CN107157949B - Method for sealing inner part of hard capsule and application thereof - Google Patents
Method for sealing inner part of hard capsule and application thereof Download PDFInfo
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- CN107157949B CN107157949B CN201710433565.2A CN201710433565A CN107157949B CN 107157949 B CN107157949 B CN 107157949B CN 201710433565 A CN201710433565 A CN 201710433565A CN 107157949 B CN107157949 B CN 107157949B
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- 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
- A61K9/4833—Encapsulating processes; Filling of capsules
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- 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
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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Abstract
The invention relates to a method for sealing the interior of a hard capsule and application thereof, wherein the method comprises the following steps: separating the capsule body and the capsule cap of the hard capsule shell, and then filling materials in the capsule body; spraying sealing liquid on the inner surface of the capsule cap to form a liquid film; and heating the capsule body filled with the materials and the capsule cap body attached with the liquid film until the capsule is completely sealed. According to the method for sealing the interior of the hard capsule, provided by the invention, the inert gas is used for carrying the sealing liquid, so that when the inner surface of a capsule cap is coated with the sealing liquid, the inert gas can protect materials in the capsule, and thus the capsule filling of liquid and easily-oxidized materials is realized; the method provided by the invention does not influence the appearance and size of the capsule, can be widely applied to capsule encapsulation of fat-soluble medicines, and can increase the bioavailability of the medicines.
Description
Technical Field
The invention relates to the technical field of capsule preparation, in particular to a method for sealing the interior of a hard capsule and application thereof.
Background
Hard capsule (hard capsule) is prepared by adding medicinal powder or adjuvants into a certain amount of medicinal extract, making into uniform powder or granule, and filling into hollow capsule, or directly packaging medicinal powder into hollow capsule. In the production of modern Chinese medicinal preparations, hard capsules are widely applied due to the advantages of relatively simple process, convenient administration, quick response, effective isolation of the unpleasant odor of the medicament and the like. However, the existing hard capsule filling technology cannot realize complete sealing, so that the oxygen-sensitive medicines are oxidized and degraded when contacting air for a long time; the filling liquid can leak, so that the filling liquid cannot be applied to the filling of liquid or oxygen-sensitive medicines.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide a method for sealing the interior of a hard capsule and application thereof, which is used for carrying sealing liquid by using inert gas, and realizing the protection of the inert gas on materials in the capsule when the sealing liquid is coated on the inner surface of a capsule cap, thereby realizing the capsule filling of liquid and easily-oxidized materials and having good tightness; the method provided by the invention does not influence the appearance and size of the capsule, can be widely applied to capsule encapsulation of fat-soluble medicines, can increase the bioavailability of the medicines, and has important significance for the deep research and development of capsule preparations.
In order to achieve the purpose, the technical scheme provided by the invention is as follows: the invention provides a method for sealing the interior of a hard capsule, which comprises the following steps: s1: separating the capsule body and the capsule cap of the hard capsule shell, and then filling materials in the capsule body; s2: spraying sealing liquid on the inner surface of the capsule cap to form a liquid film; s3: and heating the capsule body filled with the materials and the capsule cap body attached with the liquid film until the capsule is completely sealed. In S3, the heating is performed to volatilize the solvent in the sealing liquid and to seal the capsule with the adhesive in the sealing liquid.
In a further embodiment of the present invention, in S3, the heating is: heating the combined capsules in hot air at 30-40 ℃; wherein the wind speed of the hot wind is 0.1-0.5 m/s.
In a further embodiment of the present invention, in S1, the physical state of the material is liquid and/or solid.
In a further embodiment of the present invention, S2 specifically includes: carrying the sealing liquid by gas, atomizing and spraying the sealing liquid on the inner surface of the capsule cap to form a liquid film; wherein the gas is nitrogen and/or inert gas.
In a further embodiment of the present invention, in S2, the sealing liquid includes a binder and a solvent, and the mass fraction of the binder is 5% to 70%.
In a further embodiment of the invention, the raw material component of the binder comprises povidone and the solvent is ethanol.
