CN101785763B - Metformin hydrochloride enteric-coated sustained release tablet and preparation method thereof - Google Patents

Metformin hydrochloride enteric-coated sustained release tablet and preparation method thereof Download PDF

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CN101785763B
CN101785763B CN 201010105236 CN201010105236A CN101785763B CN 101785763 B CN101785763 B CN 101785763B CN 201010105236 CN201010105236 CN 201010105236 CN 201010105236 A CN201010105236 A CN 201010105236A CN 101785763 B CN101785763 B CN 101785763B
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metformin hydrochloride
enteric
sustained release
parts
release
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CN101785763A (en
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张凡
金联荪
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贵州天安药业股份有限公司
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Abstract

The invention discloses a metformin hydrochloride enteric-coated sustained release tablet which is prepared by enteric coating the metformin hydrochloride sustained release tablet. Compared with the prior art, the sustained release tablet integrates with the enteric coating technology to prepare a new form of the metformin hydrochloride enteric-coated sustained release tablet. By using the enteric coating technology, the metformin hydrochloride does not disintegrate in the stomach or stimulate the gastric mucosa, and the adverse reaction of nausea, stomachache and diarrhea caused by medicine taking can be avoided; meanwhile, the metformin hydrochloride is prevented from being damaged by gastric juice, and the bioavailability is improved. The product is a sustained release preparation, themedicine can stably release in vivo, the effective blood concentration can be maintained for a long time, the toxic and side effects caused by over-high blood concentration in a short time are avoided, the medicine taking frequency is decreased, and the patient compliance is improved as well.

Description

一种盐酸二甲双胍肠溶缓释片及其制备方法 One kind of enteric-coated sustained release tablets of metformin hydrochloride and its preparation method

技术领域 FIELD

[0001] 本发明涉及盐酸二甲双胍制剂,特别是涉及一种盐酸二甲双胍肠溶缓释片及其制备方法。 [0001] The present invention is directed to metformin hydrochloride formulations, in particular, relates to one kind of metformin hydrochloride enteric-coated sustained release tablet and preparation method thereof.

背景技术 Background technique

[0002] 盐酸二甲双胍是目前世界发达国家广泛使用的唯一口服类抗高血糖药物,可改善2型糖尿病患者对糖的耐受,降低基础及餐后血浆葡萄糖浓度。 [0002] Metformin hydrochloride is the only developed country in the world wide class of oral antihyperglycemic drugs used, type 2 diabetes can improve tolerance to sugar, reduce basal and postprandial plasma glucose concentration. 该药与磺脲类的作用机制不同,在正常人及2型糖尿病患者中不产生低血糖反应,也不产生高胰岛素血症。 Sulfonylurea drug with different mechanisms of action, and does not produce hypoglycemia in normal subjects and patients with type 2 diabetes, hyperinsulinemia not generated. 盐酸二甲双胍降血糖的主要机理是提高外周组织和肝脏对胰岛素的敏感性,降低胰岛素抵抗,减少胃肠道对葡萄糖的吸收。 The main mechanism of metformin hydrochloride is to improve the hypoglycemic peripheral tissues and liver insulin sensitivity, reduce insulin resistance, reduce gastrointestinal absorption of glucose. 因其降糖作用肯定,对血糖正常者无效;不刺激胰岛素分泌,能保持或减轻体重;在临床应用40余年来,取得了良好的降糖效果,深受临床医生和患者的欢迎。 Sure its hypoglycemic effect on normal blood glucose invalid; does not stimulate insulin secretion, to maintain or lose weight; in clinical practice 40 years, and achieved good hypoglycemic effect, by clinicians and patients welcome.

