Sealing fluid for sealing capsules

Abstract

A sealing fluid comprising an organic acid, the organic acid being lactic acid or acetic acid, an alcohol, the alcohol being isopropyl alcohol or ethanol, and optionally water, is a liquid composition for sealing a telescoping joint of a hard capsule having a body component with coaxial partial overlap.

Description

[0001] The present invention discloses a sealing fluid comprising an organic acid, an alcohol, and optionally water, wherein the organic acid is lactic acid or acetic acid, and the alcohol is isopropanol or ethanol, and the sealing fluid is a liquid composition for sealing a hard capsule having a telescopic engagement of body components having coaxially overlapping portions. Background Technology

[0002] Capsules are a well-known dosage form for pharmaceuticals, nutritional supplements, dietary supplements, and other ingredients. Hard capsules typically consist of a shell filled with one or more substances. The hard capsule shell comprises two parts: a cap and a body, both cylindrical in shape with an open end and a closed end; the outer diameter of the cylindrical open end of the body extends and contracts into the inner diameter of the cylindrical open end of the cap. Once the capsule, i.e., the body, is filled with its contents, the capsule is closed by extending and contracting the open end of the body into the open end of the cap to close it.

[0003] Hard capsules are typically manufactured using an dip molding process, in which a die pin is dipped into a melt, which is a liquid film-forming composition comprising a dissolved film-forming polymer. Upon extraction, a film forms on the die pin. The film is then peeled off the die pin; dip molding is performed separately to manufacture the cap and body.

[0004] Therefore, in the closed capsule, the cylindrical opening end of the cap partially overlaps with the cylindrical opening end of the body; that is, a portion of the inner cylindrical surface of the cap contacts a portion of the outer cylindrical surface of the body. Leakage can occur between these overlapping surfaces of the cap and the body because, for various reasons, the matching of the inner diameter of the cap and the outer diameter of the body cannot be so precise and tight as to prevent any leakage. For example, when the body is inserted into the cap, the corresponding volume of air in the cap needs to be expelled upon closure; on the other hand, overpressure may form, which could prevent the capsule from closing completely or even damage the capsule. Similarly, to avoid damaging the cap or body upon closure, the force required to slide the cap over the body must not be excessive. Therefore, there is always a certain tolerance between the cap and the body, resulting in a gap between the overlapping portions of the cap and the body.

[0005] Once the capsule is closed, the slit between the edge of the cap and the surface of the body is visible and accessible.

[0006] In some cases, it is desirable to prevent leakage of the contents from the capsule, such as when the capsule is filled with a liquid substance. For this purpose, the capsule is sealed, meaning the slit between the cap and the body is closed to create a seal. This seal can also be considered as bonding or binding the cap and body together by means of a sealing fluid. When sealing the capsule, a sealing fluid is applied to the beginning of the slit between the edge of the cap and the surface of the body. Through capillary action, the sealing fluid then diffuses and distributes into the interior of the slit. The capsule shell can be made of various film-forming polymers, such as gelatin, HPMC, pullulan, or starch. In the case of HPMC, in the dip molding process, there are two main different methods for forming a film on the mold pin: conventional gelation of HPMC at temperatures below the melt gelation temperature requires the presence of a gelling system in the melt, such as gelling gel; while hot gelation occurs at temperatures above the melt gelation temperature of HPMC and does not require the presence of an additional gelling system in the melt.

[0007] WO 2004 / 103338 A1 discloses a composition in Example 6 of HPMC E50 / water / lactic acid / propane-2-ol in a ratio of 6 / 25 / 44 / 25 (100 parts in total). The viscosity is too high to allow for immediate use in sealing capsules after filling them at a rate matching conventional capsule filling production lines in a conventional capsule filling machine. The viscosity does not allow for spray formation, and it prevents the sealing fluid from being present throughout the sealing area, implying a higher leakage rate.

[0008] The problem to be solved is to provide a sealing fluid that can be used in automated sealing machines for the automated sealing of capsules, thus enabling large-scale mass production to reduce manufacturing time and costs and waste due to product defects. The sealing fluid should allow capsules to be sealed immediately after filling at a rate matching that of conventional capsule filling production lines. Similarly, problems such as clogging should not occur.

