溶出试验

本试验用来测定正文中收载的片剂和胶囊剂在溶出要求方面是否符合药典规定。在此介绍三种类型仪器装置,其中需要采用的一种在各别正文中均加以指明。除非在各别正文中另有规定,一般均采用装置1。装置1——整套装置组成如下:一个带盖而由玻璃或其它惰性透明材料组成的1000ml的容器;一种变速驱动器和一只圆柱形     

多条溶出曲线评价盐酸二甲双胍片的溶出行为

目的：比较7个厂家盐酸二甲双胍片在4种溶出介质中的溶出曲线,评价进口制剂与仿制制剂的溶出行为。方法：采用篮法,转速为100 r·min-1,分别以pH 1.0盐酸溶液、pH 4.5醋酸盐缓冲液、pH 6.8磷酸盐缓冲液、水为溶出介质,以紫外分光光度法测定溶出曲线,采用f2因子对溶出曲线的相似度进行评价。结果：在4种不同溶出介质中,仅有1个厂家盐酸二甲双胍片的4条溶出曲线与进口制剂相似,还有4家制剂的4条溶出曲线与进口制剂均不相似。结论：多数仿制制剂的溶出曲线与参比制剂不相似,建议改进制剂处方与工艺。     

溶出条件对富马酸贝达喹啉片溶出行为的影响

建立了具有良好区分力的富马酸贝达喹啉(1)片体外溶出方法。通过考察1在不同pH介质中的平衡溶解度，证实了1的溶解度在生理pH范围内呈现pH依赖性。在此基础上，以溶出曲线差异因子(f1)为评价指标，片剂的崩解性能为辅助指标，通过测定采用不同粒径1原料药制备的自研制剂在各溶出介质中的溶出曲线，筛选出最具区分力的溶出方法，即采用篮法，以pH 1.0盐酸为溶出介质，转速为100 r/min，介质体积为900 mL。建立并优化的溶出方法可有效区分不同质量属性的自研制剂，为该类仿制药的开发提供了有效参考。     

酮洛芬肠溶胶囊的溶出速率测定

本实验对酮洛芬肠溶胶囊的溶出速率进行了方法学考察,经人工肠液为溶出介质,分别设立篮法(100和120RPM)、桨法(50和75RPM)等四种测定条件,结果显示:篮法测定离散度较小。以篮法100RPM对国内3个厂家5个批号的样品在人工肠液中的溶出速率作了考察,结果表明:尽管各批号Td间差距悬殊(6.22～87.40min),但同批号内溶出速率的离散度更大,使得各批号Td间无显著性差异(p>0.05)。     

SOTAX自动溶出仪与普通溶出仪测定西洛他唑片溶出度比较

目的以西洛他唑片为例,利用SOTAX自动溶出仪对溶出度方法作方法学验证。方法采用中国药典西洛他唑的溶出度方法,手动稀释改为自动循环测定（1mm比色皿）。结果回收率100．1％,重复性RSD为0．4％,回归方程为A=3．7655C-0．0151,r=0．9999,并对自动溶出法和手动溶出法作了比较试验,两者无显著差异。结论自动取样溶出法可以用于西洛他唑片的溶出度检测。     

枸橼酸他莫昔芬片在不同溶出介质中的溶出行为比较

目的使用光纤药物溶出度实时测定仪在四种不同溶出介质中测定国内2个厂家枸橼酸他莫昔芬片的体外溶出度曲线。方法测定波长275 nm、基准校正波长550 nm、温度37℃、转速100 r.min-1、数据采集间隔时间1 min。分别以0.02 mol.L-1盐酸溶液,pH=4.5磷酸盐缓冲液,pH=6.8磷酸盐缓冲液和水作为溶出介质,浆法,用光程为5 mm的光纤探头监测枸橼酸他莫昔芬片的溶出曲线。并应用相似因子f2法比较溶出曲线的相似性。结果 2个厂家的枸橼酸他莫昔芬片溶出度均符合《中国药典》2010年版规定,但两厂家产品的溶出过程存在差异且同一厂家在不同溶出介质中溶出行为也有很大差异。结论光纤药物溶出实时测定仪能准确连续地反映药物的溶出过程,所得数据完整、真实。     

