, as mentioned above, the inkjet ink has excellent ejection and ejection recovery properties from the nozzles of the inkjet head, so it can prevent or reduce the occurrence of nozzle chipping and other defects during the coating process. As a result, in the active ingredient-containing layer obtained by drying the coated film in the drying process, for example, an active ingredient-containing layer with a uniform thickness and no film defects can be formed. This makes it possible to manufacture solid formulations with precisely controlled active ingredient content, even when the amount of active ingredient is trace.

[0017] In the above configuration, the tablet may be a placebo tablet.

[0018] The inkjet ink for solid formulations of the present invention uses ethanol as the main solvent, so it is possible to obtain a solid formulation in which an active ingredient-containing layer is formed on at least a portion of the tablet surface without impairing abrasion resistance. Furthermore, since the inkjet ink for solid formulations of the present invention contains a viscosity modifier to increase its viscosity, the ejection and ejection recovery properties when applied by inkjet method can also be improved. As a result, an active ingredient-containing layer without film defects caused by nozzle chipping, etc., can be formed on the tablet surface, and even when the amount of active ingredient is minute, a solid formulation with precisely controlled active ingredient content can be obtained.

[0019] (Inkjet Ink for Solid Pharmaceutical Formulations) An inkjet ink for solid pharmaceutical formulations according to one embodiment of the present invention (hereinafter referred to as "inkjet ink") is described below.

[0020] The inkjet ink according to this embodiment comprises an inkjet ink composition and an active ingredient, and enables the formation of an active ingredient-containing layer (details will be described later) on at least a portion of the surface of a solid formulation by inkjet printing.

[0021] As inkjet inks, materials conforming to the standards of pharmaceuticals and pharmaceutical additives as defined by the Pharmaceuticals and Medical Devices Act, the Japanese Pharmacopoeia, and the Official Compendium of Food Additives, or materials that are pharmaceutically acceptable, can be used. Furthermore, inkjet inks can be suitably used for printing using an inkjet method. Hereinafter, "pharmaceutically acceptable" means that, within the bounds of sound medical judgment, it is suitable for use in contact with human and other mammalian tissues, does not have arbitrarily excessive toxicity, irritation, or immunogenicity, and is commensurate with a reasonable benefit / risk ratio.In addition, "inkjet method" in this specification means a printing method in which inkjet ink is ejected as droplets from a fine inkjet head, and these droplets are fixed to at least a portion of the surface of the tablet to form a solidified layer of inkjet ink.Details of the tablet will be described later.

[0022] The inkjet ink of this embodiment is preferably a non-aqueous inkjet ink. Here, "non-aqueous" in this specification means that the inkjet ink does not contain water or contains only a small amount of water. Furthermore, "contains only a small amount" specifically means that the inkjet ink contains 20% by mass or less, preferably 10% by mass or less, and more preferably 5% by mass or less, of the total mass of the inkjet ink.

[0023] The inkjet ink composition comprises at least a solvent and a viscosity modifier. In this embodiment, the inkjet ink composition is preferably a non-aqueous inkjet ink composition. The meaning of "non-aqueous" in "non-aqueous inkjet ink composition" is as described above.

[0024] The solvent preferably contains ethanol as the main solvent and is a non-aqueous solvent (or organic solvent). For example, if the tablets are uncoated tablets or orally disintegrating tablets, these tablets disintegrate in water. Therefore, by using a non-aqueous solvent as the solvent, it is possible to prevent the solvent from dissolving, disintegrating, or swelling the surface of the tablets. The solvent may consist only of ethanol, or it may contain other organic solvents. Other organic solvents that can be used include materials that conform to the standards of pharmaceuticals and pharmaceutical additives as defined by the Pharmaceuticals and Medical Devices Act, the Japanese Pharmacopoeia, and the Official Compendium of Food Additives, or pharmaceutically acceptable solvents. In this specification, "main solvent" refers to the solvent if it is used alone, and to the solvent with the highest content when multiple solvents are used in combination. The solvent content will be described later.