In a further embodiment of the present invention, the raw material components of the adhesive comprise, in parts by weight: 20-30 parts of povidone, 6-8 parts of Arabic gum, 1-2 parts of hydroxypropyl methylcellulose, 10-12 parts of gelatin, 15-20 parts of methyl-beta-cyclodextrin and 4-6 parts of agar. The raw material components of the adhesive adopted by the invention are preferably povidone K90, CAS No: 9003-39-8; acacia CAS No: 9000-01-05; hypromellose CAS No: 9004-65-3; gelatin CAS No: 9000-70-8; methyl- β -cyclodextrin CAS No: 128446-36-6 and agar CAS No: 9008-18-0.
In a further embodiment of the invention, the method of preparing the adhesive comprises the steps of: and uniformly mixing all the raw material components to obtain the adhesive.
In a further embodiment of the present invention, a method for preparing a sealing liquid includes the steps of: and uniformly mixing the adhesive and the solvent to obtain the sealing liquid.
The invention also protects the application of the method for sealing the interior of the hard capsule in preparing the hard capsule.
The technical scheme provided by the invention has the following beneficial effects: (1) according to the method for sealing the interior of the hard capsule, the sealing liquid is attached to the interior of the capsule cap in a spraying mode and the like before the hard capsule is combined, and after the capsule is locked, the sealing liquid solvent is dried to form the seal for the hard capsule, so that the seal of the liquid capsule is realized, the leakage is prevented, and meanwhile, the isolation of oxygen-sensitive solid contents from air can be realized, and the oxidation in the storage process is avoided; (2) the invention uses inert gas to carry sealing liquid, when the inner surface of the capsule cap is coated with the sealing liquid, the inert gas can protect the materials in the capsule, and the method is simple; (3) the method for sealing the interior of the hard capsule provided by the invention has no change on the appearance and the size of the capsule, and cannot influence the subsequent split charging of the hard capsule; (4) the method for sealing the interior of the hard capsule can be widely applied to a large number of fat-soluble medicines, and the bioavailability of the medicines is increased; (5) the method for sealing the interior of the hard capsule provided by the invention can reduce the use of a large amount of mesh rubber during soft capsule pressing, and avoid the condition that the disintegration time in the stomach of the capsule is delayed due to the dehydration of the soft capsule in the storage period.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Detailed Description
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. The following examples are only for illustrating the technical solutions of the present invention more clearly, and therefore are only examples, and the protection scope of the present invention is not limited thereby.
The experimental procedures in the following examples are conventional unless otherwise specified. The test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified. In the quantitative tests in the following examples, three replicates were set, and the data are the mean or the mean ± standard deviation of the three replicates. The adhesive adopted by the embodiment of the invention comprises the following raw material components: povidone K90, CAS No: 9003-39-8; acacia CAS No: 9000-01-05; hypromellose CAS No: 9004-65-3; gelatin CAS No: 9000-70-8; methyl- β -cyclodextrin CAS No: 128446-36-6 and agar CAS No: 9008-18-0.
The invention provides a method for sealing the interior of a hard capsule, which comprises the following steps:
s1: the capsule body and the capsule cap of the hard capsule shell are separated, and then the interior of the capsule body is filled with liquid and/or solid materials.
S2: carrying sealing liquid by nitrogen and/or inert gas, atomizing, and spraying on the inner surface of the capsule cap to form a liquid film; the sealing liquid comprises an adhesive and solvent ethanol, wherein the mass fraction of the adhesive is 5-70%, and the raw material component of the adhesive comprises povidone; the preparation method of the sealing liquid comprises the following steps: and uniformly mixing the adhesive and the solvent to obtain the sealing liquid.
Preferably, the raw material components of the adhesive comprise the following components in parts by weight: 20-30 parts of povidone, 6-8 parts of Arabic gum, 1-2 parts of hydroxypropyl methylcellulose, 10-12 parts of gelatin, 15-20 parts of methyl-beta-cyclodextrin and 4-6 parts of agar; the preparation method of the adhesive comprises the following steps: and uniformly mixing all the raw material components to obtain the adhesive.
S3: and (3) putting the capsule body filled with the material and the capsule cap body attached with the liquid film into hot air at the temperature of 30-40 ℃ and the air speed of 0.1-0.5 m/s for heating until the solvent in the sealing liquid is completely volatilized, and sealing the capsule completely.
The method for sealing the interior of a hard capsule according to the present invention will be further described with reference to the following specific examples.
