CN106420649A - Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet - Google Patents
Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet Download PDFInfo
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 title claims abstract description 78
- 229960005489 paracetamol Drugs 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 238000013270 controlled release Methods 0.000 title claims abstract description 24
- 229920000867 polyelectrolyte Polymers 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 22
- 238000000576 coating method Methods 0.000 claims abstract description 21
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 11
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- 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 description 2
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
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- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 claims description 2
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 2
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- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 3
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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- 229940086138 acetaminophen 80 mg Drugs 0.000 description 1
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- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
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- 229940057948 magnesium stearate Drugs 0.000 description 1
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Classifications
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明公开了一种基于聚电解质自组装膜的对乙酰氨基酚压制包衣控释片及其制备方法，属于医药技术领域。本发明所涉及的对乙酰氨基酚压制包衣控释片，由壳聚糖与海藻酸钠所组成的包衣层，与含对乙酰氨基酚的片芯，通过压制包衣技术制得，其在人工胃液(0.1M HCl溶液)中释放2h，后在模拟肠液(0.1M磷酸盐缓冲液)中释放2h，共4h内片剂外层能自主装形成一层稠厚的聚电解质复合物屏障而有效控制片芯内药物释放，使其在12h内能保持形态完整并达到控释的目的。本发明制备的对乙酰氨基酚控释片可显著延长药物在体外释放时间，与普通制剂相比在体外能够达到更平稳的释放，且制备工艺相对简单，为对乙酰氨基酚缓控释制剂的开发提供了一种新的可供选择的剂型。The invention discloses a paracetamol press-coated controlled-release tablet based on a polyelectrolyte self-assembled membrane and a preparation method thereof, belonging to the technical field of medicine. The acetaminophen press-coated controlled-release tablet involved in the present invention is made of a coating layer composed of chitosan and sodium alginate, and a tablet core containing acetaminophen, which is obtained by a press-coating technique. Released in artificial gastric juice (0.1M HCl solution) for 2 hours, and then released in simulated intestinal fluid (0.1M phosphate buffer) for 2 hours, the outer layer of the tablet can self-assemble within 4 hours to form a thick polyelectrolyte complex barrier And effectively control the drug release in the tablet core, so that it can keep the form intact and achieve the purpose of controlled release within 12 hours. The acetaminophen controlled-release tablet prepared by the invention can significantly prolong the release time of the drug in vitro, and can achieve more stable release in vitro compared with common preparations, and the preparation process is relatively simple. The development provides a new alternative dosage form.
Description
技术领域technical field
本发明涉及一种基于聚电解质自组装膜的对乙酰氨基酚压制包衣控释片及其制备方法，属于医药技术领域。The invention relates to a paracetamol press-coated controlled-release tablet based on a polyelectrolyte self-assembled membrane and a preparation method thereof, belonging to the technical field of medicine.
