Band seal, band sealing solution, method for sealing hard capsule, and hard capsule product

Abstract

The present invention addresses the problem of improving defects of shellac-containing band seals and providing a band seal having higher strength.　The problem is solved by a band sealing solution for sealing a hard capsule, the band sealing solution comprising a resin, a thickener, and a hydrophilic solvent containing an alcohol having 1 to 4 carbon atoms and water.

Description

Band seal, band seal liquid, hard capsule sealing method, and hard capsule product

[0001] This specification relates to a band seal for sealing hard capsules, a band seal liquid for sealing hard capsules, a method for sealing hard capsules, and a hard capsule product.

[0002] US Pat. No. 5,699,499 discloses that DRCAPS™ acid-resistant capsules were sealed with an ethanol solution of shellac.

[0003] International Publication No. 2013 / 175303

[0004] The inventors have found that although shellac provides acid resistance to band seals, a high shellac content reduces mechanical strength and makes the band seals more susceptible to cracking. The present invention aims to improve these drawbacks of band seals and provide band seals with higher strength.

[0005] The present invention may include the following embodiments. Item 1. A band seal for sealing hard capsules, comprising a resin and a thickener. Item 2. The band seal of Item 1, wherein the resin is a naturally derived resin. Item 3. The band seal of Item 1, wherein the resin is shellac or rosin. Item 4. The band seal of Item 1, wherein the thickener is a cellulose compound. Item 5. The band seal of Item 4, wherein the cellulose compound is at least one nonionic water-soluble cellulose compound selected from the group consisting of hydroxypropyl methylcellulose and hydroxypropyl cellulose. Item 6. The band seal of Item 1, wherein the resin content in the band seal is 35 to 98% by mass, when the total content of all components in the band seal excluding residual hydrophilic solvent components is taken as 100% by mass. Item 7. The band seal of Item 1, wherein the thickener content in the band seal is 2 to 65% by mass, when the total content of all components in the band seal excluding residual hydrophilic solvent components is taken as 100% by mass. Item 8. Item 9. A band sealing liquid for sealing hard capsules, comprising a resin, a thickener, and a hydrophilic solvent containing an alcohol having 1 to 4 carbon atoms and water. Item 9. The band sealing liquid according to Item 8, wherein the resin is a naturally occurring resin. Item 10. The band sealing liquid according to Item 8, wherein the resin is shellac or rosin. Item 11. The band sealing liquid according to Item 8, wherein the thickener is a cellulose compound. Item 12. The band sealing liquid according to Item 11, wherein, when the band sealing liquid contains a cellulose compound, the cellulose compound is at least one nonionic water-soluble cellulose compound selected from the group consisting of hydroxypropyl methylcellulose and hydroxypropyl cellulose. Item 13. The band sealing liquid according to Item 8, wherein the total content of components excluding the hydrophilic solvent in the band sealing liquid is 10 to 45% by mass, when the band sealing liquid is 100% by mass. Item 14. The band sealing liquid according to Item 8, wherein the alcohol having 1 to 4 carbon atoms is ethanol or isopropyl alcohol. Item 15. Item 9. A method for sealing a hard capsule, the method comprising: filling a hard capsule with a filler, and then applying the band sealing liquid according to Item 8 to a fitting portion between a cap portion and a body portion of the hard capsule; and drying the applied band sealing liquid.Item 16. The method according to Item 15, wherein 10 mg to 50 mg of band seal liquid is applied to one hard capsule. Item 17. A hard capsule product, the hard capsule product being filled with a filler and having the band seal according to Item 1 at a fitting portion between a cap portion and a body portion of the hard capsule.

[0006] A stronger band seal can be provided.

[0007] 1. Band Sealing Liquid One embodiment of the present invention relates to a band sealing liquid for sealing hard capsules (hereinafter, sometimes simply referred to as "capsules").

