CN111728954A - Betahistine hydrochloride soft capsule and preparation method thereof - Google Patents
Betahistine hydrochloride soft capsule and preparation method thereof Download PDFInfo
- Publication number
- CN111728954A CN111728954A CN202010279467.XA CN202010279467A CN111728954A CN 111728954 A CN111728954 A CN 111728954A CN 202010279467 A CN202010279467 A CN 202010279467A CN 111728954 A CN111728954 A CN 111728954A
- Authority
- CN
- China
- Prior art keywords
- betahistine hydrochloride
- soft capsule
- capsules
- soft
- glue solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- UUQMNUMQCIQDMZ-UHFFFAOYSA-N betahistine Chemical compound CNCCC1=CC=CC=N1 UUQMNUMQCIQDMZ-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 229960001392 betahistine hydrochloride Drugs 0.000 title claims abstract description 79
- 239000007901 soft capsule Substances 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title abstract description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000003814 drug Substances 0.000 claims abstract description 32
- 239000002775 capsule Substances 0.000 claims abstract description 31
- 239000002994 raw material Substances 0.000 claims abstract description 27
- 108010010803 Gelatin Proteins 0.000 claims abstract description 23
- 239000008273 gelatin Substances 0.000 claims abstract description 23
- 229920000159 gelatin Polymers 0.000 claims abstract description 23
- 235000019322 gelatine Nutrition 0.000 claims abstract description 23
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 23
- 239000003292 glue Substances 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000007788 liquid Substances 0.000 claims abstract description 20
- 239000000843 powder Substances 0.000 claims abstract description 17
- 239000011248 coating agent Substances 0.000 claims abstract description 13
- 238000000576 coating method Methods 0.000 claims abstract description 13
- 238000003756 stirring Methods 0.000 claims abstract description 13
- 235000015112 vegetable and seed oil Nutrition 0.000 claims abstract description 12
- 239000008158 vegetable oil Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 11
- 229910000831 Steel Inorganic materials 0.000 claims abstract description 10
- 238000001035 drying Methods 0.000 claims abstract description 10
- 238000010438 heat treatment Methods 0.000 claims abstract description 10
- 238000007873 sieving Methods 0.000 claims abstract description 10
- 239000010959 steel Substances 0.000 claims abstract description 10
- 239000012153 distilled water Substances 0.000 claims abstract description 8
- 238000000465 moulding Methods 0.000 claims abstract description 7
- 238000010298 pulverizing process Methods 0.000 claims abstract description 7
- 239000002352 surface water Substances 0.000 claims abstract description 7
- 238000005406 washing Methods 0.000 claims abstract description 7
- 239000000945 filler Substances 0.000 claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims abstract description 3
- 239000002702 enteric coating Substances 0.000 claims description 13
- 238000009505 enteric coating Methods 0.000 claims description 13
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical group NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 10
- 238000003825 pressing Methods 0.000 claims description 10
- 239000004014 plasticizer Substances 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 7
- 239000006184 cosolvent Substances 0.000 claims description 6
- 229960004050 aminobenzoic acid Drugs 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 4
- 235000019483 Peanut oil Nutrition 0.000 claims description 3
- 238000011049 filling Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000002736 nonionic surfactant Substances 0.000 claims description 3
- 239000000312 peanut oil Substances 0.000 claims description 3
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims description 3
- 235000012424 soybean oil Nutrition 0.000 claims description 3
- 239000003549 soybean oil Substances 0.000 claims description 3
- 238000005507 spraying Methods 0.000 claims description 3
- 238000003892 spreading Methods 0.000 claims description 3
- 230000007480 spreading Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 abstract description 4
- 238000007723 die pressing method Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000007787 solid Substances 0.000 abstract description 4
- 239000002552 dosage form Substances 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 19
- 238000004090 dissolution Methods 0.000 description 14
- 235000011187 glycerol Nutrition 0.000 description 8
- 230000017531 blood circulation Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 208000027530 Meniere disease Diseases 0.000 description 2
- 208000009205 Tinnitus Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940113224 gelatin pill Drugs 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 231100000886 tinnitus Toxicity 0.000 description 2