不同溶出介质中利福昔明片体外溶出行为比较

目的 考察利福昔明片自研制剂与原研制剂在不同溶出介质中体外溶出行为的相似性。方法 以国外上市的利福昔明片作为参比制剂,采用桨法进行溶出试验。溶出介质分别为p H=1.2盐酸溶液[含1.0%十二烷基硫酸钠溶液(SDS)]、p H=4.5醋酸-醋酸钠缓冲液(含1.0%SDS)、p H=6.8磷酸盐缓冲液(含1.0%SDS)和水(含1.0%SDS),采用紫外分光光度法检测含量,以相似因子(f2)法对溶出曲线的相似性进行评价。结果 在不同p H的溶出介质中,自研制剂与参比制剂比较,f2均大于50。结论 自研制剂和参比制剂在不同溶出介质中的体外溶出行为相似。     

奥美拉唑肠溶胶囊的溶出特性考察

考察了四家药厂的奥美拉唑肠溶胶囊的溶出特性,导出溶出参数,并进行了统计学分析,按照国家药品标准对其进行了全项检验,四种胶囊均符合规定,其溶出曲线形状基本相似,但其中一家产品的溶出参数与其他三家的有显著性差异,奥美拉唑肠溶胶囊的溶出曲线较能反映其内在质量。     

不同溶出介质中头孢地尼胶囊溶出曲线的相似性比较

目的采用不同溶出介质进行头孢地尼胶囊溶出度实验,考察不同溶出条件对头孢地尼胶囊溶出度的影响,同时为难溶性药物制剂质量判断提供参考。方法以盐酸溶液(稀盐酸24→1000)、水、PBS4.0缓冲溶液、PBS7.0缓冲溶液为溶出介质,绘制参比制剂和自制制剂的溶出曲线,以相似因子f2作为指标,对比自制制剂与参比制剂溶出特性。结果在这4种介质中,参比制剂与自制制剂相似高于60。结论自制制剂与参比制剂在4种不同介质中溶出行为基本一致。     

厄贝沙坦片在多种溶出介质中溶出曲线的比较研究

目的比较国产厄贝沙坦片仿制药与进口原研药在4种不同的溶出介质中的溶出曲线的相似性。方法 RC806溶出仪进行溶出实验,用高效液相色谱法定量,以pH1.2的盐酸溶液,pH4.0乙酸盐缓冲溶液,pH6.8的磷酸盐缓冲溶液和水为溶出介质,分别测得4种片的溶出曲线,并采用相似因子f2来考察其相似性。结果厄贝沙坦片的溶出曲线有很强的pH值依赖性,在pH1.2的盐酸溶液中溶出完全,而在pH4.0乙酸盐缓冲溶液、pH6.8的磷酸盐缓冲溶液和水中,国产厄贝沙坦片仿制药与进口原研药的溶出曲线有很大差异。结论国内外不同厂家的厄贝沙坦片在多种溶出介质中溶出曲线存在差异,临床应用时应加以注意;有必要加强多介质溶出曲线的监控,保证不同厂家同一品种质量的均一性和稳定性。     

阿莫西林胶囊仿制药与原研药溶出行为研究及有区分力溶出方法的建立

Objective To establish a discriminative method for the dissolution curve of amoxicillin capsules. Methods The effects of different stirring device, different stirring speeds, different dissolution media on the dissolution behavior of different manufacturers' amoxicillin capsules (250mg) were investigated by dissolution profile and f2 similarity factor. Results The dissolution test of amoxicillin capsules (250 mg) was carried out by a paddle method (with sinker) with the rotation speed of 100 r/min, temperature of 37 °C, and water as dissolution medium, which could easily and effectively distinguish the dissolution behavior of amoxicillin capsules from various manufacturers. Conclusion This method provides a reference for the further quality consistency evaluation of amoxicillin capsules.     

维生素D3软胶囊溶出度测定方法的建立

目的:建立维生素D₃软胶囊溶出度测定方法。方法:考察不同搅拌装置、不同溶出介质(表面活性剂种类/浓度、碱浓度)、不同挽拌速度对维生素D₃软肢囊溶出行为的影响,采用H PLC法对溶出样品进行测定并计算累积溶出度。结果:采用桨法(沉降篮)、转速100 r·min^-1、37℃、0.3 mol·L^-1氢氧化钠-10%曲拉通X-100为溶出介质对维生素D₃软胶囊(400、800 IU)进行溶出实验。结论:以上溶出方法可有效运用于维生素D₃软胶囊的溶出度检测,能区分国产与进口制剂的溶出行为以及同厂家不同批次间溶出行为差异,该溶出方法可为油溶性软胶囊的溶出方法开发及维生素D₃软胶囊的仿制药一致性评价工作提供参考。     

Applications of a new device (spindle) for improved characterization of drug release (dissolution) of pharmaceutical products.