[0008] In this specification, a "hard capsule" refers to a type of capsule in which the capsule shell is first produced and then the fill material is filled into the produced capsule shell. Typically, it consists of a cap and a body, and is also called a hard capsule or two-piece capsule. The "hard capsule" of the present invention does not include soft capsules, which are produced by filling the contents between two films and gluing the films together, seamless capsules, which are produced by dropping the contents together with a shell solution into a coagulation liquid, or microcapsules, which are prepared by incorporating an active ingredient inside by precipitating or emulsifying a base material. The band seal liquid contains a resin, a thickener, and a hydrophilic solvent containing a C1-C4 alcohol and water.

[0009] The resin may include naturally occurring resins and synthetic resins, such as shellac, rosin, and derivatives thereof.

[0010] Shellac is a resinous substance refined from the secretions (seedlac) of scale insects such as the lac scale insect, Laccifer lacca Kerr (Coccidae). Shellac may include white shellac obtained by refining, bleaching, and dewaxing seedlac, which has a wax content of 0.2% or less; wax-containing white shellac obtained by refining and bleaching seedlac, which has a wax content of more than 0.2% and less than 5.5%; unbleached dewaxed shellac obtained by refining and dewaxing seedlac, which has a wax content of 0.2% or less; and unbleached wax-containing shellac obtained by refining seedlac, which has a wax content of more than 0.2% and less than 5.5%. The preferred shellac is white shellac with a wax content of 0.2% or less.

[0011] Rosin is a resinous substance contained in the sap of plants of the pine family. Examples of rosin include gum rosin, wood rosin, and tall oil rosin. Gum rosin is preferred as the rosin. Rosin may also include rosin derivatives such as ester gums such as rosin esters and hydrogenated rosin esters; and pencels such as rosin esters and polymerized rosin esters.

[0012] Synthetic resin refers to a resin that is artificially produced using fossil fuels such as petroleum as a starting material.

[0013] The resin content in the band seal liquid is 8 to 40% by mass, preferably 10 to 38% by mass, when the band seal liquid is taken as 100% by mass.

[0014] The thickener may be a cellulose compound or the like.

[0015] The cellulose compound is not limited as long as it has a cellulose skeleton. A preferred cellulose compound is a nonionic water-soluble cellulose compound. A preferred nonionic water-soluble cellulose compound is at least one selected from the group consisting of hydroxypropyl methylcellulose and hydroxypropyl cellulose. Hydroxypropyl methylcellulose may be referred to as HPMC or hypromellose in this specification.

[0016] The hydroxypropyl methylcellulose can be, for example, hydroxypropyl methylcellulose as defined in the Japanese Pharmacopoeia. For example, the degree of substitution of methoxy groups in hydroxypropyl methylcellulose is preferably 16.5 to 30.0% by mass, more preferably 19.0 to 30.0% by mass, and particularly preferably 28.0 to 30.0% by mass, and the degree of substitution of hydroxypropoxy groups is preferably 4.0 to 32.0% by mass, more preferably 4.0 to 12.0% by mass, and particularly preferably 7.0 to 12.0% by mass. These degrees of substitution can be measured according to the method for measuring the degree of substitution of hydroxypropyl methylcellulose and methylcellulose as defined in the 17th Pharmacopoeia.

[0017] Among these, hydroxypropyl methylcellulose represented by the following formula is the most suitable cellulose compound because of its excellent film-forming properties and mechanical strength under low moisture conditions.

[0018] (wherein n and m represent any integers).

[0019] The hydroxypropyl methylcellulose used in the present invention includes hypromellose of substitution grades (types) 2910, 2906, and 2208 as defined in Pharmacopoeia No. 17. Of these, substitution types 2910 and 2906 are more preferred.

[0020] The hydroxypropyl methylcellulose of the present invention also includes hypromellose having the following molecular weight, which is approved for use as a food additive in Japan: <Molecular weight> Unsubstituted structural unit: 162.14 Substituted structural unit: about 180 (degree of substitution 1.19), about 210 (degree of substitution 2.37) Polymer: about 13,000 (n = about 70) to about 200,000 (n = about 1000).