- 102000016893 Amine Oxidase (Copper-Containing) Human genes 0.000 description 1
- 108010028700 Amine Oxidase (Copper-Containing) Proteins 0.000 description 1
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 1
- 206010008088 Cerebral artery embolism Diseases 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 229940087098 Oxidase inhibitor Drugs 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000001407 Vascular Headaches Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 210000003477 cochlea Anatomy 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 201000005851 intracranial arteriosclerosis Diseases 0.000 description 1
- 201000010849 intracranial embolism Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 239000003186 pharmaceutical solution Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
Classifications
-
- 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
- A61K9/4816—Wall or shell material
- A61K9/4825—Proteins, e.g. gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- 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
- A61K9/4816—Wall or shell material
-
- 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
-
- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
-
- 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
- A61K9/4891—Coated capsules; Multilayered drug free capsule shells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Botany (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicinal Preparation (AREA)
Abstract
A betahistine hydrochloride soft capsule and its preparation method, the soft capsule contains active ingredient betahistine hydrochloride, each soft capsule contains betahistine hydrochloride 4 mg-8 mg, the soft capsule includes raw materials powder or liquid medicine and two parts of glue solution, the said liquid medicine is made up of raw materials powder and filler. Dissolving gelatin, glycerol and distilled water to prepare a glue solution, coating the glue solution on the surface of a flat steel plate to enable the thickness of the glue solution to be uniform, and heating the glue solution to enable surface water to be evaporated into a soft film; pulverizing betahistine hydrochloride raw material medicine, sieving with a 80-mesh sieve, adding vegetable oil, stirring uniformly to obtain liquid medicine, placing the liquid medicine between two pieces of film, molding into capsules by pelleting, opening a template, taking out the capsules, washing twice, and drying to obtain betahistine hydrochloride soft capsules. The advantages are that: belongs to an oral solid preparation, the dosage form is soft capsule, the carrying and the use are convenient, and the moisture absorption of the medicine can be effectively prevented. The steel plate die pressing method and the rotary die pressing method are adopted for manufacturing, the process is simple, and the manufacturing is convenient.
Description
Technical Field
The invention relates to a betahistine hydrochloride soft capsule and a preparation method thereof.
Background
Betahistine hydrochloride is a diamine oxidase inhibitor. Has obvious dilating effect on cerebral blood vessels and cardiovascular blood vessels, especially on the vertebral bottom artery system, obviously increases blood flow of heart, brain and peripheral circulation, improves blood circulation, reduces systemic blood pressure, can increase blood flow of cochlea and anterior floor, thereby eliminating auditory vertigo, tinnitus and auditory occlusion, increasing capillary permeability, promoting absorption of extracellular fluid, eliminating intralymphatic edema, resisting vasoconstriction of catecholamine and reducing arterial pressure, inhibiting plasma coagulation and platelet aggregation induced by ADP, prolonging thrombosis formation time in vitro of white rats, and has slight diuretic effect. The traditional Chinese medicine composition is mainly used for Meniere's syndrome, vascular headache and cerebral arteriosclerosis in clinic, and can be used for treating acute ischemic cerebrovascular diseases, such as cerebral thrombosis, cerebral embolism, transient cerebral circulation insufficiency and the like, and also has the effect of upright vertigo, tinnitus and the like caused by hypertension.
Since the betahistine hydrochloride comes into the market, the betahistine hydrochloride is valued and popular by medical workers and patients due to the definite curative effect and less toxic and side effects, but because of the strong hygroscopicity, the betahistine hydrochloride is difficult to prepare into oral solid preparations, the clinical common use is basically limited to oral solutions and injections (including powder injections and transfusions), and because the cost is high and the carrying and the taking are inconvenient, especially for old patients, the wide application of the betahistine hydrochloride is limited.
