本文選題：替米沙坦 + 氫氯噻嗪��； 參考：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：近年來，隨著高血壓人數(shù)的增多，降壓藥的市場越來越廣闊，由于高血壓患者一般為中老年人，多數(shù)伴隨著各種各樣的其他病癥，如高血壓伴隨糖尿病、高血壓伴隨腎功能不全等。單用一種降壓藥往往很難將血壓控制在正常范圍內(nèi)，常常需要兩種及多種藥物聯(lián)合使用才能達(dá)到較理想的降壓效果。同時服用好幾種藥物，容易降低患者的依從性，不能很好的將血壓控制在安全的范圍內(nèi)，，各種高血壓引起的并發(fā)癥也會接踵而至。 若能將一種或者幾種藥物結(jié)合起來制成雙層片劑，有利于減少患者的服藥次數(shù)，同時能夠更好的控制藥物釋放速度，將血壓更好的控制在正常范圍內(nèi)。替米沙坦和氫氯噻嗪聯(lián)合用藥，能夠改善血管功能狀態(tài)，延緩或逆轉(zhuǎn)左室肥厚，降低心血管事件的發(fā)生率和死亡率，同時也降低了單獨(dú)用藥的不良反應(yīng)發(fā)生率及減輕不良反應(yīng)的程度。 本論文旨在研制一種雙層片降壓藥物----替米沙坦氫氯噻嗪雙層片。以專利ZL02827182.3為基礎(chǔ)，藥劑學(xué)、藥用輔料及《中國藥典》對片劑質(zhì)量要求為指導(dǎo)對雙層片處方和工藝進(jìn)行改進(jìn)。主要內(nèi)容如下： 1.氫氯噻嗪層采用濕法制粒，對崩解劑微晶纖維素和粘合劑淀粉漿等的用量進(jìn)行篩選。將處方優(yōu)化為1000片含氫氯噻嗪12.5g(6.25%)、乳糖129.66g(64.83%)、微晶纖維素pH10140g(20%)、微晶纖維素pH30212g(6%)氧化鐵紅0.34g(0.17%)、硬脂酸鎂1g(0.5%)、淀粉4.5g(2.25%)。該處方原輔料配比合適，制的的片劑溶出度符合質(zhì)量要求 2.替米沙坦層采用噴霧干燥法制粒，對氫氧化鈉、葡甲胺、聚維酮K25及硬脂酸鎂用量進(jìn)行篩選，將處方優(yōu)化為1000片含替米沙坦80g(16.67%)、氫氧化鈉6.72g(1.4%)、葡甲胺24g(5%)、聚維酮K2528.8g(6%)、山梨醇326.08g(67.93%)、硬脂酸鎂14.4g(3%)、純化水400g。用該處方比例噴霧干燥制粒，壓出的片劑溶出度符合質(zhì)量標(biāo)準(zhǔn)。 3.對雙層片工藝進(jìn)行優(yōu)化，建立一套生產(chǎn)替米沙坦氫氯噻嗪雙層片合適的工藝參數(shù)。結(jié)果表明當(dāng)氫氯噻嗪制粒篩網(wǎng)孔徑為30目、烘干溫度60℃、干顆粒含水量小于2.5%，替米沙坦層生產(chǎn)溫度18℃-25℃、濕度小于50%、噴霧干燥出風(fēng)溫度85℃左右、山梨醇粒徑80%大于150um時，能夠生產(chǎn)出偏重穩(wěn)定、脆碎度符合標(biāo)準(zhǔn)、溶出度達(dá)標(biāo)、有關(guān)物質(zhì)含量在要求范圍內(nèi)的雙層片。
[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

本文編號：2008167