How to shorten the disintegration time of tablets

Abstract

When manufacturing tablets using carbohydrates, tablets with maintained hardness and disintegration properties can be produced easily. [Solution] By using carbohydrate granules containing inorganic salts, it was possible to manufacture tablets that maintained hardness and disintegration properties.

Description

Technical Field

[0001] The present invention relates to a method for shortening the disintegration time of tablets and a disintegration time shortening agent for shortening the disintegration time of tablets.

Background Art

[0002] In the fields of pharmaceuticals and health foods, tablets are widely used as dosage forms. When manufacturing tablets, in order to improve workability during tableting and obtain tablets with high hardness, it is often the case that excipient particles are granulated and then tableted. However, when the hardness increases, the disintegration property in the body after ingestion may decrease, and the effective component elution from the tablets may be delayed due to remaining in the body while maintaining the dosage form for a long time. In addition, in pharmaceutical tablets, it is required to disintegrate within the specified time under the conditions defined in the disintegration test method of the Japanese Pharmacopoeia. The plain tablets of immediate-release preparations are required to disintegrate within 30 minutes in this test method. For example, hydroxypropyl cellulose is used as a binder during granulation, and tablets with high hardness are obtained, but the disintegration property is not sufficient. Examples of granulating excipient particles include, for example, JP-A-2014-156435.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] Conventionally, tablets with high hardness have not had sufficient disintegration properties. An object of the present invention is to provide a method for manufacturing tablets in which hardness and disintegration properties are maintained when manufacturing tablets using saccharides.

Means for Solving the Problems

[0005] In order to solve the aforementioned problems, the inventors conducted research and discovered that when an inorganic salt is used in combination with the manufacture of carbohydrate-containing tablets, the disintegration time of the tablets is shortened, thus completing the present invention.

[0006] In other words, the present invention is a method for shortening the disintegration time of a tablet by incorporating an inorganic salt into a tablet containing carbohydrates. Secondly, the method according to the first method, characterized in that it contains 1.5 to 3 parts by mass per 100 parts by mass of carbohydrates. Thirdly, the method according to the second method, wherein the inorganic salt is one or more selected from potassium dihydrogen phosphate, sodium chloride, potassium chloride, and sodium bicarbonate. Fourth, the method according to the first to third methods, wherein the carbohydrate is one or more selected from mannitol, erythritol, and lactose. Fifth, a method for manufacturing tablets, characterized by incorporating an inorganic salt into a tablet containing carbohydrates. Sixth, it is an inorganic salt that shortens the disintegration time of tablets containing carbohydrates.

[0007] In the present invention, a tablet containing carbohydrates is a tablet using carbohydrates as an excipient, and there are no particular restrictions on the use of components other than the excipient. Furthermore, there are no particular restrictions on the type of carbohydrate used as an excipient, and examples include erythritol, xylitol, sorbitol, mannitol, maltitol, lactitol, reduced isomaltulose, glucose, maltose, lactose, and trehalose. When considering the stability of the contained components and the hygroscopic stability of the tablet, it is preferable to use erythritol, xylitol, mannitol, maltitol, lactitol, lactose, and trehalose, preferably mannitol, erythritol, and lactose.

[0008] When using carbohydrates, it is preferable to use granulated crystalline powder. Granulation is the process of processing particles of single- or multi-component excipients into larger granules using a binder or the like. The present invention can be used regardless of the granulation method, but it is preferable to use it in wet granulation, in which water or a binder solution is dropped or sprayed onto the excipient powder to wet it, and then the moisture is dried. Examples of binders used in granulation include hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, polyvinylpyrrolidone, pregelatinized starch, and gum arabic. Various carbohydrates that can also be used as excipients can also be used as binders, such as erythritol, xylitol, sorbitol, mannitol, maltitol, lactitol, reduced isomaltulose, glucose, maltose, lactose, trehalose, dextrin, and reduced starch saccharides.

[0009] Inorganic salts are salts composed solely of inorganic substances, specifically ions (anions and cations) derived from inorganic acids and inorganic bases. Inorganic substances are compounds other than organic compounds, which have carbon atoms as their basic skeleton. By convention, allotropes of carbon, diamond, graphite, or inorganic carbonates such as carbon dioxide, carbon monoxide, sodium carbonate, and sodium bicarbonate, as well as hydrogen cyanide, cyanic acid, isocyanic acid, fulminate acid, thiocyanic acid, and salts composed of anions derived from them and cations derived from inorganic bases are classified as inorganic substances. Examples of cations constituting inorganic salts include alkali metals (lithium, sodium, potassium, etc.), alkaline earth metals (beryllium, magnesium, calcium, etc.), transition metals (iron, cobalt, nickel, etc.), zinc, aluminum, ammonium, and hydrazonium. Examples of anions include halides (fluorides, chlorides, bromides, iodides, etc.), inorganic oxoacids (carbonic acid, phosphoric acid, phosphorous acid, arsenic acid, halogenated acids, nitric acid, nitrite, sulfuric acid, sulfurous acid, boric acid, cyanic acid, isocyanic acid, fulminate, chromic acid, permanganic acid, etc.), hydrocyanic acid, thiocyanic acid, ferricyanic acid, ferrocyanic acid, and azides. Inorganic salts are formed by the combination of at least one cation and anion, and optionally, hydrogen ions or hydroxide ions. There are no particular restrictions on the inorganic salts used in this invention, but those acceptable in the field and application should be used. Furthermore, water solubility is preferable as it further improves the disintegration of the tablets. In this invention, potassium dihydrogen phosphate, potassium chloride, sodium chloride, and sodium bicarbonate are preferred. These inorganic salts can be present individually or in combination. Furthermore, the inorganic salt is used in an amount of 0.5 to 6.0 parts by mass, preferably 1.5 to 3.0 parts by mass, per 100 parts by mass of carbohydrates (including the carbohydrate used as a binder if a carbohydrate that can also be used as an excipient is used as a binder).

