药用辅料二甲亚砜有关物质测定方法改进

摘 要 目的：参考各国药典对药用辅料二甲亚砜中有关物质的测定方法进行改进。 方法: 采用气相色谱法,以二苯甲烷为内标,Agilent DB wax毛细管柱（0.32 μm×30 m, 0.5 μm）,柱温:150℃,进样口温度:230℃,FID检测器温度:250℃,分流比：20∶1,进样量:2 μl。 结果: 在该色谱条件下,二甲亚砜中各杂质能完全分离;二甲基砜在6.58～526.50 μg·ml-1 的浓度范围线性关系良好（r=0.999 9）;平均回收率为101.27%（RSD=0.46%,n=6）。 结论: 本方法准确度高、重复性好,可用于二甲亚砜有关物质的测定。     

云南磷矿石中氧化钙含量测定方法的改进

用国标EDTA容量法检测磷矿石中氧化钙含量时,存在终点难以判定等问题,实验研究改用钙羧酸作指示剂,用三乙醇胺掩蔽铁、铝和少量锰,用糊精作保护荆抑制磷酸根和铗的干扰,同时采用KOH溶液调节试样溶液的pH值≥13,用EDTA标准溶液滴定,终点颜色变化敏锐,测定氧化钙的结果准确,方法可靠.     

黏度测定方法的介绍及药典中3个药用辅料黏度测定方法的讨论

黏度是高分子药用辅料的重要物理性质,黏度的测定是高分子药用辅料质量控制的重要手段之一.但在实际工作中,黏度的测定却不象其他理化检测分析方法那样直观稳定.笔者通过对黏度测定一些基本概念的介绍及几国药典中3种药用辅料黏度测定方法的比较,进一步探讨一下黏度测定的相关问题.     

药用丁基胶塞中挥发性硫化物测定方法的改进

目的:改进药用丁基胶塞中挥发性硫化物的测定方法。方法:采用古蔡氏法装置制备样品硫斑并与标准硫斑比较。结果:该方法较现行标准方法易于判断。结论:该方法灵敏快速,操作简便,重现性好,可用于药用胶塞中挥发性硫化物的检测。     

药用辅料管理：探究药用辅料的科学监管

药用辅料作为药物制剂的重要组成成分。它具有保护、支持、加强药品的稳定性、生物利用度或病人的顺应性,有助于药品的识别,在储存或使用期间增强药品的总体安全性和有效性等作用。然而长期以来,辅料都被视为惰性物质,它并没有得到企业和研究机构甚至监管部门的重视,直至近年的“齐二药”事件中,假辅料让“良药”变“毒药”,才使药用辅料的重要性开始被人们重视起来。国家药品监管部门也加大法规建设的力度,例如,《药用辅料注册管理办法》,《药用辅料生产质量管理规范》,《药用辅料质量标准》等系列法规的颁布,但是,目前药用辅料行业仍然存在很多问题,探究药用辅料的科学监管成为既重要又紧迫的课题。     

我国药用辅料标准中存在的问题及改进对策

目的:对我国目前药用辅料标准中存在的问题进行分析。方法:结合国内药品制剂科研生产的实际和发达国家的成功经验,对健全我国药用辅料标准中的重要性进行阐述,并提出具体的改进方法。结果与结论:目前我国药用辅料标准存在的问题已经严重影响了医药科研与生产,必须进行改进。     

药用辅料黑氧化铁质量标准探讨与改进

目的:提升《中国药典》2020年版收载药用辅料黑氧化铁的质量标准.方法:参考USP43/NF38和相关文献,对药典标准已有项目进行修订,补充必要的检验项目,建立合适的方法,并进行方法验证.结果:对原标准中铅的检测方法进行了修订,建立了石墨炉原子吸收(GFAAS)测定黑氧化铁中镍的方法以及等离子体发射光谱(ICP-AES...     