[0009] The sealing fluid should provide an effective seal for the filled capsules to prevent any leakage of contents, thus a low leakage rate is desirable. The sealing fluid should not have an adverse effect on the shape, size, or stability of the capsules. The sealing fluid should be suitable for all types of capsules, particularly those using HPMC as the film-forming polymer and gellan gum as the gelling system, i.e., capsule shells made with HPMC and gellan gum as the main or even sole components of the capsule shell.

[0010] This problem is solved by a sealing composition comprising organic acids and alcohols, and optionally water.

[0011] Abbreviations and definitions used in this specification

[0012] HPMC (Hydroxypropyl Methylcellulose), also known as hydroxypropyl methylcellulose or cellulose, 2-hydroxypropyl methyl ether or cellulose hydroxypropyl methyl ether, CAS 9004-65-3 Summary of the Invention

[0013] The subject of this invention is a sealing fluid SEALFLU for sealing hard capsules, the SEALFLU comprising an organic acid ORGACID and an alcohol ALC;

[0014] ORGACID is lactic acid or acetic acid;

[0015] ALC is isopropanol or ethanol;

[0016] in

[0017] The amount of ORGACID is at least 32.5 wt%;

[0018] The amount of ALC is at least 17.5 wt%;

[0019] The wt% is based on the weight of SEALFLU;

[0020] SEALFLU does not contain HPMC;

[0021] SEALFLU has a viscosity of 100 mPa*s or less, wherein the viscosity is measured at 22°C using a rotational viscometer with a cylindrical spindle. Detailed Implementation

[0022] In one embodiment, SEALFLU does not contain any polymers commonly used in capsule preparation, such as gelatin, pullulan, starch, modified starch, or cellulose derivatives, such as HPMC.

[0023] More preferably, SEALFLU contains no polymers.

[0024] More preferably, SEALFLU contains no gelling agents.

[0025] More preferably, SEALFLU contains no substances that increase the viscosity of SEALFLU by addition, specifically not exceeding 100 mPa*s, wherein the viscosity is measured at 22°C using a rotational viscometer with a cylindrical spindle.

[0026] Preferably, the amount of ALC is at least 20 wt%; more preferably at least 25 wt%, even more preferably at least 30 wt%, especially at least 35 wt%, said wt% is based on the weight of SEALFLU.

[0027] Preferably, the amount of ALC is no more than 55 wt%, more preferably no more than 50 wt%, and even more preferably no more than 45 wt%, wherein the wt% is based on the weight of SEALFLU.

[0028] Any of the lower bounds can be combined with any of the upper bounds of the possible quantities of ALC.

[0029] Preferably, the amount of ORGACID is at least 35 wt%, said wt% is based on the weight of SEALFLU.

[0030] Preferably, the amount of ORGACID is no more than 75 wt%, more preferably at least 70 wt%, even more preferably no more than 65 wt%, especially no more than 60 wt%, even more especially no more than 55 wt%, even more especially no more than 50 wt%, specifically no more than 45 wt%, said wt% based on the weight of SEALFLU.

[0031] Any of the lower bounds can be combined with any of the upper bounds of the possible quantities of ORGACID.

[0032] Any of the lower or upper bounds of the possible quantities of ALC can be combined with any of the lower or upper bounds of the possible quantities of ORGACID.

[0033] In one embodiment, SEALFLU consists of ORGACID and ALC;

[0034] Preferably, the ORGACID is acetic acid; or

[0035] Preferably, ALC is isopropanol;

[0036] In this case, ORGACID is more preferably acetic acid and ALC is isopropanol.

[0037] In one embodiment, SEALFLU consists of ORGACID and ALC;

[0038] ORGACID is acetic acid;

[0039] The amount of acetic acid is 47.5 wt% to 80 wt%, and the amount of ALC is 20 wt% to 52.5 wt%.

[0040] Preferably, the amount of acetic acid is from 47.5 wt% to 75 wt%, and the amount of ALC is from 25 wt% to 52.5 wt%.

[0041] The wt% is based on the weight of SEALFLU;

[0042] Preferably, ALC is isopropanol.

[0043] In one embodiment, SEALFLU also includes water in addition to ORGACID and ALC;

[0044] The total amount of ORGACID, ALC and water is at least 97.5 wt%, preferably 98 wt%, more preferably at least 99 wt%, and even more preferably 100 wt%, that is, SEALFLU is composed of ORGACID, ALC and water, wherein the wt% is based on the weight of SEALFLU.