[0025] Viscosity modifiers have a viscosity-adjusting function that imparts viscosity to inkjet ink. Generally, the optimal viscosity of inkjet ink varies greatly depending on the type of inkjet head supplied by multiple manufacturers. If the viscosity of the inkjet ink is too low, the meniscus inside the inkjet head may not form stably, which can reduce the ejection performance from the nozzle of the inkjet head. In particular, when ethanol is used as the main solvent, the viscosity of the inkjet ink decreases, but by including a viscosity modifier in the inkjet ink as in this embodiment, the viscosity of the inkjet ink can be controlled to an appropriate range. As a result, good ejection performance can be achieved in various printers. Also, since ethanol is a low-boiling point solvent compared to water, for example, it tends to dry out easily inside the nozzle of the inkjet head. However, by increasing the viscosity of the inkjet ink through the addition of a viscosity modifier, the boiling point of the inkjet ink itself can also be raised. As a result, the increase in drying within the nozzle can be suppressed, and the ejection recovery performance can be improved.

[0026] The viscosity modifier of this embodiment is soluble in the solvent and preferably exists dissolved in the inkjet ink (and inkjet ink composition). Herein, "soluble" means a compound that dissolves at a solubility (25°C) of 5 g / 100 g or more, preferably 10 g / 100 g or more, and more preferably 20 g / 100 g or more. The solubility (25°C) is the mass of the compound that dissolves in 100 g of solvent at 25°C.

[0027] Examples of viscosity modifiers include polyoxyethylene sorbitan monolaurate (Tween® 20), polyoxyethylene sorbitan monopalmitate (Tween® 40), polyoxyethylene sorbitan monostearate (Tween® 60), polyethylene glycol sorbitan monooleate (Tween® 80), polyethylene glycol, lauromacrogol, polyvinylpyrrolidone with a K value of 25 or less, and shellac. By using these viscosity modifiers, inkjet inks with excellent ejection properties can be obtained. These viscosity modifiers can be used individually or in combination of two or more. Examples of polyethylene glycols include polyethylene glycol 400, polyethylene glycol 600, and polyethylene glycol 1540. In this specification, the "K value" of polyvinylpyrrolidone is a value calculated by applying the relative viscosity value (25°C) measured by a capillary viscometer to the following Fikentscher formula: K = (1.5 log η) ｒｅｌ -1) / (0.15+0.003c)+(300clogη ｒｅｌ +(c+1.5clogη ｒｅｌ ) ２ ) １／２ / (0.15c + 0.003c) ２ ) c: Concentration of polyvinylpyrrolidone in the polyvinylpyrrolidone aqueous solution (mass%) η rel : Relative viscosity of a polyvinylpyrrolidone aqueous solution at concentration c relative to water.

[0028] Furthermore, by using at least one of the viscosity modifiers exemplified above—polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, lauromacrogol, polyvinylpyrrolidone with a K value of 25 or less, and shellac—it is possible to improve the ejection performance of inkjet inks and also improve the abrasion resistance of solid formulations printed with the inkjet ink.

[0029] Furthermore, by using at least one of the viscosity modifiers exemplified above—polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, polyvinylpyrrolidone with a K value of 17 or less, and shellac—it is possible to improve the ejection performance of inkjet inks and also enhance their ejection recovery performance.

[0030] Furthermore, by using at least one of the exemplified viscosity modifiers, such as polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, lauromacrogol, and polyvinylpyrrolidone with a K value of 25 or less, it is possible to improve the discharge properties, the abrasion resistance of solid formulations printed with inkjet ink, and the discharge recovery properties.

[0031] The content of viscosity modifiers and solvents is set appropriately so that the viscosity of the inkjet ink falls within the numerical range described below. Furthermore, the content ratio of viscosity modifiers to solvents (viscosity modifier / solvent) is preferably set to a range greater than 0 and less than or equal to 1 / 2 by mass, so that the viscosity of the inkjet ink falls within the numerical range described below.