[0021] Examples of commercially available hydroxypropyl methylcellulose include the Japanese Pharmacopoeia METOLOSE (registered trademark) series and food additive METOLOSE series from Shin-Etsu Chemical Co., Ltd.; AnyCoat-C or AnyAddy (registered trademark) series from Lotte (formerly Samsung) Fine Chemicals Co., Ltd.; the METHOCEL (registered trademark) series from Dupont Corporation; and the Benecel (registered trademark) series from Ashland Co., Ltd. Hydroxypropyl cellulose may be referred to as HPC in this specification.

[0022] Hydroxypropyl cellulose also includes hydroxypropyl cellulose having a molecular weight of about 30,000 (n = about 100) to about 150,000 (n = about 2,500), which is approved for use as a food additive or pharmaceutical additive in Japan (16th JECFA. Hydroxypropyl Cellulose (Revised Specification). FNP52 Add 12, 2004). Commercially available hydroxypropyl cellulose includes the Klucel (registered trademark) series from Ashland and the NISSO HPC series from Nippon Soda Co., Ltd. For example, the NISSO HPC series includes HPC SSL (molecular weight 40,000), HPC SL (molecular weight 100,000), and HPC L (molecular weight 140,000).

[0023] The content of the thickener in the band seal liquid is 1 to 18% by mass, preferably 2 to 15% by mass, when the band seal liquid is taken as 100% by mass.

[0024] Examples of the alcohol having 1 to 4 carbon atoms include ethanol, methanol, n-propanol, 2-propanol, n-butyl alcohol, isobutyl alcohol, sec-butyl alcohol, and tert-butyl alcohol, with ethanol being preferred.

[0025] The content of the alcohol having 1 to 4 carbon atoms in the band seal liquid is 50 to 80% by mass, preferably 54 to 75% by mass, when the band seal liquid is taken as 100% by mass. The content of water in the band seal liquid is the remainder after subtracting the total content of components other than water when the band seal liquid is taken as 100% by mass.

[0026] The content of water relative to the content of the alcohol having 1 to 4 carbon atoms is, in mass ratio, 3 to 15 parts by mass of water for 50 to 82 parts by mass of the alcohol having 1 to 4 carbon atoms, preferably 6 to 9 parts by mass of water for 55 to 80 parts by mass of the alcohol having 1 to 4 carbon atoms.

[0027] The band sealing liquid may contain additives such as a dye, a plasticizer, a surfactant, etc. in addition to the resin, the thickener, and the hydrophilic solvent. Examples of plasticizers include dioctyl adipate, adipic acid polyester, epoxidized soybean oil, epoxy hexahydrophthalic acid diester, kaolin, triethyl citrate, glycerin, sesame oil, a dimethylpolysiloxane-silicon dioxide mixture, D-sorbitol, medium-chain fatty acid triglyceride, corn starch-derived sugar alcohol liquid, triacetin, concentrated glycerin, castor oil, phytosterol, diethyl phthalate, dioctyl phthalate, dibutyl phthalate, butylphthalyl butyl glycolate, propylene glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, Macrogol 1500, Macrogol 400, Macrogol 4000, Macrogol 600, Macrogol 6000, isopropyl myristate, a cottonseed oil-soybean oil mixture, glycerin monostearate, and isopropyl linoleate.

[0028] The content of the plasticizer in the band seal liquid is in the range of 0 to 5% by mass, preferably 1 to 3% by mass, when the band seal liquid is taken as 100% by mass.

[0029] Examples of surfactants to be added to the band sealing liquid include polysorbate 80, sodium lauryl sulfate, glycerin fatty acid esters, sucrose fatty acid esters, and sorbitan fatty acid esters. Preferably, the band sealing liquid does not contain sorbitan fatty acid esters or glycerin fatty acid esters. More preferably, the band sealing liquid does not contain polysorbate 80, sodium lauryl sulfate, glycerin fatty acid esters, sucrose fatty acid esters, or sorbitan fatty acid esters. More preferably, the band sealing liquid does not contain a surfactant.