Disclosure of Invention
The invention aims to provide a betahistine hydrochloride capsule and a preparation method thereof, belonging to an oral solid preparation, wherein the dosage form is a soft capsule, the carrying and the use are convenient, and the moisture absorption of the medicine can be effectively prevented.
The technical scheme of the invention is as follows:
the betahistine hydrochloride soft capsule is characterized in that: the soft capsule contains betahistine hydrochloride as an active ingredient, each soft capsule contains 4-8 mg of betahistine hydrochloride, the soft capsule comprises two parts of raw material powder or liquid medicine and glue solution, the liquid medicine consists of the raw material powder and fillers, the mass ratio of the raw material powder to the gelatin in the glue solution is 1 (31.25-37.5), and the fillers are vegetable oil.
Further, the glue solution is composed of gelatin, a plasticizer and water, wherein the mass ratio of the gelatin to the plasticizer to the water is 1 (0.6-0.68) and 1 (1-1.5), and the plasticizer is glycerol.
Further, the vegetable oil is peanut oil or soybean oil, and the mass ratio of the vegetable oil to the raw material powder is (3-5): 0.8.
Furthermore, when the soft capsule comprises two parts of raw material powder and glue solution, a cosolvent is also added into the raw material powder.
Further, the cosolvent is p-aminobenzoic acid.
Furthermore, the mass ratio of the raw material powder to the cosolvent is 1: 2.5.
Further, the outer layer of the soft capsule is also coated with an enteric coating, the enteric coating agent consists of polyvinyl alcohol, plasticizer polyethylene glycol and water, and the mass ratio of the polyvinyl alcohol to the polyethylene glycol to the water is 6:1 and 1:20 respectively.
A preparation method of betahistine hydrochloride soft capsules comprises the following specific steps:
dissolving gelatin, glycerol and distilled water to prepare a glue solution, coating the glue solution on the surface of a flat steel plate to enable the thickness to be uniform, and heating at the temperature of 70-95 ℃ to enable surface water to be evaporated into a soft film; pulverizing betahistine hydrochloride raw material medicine, sieving with a 80-mesh sieve, adding vegetable oil, stirring uniformly to obtain liquid medicine, placing the liquid medicine between two pieces of film, molding into capsules by pelleting, opening a template, taking out the capsules, washing twice, and drying to obtain betahistine hydrochloride soft capsules.
A preparation method of betahistine hydrochloride soft capsules comprises the following specific steps:
pulverizing betahistine hydrochloride, sieving with 80 mesh sieve, and placing into a filling tank of an automatic rotary capsule pressing machine for later use; mixing glycerol and water uniformly, heating to 70-80 ℃, adding gelatin, stirring, adding the nonionic surfactant p-aminobenzoic acid after the gelatin is completely dissolved, stirring uniformly, placing into a spreading box of an automatic rotary capsule pressing machine, and starting the automatic rotary capsule pressing machine to prepare the betahistine hydrochloride soft capsule.
A preparation method of betahistine hydrochloride soft capsules comprises the following specific steps:
(1) dissolving gelatin, glycerol and distilled water to prepare a glue solution, coating the glue solution on the surface of a flat steel plate to enable the thickness to be uniform, and heating at the temperature of 70-95 ℃ to enable surface water to be evaporated into a soft film;
(2) crushing the betahistine hydrochloride raw material medicine, sieving the crushed betahistine hydrochloride raw material medicine through a 80-mesh sieve, adding vegetable oil, stirring the mixture evenly to prepare liquid medicine, placing the liquid medicine between two pieces of film, molding the film into capsules by pelleting, opening a template, taking out the capsules, washing the capsules twice, and drying the capsules to obtain betahistine hydrochloride soft capsules;
(3) enteric coating
Dissolving polyvinyl alcohol phthalate and polyethylene glycol in water to prepare enteric coating solution; adding the betahistine hydrochloride soft capsule into a coating machine, starting the coating machine, uniformly spraying the enteric coating solution on the betahistine hydrochloride, and drying to obtain the betahistine hydrochloride enteric soft capsule.