[0003] 盐酸二甲双胍的副作用主要是胃肠道反应,症状主要有恶心、呕吐、厌食、腹泻等, 目前市场上的盐酸二甲双胍制剂主要有盐酸二甲双胍片、缓释片、肠溶片等。 Side [0003] Metformin is mainly gastrointestinal reactions, symptoms of nausea, vomiting, anorexia, diarrhea, metformin hydrochloride formulation currently on the market are metformin hydrochloride tablets, sustained release tablets, enteric-coated tablets and the like. 缓释片可延缓药品的释放速度,延长药效时间,降低药品在肠胃中的浓度,降低对胃肠道的副作用。 Sustained release tablets can delay the release rate of the drug, prolonged efficacy of time to reduce the concentration of the drug in the stomach, to reduce the side effects on the gastrointestinal tract. 肠溶片在胃中不崩解,不会对胃粘膜造成刺激,可以在一定程度上避免服药引起的恶心、腹痛、 腹泻等不良反应。 Enteric-coated tablets do not disintegrate in the stomach, does not cause irritation of the gastric mucosa, the medication can prevent nausea caused to some extent, abdominal pain, diarrhea and other adverse reactions.

[0004] 现有技术中也存在具有类似功能的盐酸二甲双胍片,例如专利CN1561980A公开了一种所谓的盐酸二甲双胍肠溶缓释片,在其说明书表2中公开了9组试验,其效果均不理想,上述9组试验中,效果最好的第9组试验,盐酸二甲双胍的释放度过快,而且更重要的是该申请中并未进行盐酸二甲双胍在酸液中的释放度试验,如果盐酸二甲双胍在酸液中释放度不合适,其最终的释放度试验并无意义。 [0004] The prior art also exists of metformin having a similar function, for example, patent CN1561980A discloses a so-called enteric-coated sustained-release tablets of metformin hydrochloride, disclosed in the specification of the test group 9 Table 2, the effect is not over the set of tests 9, 9 of the best set of experiments, metformin hydrochloride released too quickly, and more importantly for this application is not metformin hydrochloride in the acid release test, and if the metformin hydrochloride in the acid release is inappropriate, its final release test does not make sense.

发明内容 SUMMARY

[0005] 本发明所要解决的技术问题是如何将盐酸二甲双胍缓释片和肠溶片的优点融合在一起,提供一种盐酸二甲双胍肠溶缓释片及其制备方法。 [0005] The present invention solves the technical problem is how to fusion and advantages of metformin hydrochloride sustained release tablets with an enteric tablets, enteric-coated to provide a hydrochloride sustained release tablets of metformin and its preparation method.

[0006] 为了解决上述技术问题,本发明采用如下的技术方案: [0006] To solve the above problems, the present invention adopts the following technical solution:

[0007] 本发明盐酸二甲双胍肠溶缓释片是由盐酸二甲双胍缓释片包肠溶衣制备而成。 [0007] The present invention is metformin hydrochloride enteric-coated sustained release tablets of metformin hydrochloride is prepared with enteric coatings sustained release tablets from the package.

[0008] 按照重量份计算,制备上述肠溶缓释片的缓释片是由盐酸二甲双胍50〜70份、羧甲基纤维素钠3. 0〜6. 5份、羟丙甲纤维素18. 0〜30. 0份和聚乙烯吡咯烷酮K307. 7〜 11. 6份,以30%聚丙烯酸树脂IV乙醇溶液3. 0〜6. 0份为粘合剂制备而成。 [0008] calculated as parts by weight, the above-described sustained release tablets prepared by the enteric sustained-release tablets of metformin hydrochloride is 50~70 parts, sodium carboxymethylcellulose 3. 0~6. 5 parts, hypromellose 18. 0~30. 0 parts of polyvinylpyrrolidone and K307. 7~ 11. 6 parts polyacrylic acid resin with 30% ethanol solution IV 3. 0~6. 0 parts prepared by an adhesive.

[0009] 聚丙烯酸树脂在药物制剂中通常被用作肠溶、胃溶包衣剂。 [0009] The polyacrylic acid resin in a pharmaceutical formulation is commonly used as enteric, gastric coating agent. 我们发现其可以达到缓释的效果,因为它很难溶于水,自然遇水也不会发粘,用它做粘合剂制备的颗粒,在压力作用下结合在一起,其也会因为水的进入使得之间的镶嵌结构缓慢瓦解;而且其是成膜性包裹药物的,药物主要在碱性条件下才被释放,即可阻止药物在胃内释放速率。 We found that the sustained release effect can be achieved, because it is difficult to dissolve in water, natural water is not tacky, the particles prepared with it adhesive, bonded together under pressure, also because of its water damascene structure so that entered between the slow collapse; film-forming properties and its entrapping a drug, the drug was released mainly under basic conditions, to prevent the rate of drug release in the stomach. 可见,聚丙烯酸树脂在本发明的处方中既可用做粘合剂,也具有缓释功能。 Visible, polyacrylic acid resins in the formulation of the present invention can be used as adhesives, have sustained release functionality.