背景技术Background technique
对乙酰氨基酚是国际使用最广泛，用量最大的非处方解热镇痛药，目前国内医药市场上对乙酰氨基酚制剂产品多达几十种，剂型有针剂、胶囊、散剂、冲剂、糖浆、栓剂、滴剂及注射液等。对乙酰氨基酚具有较高的水溶性，正常成年人服用常用剂量后有大约2～3h相对较短的半衰期，普通制剂需服用多次才能维持药效，从而使血药浓度产生“峰谷”现象。当用量过大时，代谢产物对肝脏有损害，可使血红蛋白变性引起溶血，而长期大量服用对乙酰氨基酚对肾功能也有损害，特别是肾功能低下者，易出现肾绞痛或急性肾衰竭以及肝脏损害或瘀胆型肝炎，严重者可致肝昏迷甚至死亡。为此，将其制备成控释片，可降低其在体内最大血药浓度，同时较长时间维持有效血药浓度，能够有效避免“峰谷”现象，具有延长药物的治疗作用、降低肝肾损害、减少服用次数等特点。Acetaminophen is the most widely used over-the-counter antipyretic and analgesic drug in the world. At present, there are dozens of acetaminophen preparations in the domestic pharmaceutical market, and the dosage forms include injections, capsules, powders, granules, syrups, Suppositories, drops and injections, etc. Acetaminophen has high water solubility, and a normal adult has a relatively short half-life of about 2 to 3 hours after taking the usual dose. Ordinary preparations need to be taken several times to maintain the drug effect, resulting in "peaks and valleys" in blood drug concentration Phenomenon. When the dosage is too large, the metabolites will damage the liver and cause hemolysis due to the denaturation of hemoglobin. Long-term use of large amounts of acetaminophen can also damage the kidney function, especially for those with poor kidney function, who are prone to renal colic or acute renal failure. And liver damage or stasis of cholecystitis, severe cases can cause hepatic coma or even death. For this reason, preparing it into controlled-release tablets can reduce its maximum blood drug concentration in the body and maintain effective blood drug concentration for a long time, which can effectively avoid the "peak and valley" phenomenon, prolong the therapeutic effect of the drug, and reduce the risk of liver and kidney damage. Damage, reduce the number of times of taking and other characteristics.
聚电解质复合物是近年来发展起来的新型高分子复合材料，系指带有相反电荷的阳离子聚合物和阴离子聚合物之间通过静电吸引力的相互作用所形成的大分子复合网络。该复合网络对水具有特殊吸附性，吸水后的湿态聚电解质复合物通常呈透明凝胶状且不溶于水，从而可以长时间保持形态完整，阻滞药物释放，达到缓控释作用。与化学交联形成的复合物相比，聚电解质复合物相对无毒、生物相容性好、临床应用安全，且由于其原料来源丰富、价格低廉，并且在生物医学、膜分离、水果保鲜、催化剂制备等领域具有潜在用途，因而它的制备、改性及应用研究引起了国内外学者的普遍关注。Polyelectrolyte complex is a new type of polymer composite material developed in recent years, which refers to a macromolecular composite network formed by the interaction between cationic polymers and anionic polymers with opposite charges through electrostatic attraction. The composite network has special adsorption to water, and the wet polyelectrolyte complex after water absorption is usually in the form of transparent gel and insoluble in water, so that it can keep the shape intact for a long time, block the release of drugs, and achieve slow and controlled release. Compared with complexes formed by chemical cross-linking, polyelectrolyte complexes are relatively non-toxic, have good biocompatibility, and are safe for clinical application. Catalyst preparation and other fields have potential applications, so its preparation, modification and application research have attracted widespread attention from scholars at home and abroad.
由于传统的包衣技术存在溶剂残留问题，因此非溶剂包衣成为研究者研究的热点。压制包衣片是指通过二次压制使得内层片芯完全被外层高分子包衣材料包裹，通过外层高分子材料的溶蚀、溶解、脱落等实现不同的释药行为，如脉冲释药、缓释释药等。它是一种完全不使用溶剂、不需要加热的包衣技术，技术较为简单，工艺精简，工业成本消耗比较低，具有一定的研究前景。近年来越来越多种类的药物通过压制包衣实现了控释行为，但是干法包衣材料仍多为纤维素衍生物，例如羟丙基纤维素、羟丙基甲基纤维素、乙基纤维素等。Due to the problem of solvent residue in traditional coating technology, non-solvent coating has become a hot spot for researchers. Press-coated tablet means that the inner tablet core is completely covered by the outer polymer coating material through secondary compression, and different drug release behaviors are realized through the erosion, dissolution, and shedding of the outer polymer material, such as pulse release. , Sustained-release drug, etc. It is a coating technology that does not use solvents and does not require heating. The technology is relatively simple, the process is streamlined, and the industrial cost consumption is relatively low. It has certain research prospects. In recent years, more and more types of drugs have achieved controlled release behavior through compression coating, but the dry coating materials are still mostly cellulose derivatives, such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, etc. Cellulose etc.