[0010] There are no particular restrictions on the method of incorporating inorganic salts into carbohydrates. Examples include mixing the inorganic salt in its solid state with carbohydrate granules, granulating a mixture of inorganic salt and carbohydrate powder to form granules, or using an inorganic salt solution as a binder during the production of carbohydrate granules.

[0011] There are no particular restrictions on the method of manufacturing tablets, but it is preferable to manufacture tablets by conventional methods using granules of carbohydrates and inorganic salts, mixed with ingredients according to the purpose. Examples of ingredients according to the purpose include pharmaceutical active ingredients, food ingredients, disintegrants, etc. Lubricants for tablet manufacturing may also be used.

[0012] As for active pharmaceutical ingredients, any substance that can be formulated as a tablet can be used without restriction, but examples include: antihypertensive drugs, angina pectoris drugs, bronchodilators, psychotropic drugs, anxiolytics, antidepressants, hypnotics and sedatives, antiparkinsonian drugs, allergy drugs, dental and oral drugs, cardiac stimulants, antipyretic analgesics and anti-inflammatory drugs, antihistamines, antitussives, antacids, herbal medicines, antihypertensive drugs, antibiotics, antibacterial agents, antiarrhythmic drugs, coronary vasodilators, peripheral vasodilators, and hyperlipidemia. Examples of active ingredients used in antihypertensive drugs, choleretics, hormonal drugs, gout treatment drugs, antirheumatic drugs, chemotherapy drugs, antidiabetic drugs, antiemetics, antiepileptic drugs, sympathomimetic drugs, osteoporosis drugs, anticancer drugs, immunosuppressants, urological drugs, gastrointestinal drugs, cerebral metabolism improving drugs, cerebral circulation improving drugs, respiratory stimulants, vasoconstrictors, anti-vertigo drugs, expectorants, central nervous system drugs, ulcer treatment drugs, gastric mucosal repair drugs, analgesics and antispasmodics, etc.

[0013] As for food ingredients, there are no particular restrictions as long as they are active ingredients in food supplements called nutritional supplements, or active ingredients in health functional foods such as Foods for Specified Health Uses and Foods with Nutrient Function Claims. For example, various vitamins such as ascorbic acid, folic acid, carnitine, and hesperidin; various amino acids such as glutamine, ornithine, and 5-aminolevulinic acid; various amino sugars such as glucosamine and N-acetylglucosamine; various proteins such as collagen and elastin; mucopolysaccharides such as chondroitin; and various DNA. Examples include nucleic acids, minerals, catechins, various flavonoids such as polyphenols, various carotenoids such as astaxanthin, lycopene, and lycopene, various phospholipids such as phosphatidylserine and phosphatidylcholine, various fatty acids such as EPA and DHA, ubiquinones such as coenzyme Q10, various enzymes, dietary fiber, herbs, fruits and plants and their extracts, fish oil, probiotics such as lactic acid bacteria, and yeast extracts such as cysteine ​​peptide-containing yeast extract.

[0014] If the tablet is an orally disintegrating agent, a disintegrant is used. Examples of disintegrants include starches such as corn starch, potato starch, rice starch, and pregelatinized starch, as well as crospovidone, carmellose, carmellose sodium, carmellose calcium, croscarmellose sodium, hydroxypropylcellulose, carboxymethylcellulose sodium, and carboxymethyl starch sodium.

[0015] In this invention, a reduction in disintegration time means that the disintegration time of the tablet under certain conditions is shorter than that of a system without the agent of the present invention. The disintegration time of the tablet is measured by the disintegration test method described in the 18th edition of the Japanese Pharmacopoeia. [Effects of the Invention]

[0016] By adopting the configuration of the present invention, it is possible to easily shorten the disintegration time of tablets. [Modes for carrying out the invention]

[0017] Hereinafter, embodiments of the present invention will be described, but the present invention is not limited to these embodiments at all.