[0010] 前述盐酸二甲双胍肠溶缓释片的制备方法:将制备好的盐酸二甲双胍缓释片喷上肠溶包衣液包衣,即得。 [0010] The method of preparing the enteric sustained-release metformin hydrochloride tablets: The release of metformin hydrochloride tablets prepared enteric coating liquid sprayed coating, i.e., too.

[0011] 进一步的,上述制备方法为:取盐酸二甲双胍、羧甲基纤维素钠、羟丙甲基纤维素和聚乙烯吡咯烷酮K30,以30%聚丙烯酸树脂IV乙醇溶液为粘合剂,按片剂常规工艺制粒、 烘干、整粒,在整粒后的干燥颗粒中加入润滑剂混勻后压片,喷包肠溶衣液包衣,即得。 [0011] Further, the above preparation method: taking metformin hydrochloride, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and polyvinylpyrrolidone K30, 30% ethanol solution IV polyacrylic acid resin as a binder, press plate granulating agents conventional processes, drying, sieved, mixed after adding a lubricant in the tabletting granules sieved dried, spray coating enteric coating liquid, i.e., too.

[0012] 处方筛选过程 [0012] Prescription screening process

[0013] 盐酸二甲双胍极易溶于水,为了使药物缓慢释放,有效血药浓度能维持较长时间, 以达到较好的治疗目的,我们制成盐酸二甲双胍肠溶缓释片,为骨架型。 [0013] Metformin hydrochloride easily soluble in water, in order to make the drug slow release, effective blood concentration can be maintained for a long time to achieve better therapeutic purposes, we made an enteric sustained-release tablets of metformin hydrochloride as a framework type. 以每片含盐酸二甲双胍500mg,采用控释材料中的一种或数种以及不同规格、不同用量组方,进行体外释放度试验,从多个缓释处方中发现2号处方缓释效果较好,且颗粒的可压性、流动性和处方的重现性均佳,故确定处方2为本缓释片处方。 Metformin hydrochloride per tablet containing 500mg, use of a controlled release material and one or several different sizes, different dose prescriptions, in vitro release test was found better sustained release formulation No. 2 from the plurality of sustained release formulation and compressibility, flowability and particle prescription reproducibility are good, it is determined the present formulation 2 sustained release tablets.

[0014] 处方筛选过程如下表: [0014] Prescription screening process in the following table:

[0015] [0015]

Figure CN101785763BD00041

[0016] 以处方2为本缓释片基本处方,制备三批样品。 [0016] The sustained release tablet formulation of the present basic formulation 2, sample batches were prepared. 再以0. lmol/1盐酸溶液和pH6. 8 的磷酸盐缓冲液作为本品的释放介质,方法采用转篮法(中国药典2005年版二部附录)(C 第一法),转速为每分钟100转,取样点为1小时、3小时和10小时,据此条件测定了三批样品的释放度,结果如下: And then at 0. lmol / 1 hydrochloric acid solution and the phosphate buffer pH6. 8 as release medium of this product, using the rotating basket method (Chinese Pharmacopoeia 2005 Appendix) (C method), rotation speed per minute 100 rpm, sampling points 1 hour, 3 hours and 10 hours, the release rate was measured accordingly conditions the three batches, the following results:

[0017] [0017]

Figure CN101785763BD00051

[0018] 与上市肠溶片和进口缓释片的释放度曲线的比较 Comparison [0018] Listed enteric-coated tablets and sustained release tablets and imported release profile

[0019] 1、上市盐酸二甲双胍肠溶片的释放度曲线的绘制 [0019] 1, draw release profile of the enteric-coated tablets listed metformin hydrochloride

