CN112336711A - 一种赖氨葡锌口腔崩解片 - Google Patents
一种赖氨葡锌口腔崩解片 Download PDFInfo
- Publication number
- CN112336711A CN112336711A CN202011269036.1A CN202011269036A CN112336711A CN 112336711 A CN112336711 A CN 112336711A CN 202011269036 A CN202011269036 A CN 202011269036A CN 112336711 A CN112336711 A CN 112336711A
- Authority
- CN
- China
- Prior art keywords
- lysine
- zinc gluconate
- orally disintegrating
- disintegrating tablet
- fumaric acid
- 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.)
- Granted
Links
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims abstract description 23
- 239000004472 Lysine Substances 0.000 title claims abstract description 17
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 title claims abstract description 17
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims abstract description 48
- 229960000306 zinc gluconate Drugs 0.000 claims abstract description 30
- 239000011670 zinc gluconate Substances 0.000 claims abstract description 30
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 28
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims abstract description 25
- 235000011478 zinc gluconate Nutrition 0.000 claims abstract description 25
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims abstract description 24
- 239000001530 fumaric acid Substances 0.000 claims abstract description 24
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229960005337 lysine hydrochloride Drugs 0.000 claims abstract description 19
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims abstract description 18
- 229960003646 lysine Drugs 0.000 claims abstract description 16
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 14
- 229930195725 Mannitol Natural products 0.000 claims abstract description 14
- 229930006000 Sucrose Natural products 0.000 claims abstract description 14
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims abstract description 14
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 14
- 239000000594 mannitol Substances 0.000 claims abstract description 14
- 235000010355 mannitol Nutrition 0.000 claims abstract description 14
- 239000005720 sucrose Substances 0.000 claims abstract description 14
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract description 12
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229960001681 croscarmellose sodium Drugs 0.000 claims abstract description 12
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 12
- 238000005469 granulation Methods 0.000 claims abstract description 6
- 230000003179 granulation Effects 0.000 claims abstract description 6
- 239000003826 tablet Substances 0.000 claims description 24
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 21
- 239000000463 material Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- DDKJKQVNNATMAD-JEDNCBNOSA-N (2s)-2,6-diaminohexanoic acid;zinc Chemical compound [Zn].NCCCC[C@H](N)C(O)=O DDKJKQVNNATMAD-JEDNCBNOSA-N 0.000 claims description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 2
