Impact of Superdisintegrants and Film Thickness on Disintegration Time of Strip Films Loaded With Poorly Water-Soluble Drug Microparticles

Although strip films are a promising platform for delivery of poorly water-soluble drug particles via slurry casting, the effect of critical material attributes, for example, superdisintegrants (SDIs) on critical quality attributes, including film disintegration time (DT), remains underexplored. A 2-level factorial design is considered to examine the impact of the SDI type (sodium starch glycolate and croscarmellose sodium), their amount, and film thickness. SDIs were used with hydroxypropyl methylcellulose (E15LV) and glycerin solutions along with viscosity matching. Fenofibrate, a model poorly water-soluble drug, was micronized and surface modified via fluid energy milling. Significant decreases in film DT, measured using 3 different methods, were observed due to the addition of SDIs. Percentage reduction in DT was a strong function of SDI amount, and thinner films disintegrated faster. Films with either higher SDI concentrations (>9%) or films under 80 μm, exhibited fast DT (<180 s, European Pharmacopeia). All thin films (50-60 μm) exhibited immediate release (>80% in 10 min). All films achieved good content uniformity, except for those with the lowest amount of SDI, attributed to insufficient viscosity and thickness nonuniformity due to the SDI. Finally, all films achieved adequate mechanical properties, notwithstanding minor negative impact of SDIs.     

超微粉固体分散技术对丹参片指标成分溶出度的影响

目的：采用超微粉固体分散技术制备丹参片,并考察其溶出特征。方法：按《中国药典》2015年版丹参片制备方法制得丹参片DSP1作为对照品,用超微粉固体分散技术制得丹参片DSP2。高效液相色谱（HPLC）法测定2种丹参片中的丹酚酸B、丹参酮Ⅱ_A的含量,并在不同溶出介质测定各成分的溶出度,绘制溶出曲线,采用f₂相似因子法进行比较分析。结果：DSP1、DSP2的丹酚酸B含量分别为11.20,18.90 mg·g^-1原药材,丹参酮Ⅱ_A含量分别为0.45,0.71 mg·g^-1原药材;丹酚酸B、丹参酮Ⅱ_A在0.1 mol·L^-1的盐酸溶液介质中溶出曲线的相似因子分别为40,32,在0.5%十二烷基硫酸钠（SDS）水溶液中溶出曲线的相似因子分别为43,35,f₂<50,两种丹参片的溶出度有显著差异。结论：超微粉固体分散技术能显著高丹参片中的丹酚酸B、丹参酮Ⅱ_A溶出度,同时提高丹参药材的利用率,值得进一步研究推广。     

生物相关性溶出度方法研究进展

摘要：建立具有生物相关性的溶出度方法目的在于通过理想的体外溶出试验预测体内药代动力学过程。近年来,研究表明在生物相关性溶出介质中选择合适的溶出装置进行溶出试验得到的溶出曲线能较好地反映其在体内的溶出行为,计算机模拟软件可为建立合理的体外溶出度方法提供指导和依据。通过采用合适的生物相关性溶出介质、溶出装置,结合计算机模拟软件可建立A级水平的IVIVC(in vitro-in vivo correlation),可能代替生物等效性研究。     

HPLC测定二维芦丁片复方制剂中芦丁的溶出度和含量

目的 建立HPLC法测定二维芦丁片中芦丁溶出度和含量的方法。方法 溶出度测定以水（含0.5% SDS）为溶出介质,浆法,转速为75r·min-1,45min取样,取样后采用HPLC测定;含量测定采用Thermo C18柱（4.6mm×250mm,5μm）,以磷酸盐缓冲液(0.lmol·L-1 磷酸二氢钠溶液,用磷酸调节pH 值至4.4)-乙腈（80 : 20)为流动相,检测波长为254nm。结果 溶出度测定：芦丁在22.56～2.26μg·ml-1范围内呈良好的线性关系（r=1.0000） ,芦丁的平均回收率为98.2%（RSD=0.4%）,溶出液稳定,3批样品在45min时平均溶出度均在75%以上并且有较好的均一性;含量测定：线性关系良好,芦丁回收率为100.6% (RSD=0.4%, n=9)。结论 该法简单、准确、重复性好,可用于二维芦丁片中芦丁的溶出度及含量的测定。     