[0032] The inkjet ink composition of this embodiment may contain additives to the extent that they do not impair the effects of the present invention. Examples of additives include colorants, surface tension modifiers, wetting agents, water-soluble resins, surfactants, pH adjusters, chelating agents, preservatives, defoaming agents, dispersion stabilizers, reduction inhibitors, and antioxidants. The content of these additives is not particularly limited and can be set as appropriate and necessary. Since the inkjet ink composition of this embodiment is used for printing on the surface of tablets of pharmaceuticals or food products, it is preferable to use additives that conform to the standards of pharmaceuticals, pharmaceutical additives, the Japanese Pharmacopoeia, or the Japanese Food Additives Compendium as defined by the Pharmaceuticals and Medical Devices Act, or those that are pharmaceutically acceptable.

[0033] Examples of colorants include pigments and dyes. Examples of pigments include red iron(III) oxide, yellow iron(III) oxide, iron(III) oxide (black iron), carbon black, and lake pigments. These exemplified pigments can be used individually or in combination of two or more, as needed. Examples of dyes include synthetic food colorants (synthetic tar dyes), natural pigment derivatives, natural synthetic colorants, and natural food colorants. Examples of synthetic food colorants include azo dyes, triphenylmethane dyes, xanthene dyes, and indigoid dyes. Examples of azo dyes include Food Red No. 2, Food Red No. 102, Food Red No. 40, Food Yellow No. 4, and Food Yellow No. 5. Examples of triphenylmethane dyes include Food Blue No. 1 and Food Green No. 3. Examples of xanthene dyes include Food Red No. 3, Food Red No. 104, Food Red No. 105, and Food Red No. 106. Examples of indigoid dyes include Food Blue No. 2. Examples of natural pigment derivatives include copper chlorophyllin sodium. Examples of natural synthetic pigments include β-carotene. Examples of natural food pigments include anthocyanin pigments, carotenoid pigments, quinone pigments, flavonoid pigments, cochineal pigment, copper chlorophyllin sodium, cocoa pigment, and caramel pigment. The exemplified dyes can be used individually or in mixtures of two or more as needed.

[0034] The term "active ingredient" refers to the medicinal components (pharmaceutically acceptable active agents) in pharmaceuticals used for the treatment, prevention, and diagnosis of diseases in humans and animals, as well as nutritional components in foods and health foods. Specifically, examples of active ingredients include antipyretic, analgesic, and anti-inflammatory agents such as ibuprofen, hypnotics and sedatives, sleep aids, migraine medications, anxiolytics, anticonvulsants, antidepressants, antiparkinsonian drugs, psychotropic agents, central nervous system drugs, local anesthetics, skeletal muscle relaxants, autonomic nervous system agents, antispasmodics, anti-vertigo agents, cardiac stimulants, antiarrhythmics, antihypertensives, vasoconstrictors, vasodilators, circulatory system drugs, hyperlipidemia drugs, antitussives, expectorants, antitussive-expectorant drugs, bronchodilators, antidiarrheal agents, urinary system drugs, hemostatic agents, liver disease drugs, gout treatments, diabetes drugs, antihistamines, antibiotics, anticancer agents, chemotherapy agents, tonics, vitamins, herbal medicines, and herbal prescriptions. These active ingredients can be used alone or in combination of two or more.

[0035] The active ingredient may be dissolved in the solvent in the inkjet ink composition, or it may be dispersed in the solvent. In this embodiment, a viscosity modifier is included to impart viscosity to the inkjet ink and improve its discharge properties, but if the active ingredient is dispersed, it is also possible to suppress aggregation and sedimentation of the active ingredient.

[0036] The amount of active ingredient is not particularly limited and is set appropriately depending on the amount applied to the tablet surface. Since it is thought that the less inkjet ink applied to the tablet, the less abrasion the tablet will have, it is preferable to increase the amount of active ingredient as much as possible without impairing the ejection performance of the inkjet nozzle, so that the required amount of active ingredient can be applied with less ink.