Example one
The embodiment provides a method for sealing the interior of a hard capsule, which comprises the following steps:
s1: separating the capsule body and the capsule cap of the hard capsule shell, and filling the inside of the capsule body with fat-soluble solid materials.
S2: carrying sealing liquid by nitrogen, atomizing, and spraying on the inner surface of the capsule cap to form a liquid film; wherein the sealing liquid comprises adhesive povidone and solvent ethanol, and the mass fraction of the adhesive is 5%; the preparation method of the sealing liquid comprises the following steps: and uniformly mixing the adhesive and the solvent to obtain the sealing liquid.
S3: and (3) putting the capsule body filled with the materials and the capsule cap body attached with the liquid film into hot air at the temperature of 30 ℃ and the wind speed of 0.1m/s for heating until the solvent in the sealing liquid is completely volatilized, and sealing the capsule completely.
Example two
The embodiment provides a method for sealing the interior of a hard capsule, which comprises the following steps:
s1: separating the capsule body and the capsule cap of the hard capsule shell, and filling the inside of the capsule body with fat-soluble solid materials.
S2: carrying the sealing liquid by inert gas, atomizing and spraying the sealing liquid on the inner surface of the capsule cap to form a liquid film; wherein the sealing liquid comprises adhesive povidone and solvent ethanol, and the mass fraction of the adhesive is 70%; the preparation method of the sealing liquid comprises the following steps: and uniformly mixing the adhesive and the solvent to obtain the sealing liquid.
S3: and (3) putting the capsule body filled with the materials and the capsule cap body attached with the liquid film into hot air at the temperature of 40 ℃ and the air speed of 0.5m/s for heating until the solvent in the sealing liquid is completely volatilized, and sealing the capsule completely.
EXAMPLE III
The embodiment provides a method for sealing the interior of a hard capsule, which comprises the following steps:
s1: separating the capsule body and the capsule cap of the hard capsule shell, and filling the inside of the capsule body with fat-soluble solid materials.
S2: carrying sealing liquid by nitrogen, atomizing, and spraying on the inner surface of the capsule cap to form a liquid film; wherein the sealing liquid comprises adhesive povidone and solvent ethanol, and the mass fraction of the adhesive is 40%; the preparation method of the sealing liquid comprises the following steps: and uniformly mixing the adhesive and the solvent to obtain the sealing liquid.
S3: and (3) putting the capsule body filled with the materials and the capsule cap body attached with the liquid film into hot air at the temperature of 35 ℃ and the wind speed of 0.3m/s for heating until the solvent in the sealing liquid is completely volatilized, and sealing the capsule completely.
Example four
The embodiment provides a method for sealing the interior of a hard capsule, which comprises the following steps:
s1: separating the capsule body and the capsule cap of the hard capsule shell, and filling the inside of the capsule body with fat-soluble solid materials.
S2: carrying sealing liquid by nitrogen, atomizing, and spraying on the inner surface of the capsule cap to form a liquid film; wherein the sealing liquid comprises an adhesive and solvent ethanol, and the mass fraction of the adhesive is 5%; the preparation method of the sealing liquid comprises the following steps: uniformly mixing the adhesive and the solvent to obtain sealing liquid;
the adhesive comprises the following raw material components in parts by weight: 20 parts of povidone, 8 parts of Arabic gum, 1 part of hydroxypropyl methylcellulose, 12 parts of gelatin, 15 parts of methyl-beta-cyclodextrin and 6 parts of agar; the preparation method of the adhesive comprises the following steps: and uniformly mixing all the raw material components to obtain the adhesive.
S3: and (3) putting the capsule body filled with the materials and the capsule cap body attached with the liquid film into hot air at the temperature of 30 ℃ and the wind speed of 0.1m/s for heating until the solvent in the sealing liquid is completely volatilized, and sealing the capsule completely.
EXAMPLE five
The embodiment provides a method for sealing the interior of a hard capsule, which comprises the following steps:
s1: separating the capsule body and the capsule cap of the hard capsule shell, and filling the inside of the capsule body with fat-soluble solid materials.
