Effects of temperature and wavelength choice on in-situ dissolution test of Cimetidine tablets

The effects of temperature and wavelength choice on in-situ dissolution test instrument of Cimetidine were studied. Absorbance （A）〈 1.0 is required when using a fiber-optic dissolution test system. The detection wavelength of 2 （218 nm） was replaced by 244 nm to carry out this test. The absorbance of Cimetidine solution at different temperature showed an obvious change. Calibration of Cimetidine solution should be tested at the same temperature （37° C） with the test solution. A suitable wavelength with smaller tangent slope could be chosen for in-situ dissolution test of Cimetidine tablets.

Enhanced dissolution of sildenafil dry foam tablets

Sildenafil citrate is a highly selective phosphodiesterase-5(PDE-5)inhibitor.It is used for treatment of erectile dysfunction and pulmonary hypertension[1].Sildenafil citrate is categorized in BCS class 2 so it is developed as a citrate salt to increase water solubility(4.1 mg/mL)[2].The conventional product has been developed as a tablet dosage form.It is rapidly absorbed after oral administration,but gives a relatively low oral bioavailability of about 40%and late onset of action[2].Dry foam formulation technology is an alternative approach to overcome such a problem.

Evaluation of the quality of olanzapine orally disintegrated tablets by multiple dissolution curves

Objective: To investigate the dissolution behavior similarity between Self-made praeparatum and reference praeparatum in different pH menstruum,using the Olanzapine Orally Disintegrating Tablets listed in abroad as the reference praeparatum. Methods: The dissolution curve of olanzapine in Self-made praeparatum and reference praeparatum was measured,the similarity of the dissolution curve was evalued by F2 similar factor. Results: The single-point dissolution of both Self-made praeparatum and reference praeparatum within 15 min was more than 85%. Conclusion: Self-made praeparatum and reference praeparatum were similar in dissolution behavior.

Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets:Dissolution and release kinetics

A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic（LC） method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature（40 1C） using a mobile phase of acetonitrile：methanol：0.03 M ammonium acetate（p H 3.8）（30：15：55, v/v/v）, run at a flow rate of 1.5 m L/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2（paddle） at 100 rpm and 900 m L of phosphate buffer at p H 6.8 as the dissolution medium.Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

Study on Integral Dissolution Model Based on Biological Potency for Compound Chinese Materia Medica

Objective To investigate the integral dissolution model based on biological potency in order to evaluate the dissolution of Compound Chinese materia medica（CCMM） in vitro. Methods The contents of paeoniflorin, phillyrin, ginsenoside Rg1, and adenosine of ten batches of Compound Biejia Ruangan Tablet（CBRT） were determined at different times. The self-defined weighting coefficient based on the contents has been created to establish the integral dissolution model. In addition, the biological potency of CBRT was measured by MTT assay. Then, the f2 similar factor was used to evaluate the similarity of the batches. Results Compared with batch a, some batches’ f2 values of paeoniflorin and adenosine were less than 50, while f2 values of ginsenoside Rg1, phillyrin, and integral component were more than 50. Likewise, ginsenoside Rg1, phillyrin, and integral component were all in good correlation with biological dissolution. Conclusion The results of the integral dissolution based on biological test of CBRT demonstrate that the bioassay method may be a promising supplement for its quality evaluation.

Bioassay-based dissolution test of Shuanghuanglian tablet

It has been difficult to perform dissolution test on solid preparations of traditional Chinese medicines （TCMs）. TCMs are different from chemical drugs in that their chemical compositions are complicated. The measurement method based on chemical approach alone is incomplete. In order to solve this problem, in this study a bioassay-based dissolution test was developed. Microcalorimetry was used to obtain growth power-time curves and biothermodynamic parameters of Staphylococcus aureus inhibited by the solution of ShuangHuangLian （SHL） tablet, which was dissolved in phosphate buffer （pH 6.8） for different times. The results of the bioassay-based dissolution test of SHL tablet demonstrated that the bioassay method might be a promising alternative for its quality control.

Comparison of dissolution profile characteristics of 11 berberine hydrochloride tablet brands in different dissolution media

Berberine hydrochloride is commonly used to treat bacterial dysentery,gastroenteritis and other diseases.Many manufacturers are available on the market today,while the production process and formulation are quite different,which may directly affect the therapeutic effect of the drug.To this end,11 different production producers of berberine hydrochloride tablets were collected according to the pharmacopeia berberine hydrochloride dissolution method(basket method).In addition the dissolution process was carried out in four elution media with different pH,and the difference was similar(f2).Factors were calculated to evaluate in vitro dissolution requirements,and in vitro dissolution of different manufacturers of berberine hydrochloride tablets was determined by high performance liquid chromatography(HPLC).The method was verified by linearity,precision,stability and robustness.Based on the f2 value,there was a significant difference in the dissolution behavior of the formulations of most berberine hydrochloride tablet brands.This research provided the basis for further in-depth research in the later period.Although the drug specifications(0.1 g)were the same,the dissolution curve was different.This phenomenon may be attributed to the fact that the excipients and crystal form of the tablets affected the release and dissolution of the tablets in vitro.