[0037] The viscosity of the inkjet ink is preferably in the range of 2.5 mPa·s or more and 10 mPa·s or less, more preferably in the range of 2.5 mPa·s or more and 8 mPa·s or less, and even more preferably in the range of 2.5 mPa·s or more and 5 mPa·s or less, when ejected from the inkjet nozzle. By setting the viscosity of the inkjet ink to 2.5 mPa·s or more, droplet separation of the liquid ejected from the nozzle of the inkjet head can be suppressed, preventing the ejection from being disturbed by contamination of the head by separated liquid droplets and mist, and thus preventing a decrease in the accuracy of the coating amount. On the other hand, by setting the viscosity to 10 mPa·s or less, the difficulty in pushing the inkjet ink out from the nozzle can be suppressed, and good ejection can be maintained. The viscosity of the inkjet ink may be, for example, 2.5, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, or 10.0 mPa·s, or within the range of any two of the values ​​exemplified here. Furthermore, the viscosity of the inkjet ink can be obtained, for example, by measuring it using a viscometer (product name: DV2TLVTJ0, manufactured by Brookfield) under conditions of a measurement temperature of 25°C.

[0038] (Method for Manufacturing Inkjet Ink) The inkjet ink of this embodiment can be manufactured by mixing the components and active ingredients of the aforementioned inkjet ink composition in an appropriate manner. Alternatively, the inkjet ink composition may be prepared and then mixed with the active ingredients in an appropriate manner. The mixing method and the order of addition are not particularly limited. After mixing the components or the inkjet ink composition with the active ingredients, or after preparing the inkjet ink composition, the mixture is thoroughly stirred, and if necessary, filtered to remove coarse particles and foreign matter that may cause clogging. This allows the inkjet ink according to this embodiment to be obtained.

[0039] The method of mixing each component is not particularly limited; for example, the materials can be sequentially added to a container equipped with a stirring device such as a disperser, mechanical stirrer, or magnetic stirrer, and then stirred and mixed. Furthermore, the filtration method is not particularly limited; for example, centrifugal filtration or filter filtration can be employed.

[0040] (Solid preparation) The solid preparation of this embodiment has a configuration in which an active ingredient-containing layer is provided on at least a part of the surface of a tablet. Here, in this specification, "solid preparation" means including food preparations and pharmaceutical preparations, and refers to those in which an active ingredient-containing layer is provided at least on at least a part of the surface of a tablet. Also, in this specification, "tablet" means including plain tablets, orally disintegrating tablets (OD tablets), film-coated tablets, enteric-coated tablets, sustained-release tablets, and oral tablets (sublingual tablets, buccal tablets, etc.). Further, as a tablet, it may contain an active ingredient or may be a placebo tablet not containing an active ingredient. Incidentally, a plain tablet is one obtained by tabletting a raw material and is the tablet itself without coating, and means one having a disintegration time exceeding 30 seconds. Also, an orally disintegrating tablet means a tablet having a disintegration time within 30 seconds. The value of the disintegration time can be obtained, for example, by measurement using an orally disintegrating tablet measuring device (trade name: Tricop Tester (registered trademark), manufactured by Okada Seiko Co., Ltd.).

[0041] The overall shape, size, etc. of the tablet are not particularly limited and are arbitrary. Regarding the overall shape of the tablet, for example, round tablets (R shape, double R shape), caplet tablets, oval tablets, divided tablets, flat tablets, etc. can be mentioned. Here, "divided tablet" means, for example, a scored line consisting of at least one groove that facilitates tablet division is provided on the upper surface of a disk-shaped plain tablet, the upper surface is gradually recessed from the opposing edge portions toward the scored line, the lower surface of the plain tablet is gradually raised from the peripheral portion toward the center portion, curved surfaces are formed on the recessed upper surface and the raised lower surface, respectively, but by making the radius of curvature of the upper surface smaller than the radius of curvature of the lower surface, it means a plain tablet having a shape in which the center portion is thinner than the peripheral portion. Also, "flat tablet" means including, for example, round-cornered flat tablets, cornered flat tablets, etc.