[0030] The content of the surfactant in the band seal liquid is in the range of 0% by mass to less than 0.5% by mass, preferably in the range of 0% by mass to 0.3% by mass, and more preferably in the range of 0% by mass to 0.1% by mass, when the band seal liquid is taken as 100% by mass.

[0031] The content of the dye in the band seal liquid is in the range of 0% by mass to 0.5% by mass, preferably in the range of 0% by mass to 0.1% by mass, more preferably 0% by mass, when the band seal liquid is taken as 100% by mass. More preferably, the lower limit is greater than 0% by mass.

[0032] The band seal liquid can be prepared by the following method: (1) A resin and a thickener are added to a hydrophilic solvent, and the added materials are dissolved by stirring with a stirrer or the like at about 20°C to 30°C, preferably about 25°C, so as not to form lumps. (2) When a dye, surfactant, plasticizer, or the like is added, the materials are added to the solution of (1) above, and the added materials are dispersed or dissolved by stirring with a stirrer or the like at about 20°C to 30°C, preferably about 25°C, so as not to form lumps, until the added materials are uniform.

[0033] The total content of components (solid components) excluding the hydrophilic solvent in the band seal liquid is 10 to 45% by mass when the band seal liquid is taken as 100% by mass.

[0034] The shear viscosity of the band seal liquid is about 200 mPa·s to 1,500 mPa·s, and preferably about 300 mPa·s to 1,000 mPa·s.

[0035] The shear viscosity can be measured using, for example, a rheometer (MCR102) manufactured by Anton Paar Japan Co., Ltd. For the measurement, for example, a jig (CC27) or a concentric cylindrical tube (CC27 / T200 / SS) can be used. The shear viscosity value can be, for example, the value at a temperature of 25°C and a shear rate of 1 sec-1.

[0036] 2. Method for Sealing Hard Capsules and Band Sealing One embodiment of the present invention relates to a method for sealing hard capsules (hereinafter, sometimes referred to as a "sealing method").

[0037] The sealing method involves filling the hard capsule with the fill material, applying the band seal liquid described in 1. above to the mating portion between the cap and body of the hard capsule, and then drying the applied band seal liquid. Generally, the fill material is filled into the body.

[0038] Specifically, a band seal liquid at approximately 20°C to 30°C, preferably approximately 25°C, is applied to the surfaces of the body and cap portions in a generally uniform width, centered around the edge of the fitted cap portion, in the circumferential direction of the body and cap portions, one or more times, preferably once or twice. The applied band seal liquid is then dried to form a band seal and seal the fitted portion. The "uniform width" varies depending on the capsule size, but is generally approximately 2 mm to 3 mm. Drying can be carried out in a working atmosphere for approximately 3 minutes to 24 hours, preferably 5 to 10 minutes. The working atmosphere is, for example, room temperature (approximately 20°C to 28°C) and humidity of approximately 30% to 50% RH.

[0039] The capsules after fitting can be sealed using a known capsule filling and sealing machine, for example, the above-mentioned capsule filling and sealing machine or capsule sealing machine (model name: HICAPSEAL 40 / 100, manufactured by Qualicaps Co., Ltd.).

[0040] The amount of band sealing liquid to be applied is not limited as long as it is an amount that can exert a band sealing effect on the capsule. For example, it is preferable to use about 10 mg to 50 mg for one No. 0 capsule. For capsules of sizes other than No. 0 capsules, the amount can be changed depending on the capsule size.

[0041] The presence or absence of the "band seal effect" can be evaluated, for example, by the method described in WO 08 / 099835. However, although polyethylene glycol is used as the filler in WO 08 / 099835, vegetable oil (e.g., soybean oil, rice oil, canola oil, sesame oil, olive oil, etc.) may be used as the filler instead.

[0042] The band seal formed at the fitting portion of the hard capsule is composed of residues left after the hydrophilic solvent has evaporated. The residues include resins, thickeners, additives, etc., and may contain approximately 0% to 10% residual moisture.

