Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
  • A61K47/38—Cellulose; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate

Definitions

• 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.
• Patent document 1 discloses that DRCAPS (trademark) acid-resistant capsules are sealed with an ethanol solution of shellac.
• An object of the present invention is to improve such drawbacks of band seals and provide a band seal having higher strength.
• the present invention may include the following embodiments.
• Item 1. A band seal for sealing a hard capsule, comprising a resin and a thickener.
• Item 2. The band seal according to item 1, wherein the resin is a naturally occurring resin.
• Item 3. The band seal according to item 1, wherein the resin is shellac or rosin.
• Item 4. The band seal according to Item 1, wherein the thickener is a cellulose compound.
• Item 5 The band seal according to 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.
• the band seal according to item 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.
• Item 7. The band seal according to item 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.
• Item 8. A resin, a thickener, a hydrophilic solvent containing an alcohol having 1 to 4 carbon atoms and water, A band sealing liquid for sealing hard capsules, comprising: Item 9. The band seal liquid according to Item 8, wherein the resin is a naturally occurring resin. Item 10.
• Item 11 The band seal liquid according to Item 8, wherein the thickener is a cellulose compound.
• Item 12 The band seal liquid according to Item 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.
• Item 13 The band seal liquid according to item 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 100 mass %.
• the band sealing liquid according to Item 8 wherein the alcohol having 1 to 4 carbon atoms is ethanol or isopropyl alcohol.
• Item 15 A method for sealing a hard capsule, comprising: applying the band seal liquid according to Item 8 to a fitting portion between a cap portion and a body portion of the hard capsule after filling the hard capsule with a filling material; and drying the applied band seal liquid.
• Item 16 The method according to Item 15, wherein 10 mg to 50 mg of the band sealing liquid is applied to one hard capsule.
• Item 17. A hard capsule product, the hard capsule product being provided with the band seal according to Item 1 at a fitting portion between a cap portion and a body portion of a hard capsule filled with a filling material. The hard capsule product.
• band Sealing Liquid One embodiment of the present invention relates to a band sealing liquid for sealing a hard capsule (hereinafter, may be simply referred to as a "capsule").
• the term "hard capsule” refers to a type of capsule in which the capsule shell is produced first and then the filler is filled into the produced capsule shell. Usually, it is composed of a cap part and a body part, and is also called a hard capsule or a two-piece capsule.
• the "hard capsule” of the present invention does not include a soft capsule produced by filling the contents between two films and gluing the films together, a seamless capsule produced by dropping the contents together with a film solution into a coagulating liquid, and a microcapsule prepared by incorporating an active ingredient inside the capsule through precipitation or emulsification of a base material.
• the band seal liquid contains a resin, a thickener, and a hydrophilic solvent containing an alcohol having 1 to 4 carbon atoms and water.
• Resins may include naturally occurring and synthetic resins.
• naturally occurring resins include natural resins such as shellac and rosin, and derivatives thereof.
• 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 not more 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 not more than 5.5%.
• the preferred shellac is white shellac, which has a wax content of 0.2% or less.
• Rosin is a resinous substance contained in the sap of plants of the pine family. Rosin includes gum rosin, wood rosin, tall oil rosin, etc. The rosin is preferably gum rosin. Rosin may also include ester gums such as rosin esters and hydrogenated rosin esters; and rosin derivatives such as pencels such as rosin esters and polymerized rosin esters.
• Synthetic resin refers to resins that are artificially produced using petroleum and other fossil fuels as starting materials.
• 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.
• the thickener may be a cellulose compound, etc.
• the cellulose compound is not limited as long as it has a cellulose skeleton.
• the cellulose compound is preferably a non-ionic water-soluble cellulose compound.
• the non-ionic water-soluble cellulose compound is preferably at least one selected from the group consisting of hydroxypropyl methylcellulose and hydroxypropyl cellulose. Hydroxypropyl methylcellulose is sometimes referred to herein as HPMC or hypromellose.
• the hydroxypropyl methylcellulose for example, hydroxypropyl methylcellulose as specified in the Japanese Pharmacopoeia can be used.
• the degree of substitution of the methoxy group of 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
• the degree of substitution of the hydroxypropoxy group 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.
• degrees of substitution can be measured by a method conforming to the method for measuring the degree of substitution of hydroxypropyl methylcellulose and methylcellulose as described in the 17th Pharmacopoeia.
• hydroxypropyl methylcellulose is the most suitable cellulose compound due to its excellent film formability and mechanical strength at low moisture content.
• n and m are any integers.
• the hydroxypropyl methylcellulose used in the present invention includes hypromellose with substitution grades (types) of 2910, 2906, and 2208 as defined in the 17th Pharmacopoeia. Among these, substitution types 2910 and 2906 are more preferred.