HPLC法测定药用辅料乳酸中乳酸

目的建立药用辅料乳酸中乳酸的HPLC测定方法。方法采用高效液相色谱法,使用Capcell Pak C18 MG色谱柱(250 mm×4.6 mm,5μm);流动相为0.1%磷酸水溶液–乙腈(97.5∶2.5);检测波长为215 nm,体积流量为1 mL/min;柱温为35℃;进样量为20μL。结果乳酸在0.1～5.0 mg/mL与峰面积呈良好的线性关系(r=0.999 9),平均回收率为99.8%,RSD值为0.8%(n=9)。结论此方法操作便捷、经济,方法准确度、精密度、耐用性好,可作为药用辅料乳酸中乳酸测定的分析方法。     

药用辅料氨丁三醇质量标准研究及改进

目的：提升《中国药典》2020年版收载药用辅料氨丁三醇的质量标准。方法：比较国内外氨丁三醇质量标准，对现行药典标准中全部检验项目进行考察，并结合试验结果提出改进方案。结果：对性状中的外观和溶解度、化学反应鉴别、溶液的澄清度与颜色、有关物质及铁盐检查提出修订建议，将熔点第二法修改为第一法，解决了本品在乙醇中溶解度与现行标准规定不一致的问题。结论：本方案从安全性和规范性上提高并完善了氨丁三醇质量标准，为加强本品的质量控制和进一步修订质量标准提供理论参考。     

药用辅料海藻酸钠含量测定的方法研究

目的:建立容量法和分光光度法测定药用辅料海藻酸钠的含量。方法:将海藻酸钠与浓盐酸发生脱羧反应生成二氧化碳,经过量的氢氧化钠吸收,然后用盐酸滴定剩余的氢氧化钠,从而推算样品中海藻酸钠的含量;分光光度法将海藻酸钠与四硼酸钠-硫酸作用后,可与间羟基联苯反应形成紫红色化合物,通过吸光度与海藻酸钠质量的线性关系,计算得海藻酸钠的含量。结果:对容量法前处理条件进行探索优化后,平均加标回收率为96.4%,RSD为1.9%(n=6);分光光度法平均回收率为101.9%,RAD为0.45%(n=2),两方法的样品含量测定结果一致。结论:两种方法准确度高、精密度、耐用性好,均可用于药用辅料海藻酸钠的含量测定。     

应用色度仪法快速测定药用辅料蔗糖色值的可行性研究

目的：建立测定蔗糖色值的方法。方法：采用紫外-可见光分光光度仪,以4 cm比色皿于420 nm处测定溶液的吸光度,以公式计算蔗糖溶液色值;采用色度仪,校准后测定不同色号的黄色标准比色液及蔗糖溶液颜色反射率值（CIE Y 值）,并将溶液颜色反射率值折算为黄色色号;通过直线回归分析,对33批蔗糖开展研究,并对所得数据结果间的相关性进行分析,考察应用色度仪法快速测定蔗糖色值的可行性。结果：测定的33批蔗糖色值结果在13 IU~223 IU之间,溶液颜色反射率值（CIE Y 值）在85%~92%之间,折算的黄色色号在0~22之间;经回归分析,色值测定结果与色度仪法测定的溶液颜色反射率值结果的回归方程斜率P值小于0.000 1,色值测定结果及溶液黄色色号结果的回归方程斜率P值小于0.000 1,颜色反射率值与色值、色值与溶液颜色均具有较强的相关性。结论：应用色度仪法对蔗糖色值开展快速准确地测定具有可行性,同时,也进一步为改进《中国药典》标准方法提供了技术支持。     

阿托伐他汀钙片含量测定方法的改进

目的建立高效液相色谱(HPLC)测定阿托伐他汀钙片中阿托伐他汀钙的含量的方法。方法采用Alltima C18色谱柱(250 mm×4.6 mm,5μm),以乙腈-0.1%磷酸溶液(60∶40)为流动相,流速1.0mL·min~(-1),检测波长246 nm,柱温25℃。结果阿托伐他汀钙在44.6～133.8μg·m L~(-1)与峰面积呈良好的线性关系(r=0.9999);辅料以及阿托伐他汀钙强制降解产物均不干扰测定;精密度、稳定性、重复性和回收试验的RSD均小于2%,平均回收率(n=3)为99.5%～99.7%。4批阿托伐他汀钙片的含量测定结果分别为19.37、19.46、19.54和19.59 mg/片。结论该方法准确、简单、快速,能够作为阿托伐他汀钙片的含量测定方法。     

药用辅料四氟乙烷理化检测试验方法概述

目的分析概述药用辅料四氟乙烷(HFC-134a)理化检测中的试验方法,为建立复核用质量标准提供方法依据。方法对药用辅料四氟乙烷(HFC-134a)质量标准研究中理化检测的试验方法进行整理和分析,参考国家已有的工业标准、国外企业标准及中国药典的规定,概述质量标准制定中理化检测的试验方法。结果本文提供的四氟乙烷理化检测中的试验方法确信可行,能复核检测药用辅料四氟乙烷。结论采用药用辅料四氟乙烷理化检测中的试验方法,能有效检测该气体并确定产品质量。     