Characterisation of a novel, multifunctional, co-processed excipient and its effect on release profile of paracetamol from tablets prepared by direct compression

Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and dif erential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. Results: Differential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution proi les. The dissolution parameters of the 1:4 batch was faster with- m∞(90.5%), t50%(3.5 min), t70%(11.6 min) while that of ratio 1:1 was the least with- m∞(48.6%), m5min(23.8%). Their release kinetics followed a KorsmeyerPeppas model with a super case-II transport mechanism.Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specii cations. The t50% value of the 1:4 batch of tablets may i nd its usefulness in formulating drugs for which a fast onset of action is desired.

利用计算模拟技术建立头孢呋辛酯片体内、外相关性溶出度评价方法

目的利用计算模拟技术,探索建立前体药物头孢呋辛酯片的体内外相关性预测模型,用于仿制药生物等效性评估。方法参考文献中头孢呋辛酯片口服给药后的PK数据,结合参比制剂的血药浓度数据,利用GastroPlus TM软件搭建头孢呋辛酯片药代动力学模型;结合原研制剂在不同溶出条件、4种溶出介质(pH1.2盐酸溶液、pH4.0醋酸盐缓冲溶液、pH6.8磷酸盐缓冲溶液和水)中的体外溶出行为,筛选适宜的溶出条件;将在不同溶出介质中得到的溶出曲线作为体内释放曲线,预测头孢呋辛酯片在体内PK参数并与参比制剂的临床实测数据进行比较,探讨头孢呋辛酯片体内外相关的溶出度方法。结果成功建立了头孢呋辛酯片体内外相关的溶出度方法:桨法,转速为55 r/min,以pH4.0醋酸盐缓冲液900 mL为溶出介质。结论所建立的头孢呋辛酯片药代动力学预测模型,可用于仿制药的生物等效性虚拟评估,为该药物的质量与疗效一致性评价提供了新思路。

基于体外溶出评价方法对硝苯地平缓释片(Ι)一致性评价研究

建立硝苯地平缓释片(Ⅰ)体外溶出评价方法,以原研制剂为参比,评价本公司一致性研究前后的自研制剂(以下简称自制1、自制2),为质量一致性提供依据。选取0.3%吐温80的不同pH值(pH值1.0,pH值4.0,pH值6.8,水)溶液为溶出介质,采用高效液相色谱法考察0.25,0.5,1,2,3,10,12 h的释放度,从而建立体外溶出曲线方法,并进行了方法学验证,最后采用相似因子法(f_(2))将自研制剂与参比进行比较。结果表明,建立的本品体外溶出曲线方法的专属性、线性、精密度、准确度、滤膜吸附、溶液稳定性各项指标均符合要求;自制1与参比溶出行为不一致且f_(2)小于50,调整处方工艺后,自制2与参比体外溶出行为一致,且f_(2)均大于50。本品建立的体外溶出评价方法准确可靠,自制1与参比体外溶出不一致;自制2与参比溶出曲线相似,体外溶出一致。

盐酸苯海拉明缓释片的制备

目的 :制备24h缓释的盐酸苯海拉明缓释片。方法 :建立盐酸苯海拉明紫外分光光度法的含量测定方法;以片剂成型情况确定制备工艺;以释放度为评价指标,筛选盐酸苯海拉明缓释片的骨架材料,确定处方;根据优选的处方工艺制备盐酸苯海拉明缓释片,考察其质量。结果 :紫外分光光度法:在纯化水中的标准曲线:y=0.0015x+0.015,r=0.9998,线性范围:130.5~451.7μg/mL;在模拟胃液中的标准曲线:y=0.0016x-0.0074,r=0.9993,线性范围:130.5~401.5μg/mL;在模拟小肠液中的标准曲线:y=0.0016x-0.0041,r=0.9991,线性范围:130.4~401.5μg/mL;在模拟结肠液中的标准曲线:y=0.0016x-0.0179,r=0.9991,线性范围:150.5~401.5μg/mL。精密度和回收率符合规定。优选的处方工艺为:盐酸苯海拉明75mg、乙基纤维素360mg、滑石粉15mg,粉末直接压片,压力70N。通过优选的处方及制备工艺制备的盐酸苯海拉明缓释片,片剂表面光滑整洁,片重差异及在不同释放介质中的释放度均在80%以上。结论 :以乙基纤维素为骨架材料制备的不溶性盐酸苯海拉明骨架片,可缓慢释放24h,制备工艺简单,造价成本低。