• 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.
• hypromellose having the following molecular weight, which is approved for use as a food additive in Japan.
• hydroxypropyl methylcellulose examples 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 Co., Ltd.; and the Benecel (registered trademark) series from Ashland Co., Ltd. Hydroxypropyl cellulose may be referred to as HPC in this specification.
• Commercially available hydroxypropyl cellulose includes the Klucel (registered trademark) series from Ashland and the NISSO HPC series from Nippon Soda.
• the NISSO HPC series includes HPC SSL (molecular weight 40,000), HPC SL (molecular weight 100,000), and HPC L (molecular weight 140,000).
• 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.
• alcohols 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. Ethanol is preferred.
• 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, based on 100% by mass of the band seal liquid.
• the water content in the band seal liquid is the remainder excluding the total content of components other than water when the band seal liquid is taken as 100 mass %.
• the water content relative to the alcohol with 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 alcohol with 1 to 4 carbon atoms, and preferably 6 to 9 parts by mass of water for 55 to 80 parts by mass of alcohol with 1 to 4 carbon atoms.
• the band seal liquid may contain additives such as pigments, plasticizers, and surfactants.
• plasticizers include dioctyl adipate, adipate polyester, epoxidized soybean oil, epoxy hexahydrophthalic acid diester, kaolin, triethyl citrate, glycerin, sesame oil, 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, isopropylene glycol, polyoxyethylene (105) polyoxypropylene (5)
• the plasticizer content 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.
• Surfactants to be added to the band seal liquid include polysorbate 80, sodium lauryl sulfate, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, etc.
• the band seal liquid does not contain sorbitan fatty acid esters and glycerin fatty acid esters. More preferably, the band seal 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 seal liquid does not contain a surfactant.
• the surfactant content in the band seal liquid is in the range of 0% to less than 0.5% by mass, preferably in the range of 0% to 0.3% by mass, and more preferably in the range of 0% to 0.1% by mass, when the band seal liquid is taken as 100% by mass.
• 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, and 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.
• the band seal liquid can be prepared by the following method.
• a resin and a thickener are added to a hydrophilic solvent, and the added materials are dissolved by stirring at about 20° C. to 30° C., preferably at about 25° C., using a stirrer or the like so as to prevent the materials from forming lumps.
• the total content of components (solid components) excluding the hydrophilic solvent in the band seal liquid is 10 to 45 mass % when the band seal liquid is 100 mass %.
• the shear viscosity of the band seal liquid is approximately 200 mPa ⁇ s to 1,500 mPa ⁇ s, preferably approximately 300 mPa ⁇ s to 1,000 mPa ⁇ s.
• Shear viscosity can be measured, for example, using a rheometer (MCR102) from Anton Paar Japan Co., Ltd.
• MCR102 rheometer
• a jig CC27
• a concentric cylindrical tube CC27/T200/SS
• the value at a temperature of 25°C and a shear rate of 1 sec-1 can be used as the shear viscosity value.
• Certain embodiments of the present invention relate to a method for sealing hard capsules (hereinafter, may be referred to as a "sealing method").
• the sealing method includes applying the band seal liquid described in 1. above to the mating portion between the cap and body of the hard capsule after filling the hard capsule with the filling material, and then drying the applied band seal liquid. Generally, the filling material is filled into the body.
• band seal liquid at about 20°C to 30°C, preferably about 25°C is applied once or multiple times, preferably once or twice, to the surfaces of the body and cap parts in a generally constant width, centered on the edge of the cap part after fitting, so as to straddle it, in the circumferential direction of the body and cap parts, and the applied band seal liquid is dried to form a band seal and seal the fitting part.
• the "constant width" varies depending on the size of the capsule, but is generally about 2mm to 3mm. Drying can be carried out in a working atmosphere for about 3 minutes to 24 hours, preferably about 5 minutes to 10 minutes.
• the working atmosphere is, for example, room temperature (about 20°C to 28°C) and humidity about 30% RH to 50% RH.
• the capsules can be sealed after fitting using a known capsule filling and sealing machine, such as the capsule filling and sealing machine or capsule sealing machine (model name: HICAPSEAL 40/100, manufactured by Qualicaps).
• a known capsule filling and sealing machine such as the capsule filling and sealing machine or capsule sealing machine (model name: HICAPSEAL 40/100, manufactured by Qualicaps).
• band seal liquid there are no restrictions on the amount of band seal liquid to be applied, so long as it is an amount that can produce a band seal 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.
• WO 08/099835 uses polyethylene glycol as the filler
• vegetable oil e.g., soybean oil, rice oil, canola oil, sesame oil, olive oil, etc.