[0020] 取盐酸二甲双胍肠溶片,照释放度测定法(中国药典2005年版二部附录XD第二法方法2),先以0. lmol/L盐酸溶液900ml作为溶出介质,转速100转/分,依法操作,2小时后,置900mlpH6. 8磷酸盐缓冲溶液中,并分别在5、10、20、30、45分钟取样5ml (同时补液5ml),滤过,取续滤液作为供试品溶液。 [0020] taking metformin hydrochloride enteric-coated tablets, according to the release assay (Chinese Pharmacopoeia 2005 Appendix XD Method II Method 2), first to 0. lmol / L hydrochloric acid as dissolution medium 900ml, 100 rpm / min , operating according to the law, after 2 hours, set 900mlpH6. 8 phosphate buffer solution, and 5ml each at 5,10,20,30,45 min sample (5ml rehydration simultaneously), filtered, the filtrate as the test solution .

[0021] 精密量取供试品溶液Iml至IOOml容量瓶,用水稀释至刻度,摇勻,照分光光度法(附录IV A)在233nm处测定吸收度,按盐酸二甲双胍的吸收系数(E1% lem)为798计算出每片的溶出量。 [0021] The precise amount of the test solution to IOOml Iml volumetric flask, diluted with water to the mark, the absorbance was measured at 233nm according to the spectrophotometric method (Appendix IV A), metformin hydrochloride absorption coefficient (E1% lem ) 798 calculated elution amount per sheet. 结果下表: The results in the following table:

[0022] 上市盐酸二甲双胍肠溶片释放度曲线(n = 6) [0022] Listed enteric-coated tablets of metformin hydrochloride release profile (n = 6)

Figure CN101785763BD00052

[0024] 可见,普通肠溶片在2个半小时内药物已完全释放,不具备缓释功能(附图1)。 [0024] visible, enteric-coated tablets in general within two and a half hours of drug has been completely released, it does not have the function of sustained release (Figure 1).

[0025] 2、本品与进口盐酸二甲双胍缓释片的释放度曲线的比较 [0025] 2, Comparative release profile according to the inlet product of sustained-release tablets of metformin hydrochloride

[0026] 测定了本品(每批6片)与进口盐酸二甲双胍缓释片以0. lmol/1盐酸溶液和PH6. 8的磷酸盐缓冲液作为释放介质,在0. lmol/1盐酸溶液2小时和pH6. 8的磷酸盐缓冲液0. 5、1、2、3、4、6、8、10、12、M小时测定各点的释放量,测定结果见下表,绘制三批样品与进口对照品释放度曲线。 [0026] Measurement of this product (batch 6) and the inlet of metformin hydrochloride sustained release tablets in 0. lmol / 1 hydrochloric acid solution and phosphate buffer PH6. 8 as release medium, at 0. lmol / 1 hydrochloric acid solution 2 hour and phosphate buffer pH6. 8 is 0. 5,1,2,3,4,6,8,10,12, M-hour release assay at each point, the measurement results of the following table, and plotted three batches imported release reference standard curve.

[0027] 本品与对照品释放度测定结果 [0027] The product release and reference measurement result

Figure CN101785763BD00053

[0029] [0029]

Figure CN101785763BD00061

[0030] 可见,普通缓释片在前2个小时内(酸中,亦即模拟胃中)药物已经开始释放,不具备肠溶功能(附图2)。 [0030] visible, Common sustained release tablets within the first 2 hours (in acid, i.e. simulated stomach) have begun to release the drug, does not have an enteric function (Fig. 2).

[0031] 3、本品的释放度曲线 [0031] 3, a graph of the release of this product

[0032] 取本品(每批6片),以0. lmol/1盐酸溶液和pH6. 8的磷酸盐缓冲液作为本品的释放介质,绘制释放曲线。 [0032] Take this product (batch 6) to 0. lmol / 1 hydrochloric acid solution and the phosphate buffer pH6. 8 as release medium of this product, drawing release profile.