- 229960002598 fumaric acid Drugs 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- 229960003194 meglumine Drugs 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 238000007873 sieving Methods 0.000 claims description 2
- 229940083575 sodium dodecyl sulfate Drugs 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 8
- 229910052782 aluminium Inorganic materials 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000008187 granular material Substances 0.000 description 8
- 229920003023 plastic Polymers 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000012535 impurity Substances 0.000 description 7
- 238000004806 packaging method and process Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 210000000214 mouth Anatomy 0.000 description 4
- 239000012088 reference solution Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- STLFUWRAUIJKJC-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;zinc Chemical compound [Zn].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O STLFUWRAUIJKJC-BTVCFUMJSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 206010048259 Zinc deficiency Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000007908 dry granulation Methods 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 208000001140 Night Blindness Diseases 0.000 description 1
- 208000007117 Oral Ulcer Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 208000002399 aphthous stomatitis Diseases 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000008717 functional decline Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229940091251 zinc supplement Drugs 0.000 description 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Nutrition Science (AREA)
- Obesity (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Zoology (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及一种赖氨葡锌口腔崩解片，属于药物制剂技术领域。本发明所述赖氨葡锌口腔崩解片，含有盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠2‑4g、富马酸4‑6g、甘露醇（粒化）69‑73g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。本发明提供了一种稳定的赖氨葡锌口腔崩解片。
Description
技术领域
本发明涉及一种赖氨葡锌口腔崩解片，属于药物制剂技术领域。
背景技术
赖氨葡锌是用于预防和治疗缺乏赖氨酸和锌导致的疾病。市售的赖氨葡锌剂型多为颗粒剂，另外还有口服片剂、口服液体制剂、软胶囊剂等剂型。
赖氨酸是人体所需且无法自己合成的一种氨基酸，通过将其制成盐酸盐，加入处方中，制成所需的剂型。盐酸赖氨酸易溶于水，微溶于醇，不溶于醚。主要作用是促进生长，增强体质，增强食欲，改善营养不良的状况，改善失眠，提高记忆力。帮助产生抗体、激素和酶，提高机体的免疫力。也可以促进钙的吸收，治疗和防止骨质疏松症，降低血中甘油三酯的水平，预防心脑血管疾病的产生。葡萄糖酸锌为白色结晶或颗粒状粉末，易溶于水，不溶于乙醇，不溶于氯仿、乙醚等。葡萄糖酸锌是锌元素缺乏的患者普遍选用的一种补锌产品。本品制剂需要遮光密闭保存。缺锌可以出现消化功能减退、生长发育落后、免疫功能降低、智能发育延迟。严重的还可以有脱发、皮肤粗糙、皮炎、地图舌、反复的口腔溃疡、伤口愈合延迟、贫血、夜盲等疾病。
此类药品针对的患者包括一些特殊人群，比如儿童，儿童服药的依从性较差，对于口感略差的颗粒剂，难吞咽的片剂和胶囊剂等，难以达到治疗效果；另外，对于特殊环境下需要无水服药的情况，颗粒剂、片剂等服用不便；对于需要分剂量的患者，因颗粒剂包装的问题，无法精确分出合适的服用剂量。
市售的赖氨葡锌片剂，因片形较大，难以吞咽，较难被服药困难者接受。且在高温高湿环境下，产品有关物质增长迅速，导致产品质量不稳定，不易长期保存。
口腔崩解片，是一种在无水或只有少量水存在的环境下，在口腔中能快速崩解或溶解并能快速起效的片剂。一般要求口腔崩解片在口内的崩解时间在1min以内，对于水溶性好的药物，一般在35s内即可全部在口中崩解完全，药物可通过口腔和食道中的黏膜溶解和部分吸收，并且在食道中无滞留现象。