The invention provides a pharmaceutical solution prepared from betahistine hydrochloride raw material and vegetable oil, or a soft capsule prepared from betahistine hydrochloride raw material according to a specified proportion, wherein glycerin is used as a plasticizer and has strong moisture absorption capacity, so that the medicament has good stability, no odor, and is promoted to be a transparent or semitransparent soft capsule, and the appearance, dissolution rate and content of the soft capsule accord with the specifications of Chinese pharmacopoeia. The betahistine hydrochloride soft capsule is soft capsule, belongs to oral solid preparation, is convenient to carry and use, and can effectively prevent the drug from absorbing moisture. The steel plate die pressing method and the rotary die pressing method are adopted for manufacturing, the process is simple, and the manufacturing is convenient.
Detailed Description
The following examples are given for the purpose of illustration only and are not intended to limit the invention.
Example 1
Prescription
Preparation process (pressing method)
(1) Dissolving gelatin, glycerol and distilled water to prepare gelatin solution, coating the gelatin solution on the surface of a flat steel plate to enable the thickness of the gelatin solution to be uniform, heating the gelatin solution at the temperature of 70-95 ℃ to evaporate surface water, and preparing a soft film;
(2) crushing the betahistine hydrochloride raw material medicine, sieving the crushed betahistine hydrochloride raw material medicine with a 80-mesh sieve, adding peanut oil, stirring the mixture evenly to prepare liquid medicine, placing the liquid medicine between two pieces of film, molding the film into capsules by pelleting, opening a template, taking out the capsules, washing the capsules twice, and drying the capsules to obtain 200 betahistine hydrochloride soft capsules, wherein each capsule contains 4mg of betahistine hydrochloride.
According to a dissolution rate determination method (appendix of second part of Chinese pharmacopoeia), samples of the betahistine hydrochloride soft capsules are taken, dissolution rates are respectively determined, and six groups of detection results are shown in table 1:
TABLE 1 dissolution rate test results of six betahistine hydrochloride soft capsules (batch No. 190301)
| 1# | 2# | 3# | 4# | 5# | 6# |
| 95.6％ | 97.3％ | 96.5％ | 95.5％ | 98.1％ | 100.2％ |
According to the dissolution rate determination method (appendix of the second part of Chinese pharmacopoeia), samples of betahistine hydrochloride soft capsules are taken, and the dissolution rate of the products is determined at different times, and the results are shown in table 2:
TABLE 2 dissolution rate test results of betahistine hydrochloride soft capsules at different times (batch No. 190301)
| Time of day | 10 days | 20 days | 30 days | 40 days | 50 days | 60 days |
| Content (wt.) | 90％ | 89％ | 92％ | 85％ | 91％ | 92％ |
According to the dissolution rate determination method (appendix of second part of Chinese pharmacopoeia), 10 betahistine hydrochloride soft capsule samples were taken, and the content uniformity of the 10 groups was determined, and the results are shown in Table 3
TABLE 3 content uniformity of betahistine hydrochloride Soft capsules (batch No. 190301)
| Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7 | Group 8 | Group 9 | Group 10 |
| 90.3％ | 95.1％ | 96.2％ | 91.1％ | 97.8％ | 99.1％ | 92.3％ | 93.4％ | 96.1％ | 98.1％ |
Example 2
Prescription
Pulverizing betahistine hydrochloride, sieving with 80 mesh sieve, and placing into a filling tank of an automatic rotary capsule pressing machine for later use; mixing glycerol and water uniformly, heating to 70-80 ℃, adding gelatin, stirring, adding a nonionic surfactant p-aminobenzoic acid after the gelatin is completely dissolved, stirring uniformly, putting into a spreading box of an automatic rotary capsule pressing machine, and starting the automatic rotary capsule pressing machine to prepare 100 betahistine hydrochloride soft capsules, wherein each capsule contains 8mg of betahistine hydrochloride.