[0045] Preferably, when the SEALFLU includes water in addition to ORGACID and ALC, the amount of water in the SEALFLU is at least 17.5 wt%, wherein the wt% is based on the weight of the SEALFLU; in this case, the ORGACID is preferably lactic acid.

[0046] In one embodiment, SEALFLU also includes water in addition to ORGACID and ALC;

[0047] ORGACID is acetic acid;

[0048] The amount of acetic acid is 40 wt% to 60 wt%;

[0049] The amount of ALC is 20 wt% to 40 wt%;

[0050] The total amount of ORGACID, ALC and water is at least 97.5 wt%, preferably 98 wt%, more preferably at least 99 wt%, and even more preferably 100 wt%, that is, SEALFLU is composed of ORGACID, ALC and water;

[0051] The wt% is based on the weight of SEALFLU;

[0052] Preferably, ALC is isopropanol.

[0053] In one embodiment, SEALFLU also includes water in addition to ORGACID and ALC;

[0054] ORGACID is acetic acid;

[0055] The amount of acetic acid is 45 wt% to 55 wt%;

[0056] The amount of ALC is 25 wt% to 35 wt%;

[0057] The total amount of ORGACID, ALC and water is at least 97.5 wt%, preferably 98 wt%, more preferably at least 99 wt%, and even more preferably 100 wt%, that is, SEALFLU is composed of ORGACID, ALC and water;

[0058] The wt% is based on the weight of SEALFLU;

[0059] Preferably, ALC is isopropanol.

[0060] In one embodiment, SEALFLU also includes water in addition to ORGACID and ALC;

[0061] ORGACID is lactic acid;

[0062] The amount of lactic acid ranges from 32.5 wt% to 62.5 wt%.

[0063] The amount of ALC ranges from 17.5 wt% to 47.5 wt%.

[0064] The total amount of ORGACID, ALC and water is at least 97.5 wt%, preferably 98 wt%, more preferably at least 99 wt%, and even more preferably 100 wt%, that is, SEALFLU is composed of ORGACID, ALC and water;

[0065] Preferably, the ALC is ethanol and the amount of ethanol is 25 wt% to 42.5 wt%, more preferably 27.5 wt% to 42.5 wt%;

[0066] The wt% is based on the weight of SEALFLU.

[0067] In one embodiment, SEALFLU also includes water in addition to ORGACID and ALC;

[0068] ORGACID is lactic acid;

[0069] The amount of lactic acid ranges from 32.5 wt% to 55 wt%.

[0070] The amount of ALC ranged from 17.5 wt% to 42.5 wt%.

[0071] The total amount of ORGACID, ALC and water is at least 97.5 wt%, preferably 98 wt%, more preferably at least 99 wt%, and even more preferably 100 wt%, that is, SEALFLU is composed of ORGACID, ALC and water;

[0072] Preferably, ALC is ethanol and the amount of ethanol is 25 wt% to 42.5 wt%, more preferably 27.5 wt% to 42.5 wt%;

[0073] The wt% is based on the weight of SEALFLU.

[0074] In one embodiment, SEALFLU also includes water in addition to ORGACID and ALC;

[0075] ORGACID is lactic acid, and ALC is isopropanol;

[0076] The amount of lactic acid ranges from 37.5 wt% to 55 wt%.

[0077] The amount of isopropanol ranges from 17.5 wt% to 42.5 wt%.

[0078] The total amount of ORGACID, ALC and water is at least 97.5 wt%, preferably 98 wt%, more preferably at least 99 wt%, and even more preferably 100 wt%, that is, SEALFLU is composed of ORGACID, ALC and water;

[0079] The wt% is based on the weight of SEALFLU.

[0080] In one embodiment, SEALFLU also includes water in addition to ORGACID and ALC;

[0081] ORGACID is lactic acid, and ALC is isopropanol;

[0082] The amount of lactic acid is 37.5 wt% to 45 wt%;

[0083] The amount of isopropanol ranges from 35 wt% to 42.5 wt%.