[0042] The active ingredient-containing layer is composed of a dried film of the inkjet ink and contains at least an active ingredient and a viscosity modifier. Since the inkjet ink of the present embodiment is non-aqueous, when the inkjet ink is applied to the surface of the tablet, it can penetrate into the tablet to prevent or reduce dissolution, disintegration or swelling of the tablet. Thereby, it is possible to reduce or prevent the occurrence of chips, cracks, etc. in the tablet. The active ingredient-containing layer may also have a function of protecting the inside of the tablet and increasing the mechanical strength.

[0043] As described above, the active ingredient-containing layer may be provided on at least a part of the surface of the tablet. Further, the active ingredient-containing layer may be provided only on the upper surface and / or the lower surface of the tablet.

[0044] Further, different active ingredient-containing layers having different active ingredients may be provided for each arbitrary region on the tablet surface. Also, the active ingredient-containing layer may be a patterned layer having different patterning for each region on the tablet surface. Here, "patterning" means forming a geometrically regular pattern shape in the active ingredient-containing layer. For example, it means forming two or more mutually different regions due to differences in layer thickness partially or locally, the presence or absence of the active ingredient-containing layer, the presence or absence, number, shape, etc. of pores, or having two or more of the same region. Also, regions having the same pattern shape do not have to be continuous with each other and may be distributed in a pattern. The "patterned layer" means an active ingredient-containing layer subjected to such patterning. Specific examples of the patterned layer include those having a lattice-like, stripe-like, or concentric pattern shape. Also, those in which circular holes are arranged at equal intervals may be used.

[0045] In addition to the case where the active ingredient-containing layer is a single layer, it may also have a multilayer structure in which two or more layers are laminated. In this case, layers of active ingredient-containing layers having the same type and content of active ingredient may be laminated, or layers of active ingredient-containing layers in which at least one of them is different may be laminated.

[0046] The layer thickness of the active ingredient-containing layer (in the case of a multilayer structure, the total thickness) is not particularly limited and can be appropriately set according to the content of the active ingredient and the like.

[0047] Regarding the abrasion properties of solid formulations, the mass loss rate (%) obtained by the abrasion test based on the tablet abrasion test method (G6-5-181) in accordance with the 18th edition of the Japanese Pharmacopoeia is preferably less than 1%, more preferably 0.5% or less, and particularly preferably 0.2% or less. The mass loss rate (%) can be calculated using the following formula: Mass loss rate (%) = (Mass of solid formulation immediately after the abrasion test) / (Mass of solid formulation immediately before the abrasion test) × 100

[0048] As described above, the solid formulation of this embodiment has a structure in which at least one active ingredient-containing layer is provided on at least a part of its surface. The active ingredient-containing layer has various thicknesses, lamination structures, and patterning shapes, which allows for precise control of, for example, the content of the active ingredient in the solid formulation.

[0049] (Method for manufacturing a solid formulation) The method for manufacturing a solid formulation according to this embodiment includes at least a coating step of applying inkjet ink to at least a portion of the surface of a tablet, and a drying step of drying the inkjet ink applied to the surface of the tablet.

[0050] The coating process is performed by inkjet printing, forming a coating film (film) of inkjet ink. In inkjet printing involves ejecting inkjet ink as droplets from fine nozzles and adhering these droplets to at least a portion of the tablet's surface. Furthermore, inkjet printing can employ methods such as so-called one-pass (single-pass) printing, where the inkjet ink ejection nozzles are arranged perpendicular to the scanning direction of the tablet, and the active ingredient-containing layer is completed by the tablet passing below the ejection nozzles only once; or so-called shuttle (scan) printing, where the ejection nozzles primarily scan the tablet in the scanning direction (straight scanning direction), and intermittently perform sub-scans in the width direction after each primary scan to form the active ingredient-containing layer on the tablet's surface. In the former case of single-pass printing, the active ingredient-containing layer can be printed at high speed, improving productivity. In the latter case of shuttle (scan) printing, it is possible to form an active ingredient-containing layer with high-definition patterning.