According to the dissolution rate determination method (appendix of second part of Chinese pharmacopoeia), samples of the betahistine hydrochloride soft capsules are taken, the dissolution rates are respectively determined, and six groups of detection results are shown in table 4:
TABLE 4 dissolution test results of the betahistine hydrochloride soft capsules of six groups (batch No. 190302)
| 1# | 2# | 3# | 4# | 5# | 6# |
| 92.1％ | 95.3％ | 94.5％ | 98.2％ | 99.3％ | 95.6％ |
According to the dissolution rate determination method (appendix of the second part of the Chinese pharmacopoeia), samples of betahistine hydrochloride soft capsules are taken, and the dissolution rates of the products are determined at different times, and the results are shown in table 5:
TABLE 5 determination of dissolution rate of betahistine hydrochloride soft capsules at different times (batch No. 190302)
| Time of day | 10 days | 20 days | 30 days | 40 days | 50 days | 60 days |
| Content (wt.) | 88％ | 90％ | 86％ | 90％ | 93％ | 95％ |
According to the dissolution rate determination method (appendix of second part of Chinese pharmacopoeia), 10 betahistine hydrochloride soft capsule samples were taken, and the content uniformity of the 10 groups was determined, and the results are shown in Table 6
TABLE 6 content uniformity of betahistine hydrochloride Soft capsules (batch No. 190302)
| Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7 | Group 8 | Group 9 | Group 10 |
| 95.1％ | 96.2％ | 91.3％ | 94.1％ | 94.2％ | 96.1％ | 98.9％ | 92.1％ | 93.1％ | 96.2％ |
Example 3
Prescription
(1) Dissolving gelatin, glycerol and 25g of distilled water to prepare a glue solution, coating the glue solution on the surface of a flat steel plate to enable the thickness to be uniform, heating the steel plate at the temperature of 70-95 ℃ to evaporate surface water, and preparing a semitransparent soft film;
(2) pulverizing betahistine hydrochloride, sieving with a 80-mesh sieve, adding soybean oil, stirring to obtain a medicinal liquid, placing the medicinal liquid between two films, molding into a gelatin pill by pelleting, opening a template, taking out the gelatin pill, washing twice, and drying to obtain a betahistine hydrochloride soft capsule;
(3) enteric coating
Dissolving 3g of polyvinyl alcohol phthalate and 4000.5 g of polyethylene glycol in 60g of distilled water to prepare enteric coating solution; adding the betahistine hydrochloride soft capsule into a coating machine, starting the coating machine, uniformly spraying the enteric coating solution on the soft capsule, and drying to obtain 200 betahistine hydrochloride enteric soft capsules, wherein each capsule contains 4mg of betahistine hydrochloride.
The acid resistance of the above samples was measured at various times and the results are shown in Table 7:
TABLE 7 acid resistance measurement results (batch No. 190303)
| Time of day | 10 days | 20 days | 30 days | 40 days | 50 days | 60 days |
| Content (wt.) | 95％ | 97％ | 94％ | 96％ | 93％ | 95％ |
The above description is only exemplary of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A betahistine hydrochloride soft capsule is characterized in that: the soft capsule contains betahistine hydrochloride as an active ingredient, each soft capsule contains 4-8 mg of betahistine hydrochloride, the soft capsule comprises two parts of raw material powder or liquid medicine and glue solution, the liquid medicine consists of the raw material powder and fillers, the mass ratio of the raw material powder to the gelatin in the glue solution is 1 (31.25-37.5), and the fillers are vegetable oil.
2. The betahistine hydrochloride soft capsule of claim 1, characterized in that: the glue solution consists of gelatin, a plasticizer and water, wherein the mass ratio of the gelatin to the plasticizer to the water is 1 (0.6-0.68) and 1 (1-1.5), and the plasticizer is glycerol.