发明内容
发明目的：针对当前赖氨葡锌片剂存在的服用不便和稳定性问题，本发明的目的是提供一种赖氨葡锌口腔崩解片，并解决存放不稳定问题。
试验发现，在处方中加入一定量的十二烷基硫酸钠和富马酸，能够解决片剂在高温高湿环境下的不稳定问题。
本发明所述赖氨葡锌口腔崩解片，使用干法制粒压片技术，利用片剂溶胀或者崩解剂吸水产生的崩解力促使片剂迅速崩解，快速起效。
本发明所用到的十二烷基硫酸钠和富马酸均为在天津市科密欧化学试剂有限公司购买。
本发明的技术方案是：
一种赖氨葡锌口腔崩解片，含有盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠2-4g、富马酸4-6g、甘露醇（粒化）69-73g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。
十二烷基硫酸钠常用作表面活性剂，其含有两亲性基团，对水溶性和脂溶性物质的亲和性均较好；富马酸常作为芳香剂，在此处方中两种物质相互作用，可以保护本发明赖氨葡锌口崩片中的活性成分，使其与水接触减少，进而延缓其降解反应发生，使稳定性期间有关物质控制较好。
本发明创造性的发现十二烷基硫酸钠和富马酸在处方中均存在其最佳用量范围，当用量高于本声明所述范围时，口内崩解效果较差；当用量低于本发明所述范围的低限时，达不到稳定性控制效果。
优选的，本发明所述赖氨葡锌口腔崩解片，含有盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠3g、富马酸5g、甘露醇（粒化）70g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。
本发明所述的口腔崩解片使用普通的压片设备即可实现制备。所述片剂的制备方法采用干法制粒压片工艺。
具体操作可以按照以下方法进行：
第一步：将甘露醇（粒化）、盐酸赖氨酸、葡萄糖酸锌、十二烷基硫酸钠、富马酸、交联聚维酮、蔗糖、依次按处方量称取，投入湿法制粒机中，将物料混合均匀，备用；
第二步：将混匀的物料用干法制粒机进行制粒，备用；
第三步：过筛制粒，加入硬脂酸镁，混合均匀；测定含量，确定压片片重；
第四步：用压片机压片，压片冲模为φ8mm，片重200mg左右，硬度控制在3kg-4kg。
有益效果
相比于常规的剂型，口腔崩解片不需要水既可以达到吸收快，生物利用度高，肠道残留少，副作用低，还可以避免部分肝脏首过效应。对于稳定性期间考察对比颗粒剂，其外观性状基本无变化，有关物质控制较好，颗粒剂会出现结块，有关物质相对增长略快的问题。本发明的处方中加入十二烷基硫酸钠和富马酸，可以减缓其有关物质增长的问题。
本发明提供了一种稳定的赖氨葡锌口腔崩解片，适合更多人群服用，且使用方法简单，避免了用水吞服，用药方便，还能提高特殊患者的顺应性，对保存环境和对包装材料的要求，也较颗粒剂简单，可节约生产成本，适合工业化生产。
具体实施例
以下，列举实施例和比较例，对本发明进行进一步的具体说明，但本发明不受他们的限制。
实施例1 . 盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠2g、富马酸4g、甘露醇（粒化）73g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。按说明书技术方案所述制备方法制备1000片，铝塑包装。
实施例2 . 盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠3g、富马酸5g、甘露醇（粒化）71 g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。按说明书技术方案所述制备方法制备1000片，铝塑包装。
实施例3. 盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠4g、富马酸6g、甘露醇（粒化）69g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。按说明书技术方案所述制备方法制备1000片，铝塑包装。
对比例1 . 盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠6g、富马酸8g、甘露醇（粒化）70g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。参考说明书技术方案所述制备方法制备1000片，铝塑包装。
对比例2. 盐酸赖氨酸40g、葡萄糖酸锌35g、富马酸5g、甘露醇（粒化）75g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。参考说明书技术方案所述制备方法制备1000片，铝塑包装。
对比例3. 盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠3g、甘露醇（粒化）75g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。参考说明书技术方案所述制备方法制备1000片，铝塑包装。
对比例4 . 盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠0.5g、富马酸1g、甘露醇（粒化）71 g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。按说明书技术方案所述制备方法制备1000片，铝塑包装。
参考说明书技术方案所述制备方法制备1000片，铝塑包装。
试验例1：
分别取实施例1-3、对照例1-4产品进行崩解时限检查，检查方法依据2020版中国药典四部通则0921项下口崩片崩解时限检查法进行测定，结果记录于表1。
表1 崩解时限测定结果
表1数据说明：对比例1产品（十二烷基硫酸钠和富马酸用量高于本发明所述范围）口内崩解效果较差，崩解时间较长，达不到口崩片崩解时限检测的要求。
实施例1-3产品、对比例2-4产品其崩解时间较短，符合要求。说明本发明技术方案、以及低于本发明技术方案底限范围以下的十二烷基硫酸钠和富马酸用量，均能获得很好的崩解时限。
试验例2：
分别取实施例1-3、对比例1-4产品各200片，置于温恒湿箱中，温度40℃±2℃，相对湿度70%RH±5%，分别于第1月末、2月末、3月末、6月末取样观察外观并检测总杂，数据记录于表2、表3。
总杂测定：
色谱条件：高效液相色谱仪：Agilent1200 ；InertsiAmide色谱柱（250*4.6mm，5μm），检测波长203nm，；流速为1ml/min，柱温30℃，进样量为10μl.