[0051] Furthermore, the method of ejecting the inkjet ink is not particularly limited, and known methods such as continuous jet type (charge-controlled type, spray type, etc.) and on-demand type (piezo type, thermal type, electrostatic attraction type, etc.) can be employed. Also, the ejection conditions for the inkjet ink are not particularly limited and can be set as appropriate.

[0052] The amount of inkjet ink applied (discharge amount, droplet amount, or adhesion amount) can be appropriately set according to the amount of active ingredients contained in the inkjet ink, etc.

[0053] The drying process is a step in which the inkjet ink coating film that adheres to at least a portion of the surface of the tablet during the coating process is subjected to a drying treatment. The drying method is not particularly limited and can be, for example, natural drying or hot air drying. Furthermore, the drying conditions such as drying time and drying temperature (hot air temperature) are not particularly limited and can be set according to the composition and amount of inkjet ink applied.

[0054] Furthermore, the aforementioned coating process may involve multiple inkjet printing steps. That is, for example, different inkjet inks with varying types and amounts of active ingredients may be applied to different areas on the tablet surface. In this case, the drying process can be performed in a single step. Alternatively, the coating and drying processes may be repeated to form a multilayer structure of active ingredient-containing layers.

[0055] Preferred embodiments of this invention will be described in detail below. However, unless otherwise specified, the materials and their contents described in the following embodiments do not limit the scope of this invention.

[0056] (Examples 1-11) First, ethanol as a solvent, a viscosity modifier, and Blue No. 1 as a colorant were mixed to create the formulations shown in Table 1, and inkjet ink compositions according to Examples 1-11 were prepared. The viscosity of each inkjet ink composition was set to 5 mPa·s. Furthermore, all materials used in the inkjet ink compositions conformed to the standards of pharmaceutical additives as defined by the Pharmaceuticals and Medical Devices Act, the Japanese Pharmacopoeia, or the Official Compendium of Food Additives.

[0057] Next, ejection tests were conducted using the inkjet ink compositions according to each example. In the ejection tests, each inkjet ink composition was treated as a simulated inkjet ink. A RICOH MH5421MF head (product name) was used as the inkjet head, and the inkjet ink composition was printed on super fine paper (Epson Corporation) using the inkjet method. The presence or absence of nozzle defects in the printed image was then observed to confirm whether or not the inkjet ink composition was ejected from all nozzles of the head. The results are shown in Table 1. The evaluation criteria for ejection in Table 1 are as follows: ○: The inkjet ink composition is ejected from all nozzles. ×: There are nozzles from which the inkjet ink composition is not ejected.

[0058] Furthermore, the ejection recovery performance was evaluated using the inkjet ink compositions according to each example. Specifically, an inkjet head filled with the inkjet ink composition was left for 24 hours, resulting in a state where nozzle defects occurred in the printed image when printing was performed. Next, a purge was performed to eject the inkjet ink composition from all nozzles, and then it was checked again to see if any nozzle defects had occurred. This operation was repeated, and the number of purges required until nozzle defects no longer occurred was counted. The results are shown in Table 1. The evaluation criteria for ejection recovery performance in Table 1 are as follows: ○: Nozzle defects disappeared and recovery was achieved with up to two purges. △: Nozzle defects disappeared and recovery was achieved with three or more purges. ×: Recovery was not achieved.

[0059]

[0060] (Comparative Examples 1-12) First, inkjet ink compositions according to Comparative Examples 1-12 were prepared by mixing ethanol as a solvent, a viscosity modifier, and Blue No. 1 as a colorant to the formulations shown in Table 2. The viscosity of each inkjet ink composition was set to 5 mPa·s. In addition, all materials used in the inkjet ink compositions conformed to the standards of pharmaceutical additives as defined by the Pharmaceuticals and Medical Devices Act, the Japanese Pharmacopoeia, or the Official Compendium of Food Additives. Next, the inkjet ink compositions according to Comparative Examples 1-12 were subjected to ejection tests in the same manner as in Example 1, etc., and their ejection performance was evaluated. The results are shown in Table 2. In addition, for the inkjet ink compositions according to Comparative Examples 3-12, the inkjet ink composition was not ejected from all nozzles of the inkjet head, so it was not possible to evaluate the ejection recovery performance.