3. The betahistine hydrochloride soft capsule of claim 1, characterized in that: the vegetable oil is peanut oil or soybean oil, and the mass ratio of the vegetable oil to the raw material powder is (3-5): 0.8.
4. The betahistine hydrochloride soft capsule of claim 1, characterized in that: when the soft capsule comprises two parts of raw material powder and glue solution, a cosolvent is also added into the raw material powder.
5. The betahistine hydrochloride soft capsule of claim 4, characterized in that: the cosolvent is p-aminobenzoic acid.
6. The betahistine hydrochloride soft capsule of claim 4, characterized in that: the mass ratio of the raw material powder to the cosolvent is 1: 2.5.
7. The betahistine hydrochloride soft capsule of claim 1, characterized in that: the outer layer of the soft capsule is also coated with an enteric coating, the enteric coating agent consists of polyvinyl alcohol, plasticizer polyethylene glycol and water, and the mass ratio of the polyvinyl alcohol to the polyethylene glycol to the water is 6:1 and 1:20 respectively.
8. A method for preparing betahistine hydrochloride soft capsules as claimed in claim 1, which is characterized in that:
dissolving gelatin, glycerol and distilled water to prepare a glue solution, coating the glue solution on the surface of a flat steel plate to enable the thickness to be uniform, and heating at the temperature of 70-95 ℃ to enable surface water to be evaporated into a soft film; pulverizing betahistine hydrochloride raw material medicine, sieving with a 80-mesh sieve, adding vegetable oil, stirring uniformly to obtain liquid medicine, placing the liquid medicine between two pieces of film, molding into capsules by pelleting, opening a template, taking out the capsules, washing twice, and drying to obtain betahistine hydrochloride soft capsules.
9. A method for preparing betahistine hydrochloride soft capsules as claimed in claim 1, which is characterized in that:
pulverizing betahistine hydrochloride, sieving with 80 mesh sieve, and placing into a filling tank of an automatic rotary capsule pressing machine for later use; mixing glycerol and water uniformly, heating to 70-80 ℃, adding gelatin, stirring, adding the nonionic surfactant p-aminobenzoic acid after the gelatin is completely dissolved, stirring uniformly, placing into a spreading box of an automatic rotary capsule pressing machine, and starting the automatic rotary capsule pressing machine to prepare the betahistine hydrochloride soft capsule.
10. A method for preparing betahistine hydrochloride soft capsules as claimed in claim 7, which is characterized in that:
(1) dissolving gelatin, glycerol and distilled water to prepare a glue solution, coating the glue solution on the surface of a flat steel plate to enable the thickness to be uniform, and heating at the temperature of 70-95 ℃ to enable surface water to be evaporated into a soft film;
(2) crushing the betahistine hydrochloride raw material medicine, sieving the crushed betahistine hydrochloride raw material medicine through a 80-mesh sieve, adding vegetable oil, stirring the mixture evenly to prepare liquid medicine, placing the liquid medicine between two pieces of film, molding the film into capsules by pelleting, opening a template, taking out the capsules, washing the capsules twice, and drying the capsules to obtain betahistine hydrochloride soft capsules;
(3) enteric coating
Dissolving polyvinyl alcohol phthalate and polyethylene glycol in water to prepare enteric coating solution; adding the betahistine hydrochloride soft capsule into a coating machine, starting the coating machine, uniformly spraying the enteric coating solution on the betahistine hydrochloride, and drying to obtain the betahistine hydrochloride enteric soft capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010279467.XA CN111728954A (en) | 2020-04-10 | 2020-04-10 | Betahistine hydrochloride soft capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010279467.XA CN111728954A (en) | 2020-04-10 | 2020-04-10 | Betahistine hydrochloride soft capsule and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111728954A true CN111728954A (en) | 2020-10-02 |