复方对乙酰氨基酚片溶出度方法研究及溶出行为评价

目的 建立复方对乙酰氨基酚片的溶出度方法并对不同样品进行溶出曲线评价。方法采用HPLC法,使用Sepax Amethyst C18-H(4.6×150mm,5μm)色谱柱,以磷酸盐缓冲液（取0.01mol/L磷酸二氢钾溶液,用磷酸调节pH值至2.6±0.1）-甲醇（70：30）;流速：1.0ml/min;柱温：35℃;检测波长：波长切换,0～12.5min,波长为275nm,12.5～16min,波长为303nm;溶出度试验采用桨法,以900ml盐酸溶液（稀盐酸24ml,加水至1000ml）为溶出介质,转速为50r?min-1。结果 在本文色谱条件下,阿司匹林和水杨酸分别在12.54～501.60μg?ml-1(r=1.0000)和0.99～39.76μg?ml-1(r=0.9999)范围内线性关系良好;低、中、高3种浓度的平均回收率分别为98.9%、96.7%、97.7%,RSD分别为0.46%、0.65%、0.31%;溶出度方法较好地反映了不同厂家复方对乙酰氨基酚片溶出行为的差异。结论 建立的HPLC溶出度测定方法简单方便,具有较好的专属性、精密度和准确度,溶出方法较好地体现了不同厂家样品间的差异。     

Developing a quality by design approach to model tablet dissolution testing: an industrial case study

Abstract

This study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing.     

Mechanical activation of Efavirenz: the effects on the dissolution and inhibitory behavior

Abstract

A poorly water-soluble drug (Efavirenz) was mechanically activated by ball-milling. The effect of the mechanical activation on the dissolution behavior and bioavailability was investigated revealing possible correlations with the grinding action, in terms of crystallinity, particle size and morphology.With proper selection of the grinding parameters the dissolution kinetics can be controlled, both in terms of dissolution velocity and as amount of dissolved drug. In vitro biological tests show that milling does not impair the ability of Efavirenz to inhibit HIV-1 infection (p value?>0.05); the IC50 values of ground Efavirenz is indeed lower than values for the pristine micronized powder.     

右佐匹克隆定时释放片的制备研究

目的制备右佐匹克隆定时释放片,并考察其体外释药特性。方法分别以HPMC作为溶胀层包衣材料,以乙基纤维素水分散体作为控释层包衣材料,采用高效包衣机制备右佐匹克隆定时释放片,考察影响释放度的主要因素,并测定体外释放度以考察体外释药行为。结果确定了影响右佐匹克隆释放的处方因素,体外释放度研究结果表明,该制剂可达到脉冲式释放。结论右佐匹克隆定时释放片可以达成两次定时脉冲释放,符合让失眠患者快速入睡并维持6 h以上睡眠状态的设计初衷。     

《中国药典》2015年版沙门菌检查用培养基的质量探讨

摘要目的：对国产盐酸溴己新片的溶出度进行评价。方法：以原研产品作为参比制剂,以国内6家企业的6批产品作为样品,以4种溶液作为溶出介质,按照《中国药典））2010年版二部盐酸溴已新片项下方法进行溶出曲线测定,计算参比制剂与仿制制剂平均溶出率偏差,同时利用威布尔方程计算关键点Td,T50,T70点的溶出参数。结果：以水为溶出介质时,D样品的溶出曲线均与原研产品具有相似性;以pH1．2溶液作为溶出介质时,除A样品、B样品和c样品外,其余样品与原研产品的溶出曲线具有相似性;以pH4．0醋酸盐缓冲液为溶出介质时,除A样品和B样品外,其余样品与原研产品的溶出曲线具有相似性;以pH6．8磷酸盐缓冲液为溶出介质时,所有样品在120min的溶出曲线测定中最大溶出度均约为20％。威布尔方程计算结果显示国产盐酸溴己新片的工艺稳定性仍需提高。结论：虽然一些企业生产的盐酸溴己新片与原研产品的溶出行为仍存在差距,但D企业样品的溶出行为与原研产品很接近,说明国内产品的处方工艺水平能够达到与原研产品相当的要求。