[0061]

[0062] (Examples 12-22) First, ethanol as a solvent and a viscosity modifier were mixed to produce the formulations shown in Table 3, thereby preparing the inkjet ink compositions according to Examples 12-22. The viscosity of each inkjet ink composition was set to 5 mPa·s. Furthermore, all materials used in the inkjet ink compositions conformed to the standards of pharmaceutical additives as defined by the Pharmaceuticals and Medical Devices Act, the Japanese Pharmacopoeia, or the Official Compendium of Food Additives.

[0063] Next, using the inkjet ink compositions according to each example, abrasion tests were performed based on the tablet abrasion test method (G6-5-181) in accordance with the 18th edition of the Japanese Pharmacopoeia. In the abrasion tests, each inkjet ink composition of each example was treated as a pseudo-inkjet ink. That is, a placebo tablet was prepared for each example, 30 μL of the inkjet ink composition was applied to its surface, and it was allowed to air dry to prepare a sample. One placebo tablet was prepared for each example.

[0064] The placebo tablets used were flat tablets with a mass of 200 mg and a diameter of 8 mm, each containing 96% by mass of crystalline cellulose (excipient, trade name: Ceolus® PH-102, manufactured by Asahi Kasei Corporation), 3% by mass of sodium starch glycolate (disintegrant, trade name: Primojel®, manufactured by DFE Pharma Co., Ltd.), and 1% by mass of sodium stearyl fumarate (lubricant, trade name: PRUV®, manufactured by JRS Pharma LP). These tablets were manufactured by compressing them in a tablet press under a compression pressure of 5 kN.

[0065] Next, the mass of each placebo tablet coated with the inkjet ink composition (hereinafter referred to as "tablet") was measured. Then, the tablets were placed in the drum of a wear tester, and the drum was rotated 100 times at a speed of 25 rpm. Afterward, the tablets were removed from the drum and their mass was measured again, and the mass loss rate was calculated based on the following formula. Furthermore, the mass loss rates for each tablet are shown in Table 3. Mass loss rate (%) = (Mass of tablet immediately before wear test - Mass of tablet immediately after wear test) / (Mass of tablet immediately before wear test) × 100

[0066] The abrasion tester used had a drum inner diameter of 287.0 ± 4.0 mm, a depth of 38.0 ± 2.0 mm, and a drop height of 156.0 ± 2.0 mm. The evaluation criteria for the abrasion test, as shown in Table 3, were as follows: ○: Mass loss rate of the sample is less than 1% ×: Mass loss rate of the sample is 1% or more

[0067]

[0068] (Comparative Examples 13-24) First, ethanol as a solvent and a viscosity modifier were mixed to create the formulations shown in Table 4, thereby preparing inkjet ink compositions according to Comparative Examples 13-24. The viscosity of each inkjet ink composition was set to 5 mPa·s. Furthermore, all materials used in the inkjet ink compositions conformed to the standards of pharmaceutical additives as defined by the Pharmaceuticals and Medical Devices Act, the Japanese Pharmacopoeia, or the Official Compendium of Food Additives. Next, abrasion tests were conducted on the inkjet ink compositions according to Comparative Examples 13-24 in the same manner as in Example 12, etc., to evaluate their abrasion properties. The results are shown in Table 4.

[0069]

[0070] (Examples 23-30) First, ethanol as a solvent, a viscosity modifier, Blue No. 1 as a coloring agent, and ibuprofen as an active ingredient were mixed to create the formulations shown in Table 5, thereby preparing the inkjet inks according to Examples 23-30. The viscosity of each inkjet ink was set to 5 mPa·s. Furthermore, all materials used for the inkjet inks conformed to the standards of pharmaceutical additives as defined by the Pharmaceuticals and Medical Devices Act, the Japanese Pharmacopoeia, or the Official Compendium of Food Additives.