[0043] The resin content in the band seal is 35 to 98% by mass, preferably 40 to 95% by mass, when the total content of the components excluding the hydrophilic solvent component remaining in the band seal is taken as 100% by mass.

[0044] The content of the thickener in the band seal is 2 to 65% by mass, preferably 5 to 60% by mass, when the total content of the components excluding the hydrophilic solvent component remaining in the band seal is taken as 100% by mass.

[0045] The content of the plasticizer in the band seal is in the range of 0% by mass to 50% by mass, and preferably in the range of 10% by mass to 30% by mass, when the total content of the components excluding the hydrophilic solvent component remaining in the band seal is taken as 100% by mass.

[0046] Examples of surfactants to be added to the band seal liquid include polysorbate 80, sodium lauryl sulfate, glycerin fatty acid esters, sucrose fatty acid esters, and sorbitan fatty acid esters. Preferably, the band seal does not contain sorbitan fatty acid esters or glycerin fatty acid esters. More preferably, the band seal does not contain polysorbate 80, sodium lauryl sulfate, glycerin fatty acid esters, sucrose fatty acid esters, or sorbitan fatty acid esters. More preferably, the band seal does not contain a surfactant.

[0047] The content of the surfactant in the band seal is in the range of 0% by mass to less than 5% by mass, preferably in the range of 0% by mass to 3% by mass, and more preferably in the range of 0% by mass to 1% by mass, when the total content of the components excluding the hydrophilic solvent component remaining in the band seal is taken as 100% by mass.

[0048] The content of the dye in the band seal liquid is in the range of 0% by mass to 5% by mass, preferably in the range of 0% by mass to 1% by mass, and more preferably 0% by mass, when the total content of the components excluding the hydrophilic solvent component remaining in the band seal is taken as 100% by mass.

[0049] The residual moisture is calculated as the moisture content shown in the following formula.

[0050] The hard capsules sealed by band sealing are not particularly limited. Examples include hydroxypropyl methylcellulose capsules, gelatin capsules, pullulan capsules, and starch capsules. Hard capsules sealed by band sealing preferably have a certain level of acid resistance. Acid resistance means a property that satisfies at least the following condition (i):

[0051] (i) In the dissolution test described in the 18th Edition of the Japanese Pharmacopoeia (hereinafter sometimes simply referred to as the "18th Pharmacopoeia"), the dissolution rate of the contents when a test subject is immersed in the first fluid at 37°C ± 0.5°C for 2 hours is 40% or less, preferably 30% or less. The pH of the first fluid is approximately 1.2. The first fluid can be prepared, for example, by adding 7.0 ml of hydrochloric acid and water to 2.0 g of sodium chloride to make a total volume of 1000 ml.

[0052] Acid resistance preferably satisfies the above condition (i) as well as the following condition (ii). (ii) In the dissolution test, the contents are dissolved when the test subject is immersed in the second liquid at 37°C ± 0.5°C. The pH of the second liquid is approximately 6.8. The second liquid can be prepared, for example, by dissolving 3.40 g of potassium dihydrogen phosphate and 3.55 g of anhydrous disodium hydrogen phosphate in water, and adding 1 volume of water to 1000 mL of phosphate buffer. There is no limit to the time for measuring the dissolution rate of the contents in the second liquid. For example, if relatively rapid dissolution is required in the upper intestinal tract (small intestine) after reaching the intestine, the dissolution rate 45 minutes after immersion of the test subject in the second liquid is 75% or more, preferably 80%, and more preferably 90% or more. Furthermore, for example, the dissolution rate 1 hour after immersion of the test subject in the second liquid is 75% or more, preferably 80%, and more preferably 90% or more.

[0053] On the other hand, in a preparation intended to deliver a drug to the lower intestinal tract by suppressing dissolution until the drug reaches the lower intestinal tract (such as the large intestine), it is preferable that the dissolution rate reaches 75% or more after 60 minutes or more has elapsed since the test subject was immersed in the second liquid. Note that, to prevent the drug from being excreted intact from the body, it is preferable that 75% or more is dissolved within 12 hours.