[0033] 上述数据图表可见:本盐酸二甲双胍肠溶缓释片兼具肠溶、缓释功能,较单纯肠溶片、缓释片有优势(附图3)。 [0033] The data table can be seen: The enteric-coated sustained-release tablets of metformin hydrochloride both an enteric, sustained-release function, more simple enteric-coated tablets, sustained release tablets have the advantage (Figure 3).

[0034] 同时对试制的样品(090504)进行了影响因素试验(光照试验、高温试验、高湿试验),方法与结果如下: [0034] Also for the sample trial (090,504) of the test factors (light test, high-temperature test, humidity test), methods and results are as follows:

[0035] (1)光照试验 [0035] (1) Light Test

[0036] 在室温条件下,本品去除外包装将样品平摊在平皿里,在45001UX光强度下放置5,10天后取样检测。 [0036] At room temperature, the product is removed the sample flat on the outer plates, the sample is placed is detected at days 5,10 45001UX light intensity. 试验数据见下表: Test data in the table below:

Figure CN101785763BD00071

[0038] [0038]

Figure CN101785763BD00081
Figure CN101785763BD00091

[0040] [0040]

Figure CN101785763BD00101

[0041] 本品经加速试验(40°C、RH75% )模拟上市包装放置6个月,室温长期留样考查6 个月检验各项考察指标,结果均符合规定。 [0041] This product was accelerated test (40 ° C, RH75%) simulate commercial packaging for 6 months at room temperature to stay long test samples examined six months of the indexes, are in line with the results. 说明本品是较稳定的。 Description The product is more stable.

[0042] 与现有技术相比,本发明优化了处方工艺,制备产品工艺性能良好,易于成型,片重较小,易于患者服用。 [0042] Compared with the prior art, the present invention optimizes the process of formulation, good product preparation process performance, ease of molding, the smaller tablet weight, easy to take the patient. 并将缓释片和肠溶片融合在一起,制备出来盐酸二甲双胍肠溶缓释片这种新剂型,由于使用了肠溶片这种剂型,所以使得二甲双胍在胃中不崩解,不对胃粘膜造成刺激,可以避免服药引起的恶心、腹痛、腹泻等不良反应,同时本品又是缓释制剂,可以延缓药品的释放速度,减少药品的服用次数。 And enteric-coated tablets and sustained release tablets fusion together to prepare enteric-coated sustained-release tablets of metformin hydrochloride out of the new formulations, enteric-coated tablets due to the use of such dosage forms, it is not so metformin disintegration in the stomach, not the gastric mucosa cause irritation, avoid medication-induced nausea, abdominal pain, diarrhea and other adverse reactions, while the product is extended release formulation, the release rate of the drug can delay, reduce the frequency of taking drugs.

附图说明 BRIEF DESCRIPTION

[0043] 图1上市盐酸二甲双胍肠溶片释放曲线图 [0043] FIG 1 listed enteric-coated tablets of metformin hydrochloride release profiles

[0044] 图2本品与进口对照品释放度曲线图 [0044] FIG. 2 and imported product release reference graph

[0045] 图3本品的释放度曲线图 [0045] The graph of FIG. 3 release product

具体实施方式 Detailed ways

[0046] 实施例1 : [0046] Example 1:

[0047] 1、制剂处方:盐酸二甲双胍500g、羧甲基纤维素钠40g、羟丙甲纤维素200g、聚乙烯吡咯烷酮K30 80g、30%聚丙烯酸树脂(IV号乙醇溶液60〜120ml、硬酯酸镁1%、肠溶衣粉(类白色,湖州展望药业有限公司的肠溶包衣剂)和乙醇适量,制成500mg盐酸二甲双胍/片的肠溶缓释片。 [0047] 1, pharmaceutical formulations: metformin hydrochloride 500g, sodium carboxymethyl cellulose 40g, hypromellose 200g, polyvinylpyrrolidone K30 80g, 30% polyacrylic acid resin (IV No. ethanol solution 60~120ml, stearate 1% magnesium, enteric coating powder (white, Huzhou Looking enteric coating agent Pharmaceutical Co., Ltd.) and the amount of ethanol to prepare an enteric sustained-release tablets 500mg metformin hydrochloride / tablet.