流动相A：磷酸盐缓冲液-乙腈（32:68）
流动相B：磷酸盐缓冲液-乙腈（95:5）
按下表进行梯度洗脱：
混合对照品溶液的配置：取盐酸赖氨酸80.00mg、葡萄糖酸锌80.00mg至20ml量瓶中，加水使溶解，并稀释至刻度，摇匀，得对照品储备液①，精密量取对照品储备液①5ml至10ml量瓶中，加水稀释至刻度，摇匀，即得。
供试品溶液的制备，取普通赖氨葡锌颗粒，赖氨葡锌口崩片分别用水溶解，设计合理的稀释步骤，将其稀释成含有盐酸赖氨酸和葡萄糖酸锌的浓度与对照品溶液相当；赖氨葡锌颗粒剂因处方中盐酸赖氨酸的处方量较大，所以需要按照盐酸赖氨酸的配置浓度与对照品溶液相当即可。
空白对照溶液的配置，取除活性成分外的各辅料，按处方量配置空白辅料，用与供试品溶液相同的配制方法制备空白对照溶液。
分别将混合对照品溶液、供试品溶液、空白对照溶液分别10μl注入液相色谱仪，记录色谱图。
下表是加速6个月稳定性期间检测的不同样品有关物质的变化情况，杂质含量指代总杂含量（%）。
表2 实施例1-3、对比例1-3产品外观变化汇总
表2数据说明：对比例2、对比例3产品在稳定性试验箱加速条件放置6个月后其片子颜色与0天比较明显变深，实施例1-3和对比例1产品外观无明显变化，说明适宜量十二烷基硫酸钠和富马酸的加入，对产品的稳定起了积极的作用。
表3 实施例1-3、对比例1-3产品总杂情况汇总
表3数据说明：在相同材质的包装条件下，在相同的实验环境下，实施例1-3产品、对比例1产品总杂变化很小，说明合适量十二烷基硫酸钠和富马酸的加入，对产品的稳定性起了很好的积极作用。
对比例2-4样品总杂升高明显，说明十二烷基硫酸钠和富马酸的加入量低于本发明范围下限时，不能控制本发明所述口崩片的稳定性。
Claims (3)
1.一种赖氨葡锌口腔崩解片，其特征在于，含有盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠2-4g、富马酸4-6g、甘露醇（粒化）69-73g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。
2.根据权利要求1所述所述赖氨葡锌口腔崩解片，其特征在于，含有盐酸赖氨酸40g、葡萄糖酸锌35g、十二烷基硫酸钠3g、富马酸5g、甘露醇（粒化）70g、蔗糖4g、交联羧甲基纤维素钠40g、硬脂酸镁2g。
3.权利要求1所述所述赖氨葡锌口腔崩解片的制备方法，其特征在于，包括如下步骤：
第一步：将甘露醇（粒化）、盐酸赖氨酸、葡萄糖酸锌、十二烷基硫酸钠、富马酸、交联聚维酮、蔗糖、依次按处方量称取，投入湿法制粒机中，将物料混合均匀，备用；
第二步：将混匀的物料用干法制粒机进行制粒，备用；
第三步：过筛制粒，加入硬脂酸镁，混合均匀；测定含量，确定压片片重；
第四步：用压片机压片，硬度控制在3kg-4kg。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011269036.1A CN112336711B (zh) | 2020-11-13 | 2020-11-13 | 一种赖氨葡锌口腔崩解片 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011269036.1A CN112336711B (zh) | 2020-11-13 | 2020-11-13 | 一种赖氨葡锌口腔崩解片 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112336711A true CN112336711A (zh) | 2021-02-09 |
| CN112336711B CN112336711B (zh) | 2021-09-14 |
Family
ID=74363656
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011269036.1A Active CN112336711B (zh) | 2020-11-13 | 2020-11-13 | 一种赖氨葡锌口腔崩解片 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112336711B (zh) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634013A (zh) * | 2004-10-25 | 2005-07-06 | 北京科信必成医药科技发展有限公司 | 葡萄糖酸锌口腔崩解片及其制备工艺 |
| FR2870738A1 (fr) * | 2004-05-26 | 2005-12-02 | Oreal | Composition cosmetique comprenant des microspheres |
| CN1943594A (zh) * | 2006-09-20 | 2007-04-11 | 张国清 | 一种赖氨酸磷酸氢钙口腔崩解片 |
| CN102793681A (zh) * | 2011-05-23 | 2012-11-28 | 江苏豪森药业股份有限公司 | 包含苯并咪唑衍生物的固体药物组合物 |
| CN107823150A (zh) * | 2017-10-25 | 2018-03-23 | 北京素维生物科技有限公司 | 一种可快速分散的片剂及其制备方法 |
-
2020
- 2020-11-13 CN CN202011269036.1A patent/CN112336711B/zh active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2870738A1 (fr) * | 2004-05-26 | 2005-12-02 | Oreal | Composition cosmetique comprenant des microspheres |
| CN1634013A (zh) * | 2004-10-25 | 2005-07-06 | 北京科信必成医药科技发展有限公司 | 葡萄糖酸锌口腔崩解片及其制备工艺 |
| CN1943594A (zh) * | 2006-09-20 | 2007-04-11 | 张国清 | 一种赖氨酸磷酸氢钙口腔崩解片 |
| CN102793681A (zh) * | 2011-05-23 | 2012-11-28 | 江苏豪森药业股份有限公司 | 包含苯并咪唑衍生物的固体药物组合物 |