The safety of pharmaceutical excipients

The most important part of a medicine as far as its weight is concerned, is constituted by its excipients, which have the important functions of guaranteeing the dosage, stability and bioavailability of the active principle. The components employed as excipients must present the characteristics required by their technological function but, as with any substance administered to man, they must also correspond to suitable safety requirements. In fact, in the past the importance of evaluating the possible adverse effects of excipients was underestimated, because their inertia and innocuity were taken for granted. The safety profile of these substances is more deeply researched as regards the toxicological aspect only if they are also employed in the food industry (anti-oxidants, sweeteners, colouring agents, etc.). Indeed, in this case, the International Toxicological Committees (among which the Joint Expert Committee on Food Additives, a mixed committee of the WHO/FAO) demand thorough studies in laboratory animals, with the intent of protecting the consumer's safety. Tackling the question of the toxicity of excipients thoroughly is not a simple matter for several reasons: the large number of substances on the market and the diversity of their chemical profiles, their sources, their technological functions, and the presence of secondary products and/or contaminants that may be the true causes of adverse effects. In this article we shall review the principal classes of excipients and their respective side effects. Then we shall proceed to their toxicological evaluation, giving examples of: (a) intrinsic toxicity, or adverse effects that may be encountered in the whole population; and (b) specific toxicity, which manifests only in people who are carriers of a transmissible disease or who are genetically predisposed, such as people with allergies and intolerances.     

辛酸钠药用辅料的制备及质量控制

目的 制备药用辅料辛酸钠.方法 以正辛酸及氢氧化钠为原料,控制反应终点pH 8～10,喷雾干燥.结果 所制辛酸钠经结构确证和质量分析,符合药用辅料要求.结论 合成方法简便易行,质量控制指标可用于工业化生产.     

海藻糖作为药用辅料的安全性评价

目的 评价海藻糖作为药用辅料使用的总体安全性。方法 以SD大鼠为试验对象,测定急性经口毒性;以健康白色家兔为试验对象,测定皮肤、眼刺激性;以豚鼠为试验对象,测定皮肤变态反应（致敏）性;以SD大鼠为试验对象,采用肌肉注射的方法进行90d给药试验,测定长期毒性。结果 在本试验条件下,海藻糖对SD大鼠急性经口毒性为实际无毒,对家兔皮肤、眼睛无刺激性,对豚鼠皮肤的致敏强度为弱致敏物,SD大鼠连续90d肌肉注射给药试验未观察到海藻糖明显的毒性反应,其无毒作用剂量＞200 mg/kg。结论 海藻糖作为药用辅料,安全性良好。     

Evaluation of hydroperoxides in common pharmaceutical excipients

While the physical properties of pharmaceutical excipients have been well characterized, impurities that may influence the chemical stability of formulated drug product have not been well studied. In this work, the hydroperoxide (HPO) impurity levels of common pharmaceutical excipients are measured and presented for both soluble and insoluble excipients. Povidone, polysorbate 80 (PS80), polyethylene glycol (PEG) 400, and hydroxypropyl cellulose (HPC) were found to contain substantial concentrations of HPOs with significant lot-to-lot and manufacturer-to-manufacturer variation. Much lower HPO levels were found in the common fillers, like microcrystalline cellulose and lactose, and in high molecular weight PEG, medium chain glyceride (MCG), and poloxamer. The findings are discussed within the context of HPO-mediated oxidation and formulating drug substance sensitive to oxidation. Of the four excipients with substantial HPO levels, povidone, PEG 400, and HPC contain a mixture of hydrogen peroxide and organic HPOs while PS80 contains predominantly organic HPOs. The implications of these findings are discussed with respect to the known manufacturing processes and chemistry of HPO reactivity and degradation kinetics. Defining critical HPO limits for excipients should be driven by the chemistry of a specific drug substance or product and can only be defined within this context.     

Managing the microbiological quality of pharmaceutical excipients

The microbiological quality of the pharmaceutical excipients used to manufacture pharmaceutical and over-the-counter drug products may significantly affect the outcome of individual processing steps and the microbiological attributes of the final drug products. Unlike active pharmaceutical ingredients, excipients are purchased from multiple suppliers and in many cases are produced for the food, cosmetics, consumer products, photographic, and paint industries and not specifically for the pharmaceutical industry, so the management of their microbiological quality is less straight- forward. This article discusses the qualification of suppliers, excipient production methods, compendial standards, regulatory controls, and microbial limits testing of excipients. Emphasis is given to risk assessment associated with pharmaceutical excipients.