S2: carrying the sealing liquid by inert gas, atomizing and spraying the sealing liquid on the inner surface of the capsule cap to form a liquid film; wherein the sealing liquid comprises an adhesive and solvent ethanol, and the mass fraction of the adhesive is 70%; the preparation method of the sealing liquid comprises the following steps: uniformly mixing the adhesive and the solvent to obtain sealing liquid;
the adhesive comprises the following raw material components in parts by weight: 30 parts of povidone, 6 parts of Arabic gum, 2 parts of hydroxypropyl methylcellulose, 10 parts of gelatin, 20 parts of methyl-beta-cyclodextrin and 4 parts of agar; the preparation method of the adhesive comprises the following steps: and uniformly mixing all the raw material components to obtain the adhesive.
S3: and (3) putting the capsule body filled with the materials and the capsule cap body attached with the liquid film into hot air at the temperature of 40 ℃ and the air speed of 0.5m/s for heating until the solvent in the sealing liquid is completely volatilized, and sealing the capsule completely.
EXAMPLE six
The embodiment provides a method for sealing the interior of a hard capsule, which comprises the following steps:
s1: separating the capsule body and the capsule cap of the hard capsule shell, and filling the inside of the capsule body with fat-soluble solid materials.
S2: carrying sealing liquid by nitrogen, atomizing, and spraying on the inner surface of the capsule cap to form a liquid film; wherein the sealing liquid comprises an adhesive and solvent ethanol, and the mass fraction of the adhesive is 40%; the preparation method of the sealing liquid comprises the following steps: uniformly mixing the adhesive and the solvent to obtain sealing liquid;
the adhesive comprises the following raw material components in parts by weight: 25 parts of povidone, 7 parts of Arabic gum, 1.5 parts of hydroxypropyl methylcellulose, 11 parts of gelatin, 18 parts of methyl-beta-cyclodextrin and 5 parts of agar; the preparation method of the adhesive comprises the following steps: and uniformly mixing all the raw material components to obtain the adhesive.
S3: and (3) putting the capsule body filled with the materials and the capsule cap body attached with the liquid film into hot air at the temperature of 35 ℃ and the wind speed of 0.3m/s for heating until the solvent in the sealing liquid is completely volatilized, and sealing the capsule completely.
Comparative example 1
The comparative example provides a method for sealing the interior of a hard capsule, comprising the following steps:
s1: separating the capsule body and the capsule cap of the hard capsule shell, and filling the inside of the capsule body with fat-soluble solid materials.
S2: carrying sealing liquid by nitrogen, atomizing, and spraying on the inner surface of the capsule cap to form a liquid film; wherein the sealing liquid comprises an adhesive and solvent ethanol, and the mass fraction of the adhesive is 40%; the preparation method of the sealing liquid comprises the following steps: uniformly mixing the adhesive and the solvent to obtain sealing liquid;
the adhesive comprises the following raw material components in parts by weight: 25 parts of povidone, 7 parts of Arabic gum, 1.5 parts of hydroxypropyl methylcellulose, 18 parts of methyl-beta-cyclodextrin and 5 parts of agar; the preparation method of the adhesive comprises the following steps: and uniformly mixing all the raw material components to obtain the adhesive.
S3: and (3) putting the capsule body filled with the materials and the capsule cap body attached with the liquid film into hot air at the temperature of 35 ℃ and the wind speed of 0.3m/s for heating until the solvent in the sealing liquid is completely volatilized, and sealing the capsule completely.
Comparative example No. two
The comparative example provides a method for sealing the interior of a hard capsule, comprising the following steps:
s1: separating the capsule body and the capsule cap of the hard capsule shell, and filling the inside of the capsule body with fat-soluble solid materials.
S2: carrying sealing liquid by nitrogen, atomizing, and spraying on the inner surface of the capsule cap to form a liquid film; wherein the sealing liquid comprises an adhesive and solvent ethanol, and the mass fraction of the adhesive is 40%; the preparation method of the sealing liquid comprises the following steps: uniformly mixing the adhesive and the solvent to obtain sealing liquid;
the adhesive comprises the following raw material components in parts by weight: 25 parts of povidone, 7 parts of Arabic gum, 1.5 parts of hydroxypropyl methylcellulose, 11 parts of gelatin and 5 parts of agar; the preparation method of the adhesive comprises the following steps: and uniformly mixing all the raw material components to obtain the adhesive.