• WO 08/099835 uses polyethylene glycol as the filler
• vegetable oil e.g., soybean oil, rice oil, canola oil, sesame oil, olive oil, etc.
• the band seal formed at the fitting part 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.
• the resin content in the band seal is 35 to 98% by mass, and 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.
• 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.
• the plasticizer content in the band seal is in the range of 0% to 50% by mass, preferably 10% 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.
• Surfactants to be added to the band seal liquid include polysorbate 80, sodium lauryl sulfate, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, etc.
• the band seal does not contain sorbitan fatty acid esters and 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.
• the surfactant content in the band seal is in the range of 0% to less than 5% by mass, preferably in the range of 0% to 3% by mass, and more preferably in the range of 0% 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.
• the content of the dye in the band seal liquid is in the range of 0% to 5% by mass, preferably in the range of 0% to 1% by mass, and 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.
• the residual moisture is calculated as the moisture content shown in the following formula.
• the hard capsule sealed by band sealing is not particularly limited, and examples thereof include hydroxypropylmethylcellulose capsules, gelatin capsules, pullulan capsules, and starch capsules. It is preferable that the hard capsule sealed by the band seal has a certain degree of acid resistance. Acid resistance refers to a property that satisfies at least the following condition (i).
• the dissolution rate of the contents when the test subject is immersed in the first liquid at 37°C ⁇ 0.5°C for 2 hours is 40% or less, preferably 30% or less.
• the pH of the first liquid is about 1.2.
• the first liquid can be prepared, for example, by adding 7.0 ml of hydrochloric acid and water to 2.0 g of sodium chloride to make 1000 ml.
• Acid resistance preferably satisfies the above condition (i) as well as the following condition (ii).
• the pH of the second liquid is about 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.
• the dissolution rate 45 minutes after immersing the test subject in the second liquid is 75% or more, preferably 80%, and more preferably 90% or more.
• the dissolution rate 1 hour after immersing the test subject in the second liquid is 75% or more, preferably 80%, and more preferably 90% or more.
• the dissolution rate reaches 75% or more 60 minutes or more after the test subject is immersed in the second liquid. Furthermore, to prevent the drug from being excreted directly from the body, it is preferable that 75% or more is dissolved within 12 hours.
• the hard capsule sealed by the band seal has a certain degree of strength.
• the strength can be measured by the following method. A sample (hard capsule filled with vegetable oil) is placed in a desiccator with a saturated potassium carbonate salt to create a constant humidity atmosphere, and the desiccator is sealed and conditioned for one week at 25° C. In addition, in the presence of a saturated potassium carbonate aqueous solution, an atmosphere with a relative humidity of about 43% can be created. Pressure is applied to the test sample using the following method, and the pressurized test sample is placed on paper (such as Kimtowel) to check for leakage of the filled vegetable oil.
• paper such as Kimtowel
• an Autograph Model: EZ-LX (Shimadzu Corporation) can be used.
• a jig for example, a flat disk type can be used.
• the compression speed can be 50 mm/min, and the pressure can be, for example, 10 N or 15 N.
• Hard Capsule Product One embodiment of the present invention relates to a hard capsule product, which is filled with a filler and has a band seal at the mating portion between a cap portion and a body portion of the hard capsule.
• the band seal liquid for forming the band seal is as described in the above item 1.
• the method for forming the band seal and the components of the band seal are as described in the above item 2.
• the filling may be a liquid, semi-solid or powder.
• the powder is preferably a fine powder.
• the liquid is a liquid that is used pharmaceutical or edible.
• the liquid is intended to have liquid properties at room temperature (approximately 20°C to 28°C).
• liquids include polyethylene glycol, fatty oils, glycerin, surfactants, etc.
• Polyethylene glycol for example, has a molecular weight of approximately 200 to 600 (PEG 200 to 600). The molecular weight is specified according to the manufacturer's specifications.
• An example of a fatty oil is vegetable oil.
• a semi-solid is a substance with a melting point of about 30° C. to 50° C.
• a semi-solid substance is a substance that is medicamentally or edibly acceptable.
• PEG 1000 polyethylene glycol
• the filling may include a pharma- ceutically acceptable active ingredient, and the filling may include a edible acceptable ingredient.
• Shellac The shellac used was a dry transparent white shellac manufactured by Nippon Shellac Kogyo Co., Ltd. 2.
• 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.
• HPCs used were 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. 3. Rosin The rosin used was manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. 4. Hard capsules HPMC capsules were used as hard capsules. The capsule size was No. 1.
• band seal liquid of the examples was prepared using the materials in the amounts shown in Tables 2 and 3, and in the following manner.
