降压药替米沙坦氢氯噻嗪双层片制剂研发
发布时间:2018-06-12 03:43
本文选题:替米沙坦 + 氢氯噻嗪 ; 参考:《山西医科大学》2014年硕士论文
【摘要】:近年来,随着高血压人数的增多,降压药的市场越来越广阔,由于高血压患者一般为中老年人,多数伴随着各种各样的其他病症,如高血压伴随糖尿病、高血压伴随肾功能不全等。单用一种降压药往往很难将血压控制在正常范围内,常常需要两种及多种药物联合使用才能达到较理想的降压效果。同时服用好几种药物,容易降低患者的依从性,不能很好的将血压控制在安全的范围内,,各种高血压引起的并发症也会接踵而至。 若能将一种或者几种药物结合起来制成双层片剂,有利于减少患者的服药次数,同时能够更好的控制药物释放速度,将血压更好的控制在正常范围内。替米沙坦和氢氯噻嗪联合用药,能够改善血管功能状态,延缓或逆转左室肥厚,降低心血管事件的发生率和死亡率,同时也降低了单独用药的不良反应发生率及减轻不良反应的程度。 本论文旨在研制一种双层片降压药物----替米沙坦氢氯噻嗪双层片。以专利ZL02827182.3为基础,药剂学、药用辅料及《中国药典》对片剂质量要求为指导对双层片处方和工艺进行改进。主要内容如下: 1.氢氯噻嗪层采用湿法制粒,对崩解剂微晶纤维素和粘合剂淀粉浆等的用量进行筛选。将处方优化为1000片含氢氯噻嗪12.5g(6.25%)、乳糖129.66g(64.83%)、微晶纤维素pH10140g(20%)、微晶纤维素pH30212g(6%)氧化铁红0.34g(0.17%)、硬脂酸镁1g(0.5%)、淀粉4.5g(2.25%)。该处方原辅料配比合适,制的的片剂溶出度符合质量要求 2.替米沙坦层采用喷雾干燥法制粒,对氢氧化钠、葡甲胺、聚维酮K25及硬脂酸镁用量进行筛选,将处方优化为1000片含替米沙坦80g(16.67%)、氢氧化钠6.72g(1.4%)、葡甲胺24g(5%)、聚维酮K2528.8g(6%)、山梨醇326.08g(67.93%)、硬脂酸镁14.4g(3%)、纯化水400g。用该处方比例喷雾干燥制粒,压出的片剂溶出度符合质量标准。 3.对双层片工艺进行优化,建立一套生产替米沙坦氢氯噻嗪双层片合适的工艺参数。结果表明当氢氯噻嗪制粒筛网孔径为30目、烘干温度60℃、干颗粒含水量小于2.5%,替米沙坦层生产温度18℃-25℃、湿度小于50%、喷雾干燥出风温度85℃左右、山梨醇粒径80%大于150um时,能够生产出偏重稳定、脆碎度符合标准、溶出度达标、有关物质含量在要求范围内的双层片。
[Abstract]:In recent years, with the increase in the number of hypertension, the market of antihypertensive drugs is more and more broad. Because hypertension patients are generally middle-aged and elderly, most of them are accompanied by a variety of other diseases, such as hypertension with diabetes, Hypertension accompanied by renal insufficiency and so on. It is difficult to control blood pressure in a single antihypertensive drug, and two or more drugs are often needed to achieve an ideal antihypertensive effect. Taking several drugs at the same time can easily reduce the patient's compliance, and it cannot control the blood pressure in a safe range. Complications caused by high blood pressure can also follow. If you can combine one or more drugs together to make a bilayer tablet, it will help to reduce the number of times the patient takes the medicine and at the same time better control the release rate of the drug. Better control of blood pressure within normal range. Telmisartan combined with hydrochlorothiazide can improve vascular function, delay or reverse left ventricular hypertrophy, and reduce the incidence and mortality of cardiovascular events. At the same time, the incidence of adverse reactions and the degree of adverse reactions were reduced. In this paper, a double-layer antihypertensive drug, telmisartan hydrochlorothiazide bilayer tablet, was developed. Based on the patent ZL02827182.3, the formulation and process of double-layer tablets were improved under the guidance of pharmacology, pharmaceutical excipients and the quality requirements of Chinese Pharmacopoeia. The main contents are as follows: 1. Hydrochlorothiazide layer was made by wet granulation. The amount of disintegrant microcrystalline cellulose and adhesive starch slurry were screened. The formula was optimized as 1000 tablets containing 12.5g of chlorothiazide, 64.83g / L lactose 129.66g / L, pH 10140g / L of microcrystalline cellulose, pH 30212g / L of microcrystalline cellulose, 0.34g / 0.17C of ferric oxide red, 1 g / 0.5mg of magnesium stearate and 4.5g / 2.25g / L of starch. The dissolution of the tablets was in accordance with the quality requirement of 2. 5%. The amount of sodium hydroxide, meglumine, polyvinylethone K25 and magnesium stearate were screened by spray drying method in telmisartan layer. The formulation was optimized to 1000 tablets containing telmisartan 80g / L 16.67m, sodium hydroxide 6.72g-1. 4), meglumine 24 g / L, polyvinylethone K2528.8 g / 6 / L, sorbitol 326.08 g / 67.93%, magnesium stearate 14.4g / 3C, purified water 400g / g. The dissolution of tablets prepared by spray drying with this prescription was in accordance with the quality standard of 3. 3%. The optimum process parameters for the production of telmisartan hydrochlorothiazide bilayers were established. The results show that when the pore diameter of hydrochlorothiazide granulation screen is 30 mesh, the drying temperature is 60 鈩
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