A crescent spindle (patent pending) is described which may be used in place of the USP paddle component in USP dissolution apparatus 2. The new spindle is curve shaped, corresponding to the bottom of a dissolution vessel, with attached bristles to fill in the gap between the spindle and the surface of the vessel. The geometry of the new spindle provides more efficient mixing than the USP paddle and prevents accumulation of disintegrated material (no cone formation). Using the new spindle, in comparison with the USP paddle, dissolution characteristics of three drug products: 250 mg amoxicillin capsules, 15.6 g acetylsalicylic acid (ASA) boluses and 200 mg carbamzepine tablets were evaluated. The experimental conditions for dissolution testing with the two stirring devices included; 900 ml of 0.05 M phosphate buffer, pH 6.8 with 50 rpm, 900 ml of 0.05 M acetate buffer, pH 4.5-ethanol (7:3) with 50 rpm, and water containing 1% sodium lauryl sulphate with 75 rpm for amoxicillin capsules, ASA boluses and carbamazepine tablets, respectively. Uncharacteristic of the test products, which are fast release, the USP paddle provides significantly slower drug release. For example, 90 min for <80% drug release vs. 10 min for >90% for amoxicillin capsules and 6 h for 80% vs. 30 min for >90% for ASA boluses with USP paddle vs. the new spindle. In case of the carbamazepine tablets, three products which are bioequivalent and prescribed interchangeably, the USP paddle method shows significantly different dissolution characteristics. However, with the new device, all these products show similar drug release characteristics, a better reflection of product release characteristics and in vivo drug release behaviour. Compared with the USP paddle, the suggested device (spindle) provides improved stirring and mixing which appears to provide more appropriate (biorelevant) characterization of pharmaceutical products.     

Choice of rotation speed (rpm) for bio-relevant drug dissolution testing using a crescent-shaped spindle.

Recently a new crescent-shaped spindle has been proposed to address the issues related to poor hydrodynamics of the USP paddle apparatus and its associated artifacts of high variability and lack of bio-relevant results. For improved comparison of drug dissolution characterization, it is highly desirable to conduct testing using common experimental conditions such as spindle rotation speed. A study was conducted in which different products were tested using the crescent-shaped spindle to propose a common rpm speed for improved comparative drug dissolution testing. Conventional- (200 mg) and extended-release (200 and 400 mg) carbamazepine tablets of multiple brands and amoxicillin capsules (250 and 500 mg) were analysed using the crescent- shaped spindle at 25, 50 and/or 75 rpm. Drug release was evaluated for 1.5h for amoxicillin and for 3.0 and 24h for conventional- and extended-release carbamazepine tablets products respectively. The dissolution media used were 0.05 M phosphate buffer for amoxicillin capsules and water containing 0.5% sodium lauryl sulphate for carbamazepine tablet products. All products showed characteristic drug release profiles, reflecting the fast and slow drug release natures of the products tested with complete drug release within expected time durations. Based on an expected maximum drug release criterion of 85% in a reasonable time, at a relatively slow drug release rate and within a dosing interval, a spindle speed of 25 rpm was found to be the most appropriate. Thus, it is concluded that drug products can be analysed using a single spindle type (crescent) with a single rpm (25) which would, not only result in simpler dissolution procedures, but also provide enhanced efficiencies from economical and regulatory aspects.     

Optimization and statistical evaluation of dissolution tests for indinavir sulfate capsules

An optimization, statistically based on t-student test, to set up dissolution test conditions for indinavir sulfate capsules is presented. Three dissolution media, including that reported in United States Pharmacopeial Forum, and two apparatus, paddle and basket, were applied. Two different indinavir sulfate capsules, products A and B, were evaluated. For a reliable statistical analysis eighteen capsules were assayed in each condition based on the combination of dissolution medium and apparatus. All tested media were statistically equivalent (P > 0.05) for both drug products when paddle apparatus was employed at the stirring speed of 50 rpm. The use of basket apparatus at the stirring speed of 50 rpm caused significant decrease in the drug release percent for the product B (P < 0.05). The best dissolution conditions tested, for products A and B, were applied to evaluate capsules dissolution profiles. Twelve dosage units were assayed and dissolution efficiency concept was used, for each condition, to obtain results with statistical significance (P > 0.05). Optimal conditions to carry out the dissolution test were 900 ml of 0.1 M hydrochloric acid as dissolution medium, basket at 100 rpm stirring speed and 260 nm ultraviolet detection.     

Cause of high variability in drug dissolution testing and its impact on setting tolerances.