[0018] In the examples and comparative examples, the following substances were used. (Carbohydrate) Mannitol (crystalline): Mannitol P / Mitsubishi Corporation Life Science Mannitol (spherical granules): Mannitol Q / Mitsubishi Corporation Life Science Lactose: Pharmatose 200M / DFE Pharma Erythritol: Erythritol fine powder / Mitsubishi Chemical (Inorganic salt) Sodium chloride / Fujifilm Wako Pure Chemical Industries Potassium chloride / Fujifilm Wako Pure Chemical Industries Sodium hydrogen carbonate / Fujifilm Wako Pure Chemical Industries Potassium dihydrogen phosphate / Fujifilm Wako Pure Chemical Industries (Binder) Hydroxypropyl cellulose: HPC-SSL / Nippon Soda (Lubricant) Magnesium stearate / Fujifilm Wako Pure Chemical Industries (Disintegrant) Crospovidone: Kollidon CL-F / BASF

[0019] (Manufacture of granules) The granules, which are the raw materials of the tablets, were manufactured using a fluidized bed granulation dryer (model: FLO-1 / Freund Industry).

[0020] (Manufacture of tablets) The tablets used in the examples and comparative examples were manufactured using a single-shot tableting machine (NS-T100 / Special Measurement), with the dosage form: Φ8 mm, flat, tablet weight: 180 mg, and forming load: 8 kN.

[0021] (Measurement of tablet hardness) The hardness of the tablets used in the examples and comparative examples was measured using a tablet altimeter (tablet breaking strength measuring instrument TH-303S / Toyama Sangyo) (n = 5).

[0022] (Collapse test) In the examples and comparative examples, the disintegration test for tablets was performed using a disintegration tester (NT-200 / Toyama Sangyo) and measured according to the method described in the 18th edition of the Japanese Pharmacopoeia (test solution: water, auxiliary disc: not used).

[0023] (Carbohydrate granules) Carbohydrate granules were granulated using the raw material powder and binder solution according to the formulation (parts by mass) shown in Table 1.

[0024] [Table 1] [Examples]

[0025] (Effects of various inorganic salts) Tablets were manufactured using the tablet formulations (parts by mass) shown in Table 2, and their disintegration time was measured. The results are shown in Table 2. Compared to tablets made using comparative preparation 1, which is a granule that does not contain inorganic salts, tablets manufactured using preparations 1 to 4, which contain various inorganic salts, showed a significant reduction in disintegration time.

[0026] [Table 2]

[0027] (Method of compounding inorganic salts) Tablets were manufactured using the tablet formulations (parts by mass) shown in Table 3, and their disintegration time was measured. The results are shown in Table 3. Compared to tablets made using comparative preparation 2, which is a granule that does not contain inorganic salts, tablets made using preparation 5, preparation 6, which uses inorganic salts as a binder solution, and preparation 7, which uses inorganic salts as both a raw material and a binder solution during the production of carbohydrate granules, showed a significant reduction in disintegration time.

[0028] [Table 3]

[0029] (Types of carbohydrates) Tablets were manufactured using the tablet formulations (parts by mass) shown in Table 4, and their disintegration time was measured. The results are shown in Table 4. Mannitol (Example 8, Comparative Example 3), lactose (Examples 9, 10, Comparative Example 4), and erythritol (Examples 11, 12, Comparative Example 5) were used as carbohydrates. In all systems, tablets produced using preparations containing various inorganic salts showed a significant reduction in disintegration time compared to tablets produced using comparative preparations that did not contain inorganic salts.

[0030] [Table 4]

[0031] (Disintegrant) Tablets were manufactured using the tablet formulations (parts by mass) shown in Table 5, and their disintegration time was measured. The results are shown in Table 5. In all three systems—those without a disintegrant (Example 13, Comparative Example 6), those containing 1% (Example 14, Comparative Example 7), and those containing 3% (Example 15, Comparative Example 6)—tablets manufactured using preparations containing various inorganic salts showed a significant reduction in disintegration time compared to tablets manufactured using comparative preparations without inorganic salts.

[0032] [Table 5] [Industrial applicability]

[0033] This invention makes it possible to obtain tablets with superior disintegration properties compared to conventional tablets.

Claims

1. A method for shortening the disintegration time of tablets by adding inorganic salts to tablets containing carbohydrates.

2. The method according to claim 1, characterized in that it contains 1.5 to 3 parts by mass of inorganic salt per 100 parts by mass of carbohydrates.

3. The method according to claim 2, wherein the inorganic salt is one or more selected from potassium dihydrogen phosphate, sodium chloride, potassium chloride, and sodium bicarbonate.

4. The method according to claims 1 to 3, wherein the carbohydrate is one or more selected from mannitol, erythritol, and lactose.

5. A method for producing tablets, characterized by incorporating an inorganic salt into a tablet containing carbohydrates.

6. An inorganic salt-based agent that shortens the disintegration time of tablets containing carbohydrates.

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