| CN107823150A (zh) * | 2017-10-25 | 2018-03-23 | 北京素维生物科技有限公司 | 一种可快速分散的片剂及其制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| JINICHI FUKAMI ET AL.: "Development of fast disintegrating compressed tablets using amino acid as disintegration accelerator: evaluation of wetting and disintegration of tablet on the basis of surface free energy", 《CHEM PHARM BULL (TOKYO)》 * |
| 钟正贤等: "L-赖氨酸锌片兔体内生物利用度研究", 《广西科学》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112336711B (zh) | 2021-09-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5532274A (en) | Orally administerable drugs for the treatment of central dopamine deficiency conditions | |
| CN107669683B (zh) | 含有西格列汀与二甲双胍的药物组合物 | |
| US11883399B2 (en) | Bromocriptine formulations | |
| AU2013304795B2 (en) | Solid pharmaceutical preparation containing levothyroxine | |
| EP1707192A2 (en) | Pharmaceutical composition | |
| CN112716903B (zh) | 一种氨氯地平干混悬剂及其制备方法 | |
| JP2916227B2 (ja) | ビタミンｂ▲下１▼▲下２▼類含有組成物 | |
| EP4079295A1 (en) | Composition having improved solubility and bioavailability of olaparib | |
| CN113456604A (zh) | 一种枸橼酸西地那非口崩片及其制备方法 | |
| CN112336711B (zh) | 一种赖氨葡锌口腔崩解片 | |
| WO2021042278A1 (zh) | 一种阿昔莫司多单元缓释微丸片及其制备方法 | |
| JP2006176496A (ja) | 固形剤およびその製造方法 | |
| US6248361B1 (en) | Water-soluble folic acid compositions | |
| CN110917157B (zh) | 含炔基化合物的药物组合物、其制备方法及应用 | |
| JP2022130003A (ja) | 漢方エキス又は植物性生薬エキスを含む固形製剤及びその製造方法、並びに固形製剤の崩壊性を向上させる方法 | |
| CN114272219A (zh) | 一种盐酸多奈哌齐片及其制备方法 | |
| CN103315983B (zh) | 一种雷沙吉兰制剂及其制备方法 | |
| CN113230218A (zh) | 一种Ca-AKG咀嚼片及其制备方法 | |
| CN106890146A (zh) | 一种磷酸奥司他韦分散片及其制备方法 | |
| WO2007049626A1 (ja) | カベルゴリン含有経口固形製剤 | |
| CN104644601B (zh) | 一种卡培他滨片剂 | |
| JP2864737B2 (ja) | 徐放性製剤用基剤並びに徐放性製剤及び該製剤の製造方法 | |
| CN103860497A (zh) | 一种美洛昔康分散片及其制备方法 | |
| EP4327805A1 (en) | 13c methacetin granule, and preparation method therefor and use thereof | |
| JPH115739A (ja) | ベザフィブラート含有持続性製剤およびその製造方法 |
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 | ||
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20210726 Address after: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province Applicant after: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Address before: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province Applicant before: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Applicant before: Dijia Pharmaceutical Group Co.,Ltd. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Lysine zinc gluconate orally disintegrating tablet Effective date of registration: 20211025 Granted publication date: 20210914 Pledgee: Bank of China Limited Weihai Branch Pledgor: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Registration number: Y2021980010533 |