Considering a variable mixing/stirring and flow pattern in a drug dissolution vessel as a likely source of high variability in results, experiments were conducted using USP paddle apparatus by placing (aligned to the walls) a metal strip (1.7 mm thickx6.4 mm wide) in a dissolution vessel. The metal strip forces the undisintegrated tablet to settle about 3 mm away from the centre, facilitates spread of disintegrated material and diminishes the cone formation at the bottom of the vessel. To assess the impact of this altered environment in the vessel, but still maintaining the vessel dimensions within required specifications, drug release characteristics were evaluated for products having different formulation/manufacturing attributes. Tests were conducted with calibrator tablets (USP prednisone and salicylic acid tablets and FDA proposed NCDA No. 2 prednisone tablets) and two commercially available products (250 mg amoxicillin capsules and 5 mg glibenclamide tablets). Except for the glibenclamide tablet product, all products gave significantly (P<0.01) higher dissolution results with vessels containing metal strip than without. The extent of increased dissolution with the metal strip varied from product to product i.e. USP prednisone tablet was the smallest (14.4%) and NCDA No. 2 was the largest (88.4%). Based on the results obtained from this study, it is concluded that employing the current apparatuses, in many cases products will provide lower than anticipated results which may not be reflective of the product drug release characteristics. Test-to-test variability, within or between laboratories, can also be very high depending on the settling position of the product once dropped in the vessel and/or due to slight aberration in the walls of the vessel by altering the extent of spread of disintegrated material at the bottom of the vessel. Thus, dissolution testing will require wider tolerances to be useful for comparison of batch-to-batch or interlaboratory results.     

尼群地平片溶出度测定

目的采用不同方法考察市售尼群地平口服片剂和软胶囊的溶出度 ,并提出尼群地平溶出度检查的标准。方法用含不同浓度的十二烷基硫酸钠 (SDS)醋酸盐缓冲液 (pH 4 5 )为溶出介质 ,采用紫外分光光度法检查 ,比较不同厂家尼群地平片和尼群地平软胶囊的体外溶出度。用相似因子法对片剂溶出度数据进行统计分析。结果用 0 3 %SDS醋酸盐缓冲液 (pH 4 5 ) ,除B片和D片之间的 (B片 D片 )相似因子F2 >5 0外 ,其余的F2 ≤ 5 0 ,可以显示出不同厂家生产的尼群地平片的溶出度差异。而用 0 1 %SDS醋酸盐缓冲液可以显示出尼群地平软胶囊与片剂的溶出度差异。结论不同厂家生产的尼群地平片的溶出度存在较大的差异 ,尼群地平片和软胶囊在溶出度方面整体存在较大差异 ,建议《中华人民共和国药典》规定尼群地平片剂的溶出度检查     

氢溴酸右美沙芬胶囊溶出速率的实验

目的研究氢溴酸右美沙芬胶囊体外溶出速率的方法。方法溶出度测定法,溶出介质为0.1mol.L-1盐酸溶液,氢溴酸右美沙芬胶囊的溶出量采用高效液相色谱法测定。结果氢溴酸右美沙芬浓度在0.1～0.3mg.mL-1范围内与各自的峰面积呈良好的线性关系,r为0.9998。平均回收率为99.7%,RSD 0.5%。该样品30min溶出量在90%以上。结论本方法用于氢溴酸右美沙芬胶囊中氢溴酸右美沙芬的溶出度测定可行。     

维生素D2软胶囊溶出度测定方法的建立#br#

目的 建立维生素D2软胶囊溶出度曲线测定的方法,评价国内维生素D2软胶囊与原研之间的体外溶出行为。方法 采用桨法(沉降篮),转速100r/min,以高效液相法测定维生素D2软胶囊在不同溶出介质中的溶出度并绘制溶出曲线。结果 在0.5mol/L NaOH-10%曲拉通X-100介质中国产维生素D2软胶囊与原研在90min溶出度均可达到80%以上。结论 该方法可用于维生素D2软胶囊的溶出度测定。     

维生素D2软胶囊溶出度测定方法的建立#br#

目的 建立维生素D2软胶囊溶出度曲线测定的方法,评价国内维生素D2软胶囊与原研之间的体外溶出行为。方法 采用桨法(沉降篮),转速100r/min,以高效液相法测定维生素D2软胶囊在不同溶出介质中的溶出度并绘制溶出曲线。结果 在0.5mol/L NaOH-10%曲拉通X-100介质中国产维生素D2软胶囊与原研在90min溶出度均可达到80%以上。结论 该方法可用于维生素D2软胶囊的溶出度测定。