S3: and (3) putting the capsule body filled with the materials and the capsule cap body attached with the liquid film into hot air at the temperature of 35 ℃ and the wind speed of 0.3m/s for heating until the solvent in the sealing liquid is completely volatilized, and sealing the capsule completely.
The hard capsules of the first to sixth seals of the examples of the present invention were systematically evaluated for their effects by functional tests, and the hard capsules of the first and second comparative examples were used as controls.
1. Bioavailability of
Bioavailability (F) refers to the relative amount of a drug that is absorbed into the systemic blood circulation after being administered by the extravascular route. F ═ (a/D) × 100%; a is the total amount of the medicine in the body, and D is the dosage. Many factors influence the bioavailability, including the size of the drug particles, the crystal form, the compactness of the filling agent, the excipient, the production process and the like, and the bioavailability is an index for evaluating the absorption degree of the preparation.
The solid fat-soluble materials (certain fat-soluble medicines) adopted in the first embodiment to the sixth embodiment and the first comparative example and the second comparative example are all the same in properties, and the bioavailability of the closed hard capsules obtained by different sealing methods is detected (the bioavailability and the bioequivalence test guiding principle of the pharmaceutical preparation are determined according to the Chinese pharmacopoeia 2015 year version 9011) to represent the influence of different methods on the bioavailability. The bioavailability of the hard capsules of the fat-soluble drug sold in the pharmacy is recorded as 1, and the calculated relative bioavailability of the capsules of other groups is recorded in table 1 below.
TABLE 1 Effect on bioavailability
| Group of | Relative bioavailability | Group of | Relative bioavailability |
| Example one | 1.265 | Example four | 1.463 |
| Example two | 1.257 | EXAMPLE five | 1.459 |
| EXAMPLE III | 1.279 | EXAMPLE six | 1.468 |
| Comparative example 1 | 1.035 | Comparative example No. two | 1.136 |
2. Disintegration time
Disintegration refers to the physical dissolution process of a pharmaceutical formulation prior to absorption. The disintegration time refers to the time for pills, tablets and capsules to be disintegrated into granules under certain conditions, and is a main factor influencing the bioavailability of oral medicaments.
According to the examination method of disintegration time limit of Chinese pharmacopoeia 95 edition, disintegration means that the solid preparation is disintegrated and dissolved or broken into particles in the examination time limit, and the particles except insoluble coating materials or broken capsule shells should pass through a screen. The determination of disintegration time limit adopts a lifting disintegration apparatus, the common tablet can be completely disintegrated within 15min, the hard capsule in the capsule can be completely disintegrated within 30min, and the soft capsule can be completely disintegrated within 1 h.
The solid fat-soluble materials (certain fat-soluble medicines) adopted in the first to sixth embodiments, the first comparative example and the second comparative example of the invention have the same properties, the disintegration time of the closed hard capsules obtained by different sealing methods is detected (determined according to 95 th edition of Chinese pharmacopoeia) to represent the influence of different methods on the disintegration time, the results obtained by the determination are shown in the following table 2, and the disintegration time of the hard capsules of the fat-soluble medicines sold in a pharmacy is 28.54 min.
TABLE 2 Effect on disintegration time
| Group of | Disintegration time (min) | Group of | Disintegration time (min) |
| Example one | 25.28 | Example four | 21.14 |
| Example two | 25.16 | EXAMPLE five | 20.93 |
| EXAMPLE III | 25.03 | EXAMPLE six | 20.81 |
| Comparative example 1 | 28.15 | Comparative example No. two | 26.37 |
It should be noted that, in addition to the cases listed in the first to sixth examples, it is also possible to select other preparation method parameters and raw material component ratios.