[0054] It is preferable that the hard capsule sealed with a band seal have a predetermined strength. The strength can be measured by the following method. A sample (a hard capsule filled with vegetable oil) is placed in a desiccator in an atmosphere containing saturated potassium carbonate salt and maintained at a constant humidity, and the desiccator is sealed and conditioned at 25°C for one week. Note that an atmosphere with a relative humidity of approximately 43% can be created in the presence of a saturated potassium carbonate aqueous solution. Pressure is applied to the test sample by the following method, and the pressurized test sample is placed on paper (such as Kimtowel) to check for leakage of the filled vegetable oil.

[0055] For the compression test, for example, an Autograph Model: EZ-LX (Shimadzu Corporation) can be used. For example, a flat disk can be used as a jig. The compression speed can be 50 mm / min, and the pressure can be, for example, 10 N or 15 N.

[0056] 3. Hard Capsule Product One embodiment of the present invention relates to a hard capsule product, which includes a cap portion and a body portion of a hard capsule filled with a filler and a band seal at the mating portion.

[0057] The band seal liquid for forming the band seal is as described in 1. above. The method for forming the band seal and the components of the band seal are as described in 2. above. The filler may be a liquid, semi-solid, or powder. The powder is preferably a fine powder.

[0058] The liquid is a liquid that is used pharmaceutical or edible. The liquid is intended to have liquid-like physical properties at room temperature (approximately 20°C to 28°C). Examples of liquids include polyethylene glycol, fatty oil, glycerin, surfactants, etc. Polyethylene glycol, for example, has a molecular weight of approximately 200 to 600 (PEG 200-600). The molecular weight is specified according to the manufacturer's instructions. The fatty oil is, for example, vegetable oil.

[0059] A semi-solid is a substance with a melting point of about 30°C to 50°C. The semi-solid substance is a substance that is pharmaceutically or edibly acceptable. For example, polyethylene glycol (PEG1000) with a molecular weight of about 1000 is used. The filling may contain a pharmaceutically acceptable active ingredient. The filling may also contain an ingredient that is edibly acceptable.

[0060] The present invention will be described in more detail below with reference to examples. However, the present invention should not be construed as being limited to these examples. I. Materials Used The materials used in the examples and comparative examples are as follows. 1. Shellac Dried transparent white shellac manufactured by Nippon Shellac Kogyo Co., Ltd. was used. 2. Cellulose Compounds HPMC used were HPMC2910 (TC-5E: viscosity grade 3), HPMC2910 (TC-5M: viscosity grade 4.5), HPMC2910 (TC-5R: viscosity grade 6), HPMC2910 (TC-5S: viscosity grade 15), HPMC2910 (60SH-50: viscosity grade 50), and HPMC2906 (65SH-50: viscosity grade 50) from the Metrose series manufactured by Shin-Etsu Chemical Co., Ltd. For HPC, HPC SSL (molecular weight 40,000), HPC SL (molecular weight 100,000), and HPC L (molecular weight 140,000) from the NISSO HPC series manufactured by Nippon Soda Co., Ltd. were used. 3. Rosin For rosin, rosin manufactured by Fujifilm Wako Pure Chemical Corporation was used. 4. Hard capsule For hard capsule, HPMC capsule was used. The capsule size was No. 1.

[0061] II. Preparation of Band Seal Liquid The band seal liquids of the examples were prepared using the ingredients in the amounts shown in Tables 2 and 3, according to the following procedure.