仿制药盐酸达拉他韦片与原研药DAKLINZA^(®)体外溶出一致性评价研究

目的建立盐酸达拉他韦片溶出方法,考察自制制剂与原研药DAKLINZA®在多种溶出介质中的溶出相似性,为该品种的仿制药研发提供参考。方法采用桨法,分别以pH1.0盐酸、pH4.5醋酸盐、pH6.8磷酸盐缓冲液(含0.15%苄泽35)为溶出介质,采用高效液相色谱法检测盐酸达拉他韦片,应用系统的方法学,对自制制剂与参比制剂溶出曲线相似性进行验证。结果所建立的溶出方法线性、准确度良好,自制制剂与参比制剂在pH1.0盐酸介质中15min时,溶出度均大于85%;在pH4.5醋酸盐、pH6.8磷酸盐缓冲液(含0.15%苄泽35)介质中,溶出曲线f2值均大于50,说明二者溶出具有相似性。结论自制制剂与参比制剂在多种溶出介质中溶出相似,说明二者体外溶出一致。

基于硝苯地平控释片体外研究预测制剂的生物等效性

目的基于对硝苯地平控释片自制的放大样品与参比制剂的溶出结果,通过药物溶出度及渗透速率测试系统预测体内外的一致性。方法首先,对比研究了自制硝苯地平控释片与参比制剂(拜新同)的溶出曲线;再采用MacroFlux型药物溶出度及渗透速率测试系统测定了硝苯地平控释片在空腹小肠模拟液(pH6.5)中的渗透速率以及渗透量;对比研究了参比制剂与受试制剂的释放与吸收过程。结果自制硝苯地平控释片在4种溶出介质中的溶出行为与参比制剂相似,药物体外溶出度—渗透速率测试结果显示,受试制剂溶出速率以及渗透速率均与参比制剂接近,最终与参比制剂生物等效。结论硝苯地平控释片结合体外溶出和药物溶出度及渗透速率测试系统的结果,可以快速预测评价受试制剂的生物等效性情况,为仿制药在人体的生物等效性评价提供了有力的技术支撑。

贝前列素钠缓释片制备及体外释放研究

目的制备非pH依赖性的贝前列素钠缓释片。方法筛选处方中pH调节剂种类、pH调节剂用量、缓释材料用量,与参比制剂对比研究pH 1.2盐酸溶液和pH 6.8磷酸盐缓冲液中的释放曲线,采用f2相似因子比较体外释放行为,利用星点设计试验优化得到最佳处方。结果采用7.07%的枸橼酸作为pH调节剂、54.47%的聚醋酸乙烯/聚乙烯吡咯烷酮共聚物作为缓释材料,可获得非pH依赖性的释放曲线,且释放曲线与参比制剂相似(f_(2)>50)。结论pH调节剂在缓释制剂中可调控微环境pH值,使贝前列素钠实现非pH依赖性的释放行为。

血塞通片体外溶出行为研究

目的 建立血塞通片溶出度检验方法,测定血塞通片中三七皂苷R_(1)、人参皂苷Rg_(1)、人参皂苷Re、人参皂苷Rb_(1)和人参皂苷Rd的整合溶出度。方法 以小杯法进行溶出度实验,采用高效液相色谱法(HPLC)测定5种指标成分的溶出量,采用质量分数权重系数法进行溶出度整合。绘制溶出曲线,采用f_(2)相似因子法比较各成分溶出曲线与整合溶出曲线的相似性,对整合溶出数据进行模型拟合,计算溶出参数T_(50)、T_(d)和T_(85)。结果 以水为溶出介质,转速50 r/min,60 min取样。5种指标成分溶出曲线与整合溶出度溶出曲线的f_(2)相似因子分别为64.5,61.6,79.8,60.0和68.2。溶出数据拟合模型以Weibull模型最优,溶出参数T_(50)、T_(d)和T_(85)分别为12.29 min、18.09 min和56.09 min。结论 建立的溶出度检查方法准确、可行,采用质量分数权重系数法整合溶出度能较好地表征血塞通片的体外溶出行为,可为血塞通片的质量一致性评价研究及质量控制提供技术借鉴。

流池溶出度法在阿司匹林肠溶片中的应用研究

目的建立阿司匹林肠溶片新的溶出度测定方法,并考察仿制药与参比制剂溶出行为的差异。方法采用流通池开环系统,以pH 1.2盐酸溶液、pH 4.5醋酸盐缓冲液、pH 6.0和pH 6.8磷酸盐缓冲液为溶出介质,流速为4 mL/min,定时取样,测定阿司匹林肠溶片的溶出度。通过模型依赖的平均标准偏差法,拟合后评价仿制药与参比制剂溶出度曲线相似性,通过f2-bootstrap法评价批间溶出行为一致性。结果国内5个厂家中仅1家市售产品与参比制剂溶出度曲线相似;试验涉及的6个厂家中有2家市售产品批间溶出行为相似。结论所建方法设计符合人体生理特点,可用于阿司匹林肠溶片溶出度测定。