[0071] Next, the ejection and ejection recovery properties of the inkjet inks according to Examples 23 to 30 were evaluated in the same manner as in Example 1. In addition, abrasion tests were performed on tablets coated with 17 mg of inkjet ink on each side (34 mg total) using a RICOH MH5421MF print head, and the abrasion properties were evaluated. The results are shown in Table 5.

[0072]

[0073] (Results) As can be seen from Table 1, all of the inkjet ink compositions according to Examples 1 to 11 were confirmed to have good ejection properties. In particular, the inkjet ink compositions of Examples 1 to 6, 8, 10, and 11 had good ejection properties as well as ejection recovery properties. On the other hand, the inkjet ink compositions according to Comparative Examples 3 to 12 did not have good ejection properties, as shown in Table 2, even though the mixing ratio was adjusted to have a viscosity of 5 mPa·s, similar to Example 1. From these results, it was found that even if the viscosity modifier is similar to that which is used to impart the same viscosity to the inkjet ink composition, differences in ejection performance can occur depending on the type of viscosity modifier, and that the viscosity modifiers used in Examples 1 to 11 exhibited superior ejection properties compared to the viscosity modifiers used in Comparative Examples 3 to 12.

[0074] Furthermore, as can be seen from Tables 3 and 4, the inkjet ink compositions of Examples 12 to 22 and Comparative Examples 15 to 24 were found to have a mass loss rate of less than 1%, and all were confirmed to have excellent abrasion resistance. In contrast, Comparative Examples 13 and 14 had a mass loss rate of 1% or more, and it was confirmed that their abrasion resistance was equivalent to or reduced compared to, for example, the case where water was used as the solvent.

[0075] Furthermore, as can be seen from Table 5, the inkjet inks of Examples 23 to 30, which contained ibuprofen as the active ingredient, were confirmed to have good ejection properties, ejection recovery properties, and abrasion resistance.

Claims

1. An inkjet ink for solid formulations, comprising: ethanol as a main solvent; an active ingredient soluble in ethanol; and a viscosity modifier for adjusting the viscosity of the inkjet ink for solid formulations, wherein the viscosity modifier is at least one selected from the group consisting of polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, lauromacrogol, polyvinylpyrrolidone with a K value of 25 or less, and shellac.

2. The inkjet ink for solid formulations according to claim 1, wherein the viscosity modifier is at least one selected from the group consisting of polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, polyvinylpyrrolidone with a K value of 17 or less, and shellac.

3. The inkjet ink for solid formulations according to claim 1, wherein the viscosity modifier is at least one selected from the group consisting of polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyethylene glycol sorbitan monooleate, polyethylene glycol, lauromacrogol, and polyvinylpyrrolidone with a K value of 25 or less.

4. The inkjet ink for solid formulations according to claim 1, wherein the solvent consists solely of the ethanol.

5. The inkjet ink for solid formulations according to claim 1, wherein the viscosity is in the range of 2.5 mPa·s or more and 10 mPa·s or less at 25°C.

6. A solid formulation wherein at least a portion of the surface of the tablet is provided with an active ingredient-containing layer consisting of a dried film of the inkjet ink for solid formulations described in any one of claims 1 to 5.

7. The solid formulation according to claim 6, wherein the tablet is a placebo tablet.

8. A method for producing a solid formulation, comprising: a coating step of applying the inkjet ink for solid formulations described in any one of claims 1 to 5 to at least a portion of the surface of a tablet using an inkjet method to form a coating film of the inkjet ink for solid formulations; and a drying step of drying the coating film to form an active ingredient-containing layer consisting of a dried film of the inkjet ink for solid formulations.

9. The method for producing a solid formulation according to claim 8, wherein the tablet is a placebo tablet.

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