本文選題：氫溴酸右美沙芬 + 聚克立林鉀�。� 參考：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:本研究擬使用聚克立林鉀作為矯味劑,應(yīng)用正交設(shè)計(jì)法及相關(guān)分析優(yōu)選氫溴酸右美沙芬分散片處方,建立質(zhì)量控制標(biāo)準(zhǔn),并考察其穩(wěn)定性。方法:先將氫溴酸右美沙芬與聚克立林鉀進(jìn)行離子交換,制備成載藥樹脂,再與片劑中常用輔料如填充劑、黏合劑、崩解劑混合制成軟材后制備顆粒,添加潤(rùn)滑劑混合均勻后壓制成型。通過輔料干擾性考察試驗(yàn)、原輔料相容性試驗(yàn)、處方篩選試驗(yàn)和工藝研究試驗(yàn),通過溶出度及穩(wěn)定性考察試驗(yàn),最終確定了氫溴酸右美沙芬分散片的處方和工藝。摸索氫溴酸右美沙芬的高效液相色o}條件,建立其質(zhì)量控制的方法。通過破壞性實(shí)驗(yàn)、影響因素、加速、長(zhǎng)期試驗(yàn),進(jìn)一步考察了處方和工藝的可操作性和穩(wěn)定性,對(duì)處方做最后的驗(yàn)證。結(jié)果:⑴氫溴酸右美沙芬與聚克立林鉀制備藥樹脂中,選擇聚克立林鉀樹脂型號(hào)IRP-88,最合適的藥物與樹脂配比為1:1,通過初步的處方篩選確定四種輔料,采用三水平四因素正交試驗(yàn),得出最佳處方為15%CCNa、20%乳糖、20%木糖醇、20%HPC,其他因素不變的情況下,崩解劑交聯(lián)羧甲基纖維素鈉(CCNa)選擇內(nèi)外加法為最優(yōu);⑵該分散片除在水中溶出較慢外,在其他3種介質(zhì)(0.1mol/L HCl、p H4.5醋酸-醋酸鈉緩沖液、p H6.8磷酸鹽緩沖液)中溶出均較快;⑶質(zhì)量控制方法選用流動(dòng)相甲烷磺酸溶液-乙腈(70:30);檢測(cè)波長(zhǎng):280nm,流速:1.0m L/min;⑷輔料不干擾測(cè)定,線性關(guān)系好,精密度高,重復(fù)性、穩(wěn)定性、回收率良好;⑸3批制劑的含量測(cè)定結(jié)果分別為100.0%、100.39%和99.88%,總平均含量為99.99%,RSD為1.54%,結(jié)果復(fù)合要求;⑹影響因素試驗(yàn)結(jié)果表明:原料藥和本品不耐強(qiáng)酸堿和氧化劑,本品在高溫(60℃)及高濕(相對(duì)濕度92.5%)條件下有關(guān)物質(zhì)略有增加,因此本品應(yīng)避免高溫下長(zhǎng)期存放,同時(shí)需要防潮包裝;⑺加速試驗(yàn)表明參比制劑與自制樣品的有關(guān)物質(zhì)變化趨勢(shì)基本一致,均略有增加,且對(duì)照藥品的增加趨勢(shì)較自制品明顯,但限度均在合格范圍內(nèi)。長(zhǎng)期實(shí)驗(yàn)仍在進(jìn)行中。結(jié)論:本課題以聚克立林鉀樹脂與右美沙離子交換吸附制備藥樹脂,方法有效可靠,初步確定處方中的輔料后,應(yīng)用正交設(shè)計(jì)試驗(yàn)得到最合理的處方,并進(jìn)一步考察了不同崩解劑對(duì)制劑的影響,確定最合理的加入方法為內(nèi)外加法,并對(duì)制劑進(jìn)行了分散均勻性以及溶出度的考察,最終制備的右美沙芬分散片均勻、硬度適宜、外觀整潔、崩解迅速。質(zhì)量控制方法采用高效液相色譜法,專屬性試驗(yàn)、線性關(guān)系考察、精密度試驗(yàn)、重復(fù)性試驗(yàn)、穩(wěn)定性試驗(yàn)、回收率試驗(yàn)均符合規(guī)定,方法使用方便、輔料干擾小、精密度高,可用于氫溴酸右美沙芬含量測(cè)定及有關(guān)物質(zhì)檢查。穩(wěn)定性試驗(yàn)合理全面,確定了藥物的存儲(chǔ)條件應(yīng)密封防潮,制劑穩(wěn)定性符合規(guī)定。
[Abstract]:Objective: to establish a quality control standard and evaluate the stability of dextromethorphan hydrobromide dispersible tablets by orthogonal design and correlation analysis.Methods: dextromethorphan hydrobromide was exchanged with potassium polysporin to prepare the drug loaded resin, and then the granules were prepared from dexmethorphan hydrobromide and the commonly used excipients such as fillers, adhesives and disintegrators.The lubricant is mixed evenly and then pressed into shape.The formulation and process of dextromethorphan hydrobromide dispersible tablets were determined by interference test of excipient, compatibility test of raw and auxiliary materials, prescription screening test and technological research test.A method for quality control of dextromethorphan hydrobromide was established.Through destructive experiments, influencing factors, accelerating and long term experiments, the maneuverability and stability of the prescription and process were further investigated, and the final verification of the prescription was made.Results in the preparation of drug resin with dextromethorphan hydrobromide and polykerelin potassium, the most suitable ratio of drug to resin was 1: 1. Four kinds of excipients were determined by preliminary prescription screening.By using the orthogonal test of three water and four factors, the optimum prescription was obtained: 15 NaOH 20% lactose 20% xylitol 20% xylitol 20HPC.If other factors were not changed, the disintegrant cross-linked carboxymethyl cellulose sodium (CCNA) was selected as the best addition method.(2) the dispersible tablets, except for the slow dissolution in water, were rapidly dissolved in 0.1 mol / L HClH4.5 acetic acid-sodium acetate buffer solution (p H6.8 phosphate buffer).3 the mobile phase methanesulfonic acid solution-acetonitrile 70: 30 was used as the quality control method, the detection wavelength was 1: 280 nm, the flow rate was 1: 1.0 mL / min, the linear relationship was good, the precision was high, the repeatability, the stability and the recovery were good.The determination results of 53 batches of preparation were 100.39% and 99.888.The total average content was 99.9999 (RSD = 1.54). The results showed that the raw material and the product were not resistant to strong acid, alkali and oxidant.This product in the high temperature of 60 鈩，

本文編號(hào)：1736871