[0084] The total amount of ORGACID, ALC and water is at least 97.5 wt%, preferably 98 wt%, more preferably at least 99 wt%, and even more preferably 100 wt%, that is, SEALFLU is composed of ORGACID, ALC and water;

[0085] The wt% is based on the weight of SEALFLU.

[0086] In one embodiment, SEALFLU consists of ORGACID, ALC, and water;

[0087] Preferably, ORGACID is lactic acid; or

[0088] Preferably, ALC is isopropanol;

[0089] More preferably, ORGACID is lactic acid and ALC is isopropanol.

[0090] In one embodiment, SEALFLU consists of ORGACID, ALC, and water;

[0091] The amount of ORGACID is 40 wt%.

[0092] The amount of ALC was 40 wt%.

[0093] The wt% is based on the weight of SEALFLU;

[0094] Preferably, ORGACID is lactic acid; or

[0095] Preferably, ALC is isopropanol;

[0096] More preferably, ORGACID is lactic acid and ALC is isopropanol.

[0097] Any water can be demineralized water.

[0098] The viscosity of SEALFLU can be 100 mPa*s or less, preferably 75 mPa*s or less, more preferably 60 mPa*s or less, even more preferably 50 mPa*s or less, especially 45 mPa*s or less, and even more particularly 40 mPa*s or less, wherein the viscosity is measured at 22°C using a rotational viscometer with a cylindrical spindle.

[0099] In one embodiment, the viscosity of SEALFLU is equal to or lower than that of pure lactic acid, wherein the viscosity is measured at 22°C using a rotational viscometer with a cylindrical spindle.

[0100] Another subject of the present invention is a method for preparing SEALFLU, wherein ORGACID and ALC are mixed with any water;

[0101] SEALFLU, ORGACID, and ALC are as defined herein and in all its embodiments.

[0102] The mixing of ORGACID, ALC, and water can be done in any order.

[0103] Another subject of the invention is a method for sealing hard capsules, the capsule shell of which consists of a cap and a body, wherein the body is telescopically inserted into the cap to provide a slit between the overlapping portions of the cap and the body;

[0104] The sealing is achieved by applying SEALFLU to the slit;

[0105] SEALFLU is defined herein and in all its embodiments.

[0106] The capsule is filled and closed before sealing. When closed, the capsule cap and body telescopically engage together. This engagement can be achieved, for example, by inserting the body into the cap, i.e., the body sliding into the cap, or other methods. The cap and body partially overlap within the closed capsule. This creates a slit between the overlapping portions of the cap and body. When sealing the capsule, a sealing fluid is applied to the slit, specifically to the beginning portion of the slit accessible from the outside of the capsule. The beginning portion of the slit is located between the edge of the cap and the surface of the body.

[0107] SEALFLU can be applied evenly around the capsule, thus it can be applied to the slit or only to the slit. SEALFLU can be applied to the slit covering its entire length, or only to one or more portions of the slit length. Preferably, SEALFLU is applied over the entire length of the slit.

[0108] SEALFLU can be applied by spraying it onto the slits or capsules, and thus onto the slits as well.

[0109] When SEALFLU is applied to the capsule, that is, to the slit, SEALFLU can be at ambient temperature or below ambient temperature.

[0110] After applying SEALFLU to the slit, the capsule can be dried. This drying can be done, for example, to remove any excess SEALFLU. It can also be done to ensure that the surfaces of the overlapping portion of the cap and body—that is, the surfaces of the cap and body forming the slit—are firmly bonded together.

[0111] Another subject of the invention is a sealed capsule obtainable by the method METHSEAL; wherein METHSEAL is as defined herein and in all its embodiments.

[0112] The capsules suitable for the method of sealing hard capsules according to the present invention may have a shell made of a known film-forming polymer such as gelatin, HPMC, pullulan, or starch. The capsule shell may include additional components, such as a gelling system, typically gellan gum. In one embodiment, the method of sealing hard capsules according to the present invention is a method for sealing hard capsules in which the film-forming polymer of the capsule shell is gelatin, HPMC, pullulan, or starch; in one embodiment, the film-forming polymer is HPMC, and the capsule shell contains gellan gum. The amount of gellan gum in the capsule shell may be from 0.01 wt% to 10 wt%, preferably from 0.01 wt% to 7 wt%, more preferably from 0.1 wt% to 7 wt%, even more preferably from 1 wt% to 7 wt%, especially from 3 wt% to 6 wt%, and even more preferably from 4 wt% to 6 wt%, said wt% based on the weight of HPMC.