The technical scheme provided by the invention has the following beneficial effects: (1) according to the method for sealing the interior of the hard capsule, the sealing liquid is attached to the interior of the capsule cap in a spraying mode and the like before the hard capsule is combined, and after the capsule is locked, the sealing liquid solvent is dried to form the seal for the hard capsule, so that the seal of the liquid capsule is realized, the leakage is prevented, and meanwhile, the isolation of oxygen-sensitive solid contents from air can be realized, and the oxidation in the storage process is avoided; (2) the invention uses inert gas to carry sealing liquid, when the inner surface of the capsule cap is coated with the sealing liquid, the inert gas can protect the materials in the capsule, and the method is simple; (3) the method for sealing the interior of the hard capsule provided by the invention has no change on the appearance and the size of the capsule, and cannot influence the subsequent split charging of the hard capsule; (4) the method for sealing the interior of the hard capsule can be widely applied to a large number of fat-soluble medicines, and the bioavailability of the medicines is increased; (5) the method for sealing the interior of the hard capsule provided by the invention can reduce the use of a large amount of mesh rubber during soft capsule pressing, and avoid the condition that the disintegration time in the stomach of the capsule is delayed due to the dehydration of the soft capsule in the storage period.
It is to be noted that, unless otherwise specified, technical or scientific terms used herein shall have the ordinary meaning as understood by those skilled in the art to which the invention pertains. Unless specifically stated otherwise, the relative steps, numerical expressions, and values of the components and steps set forth in these embodiments do not limit the scope of the present invention. In all examples shown and described herein, unless otherwise specified, any particular value should be construed as merely illustrative, and not restrictive, and thus other examples of example embodiments may have different values.
In the description of the present invention, it is to be understood that the terms "first", "second" and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implying any number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present invention, "a plurality" means two or more unless specifically defined otherwise.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention, and all of the technical solutions are covered in the protective scope of the present invention.
Claims (3)
1. A method for sealing the interior of a hard capsule is characterized by comprising the following steps:
s1: separating a capsule body and a capsule cap of a hard capsule shell, and then filling materials in the capsule body;
s2: spraying sealing liquid on the inner surface of the capsule cap to form a liquid film;
s3: heating the capsule body filled with the materials and the capsule cap body attached with the liquid film until the capsule is completely sealed;
the S2 specifically includes: carrying sealing liquid by gas, atomizing and spraying the sealing liquid on the inner surface of the capsule cap to form a liquid film; wherein the gas is nitrogen;
in the step S2, the sealing liquid comprises an adhesive and a solvent, wherein the mass fraction of the adhesive is 5-70%;
the raw material components of the adhesive comprise povidone, and the solvent is ethanol;
the adhesive comprises the following raw material components in parts by weight: 20-30 parts of povidone, 6-8 parts of Arabic gum, 1-2 parts of hydroxypropyl methylcellulose, 10-12 parts of gelatin, 15-20 parts of methyl-beta-cyclodextrin and 4-6 parts of agar;
in S3, the heating is: heating the combined capsules in hot air at 30-40 ℃; wherein the wind speed of the hot wind is 0.1-0.5 m/s;
in the step S1, the physical state of the material is liquid and/or solid.
2. The method of sealing the inside of a hard capsule according to claim 1,
the preparation method of the adhesive comprises the following steps: and uniformly mixing all the raw material components to obtain the adhesive.
3. The method of sealing the inside of a hard capsule according to claim 1,
the preparation method of the sealing liquid comprises the following steps: and uniformly mixing the adhesive and the solvent to obtain the sealing liquid.
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| CN108143724A (en) * | 2018-03-05 | 2018-06-12 | 上海祺宇生物科技有限公司 | A kind of high oxygen-impermeable plant hollow capsule and preparation method thereof |
| CN108261407A (en) * | 2018-03-05 | 2018-07-10 | 上海祺宇生物科技有限公司 | A kind of hypromellose Capsules for being used to suck medicament |
| CN108498479A (en) * | 2018-04-16 | 2018-09-07 | 绍兴康可胶囊有限公司 | A kind of filling liquid type empty hard capsule |
| US20210154099A1 (en) * | 2019-11-22 | 2021-05-27 | Karl Wei Cao | Top liquid fill method and apparatus for hard capsules |
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| CN1440740A (en) * | 2002-02-26 | 2003-09-10 | 潮州市药用胶囊厂 | New technology for filling soft preparation into hard capsule |
| CN2704543Y (en) * | 2003-10-13 | 2005-06-15 | 潮州市药用胶囊厂 | Full-automatic hard capsule liquid and soft body filling machine |
| CN104940161A (en) * | 2015-06-10 | 2015-09-30 | 绍兴康可胶囊有限公司 | Preparation method of sealing compound for hard hollow capsules |
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