氢溴酸右美沙芬分散片的研究

发布时间：2018-04-11 16:59

  本文选题：氢溴酸右美沙芬 + 聚克立林钾　； 参考：《天津医科大学》2017年硕士论文

【摘要】：目的:本研究拟使用聚克立林钾作为矫味剂,应用正交设计法及相关分析优选氢溴酸右美沙芬分散片处方,建立质量控制标准,并考察其稳定性。方法:先将氢溴酸右美沙芬与聚克立林钾进行离子交换,制备成载药树脂,再与片剂中常用辅料如填充剂、黏合剂、崩解剂混合制成软材后制备颗粒,添加润滑剂混合均匀后压制成型。通过辅料干扰性考察试验、原辅料相容性试验、处方筛选试验和工艺研究试验,通过溶出度及稳定性考察试验,最终确定了氢溴酸右美沙芬分散片的处方和工艺。摸索氢溴酸右美沙芬的高效液相色o}条件,建立其质量控制的方法。通过破坏性实验、影响因素、加速、长期试验,进一步考察了处方和工艺的可操作性和稳定性,对处方做最后的验证。结果:⑴氢溴酸右美沙芬与聚克立林钾制备药树脂中,选择聚克立林钾树脂型号IRP-88,最合适的药物与树脂配比为1:1,通过初步的处方筛选确定四种辅料,采用三水平四因素正交试验,得出最佳处方为15%CCNa、20%乳糖、20%木糖醇、20%HPC,其他因素不变的情况下,崩解剂交联羧甲基纤维素钠(CCNa)选择内外加法为最优;⑵该分散片除在水中溶出较慢外,在其他3种介质(0.1mol/L HCl、p H4.5醋酸-醋酸钠缓冲液、p H6.8磷酸盐缓冲液)中溶出均较快;⑶质量控制方法选用流动相甲烷磺酸溶液-乙腈(70:30);检测波长:280nm,流速:1.0m L/min;⑷辅料不干扰测定,线性关系好,精密度高,重复性、稳定性、回收率良好;⑸3批制剂的含量测定结果分别为100.0%、100.39%和99.88%,总平均含量为99.99%,RSD为1.54%,结果复合要求;⑹影响因素试验结果表明:原料药和本品不耐强酸碱和氧化剂,本品在高温(60℃)及高湿(相对湿度92.5%)条件下有关物质略有增加,因此本品应避免高温下长期存放,同时需要防潮包装;⑺加速试验表明参比制剂与自制样品的有关物质变化趋势基本一致,均略有增加,且对照药品的增加趋势较自制品明显,但限度均在合格范围内。长期实验仍在进行中。结论:本课题以聚克立林钾树脂与右美沙离子交换吸附制备药树脂,方法有效可靠,初步确定处方中的辅料后,应用正交设计试验得到最合理的处方,并进一步考察了不同崩解剂对制剂的影响,确定最合理的加入方法为内外加法,并对制剂进行了分散均匀性以及溶出度的考察,最终制备的右美沙芬分散片均匀、硬度适宜、外观整洁、崩解迅速。质量控制方法采用高效液相色谱法,专属性试验、线性关系考察、精密度试验、重复性试验、稳定性试验、回收率试验均符合规定,方法使用方便、辅料干扰小、精密度高,可用于氢溴酸右美沙芬含量测定及有关物质检查。稳定性试验合理全面,确定了药物的存储条件应密封防潮,制剂稳定性符合规定。
[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，

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