本发明将阳离子聚合物与阴离子聚合物的物理混合物作为压制包衣技术的包衣材料，当制剂接触胃液时，表面阳离子型聚合物会逐渐质子化，而阴离子型聚合物处于非电离状态，随着消化液环境pH逐渐升高，制剂表面的阴离子型聚合物逐渐离子化带负电荷，与带正电荷的阳离子型聚合物通过静电作用在制剂表面形成水不溶性聚电解质复合物膜，从而能够控制片芯中药物的释放。In the present invention, the physical mixture of cationic polymer and anionic polymer is used as the coating material of the compression coating technology. When the preparation contacts gastric juice, the cationic polymer on the surface will gradually protonate, while the anionic polymer is in a non-ionized state. As the pH of the digestive juice environment gradually increases, the anionic polymer on the surface of the preparation is gradually ionized and negatively charged, and forms a water-insoluble polyelectrolyte complex film on the surface of the preparation through electrostatic interaction with the positively charged cationic polymer, thereby controlling Drug Release from the Tablet Core.
发明内容Contents of the invention
本发明的目的在于提供一种稳定性好、疗效可靠，不良反应小的以对乙酰氨基酚为主药制成的压制包衣控释片及其制备方法，包含对乙酰氨基酚、阳离子聚合物、阴离子聚合物、填充剂和润滑剂，其特征在于将上述材料制成的压制包衣片，外形是向外圆凸型，片芯直径为6mm，整个包衣片直径为8mm，外表光滑完整，在体外释放过程中其包衣层能自主形成聚电解质复合物膜，在12h内能保持形态完整并以恒速或接近恒速释放药物这样特点的制剂。The object of the present invention is to provide a press-coated controlled-release tablet made of acetaminophen as the main ingredient with good stability, reliable curative effect and small adverse reactions and a preparation method thereof, which comprises acetaminophen, cationic polymer , anionic polymers, fillers and lubricants, characterized in that the press-coated tablets made of the above-mentioned materials have an outwardly convex shape, a core diameter of 6mm, and a diameter of the entire coated tablet of 8mm, with a smooth and complete appearance , in the process of in vitro release, its coating layer can independently form a polyelectrolyte complex film, which can maintain the shape integrity within 12 hours and release the drug at a constant or near-constant rate.
本发明选择阳离子和阴离子聚合物为骨架材料，将二者按一定比例物理混合直接压片，使其在2h内以0.1M HCl溶液为溶出介质，2～12h内以0.1M磷酸盐缓冲液为溶出介质的溶出条件下，通过物理交联自组装形成聚电解质复合物膜。这种物理交联方法制备聚电解质复合物膜相比通过化学交联更加简单可行，且所需的释放条件与人体生理环境相符合。The present invention selects cationic and anionic polymers as skeleton materials, physically mixes the two according to a certain ratio and directly compresses them into tablets, so that 0.1M HCl solution is used as the dissolution medium within 2 hours, and 0.1M phosphate buffer solution is used as the dissolution medium within 2 to 12 hours. Under the dissolution conditions of the dissolution medium, the polyelectrolyte complex film is formed through physical cross-linking self-assembly. Compared with chemical crosslinking, the preparation of polyelectrolyte complex membranes by this physical crosslinking method is simpler and feasible, and the required release conditions are consistent with the physiological environment of the human body.