[0113] Example

[0114] Materials and abbreviations

[0115] In this example, the capsules used were from Suzhou Capsugel Co., Ltd. (Capsugel, now a subsidiary of Lonza Ltd, Basel, Switzerland). DRcaps capsules contain HPMC-based formulations and gellan gum, and possess delayed-release properties. The capsules are manufactured by Suzhou Capsule Co., Ltd. (now a subsidiary of Lonza GmbH in Basel, Switzerland). Capsule design.

[0116] CFS Capsule Filling and Sealing

[0117] CFS 1200 is produced by Suzhou Capsule Co., Ltd. (now a subsidiary of Lonza GmbH in Basel, Switzerland). TM This is a CFS machine designed for laboratory and pilot plant scale operations, with an operating speed of approximately 1,200 capsules per hour. CFS has three operational steps: filling, sealing, and drying. Drying is accomplished by blowing air at a predetermined temperature.

[0118] HPMC (hydroxypropyl methylcellulose), also known as hydroxypropyl methylcellulose or cellulose, 2-hydroxypropyl methyl ether or cellulose hydroxypropyl methyl ether, CAS 9004-65-3

[0119] IPA 80wt% isopropanol aqueous solution

[0120] Lactic acid (S) - Lactic acid accounts for approximately 90%. EXPERT Ph Eur, BP, E 270, Merck KGaA, Darmstadt, Germany

[0121] Technical data sheet for 90% lactic acid from Merck: 20 to 40 mPa*s at 20°C

[0122] Lactic acid viscosity (literature): 37 to 39 mPa*s at ambient temperature.

[0123] At 35℃, it is 21.2 mPa*s.

[0124] LEMS Liquid Encapsulation Micro-jet Sealing

[0125] LEMS 70 70 refers to the LEMS system of Suzhou Capsule Co., Ltd. (now a subsidiary of Lonza GmbH in Basel, Switzerland), a type of CFS used for production-scale operations.

[0126] The machine operates at a maximum speed of 55,000 capsules per hour, with capsule sizes ranging from 000, 00el, 00, 0el, 0, 1, 2, 3, 4.

[0127] rpm revolutions per minute

[0128] (A) Sealing fluid: a solution of lactic acid / isopropanol / water in a 40 / 40 / 20 (w / w / w) ratio.

[0129] Sealing fluid (A1)

[0130] For 100g of sealed fluid solution:

[0131] ●44.44g of lactic acid

[0132] ●50g IPA

[0133] ●5.56g of demineralized water

[0134] A sealed fluid solution is prepared by adding three components in the following order: lactic acid, water, and then IPA. The solution is then mixed using a magnetic stirrer.

[0135] Use a sealing fluid to seal the capsule at ambient temperature.

[0136] (B) General description of the seal

[0137] Two different sealing machines were used: CFS 1200 and LEMS 70.

[0138] CFS 1200 is used at a rate of approximately 1200 capsules per hour.

[0139] LEMS is used at a rate of approximately 40,000 capsules per hour.

[0140] The example uses a capsule with a size of 0.

[0141] (C) Leakage Rate Detection

[0142] Disperse the sealed capsules on white paper on a tray and store overnight (approximately 12 hours) at ambient temperature and pressure.

[0143] The tray was then placed in a vacuum chamber, and a vacuum of 250 mbar was applied for 20 minutes. The tray was then removed from the vacuum chamber, and the capsules were visually inspected on a light stage to observe for potential leaks, which were characterized by oily stains spreading beneath the leaked capsules in the paper. The leakage rate was expressed as a percentage of the total number of leak test capsules.

[0144] The capsule may have been placed on paper on the tray for a week, and the leakage rate may have been further determined by visual inspection.

[0145] In laboratory-scale operations, such as on the CFS 1200, a leakage rate of 0.5% or less is acceptable.

[0146] In pilot plant-scale / production-scale operations, such as on LEMS, a leakage rate of 0.05% or less is acceptable.