[0062]

[0063]

[0064] The materials were added to a solvent (a mixed solvent of water and ethanol, or a mixed solvent of water and isopropyl alcohol) and stirred with a stirrer at room temperature until the added materials were dissolved without forming lumps. The band seal liquid of the comparative example was prepared using the materials in the amounts shown in Tables 2 and 3, and was carried out as follows: (1) Shellac (and, if necessary, sorbitan fatty acid ester or glycerin fatty acid ester) was added to a mixed solvent of water and ethanol, and stirred with a stirrer at room temperature until the added materials were dissolved without forming lumps. (2) Rosin was added to the shellac liquid prepared in (1) above, and stirred with a stirrer at room temperature until the rosin was uniform.

[0065] III. Sealing of Hard Capsules Hard capsules for dissolution testing were prepared as follows. A powder mixture of lactose, acetaminophen, and EXPLOTAB in a ratio of 70:20:10 was used as the fill material. 300 mg of the fill material was filled into the capsule, and the cap and body were fitted together. The prepared band seal liquid was repeatedly applied circumferentially across the fitting in a 2 mm width until the specified mass was reached. After application, the capsules were air-dried for at least 15 minutes, and the entire capsule was weighed to measure the mass of the applied band seal liquid. The room temperature during the experiment was 23-27°C, and the relative humidity was 45-65%.

[0066] Hard capsules for measuring the cracking rate were prepared as follows: 400 μL of soybean oil was filled into the hard capsules, and the capsules were sealed with a band seal in the same manner as the capsules for the dissolution test.

[0067] IV. Evaluation Method 1. Measurement of Shear Viscosity of Band Seal Liquid The shear viscosity of the band seal liquid was measured using a rheometer (MCR102) manufactured by Anton Paar Japan Co., Ltd. A jig (CC27) and a concentric cylindrical tube (CC27 / T200 / SS) were used for the measurement. The shear viscosity was measured at a temperature of 25°C and a shear rate of 1 sec-1.

[0068] 2. Capsule Dissolution Test In principle, the dissolution test procedures in the 18th edition of the Japanese Pharmacopoeia were applied. However, since the Japanese Pharmacopoeia does not specify the solubility of empty hard capsules themselves, the capsules were filled with the above-mentioned filling materials, sealed with a band seal, and the dissolution of the filling materials was evaluated to evaluate the solubility (dissolution characteristics) of the capsules themselves. The test samples were tested according to the dissolution test method specified in the Japanese Pharmacopoeia (18th Pharmacopoeia, 6.10-1.2 paddle method (paddle rotation speed: 50 rpm) and using a sinker corresponding to Figure 6.10-2a), and the time course of the dissolution rate of acetaminophen was measured. A Distek Bath-type dissolution tester, Model 2100 or 2500, was used for the dissolution test. The same volume of acetaminophen was separately dissolved in the solution in the dissolution tester bath. The absorbance at 244 nm when the entire volume was dissolved was set at 100%, and the dissolution rate was calculated from the absorbance at 244 nm of the solution in the dissolution tester bath, which increased as acetaminophen was dissolved from the capsules. The n value was set at 3 or 6, and the average value was used to calculate the dissolution rate. Note that 900 mL of the following first solution was used as the buffer solution. The temperature of the solution in the bath was 37±2°C in both cases. First solution: 2.0 g of sodium chloride was dissolved with 7.0 mL of hydrochloric acid and water, and the volume was adjusted to 1000 mL (pH approximately 1.2).

[0069] 3. Capsule Crack Test The prepared capsules were placed in a desiccator conditioned with saturated potassium carbonate, sealed, and conditioned at 25°C for one week. Under these conditions, a relative humidity of 43% could be achieved. A compression test was then conducted using the conditioned capsules as test samples. An autograph Model EZ-LX (Shimadzu Corporation) was used for the compression test. A flat disk-type tool was used, with a compression speed of 50 mm / min and pressures of 10 N and 15 N. Leakage from the compressed test samples was confirmed by placing the test samples on paper (e.g., Kimtowel) and observing whether the filled vegetable oil adhered to the paper. The n values ​​for the test samples are shown in Tables 4 and 5.

[0070] V. Results Tables 4 and 5 show the components of the band seal excluding the solvent component, and the results of the dissolution test and crack test for the HPMC capsules sealed by applying each band seal liquid.