[0048] 2、制备工艺 [0048] 2, Preparation of

[0049] (1)粘合剂的配制 Formulation [0049] (1) binder

[0050] 精密称取聚丙烯酸树脂IV号适量,用95%乙醇配制成浓度为30%的溶液,备用。 [0050] Accurately weighed amount polyacrylic acid resin No. IV, formulated with 95% ethanol to a concentration of 30% solution, standby.

[0051] (2)片芯的制备 [0051] (2) Preparation of tablet core

[0052] 取主药盐酸二甲双胍与辅料羧甲基纤维素钠、羟丙甲纤维素、聚乙烯吡咯烷酮K30 充分混勻后过60目筛,以30%聚丙烯酸树脂IV乙醇溶液60〜120ml为粘合剂,制软材,24 目筛制粒,50°C烘干30分钟后M目筛整粒,加入整粒后粒料(重量)的硬酯酸镁充分混勻,压制成1000片。 [0052] Take the main drug metformin hydrochloride and excipients, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone K30 after thoroughly mixed through a 60 mesh screen, polyacrylic acid resin with 30% ethanol solution 60~120ml visco IV mixture, made of soft material, 24-mesh sieve granulator, 50 ° C for 30 minutes baking M mesh sieve pellets (by weight) of magnesium stearate was added after the whole thoroughly mixed and compressed into 1000.

[0053] (3)包肠溶衣 [0053] (3) enteric coated

[0054] 称取肠溶衣粉适量,缓缓加入70%的乙醇溶液中,配制成6%的包衣液,在磁力搅拌器上不停地搅拌,直至完全溶解,取片芯置包衣锅内,锅转速30〜40转/分钟,锅内温度为40〜50°C,不间断喷包衣液至片芯上,直至均勻包上一层肠溶衣,干燥即得。 [0054] The enteric coated powder amount was weighed, was slowly added a solution of 70% ethanol to prepare a coating solution 6%, kept stirred on a magnetic stirrer until complete dissolution, is set to take the core coated pot, pan speed of 30 to 40 rev / min, the pot temperature is 40~50 ° C, the coating liquid onto the continuous ejection core until uniformly coated with a layer of enteric coating, and dried to obtain.

[0055] 实施例2 : [0055] Example 2:

[0056] 制剂处方:盐酸二甲双胍500g、羧甲基纤维素钠30g、羟丙甲纤维素300g、聚乙烯吡咯烷酮K30 116g、20%聚丙烯酸树脂IV号60〜120ml、硬酯酸镁1.0%、肠溶衣粉(类白色,湖州展望药业有限公司的肠溶包衣剂)和乙醇适量,按照实施例1的方法制成500mg盐酸二甲双胍/片的肠溶缓释片。 [0056] The pharmaceutical formulations: metformin hydrochloride 500g, sodium carboxymethyl cellulose 30g, hypromellose 300g, polyvinylpyrrolidone K30 116g, 20% polyacrylic acid resin No. IV 60~120ml, magnesium stearate 1.0%, intestinal powder coating solution (white, Huzhou Looking enteric coating agent Pharmaceutical Co., Ltd.) and the amount of ethanol to prepare an enteric sustained-release tablets 500mg metformin hydrochloride / tablet according to the method of Example 1.

[0057] 实施例3 : [0057] Example 3:

[0058] 制剂处方:盐酸二甲双胍500g、羧甲基纤维素钠30g、羟丙甲纤维素300g、聚乙烯吡咯烷酮K30 116g、20%聚丙烯酸树脂II号60〜120ml、硬酯酸镁1. 0%、肠溶衣粉(类白色,湖州展望药业有限公司的肠溶包衣剂)和乙醇适量,按照实施例1的方法制成500mg盐酸二甲双胍/片的肠溶缓释片。 [0058] The pharmaceutical formulations: metformin hydrochloride 500g, sodium carboxymethyl cellulose 30g, hypromellose 300g, polyvinylpyrrolidone K30 116g, 20% polyacrylic acid resin II, 60~120ml, magnesium stearate 1.0% enteric coating powder (white, Huzhou Looking enteric coating agent Pharmaceutical Co., Ltd.) and the amount of ethanol to prepare an enteric sustained-release tablets 500mg metformin hydrochloride / tablet according to the method of Example 1.