沙库巴曲缬沙坦钠片体外溶出方法的建立及评价

目的 建立沙库巴曲缬沙坦钠片体外溶出测定方法,并对仿制制剂与参比制剂进行溶出曲线相似性的评价。方法 溶出度试验采用桨法,转速50 r·min^(-1);以0.1 mol·L^(-1)盐酸溶液、pH4.5醋酸盐缓冲液、pH6.8磷酸盐缓冲液、水各900mL为溶出介质;采用高效液相色谱法测定溶出量。结果 建立的体外溶出测定方法专属性、线性、准确度、重复性及精密度良好,供试品溶液室温放置48 h稳定;所有制剂样品在pH4.5醋酸盐缓冲液、pH6.8磷酸盐缓冲液及水中均能完全溶出,30min溶出量均>85%;3批仿制制剂与参比制剂溶出曲线的相似因子(f2)在0.1mol·L^(-1)盐酸溶液、pH4.5醋酸盐缓冲液、pH6.8磷酸盐缓冲液及水中分别为66~92、65~72、58~63及72~79。结论 体外不同生理pH溶出介质中,仿制制剂与参比制剂的溶出曲线相似因子(f2)均大于50,溶出曲线均相似,体外溶出行为一致,可为后续体内生物等效评价提供参考。

盐酸苯海拉明微丸型口腔崩解片的制备工艺研究

采用挤出滚圆及包衣制备缓释微丸,湿法制粒法制备辅料颗粒,将缓释微丸、辅料颗粒及外加物料混合压片制备了盐酸苯海拉明口腔崩解片。结果表明:盐酸苯海拉明与微晶纤维素以质量比1∶1混合后挤出滚圆,并采用乙基纤维素乙醇溶液包衣制备缓释微丸,然后再与其他辅料混合压片制备口腔崩解片,其溶出曲线与原研制剂不同介质中体外溶出相似。采用缓释微丸压片的方法制备口腔崩解片可以减缓药物溶出速度,达到与原研制剂不同介质中溶出曲线相似目的,该技术可为其他溶出类似口腔崩解片的研究开发提供参考。

维生素C片含量测定的HPLC法及溶出度方法的研究

目的建立测定维生素C片含量的高效液相色谱(high performance liquid chromatography,HPLC)法,并通过新建的维生素C片溶出度的测定方法提高其质量控制标准。方法HPLC测定法:色谱柱为菲罗门C_(18)柱(250 mm×4.6 mm,5μm),流动相为0.1 mol·L^(-1)磷酸二氢钾溶液(用磷酸调节pH值至2.5)-甲醇(92∶8),流速为0.8 mL·min^(−1),检测波长为243 nm,柱温为30℃,进样量为10μL;溶出度测定法:按照溶出度与释放度测定法(《中华人民共和国药典》2020年版四部附录0931第一法),以0.1 mol·L^(-1)盐酸溶液1000 mL为溶剂,转速为50 r·min^(−1),20 min时取样。结果维生素C在20~140μg·m L^(-1)范围内与其峰面积线性关系良好,y=37487.239x−6860.622(r=0.99996),平均回收率为100.16%,RSD值为0.48%(n=9);其在水、0.1 mol·L^(-1)盐酸溶液、pH 4.0醋酸盐缓冲液、pH 6.8磷酸盐缓冲液各1000 mL的溶出介质中的溶出曲线差异明显,选择0.1 mol·L^(-1)盐酸溶液为溶出介质对5个企业的样品进行测定,均在10 min全部溶出并进入平台。结论所建立的方法使检测的准确性更高、专属性更强、重复性更好,具有可信、精准的优势,能更有效地对维生素C片进行质量控制。

基于光学显微及电镜分析技术的土霉素片溶出行为解析

目的 建立土霉素片溶出度测定方法,考察不同企业产品体外溶出行为的差异;利用光学显微、电镜分析技术追溯引发溶出行为差异的根本原因。方法 采用桨法-HPLC法测定溶出度,采用光学显微及电镜分析技术对片芯中土霉素与辅料形态与溶出行为进行分析。结果 土霉素在18.5~92.6μg/mL浓度范围内线性关系良好,平均回收率为98.4%,RSD为0.7%(n=9),方法准确可靠。偏光显微镜法和扫描电镜法的分析结果显示制剂中原、辅料的晶体形态与存在状态与药物的溶出行为存在一定的相关性。结论 对于多晶型药物,利用光学显微及电镜分析与溶出度相结合的方法可更有效、全面地评价其口服固体制剂的质量。