[0071]

[0072]

[0073] Comparative Example 1 is the band seal described in Patent Document 1. Comparative Example 2 is a formulation similar to Comparative Example 1, but omitting the surfactants sorbitan fatty acid ester and glycerin fatty acid ester. Comparative Example 3 is a band seal containing only HPMC. Comparative Example 4 is a band seal containing only shellac. Shellac alone provided insufficient strength when compressed. When evaluated based on Comparative Example 1, Examples 1 to 10 and Examples 12 to 17 had lower cracking rates at a compression of 10 N. Furthermore, as shown in Example 9, strength was maintained even when shellac was replaced with rosin. Examples 1 to 17 had lower cracking rates at a compression of 15 N compared to Comparative Example 1. Compression of approximately 15 N may occur during capsule transport or removal from blister packaging. Therefore, the results of the cracking test demonstrate that the band seal of the present invention can ensure sufficient strength even under such conditions.

[0074] In Examples 1 to 8 and Examples 11 to 17, the elution rate was below 40% and the acid resistance was also good.

[0075] Comparative Example 2 differs from Comparative Example 1 in that it does not contain a sorbitan fatty acid ester or a glycerin fatty acid ester. Since the cracking rate at a compression of 10 N in Comparative Example 2 was higher than that in Comparative Example 1, it was considered that the strength of Comparative Example 1 depended on the sorbitan fatty acid ester and the glycerin fatty acid ester.

[0076] From the above, it was shown that the brittleness of the band seal can be improved by adding a thickener to the band seal.

Claims

1. A band seal for sealing hard capsules, comprising a resin and a thickener.

2. The band seal according to claim 1, wherein the resin is a naturally occurring resin.

3. The band seal according to claim 1, wherein the resin is shellac or rosin.

4. The band seal according to claim 1, wherein the thickening agent is a cellulose compound.

5. The band seal according to claim 4, wherein the cellulose compound is at least one non-ionic water-soluble cellulose compound selected from the group consisting of hydroxypropyl methylcellulose and hydroxypropyl cellulose.

6. The band seal according to claim 1, wherein the resin content in the band seal is 35 to 98% by mass when the total content of the components excluding the residual hydrophilic solvent component in the band seal is taken as 100% by mass.

7. The band seal according to claim 1, wherein the content of the thickener in the band seal is 2 to 65% by mass when the total content of the components excluding the residual hydrophilic solvent component in the band seal is taken as 100% by mass.

8. A band sealing liquid for sealing hard capsules, comprising: a resin; a thickener; and a hydrophilic solvent comprising an alcohol having 1 to 4 carbon atoms and water.

9. The band seal liquid according to claim 8, wherein the resin is a naturally occurring resin.

10. The band sealing liquid according to claim 8, wherein the resin is shellac or rosin.

11. The band seal liquid according to claim 8, wherein the thickener is a cellulose compound.

12. The band seal liquid according to claim 11, wherein when the band seal liquid contains a cellulose compound, the cellulose compound is at least one nonionic water-soluble cellulose compound selected from the group consisting of hydroxypropyl methylcellulose and hydroxypropyl cellulose.

13. The band seal liquid according to claim 8, wherein the total content of the components excluding the hydrophilic solvent in the band seal liquid is 10 to 45 mass % when the band seal liquid is taken as 100 mass %.

14. The band sealing liquid according to claim 8, wherein the alcohol having 1 to 4 carbon atoms is ethanol or isopropyl alcohol.

15. A method for sealing a hard capsule, comprising: applying the band seal liquid according to claim 8 to a mating portion between a cap portion and a body portion of the hard capsule after the hard capsule has been filled with a filling material; and drying the applied band seal liquid.

16. The method according to claim 15, wherein 10 mg to 50 mg of band sealing liquid is applied to one hard capsule.

17. A hard capsule product, comprising the band seal according to claim 1 at a fitting portion between a cap portion and a body portion of a hard capsule filled with a filler.

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