本发明中所述的外层包衣层由阳离子聚合物和阴离子聚合物组成；内层片芯由药物、填充剂和润滑剂组成。阳离子型聚合物选自平均分子量不小于100kDa的不同脱乙酰度(70～95％)的壳聚糖，优选为90.21％脱乙酰度的壳聚糖；阴离子型聚合物选自分子量不小于100kDa的海藻酸钠，分子量不小于100kDa的卡拉胶，分子量不小于100kDa的羧甲基纤维素钠中的一种或其组合物，优选为海藻酸钠；填充剂选自微晶纤维素、乳糖、淀粉中的一种或其任意组合，优选为微晶纤维素和乳糖；润滑剂选自硬脂酸镁、硬脂酸钠、滑石粉中的一种或其任意组合，优选为硬脂酸镁。The outer coating layer in the present invention is composed of cationic polymer and anionic polymer; the inner tablet core is composed of medicine, filler and lubricant. The cationic polymer is selected from chitosan with an average molecular weight of not less than 100kDa with different degrees of deacetylation (70-95%), preferably chitosan with a degree of deacetylation of 90.21%; the anionic polymer is selected from chitosan with a molecular weight of not less than 100kDa Sodium alginate, one of carrageenan with a molecular weight of not less than 100kDa, sodium carboxymethylcellulose with a molecular weight of not less than 100kDa, or a combination thereof, preferably sodium alginate; the filler is selected from microcrystalline cellulose, lactose, and starch One or any combination thereof, preferably microcrystalline cellulose and lactose; the lubricant is selected from one or any combination of magnesium stearate, sodium stearate, talcum powder, preferably magnesium stearate.
本发明中的对乙酰氨基酚压制包衣控释片各组分含量按重量计的百分比如下：The percentage by weight of each component content of the paracetamol press-coated controlled-release tablet in the present invention is as follows:
制备方法包括以下步骤：将处方量的对乙酰氨基酚、微晶纤维素、乳糖、硬脂酸镁混匀，直接压片得到对乙酰氨基酚片芯；将处方量的壳聚糖、海藻酸钠混匀，取一半量其混合物均匀填充于冲模底部，将片芯置于其中心后再填充另外一半量的混合物进行包裹，二次直接压片即得。The preparation method comprises the following steps: uniformly mixing paracetamol, microcrystalline cellulose, lactose and magnesium stearate in prescribed quantities, and directly compressing tablets to obtain paracetamol tablet cores; mixing chitosan and alginic acid in prescribed quantities Mix the sodium evenly, take half of the mixture and fill it evenly at the bottom of the die, place the tablet core in the center and then fill the other half of the mixture for wrapping, and then directly compress the tablet twice.
本发明中的对乙酰氨基酚压制包衣控释片的外形是向外圆凸型，片芯直径为6mm，整个包衣片直径为8mm，外表光滑完整，重量差异、脆碎度均符合要求。The shape of the paracetamol press-coated controlled-release tablet in the present invention is outwardly convex, the diameter of the tablet core is 6 mm, and the diameter of the entire coated tablet is 8 mm. The appearance is smooth and complete, and the weight difference and friability all meet the requirements. .
本发明的具体技术方案如下：Concrete technical scheme of the present invention is as follows:
一种对乙酰氨基酚压制包衣控释片，主要由外层包衣骨架材料、片芯药物与填充剂构成。包衣骨架材料与胃肠液接触后，在片剂周围形成一层聚电解质复合物屏障。通过调节包衣层阳离子和阴离子聚合物的比例、包衣层和片芯的含药比、填充剂的种类及用量，使其能在特定的时间内形成聚电解质复合物膜，并且在整个释放过程中保持形态完整，进而改变片芯和壳层的释药速率，实现片剂整体控释释药。The invention relates to a paracetamol press-coated controlled-release tablet, which is mainly composed of an outer coating skeleton material, a tablet core drug and a filler. After the coating matrix material comes into contact with gastrointestinal fluids, it forms a polyelectrolyte complex barrier around the tablet. By adjusting the ratio of cationic and anionic polymers in the coating layer, the drug content ratio of the coating layer and tablet core, the type and amount of fillers, it can form a polyelectrolyte complex film within a specific time and release During the process, the shape is kept intact, and then the drug release rate of the tablet core and shell layer is changed, and the overall controlled release of the tablet is realized.