[0147] (D) Viscosity

[0148] Equipment used for measuring viscosity:

[0149] The BROOKFIELD DV-II+ viscometer, manufactured by AMETEK Brookfield, Middleboro, MA, USA, features a chamber SC4-13R and a cylindrical spindle 18.

[0150] The temperature chamber must be regulated by a water bath at 22℃±0.1℃.

[0151] Use a syringe to introduce sealing fluid to fill half of the viscosity chamber.

[0152] Then, introduce the spindle and completely fill the chamber with sealing fluid, with the sealing fluid at least 1 mm from the edge. Check for air bubbles to avoid viscosity measurement errors.

[0153] The viscometer speed was selected to be as high as possible for optimal measurement accuracy.

[0154] Measure the viscosity after 10 minutes.

[0155] Viscosity value = average of two measurements

[0156] Specific details are given in Tables 6 and 7.

[0157]

[0158]

[0159]

[0160] (1) Brookfield viscosity at 22°C with spindle 18 and speed 100 rpm.

[0161] Example 1 - Using CFS 1200 sealing

[0162] (1a) Using oil filler

[0163] The capsules were filled with peanut oil in a CFS 1200. Peanut oil has a very low viscosity (74.9 mPa*s-Brookfeld viscosity at 22°C), making it particularly prone to leakage and therefore a good model for leak rate testing. Each capsule was filled with the same amount of oil. The capsules were then closed and moved to the sealed position in the CFS 1200.

[0164] (1b) Sealing

[0165] Each capsule was sealed on a CFS 1200 with 20 mg of sealing fluid per capsule, the sealing fluid having been prepared according to (A1), and the sealing fluid was sprayed around the outward end and the open end of the gap provided by the overlap of the capsule's telescopically joined cap and body.

[0166] No problems such as sealing machine blockage were observed.

[0167] (1c) Drying

[0168] The drying temperature in CFS 1200 is 25°C.

[0169] (1d) Results

[0170] Leakage rate testing was completed according to (C). The results are shown in Table 1.

[0171] No leaks were detected prior to entering the vacuum chamber.

[0172] Table 1 Number of sealed capsules Leakage rate [%) After the vacuum chamber One week later 1062 0.0 0.0

[0173] The size, shape, and stability of the capsule are not affected by the sealing.

[0174] Example 2 - Using LEMS 70 seal

[0175] (2a) Use oil filler

[0176] Fill the capsules with sunflower oil. Sunflower oil has a very low viscosity (53 mPa*s-Brookfeld viscosity at 22°C), making it particularly prone to leakage and therefore a good model for leak rate testing. Fill each capsule with the same amount of oil. Then close the capsules.

[0177] (2b) Sealing

[0178] In LEMS 70, each capsule is sealed with 25 mg of sealing fluid per capsule, which has been prepared according to (A1). The sealing fluid is sprayed onto the capsule, including spraying around the outward end and the open end of the gap provided by the overlap of the capsule's telescopically engaged cap and body.

[0179] No problems such as sealing machine blockage were observed.

[0180] (2c) Drying

[0181] The drying temperature in LEMS 70 is 35°C.

[0182] (2d) Results

[0183] Leakage rate testing was completed according to (C). The results are shown in Table 2.

[0184] No leaks were detected prior to entering the vacuum chamber.

[0185]

[0186]

[0187] Seven repeated runs yielded an acceptable and comparable leakage rate.

[0188] The size, shape, and stability of the capsule are not affected by the sealing.

[0189] Example 3

[0190] Repeat Example 1, the specific details of which are given in Tables 3 to 5. Prepare the sealing fluid according to (A) using the composition given in Tables 3 to 5. Complete the seal using CFS 1200 according to (B), and complete the leak rate test according to (C).

[0191] No leaks were observed before the vacuum chamber was reached during each run.

[0192] No problems such as sealing machine blockage were observed.

[0193] All runs showed an acceptable leakage rate.

[0194] The size, shape, and stability of the capsule are not affected by the sealing.