• the materials were added to a solvent (a mixed solvent of water and ethanol, or a mixed solvent of water and isopropyl alcohol), and the mixture was 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 in the following manner.
• Shellac (and, as necessary, sorbitan fatty acid ester and glycerin fatty acid ester) was added to a mixed solvent of water and ethanol, and the mixture was stirred with a stirrer at room temperature until the added material was dissolved without forming lumps.
• Rosin was added to the shellac liquid prepared in (1) above, and the mixture was stirred with a stirrer at room temperature until the rosin became uniform.
• Hard capsules for dissolution tests were prepared as follows. A powder mixture of lactose, acetaminophen, and EXPLOTAB in a ratio of 70:20:10 was used as the filling material for the hard capsules. 300 mg of the filling material was filled into the capsules, and the cap and body were fitted together. The prepared band seal liquid was repeatedly applied in the circumferential direction across the fitting part in a width of 2 mm until a specified mass was reached. After application, the capsules were air-dried for 15 minutes or more, the entire capsule was weighed, and the mass of the applied band seal liquid was measured. The room temperature during the experiment was 23-27°C, and the relative humidity was 45-65%.
• Hard capsules for measuring the cracking rate were prepared as follows: 400 ⁇ L of soybean oil was filled into the hard capsules, and they were sealed with a band seal in the same way as the capsules for the dissolution test.
• Capsule dissolution test In principle, the dissolution test in the 18th edition of the Japanese Pharmacopoeia was applied. However, since the Japanese Pharmacopoeia does not specify the solubility of empty hard capsules themselves, this time, capsules filled with the above-mentioned fillings and sealed with a band seal were used as test samples, and the dissolution of the fillings was evaluated to evaluate the solubility (dissolution characteristics) of the capsules themselves.
• 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 change in the dissolution rate of acetaminophen was measured.
• Dissolution tests were performed using a Bath-type dissolution tester Model 2100 or 2500 manufactured by Distek.
• the absorbance at 244 nm of the solution in the dissolution tester bath when the same volume of acetaminophen was dissolved in its entirety separately was taken as 100%, and the dissolution rate was calculated from the absorbance at 244 nm of the solution in the dissolution tester bath, which increased with the dissolution of acetaminophen from the capsule.
• the number of n was set to 3 or 6, and the average dissolution rate was used.
• 900 mL of the following first solution was used as the buffer solution. In both cases, the temperature of the solution in the bath was set to 37 ⁇ 2°C.
• 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 was approximately 1.2).
• Capsule cracking test The prepared capsules were placed in a desiccator conditioned with saturated potassium carbonate, sealed, and conditioned for one week at 25°C. Under these conditions, an atmosphere with a relative humidity of 43% can be created. Next, the capsules that had been conditioned were used as test samples and subjected to a compression test. For the compression test, an autograph Model: EZ-LX (Shimadzu Corporation) was used. The jig used was a flat disk, the compression speed was 50 mm/min, and the pressure was 10N and 15N. Leakage from the compressed test sample was confirmed by placing the test sample on paper (Kimtowel, etc.) and checking whether the filled vegetable oil adhered to the paper. The n numbers of test samples are shown in Tables 4 and 5.
• Results Tables 4 and 5 show the components of the band seal except for the solvent component, and the results of the dissolution test and the crack test of the HPMC capsules sealed by applying each band seal liquid.
• Comparative Example 1 is the band seal described in Patent Document 1.
• Comparative Example 2 is a formulation in which the surfactants sorbitan fatty acid ester and glycerin fatty acid ester are omitted from Comparative Example 1.
• Comparative Example 3 is a band seal containing only HPMC.
• Comparative Example 4 is a band seal containing only shellac. Shellac alone was insufficient in strength when compressed. When evaluated based on Comparative Example 1, the cracking rate at a compression of 10N was low in Examples 1 to 10 and Examples 12 to 17. Furthermore, as shown in Example 9, strength was maintained even when shellac was replaced with rosin. Compared to Comparative Example 1, Examples 1 to 17 had a lower cracking rate at a compression of 15N. Compression of about 15N may occur during capsule transportation or when capsules are removed from blister packaging. Therefore, the results of the cracking test show that the band seal of the present invention can ensure sufficient strength even under such conditions.
• Examples 1 to 8 and Examples 11 to 17 had elution rates below 40% and good acid resistance.
• Comparative Example 2 differs from Comparative Example 1 in that it does not contain sorbitan fatty acid esters or glycerin fatty acid esters. Since the breaking rate at a compression of 10 N in Comparative Example 2 is higher than that in Comparative Example 1, it is believed that the strength of Comparative Example 1 depends on the sorbitan fatty acid esters and glycerin fatty acid esters.

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