本发明针对现有的对乙酰氨基酚制剂中大多为普通片剂，具有血浓波动大，服药次数多，等问题，成功制备了内含6mm含药片芯，外形光滑完整的8mm对乙酰氨基酚压制包衣控释片，该制剂可显著延长药物在体内释放时间，与普通制剂相比在体外能够达到更平稳的释放，提高了药物的口服生物利用度，且制备工艺相对简单。Aiming at the problems that most of the existing acetaminophen preparations are ordinary tablets, which have large fluctuations in blood concentration and many times of taking medicine, etc., the present invention successfully prepares 8mm acetaminophen containing a 6mm drug-containing tablet core and a smooth and complete shape. Compression-coated controlled-release tablet, the preparation can significantly prolong the release time of the drug in vivo, and can achieve more stable release in vitro compared with common preparations, improve the oral bioavailability of the drug, and the preparation process is relatively simple.
具体实施方式detailed description
下面结合实例对本发明更详细地进行解释和说明，应当理解，所给出的实施例只是举例说明性的，其不以任何方式对本发明的范围构成任何限制。The present invention will be explained and described in more detail below in conjunction with examples. It should be understood that the given examples are only illustrative and do not limit the scope of the present invention in any way.
实施例1制备10粒对乙酰氨基酚压制包衣控释片Example 1 Preparation of 10 acetaminophen compression-coated controlled-release tablets
片芯：Chip:
外层：Outer layer:
壳聚糖 600mgChitosan 600mg
海藻酸钠 600mgSodium Alginate 600mg
制备方法：将对乙酰氨基酚与各辅料分别过80目筛，按处方量称取对乙酰氨基酚及辅料，依照等量递增法充分混合均匀，过筛混匀，采用外加法加入适量硬脂酸镁，充分混匀后，采用粉末直接压片法制备对乙酰氨基酚片芯。将处方量的壳聚糖、海藻酸钠分别过80目筛依照等量递增法充分混合均匀，过筛混匀，取一半量包衣材料均匀填充于冲模底部，将片芯置于其中心后再填充另外一半量的包衣材料，二次直接压片即得。Preparation method: Pass acetaminophen and each auxiliary material through an 80-mesh sieve respectively, weigh the acetaminophen and auxiliary materials according to the prescription amount, fully mix them evenly according to the equal-volume increasing method, sieve and mix evenly, and add appropriate amount of stearin by external addition method Magnesium acid magnesium, after fully mixing, the acetaminophen tablet core is prepared by powder direct compression method. Pass the prescribed amount of chitosan and sodium alginate through an 80-mesh sieve and mix well according to the method of equal increments, sieve and mix evenly, take half of the coating material and fill it evenly at the bottom of the die, place the tablet core in the center Then fill another half of the coating material, and directly compress the tablet for the second time.
实施例2制备10粒对乙酰氨基酚压制包衣控释片Example 2 Preparation of 10 acetaminophen compression-coated controlled-release tablets
片芯：Chip:
外层：Outer layer:
壳聚糖 11mgChitosan 11mg
海藻酸钠 109mgSodium Alginate 109mg
制备方法：将对乙酰氨基酚与各辅料分别过80目筛，按处方量称取对乙酰氨基酚及辅料，依照等量递增法充分混合均匀，过筛混匀，采用外加法加入适量硬脂酸镁，充分混匀后，采用粉末直接压片法制备对乙酰氨基酚片芯。将处方量的壳聚糖、海藻酸钠分别过80目筛依照等量递增法充分混合均匀，过筛混匀，取一半量包衣材料均匀填充于冲模底部，将片芯置于其中心后再填充另外一半量的包衣材料，二次直接压片即得。Preparation method: Pass acetaminophen and each auxiliary material through an 80-mesh sieve respectively, weigh the acetaminophen and auxiliary materials according to the prescription amount, fully mix them evenly according to the equal-volume increasing method, sieve and mix evenly, and add appropriate amount of stearin by external addition method Magnesium acid magnesium, after fully mixing, the acetaminophen tablet core is prepared by powder direct compression method. Pass the prescribed amount of chitosan and sodium alginate through an 80-mesh sieve and mix well according to the method of equal increments, sieve and mix evenly, take half of the coating material and fill it evenly at the bottom of the die, place the tablet core in the center Then fill another half of the coating material, and directly compress the tablet for the second time.