[0059] 实施例4 :[0060] 制剂处方:盐酸二甲双胍700g、羧甲基纤维素钠65g、羟丙甲纤维素180g、聚乙烯吡咯烷酮K30 77g、40%聚丙烯酸树脂III号60〜120ml、硬酯酸镁1. 0%、肠溶衣粉(类白色,湖州展望药业有限公司的肠溶包衣剂)和乙醇适量,按照实施例1的方法制成500mg盐酸二甲双胍/片的肠溶缓释片。 [0059] Example 4: [0060] The pharmaceutical formulations: metformin hydrochloride 700g, sodium carboxymethyl cellulose 65g, hypromellose 180g, polyvinylpyrrolidone K30 77g, 40% polyacrylic acid resin No. III 60~120ml, hard magnesium carbonate 1.0%, the enteric coating powder (white, Huzhou Looking enteric coating agent Pharmaceutical Co., Ltd.) and the amount of ethanol to produce 500mg metformin hydrochloride / sheet according to Example 1 of the enteric buffer release tablets.

Claims (3)

1. 一种盐酸二甲双胍肠溶缓释片,其特征在于所述缓释片是由盐酸二甲双胍、羧甲基纤维素钠、羟丙甲纤维素和聚乙烯吡咯烷酮,以聚丙烯酸树脂IV的乙醇溶液为粘合剂制备而成,其中所述盐酸二甲双胍50〜70份、羧甲基纤维素钠3. 0〜6. 5份、羟丙甲纤维素18. 0〜30. 0份和聚乙烯吡咯烷酮K 30 7. 7〜11. 6份,以聚丙烯酸树脂IV的乙醇溶液3. 0〜6. 0份为粘合剂,且按照重量份计算,所述聚丙烯酸树脂IV的乙醇溶液的浓度为20%〜40%。 An enteric-coated sustained-release tablets of metformin hydrochloride, wherein said release sheet is metformin hydrochloride, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose and polyvinyl pyrrolidone, polyacrylic acid resin ethanol solution IV prepared by an adhesive, wherein said parts of 50~70 metformin hydrochloride, sodium carboxymethylcellulose 3. 0~6. 5 parts, hypromellose 0~30 18. 0 parts of polyvinylpyrrolidone and K 30 7. 7~11. 6 parts polyacrylic acid resin to an ethanol solution IV 3. 0~6. 0 parts by an adhesive, and the parts in accordance with the weight, the concentration of the ethanol solution of polyacrylic acid resin IV is 20% ~ 40%.
2.权利要求1所述的盐酸二甲双胍肠溶缓释片的制备方法,其特征在于:将制备好的盐酸二甲双胍缓释片喷上肠溶包衣液包衣,即得。 Hydrochloride according to claim 1 Preparation of enteric-coated sustained-release tablets of metformin, wherein: the sustained release tablets of metformin hydrochloride prepared enteric coating liquid sprayed coating, i.e., too.
3.按照权利要2所述的盐酸二甲双胍肠溶缓释片的制备方法,其特征在于:取盐酸二甲双胍、羧甲基纤维素钠、羟丙甲基纤维素和聚乙烯吡咯烷酮K30,以30%聚丙烯酸树脂IV 乙醇溶液为粘合剂,按片剂常规工艺制粒、烘干、整粒,在整粒后的干燥颗粒中加入润滑剂混勻后压片,喷肠溶包衣液包衣,即得。 3. The method of preparing enteric claim metformin hydrochloride sustained release tablets to claim 2, wherein: taking metformin hydrochloride, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and polyvinylpyrrolidone K30, 30% polyacrylic acid resin IV ethanol solution as a binder, the tablet according to a conventional granulating process, dried, sieved, added after mixing a lubricant in the granulated particles were dried in tablet, enteric coating liquid jet coating , that is, too.
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