Family
ID=72647865
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010279467.XA Pending CN111728954A (en) | 2020-04-10 | 2020-04-10 | Betahistine hydrochloride soft capsule and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111728954A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1686133A (en) * | 2005-04-01 | 2005-10-26 | 徐新盛 | Soft capsule medicinal preparation |
| CN101797237A (en) * | 2010-03-23 | 2010-08-11 | 西南大学 | Betahistine mesilate orally disintegrating tablet and preparation method thereof |
| WO2019205030A1 (en) * | 2018-04-25 | 2019-10-31 | 人福普克药业（武汉）有限公司 | Amantadine hydrochloride soft capsule and preparation method therefor |
| CN110664765A (en) * | 2018-07-02 | 2020-01-10 | 北京人福军威医药技术开发有限公司 | Betahistine sublingual tablet and preparation method and application thereof |
-
2020
- 2020-04-10 CN CN202010279467.XA patent/CN111728954A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1686133A (en) * | 2005-04-01 | 2005-10-26 | 徐新盛 | Soft capsule medicinal preparation |
| CN101797237A (en) * | 2010-03-23 | 2010-08-11 | 西南大学 | Betahistine mesilate orally disintegrating tablet and preparation method thereof |
| WO2019205030A1 (en) * | 2018-04-25 | 2019-10-31 | 人福普克药业（武汉）有限公司 | Amantadine hydrochloride soft capsule and preparation method therefor |
| CN110664765A (en) * | 2018-07-02 | 2020-01-10 | 北京人福军威医药技术开发有限公司 | Betahistine sublingual tablet and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 王云云主编: "《药物制剂技术》", 31 August 2016, 重庆大学出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1832282A1 (en) | Band seal for hard capsule | |
| KR20010075502A (en) | Coated medicament forms with controlled active substance release | |
| CN105496981B (en) | A kind of chitosan oligosaccharide tablet and preparation method thereof | |
| CN114886874B (en) | Oral instant film and preparation method thereof | |
| CN111956652A (en) | Sildenafil oral film agent medicine composition and preparation method thereof | |
| CN104000796B (en) | Coating auxiliary materials, preparation method and coating method for Chinese herb extract preparations | |
| CN107982241B (en) | Potassium sodium dehydroandroan drographolide succinate enteric preparation and preparation method thereof | |
| CN111728954A (en) | Betahistine hydrochloride soft capsule and preparation method thereof | |
| CN107982240B (en) | Potassium sodium dehydroandroan drographolide succinate enteric coated granules capable of being accurately dissolved out and preparation method thereof | |
| CN108785268B (en) | Sotalol hydrochloride preparation and preparation method thereof | |
| CN101152197B (en) | Compound glycyrrhizin dropping pills and method for preparing the same | |
| CN112716956B (en) | Daily-use compound preparation for treating cold and preparation method thereof | |
| CN105193769B (en) | A kind of preparation method of bagodryl hydrochloride oral quick-dissolving film preparation | |
| CN1733109A (en) | Soft capsule for treating coronary disease and process for preparing the same | |
| CN1775208A (en) | Liver-tonifying formulation prepared from silymarin and its preparing method | |
| CN103893151B (en) | A kind of venlafaxine hydrochloride slow-release capsule and preparation method thereof | |
| CN100364506C (en) | Drop pills preparation in use for treating bronchitis and preparation method | |
| CN100348169C (en) | Saussurea involucrata drop pill and its preparation method | |
| CN109330985A (en) | A kind of vitamin C vaginal tablets and preparation method thereof | |
| CN100375613C (en) | Schizandrol dripping pills for decreasing aminopherase and method for preparing the same | |
| CN100364509C (en) | Compound drop pills of dahurian rhododendron leaf and preparation method | |
| CN102397443A (en) | Stagnation eliminating and pain stopping babu paste for treating proliferation of mammary gland and preparation method thereof | |
| CN1626147A (en) | Medication for treating coronary heart disease and angina | |
| CN106727437A (en) | A kind of tenofovir disoproxil fumarate spansule and preparation method thereof | |
| CN100358500C (en) | Fleabane and earthworm dripping pill and its preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201002 |