实施例3制备10粒对乙酰氨基酚压制包衣控释片Example 3 Preparation of 10 acetaminophen compression-coated controlled-release tablets
片芯：Chip:
外层：Outer layer:
对乙酰氨基酚 80mgAcetaminophen 80mg
壳聚糖 600mgChitosan 600mg
海藻酸钠 600mgSodium Alginate 600mg
制备方法：将对乙酰氨基酚与各辅料分别过80目筛，按处方量称取对乙酰氨基酚及辅料，依照等量递增法充分混合均匀，过筛混匀，采用外加法加入适量硬脂酸镁，充分混匀后，采用粉末直接压片法制备对乙酰氨基酚片芯。将处方量的对乙酰氨基酚、壳聚糖、海藻酸钠分别过80目筛依照等量递增法充分混合均匀，过筛混匀，取一半量包衣材料均匀填充于冲模底部，将片芯置于其中心后再填充另外一半量的包衣材料，二次直接压片即得。Preparation method: Pass acetaminophen and each auxiliary material through an 80-mesh sieve respectively, weigh the acetaminophen and auxiliary materials according to the prescription amount, fully mix them evenly according to the equal-volume increasing method, sieve and mix evenly, and add appropriate amount of stearin by external addition method Magnesium acid magnesium, after fully mixing, the acetaminophen tablet core is prepared by powder direct compression method. Pass the prescribed amount of acetaminophen, chitosan, and sodium alginate through an 80-mesh sieve and mix well according to the method of equal increments, sieve and mix evenly, take half of the coating material and fill it evenly at the bottom of the die, and put the tablet core After placing it in the center, fill another half of the coating material, and perform direct compression twice to obtain the tablet.
试验实施例：Test example:
以下提供一个对比实例：市售对乙酰氨基酚片与本发明涉及的对乙酰氨基酚压制包衣控释片在相同介质中的释放随时间的变化。根据《中国药典》2015版通则中溶出度测定法第一法对本发明制剂与普通片的体外溶出度进行考察对比，溶出试验是在37℃，2h内以900mL的0.1M HCl溶液为溶剂，2～12h内以900mL的0.1M磷酸盐缓冲液为溶剂，以转速为100rpm，紫外分光光度法进行检测。普通片剂在30min内溶出达到90％以上，本发明的释放度参数如下(下面提及的百分数是重量百分数)：A comparative example is provided below: the release over time of commercially available acetaminophen tablets and the acetaminophen compression-coated controlled-release tablets involved in the present invention in the same medium. According to "Chinese Pharmacopoeia" 2015 edition general rules, the first method of dissolution test method is used to investigate and compare the in vitro dissolution rate of the preparation of the present invention and ordinary tablets. The dissolution test is at 37 ° C, with 900 mL of 0.1M HCl solution as solvent within 2 hours, 2 Within 12 hours, use 900mL of 0.1M phosphate buffer as a solvent, at a rotation speed of 100rpm, and perform detection by ultraviolet spectrophotometry. Common tablet dissolves and reaches more than 90% in 30min, and the release parameter of the present invention is as follows (percentage mentioned below is percentage by weight):
结果表明，本发明制备的对乙酰氨基酚压制包衣控释片外观光滑完整，与普通制剂相比在体外能够达到更平稳的释放，延长药物作用时间，提高了药物的口服生物利用度，且制备工艺相对简单。The results show that the paracetamol compression-coated controlled-release tablet prepared by the present invention has a smooth and complete appearance, can achieve more stable release in vitro compared with common preparations, prolong the drug action time, and improve the oral bioavailability of the drug, and The preparation process is relatively simple.
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Application publication date: 20170222 |