[0195] Table 3 run Sealing fluid (A2) Number of sealed capsules Leakage rate [%) Acetic acid / isopropanol (w / w) After the vacuum chamber One week later 3-20 70 / 30 443 0.2％ not applicable 3-21 50 / 50 105 0％ not applicable

[0196] Table 4 run Sealing fluid (A3) Number of sealed capsules Leakage rate [%) <![CDATA[(A3) Lactate / EtOH / H2O (w / w / w)]]> After the vacuum chamber One week later 3-30 50 / 30 / 20 1212 0.0 0.0 3-31 40 / 36 / 24 573 0.0 0.0 3-32 35 / 39 / 26 557 0.0 0.0

[0197]

[0198]

[0199] (1) No further leaks occurred after one week, which means that the leakage rate remained unchanged.

Claims

1. A sealing fluid SEALFLU for sealing hard capsules, said SEALFLU comprising an organic acid ORGACID and an alcohol ALC; ORGACID is lactic acid or acetic acid; ALC is isopropanol or ethanol; in The amount of ORGACID is at least 32.5 wt%; The amount of ALC is at least 17.5 wt%; The wt% is based on the weight of SEALFLU; SEALFLU does not contain HPMC; SEALFLU has a viscosity of 100 mPa*s or less, which is measured at 22°C using a rotational viscometer with a cylindrical spindle.

2. The SEALFLU according to claim 1, wherein SEALFLU consists of ORGACID and ALC.

3. The SEALFLU according to claim 2, wherein ORGACID stands for acetic acid.

4. The SEALFLU according to claim 2 or 3, wherein ALC is isopropanol.

5. The SEALFLU according to claim 3, wherein The amount of acetic acid ranges from 47.5 wt% to 80 wt%, and the amount of ALC ranges from 20 wt% to 52.5 wt%. The wt% is based on the weight of SEALFLU.

6. The SEALFLU according to claim 1, wherein In addition to ORGACID and ALC, SEALFLU also includes water; The total amount of ORGACID, ALC and water is at least 97.5 wt%, where the wt% is based on the weight of SEALFLU.

7. The SEALFLU according to claim 6, wherein The amount of water in SEALFLU is at least 17.5 wt%, where the wt% is based on the weight of SEALFLU.

8. The SEALFLU according to claim 6 or 7, wherein ORGACID is acetic acid; The amount of acetic acid is 40 wt% to 60 wt%; The amount of ALC is 20 wt% to 40 wt%; The wt% is based on the weight of SEALFLU.

9. The SEALFLU according to claim 8, wherein ALC is isopropanol.

10. The SEALFLU according to claim 6 or 7, wherein ORGACID is lactic acid; The amount of lactic acid ranged from 32.5 wt% to 62.5 wt%. The amount of ALC ranged from 17.5 wt% to 47.5 wt%; The wt% is based on the weight of SEALFLU.

11. The SEALFLU according to claim 10, wherein ALC is ethanol; The amount of ethanol ranges from 25 wt% to 42.5 wt%. The wt% is based on the weight of SEALFLU.

12. The SEALFLU according to claim 10, wherein ALC is isopropanol; The amount of lactic acid ranges from 37.5 wt% to 55 wt%. The amount of isopropanol ranges from 17.5 wt% to 42.5 wt%. The wt% is based on the weight of SEALFLU.

13. The SEALFLU according to claim 12, wherein The amount of lactic acid ranges from 37.5 wt% to 45 wt%. The amount of isopropanol ranges from 35 wt% to 42.5 wt%. The wt% is based on the weight of SEALFLU.

14. The SEALFLU according to claim 6 or 7, wherein SEALFLU is composed of ORGACID, ALC, and water.

15. The SEALFLU according to claim 14, wherein ORGACID is lactic acid.

16. The SEALFLU according to claim 14, wherein And ALC is isopropanol.

17. The SEALFLU according to claim 14, wherein The amount of ORGACID is 40 wt%; The amount of ALC was 40 wt%. The wt% is based on the weight of SEALFLU.

18. A method for preparing SEALFLU, wherein Mix ORGACID and ALC with any water; SEALFLU, ORGACID, and ALC are defined as in any one of claims 1 to 17.

19. A method for sealing a hard capsule, the capsule shell comprising a cap and a body, wherein the body is telescopically inserted into the cap to provide a slit between the overlapping portions of the cap and the body; The sealing is achieved by applying SEALFLU to the slit; SEALFLU is defined as in any one of claims 1 to 17.

20. A sealed hard capsule obtainable by the method METHSEAL; wherein METHSEAL is as defined in claim 19.

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