HPLC及TLC用于复方盐酸曲马多分散片有关物质的测定

目的建立HPLC测定复方盐酸曲马多分散片有关物质.方法采用高效液相色谱法和薄层色谱法.结果盐酸曲马多在此条件下的检测限为7.5 ng,对乙酰氨基酚在此条件下的检测限为0.2 μg,对氯苯乙酰胺在此条件下的检测限为0.05 μg.方法灵敏、可靠.结论采用HPLC和TLC有效检验出复方盐酸曲马多分散片中的杂质.     

HPLC及TLC用于复方盐酸曲马多分散片有关物质的测定

目的建立HPLC测定复方盐酸曲马多分散片有关物质。方法采用高效液相色谱法和薄层色谱法。结果盐酸曲马多在此条件下的检测限为7.5 ng,对乙酰氨基酚在此条件下的检测限为0.2μg,对氯苯乙酰胺在此条件下的检测限为0.05μg。方法灵敏、可靠。结论采用HPLC和TLC有效检验出复方盐酸曲马多分散片中的杂质。     

对乙酰氨基酚分散片的制备及其质量检查

目的制备对乙酰氨基酚分散片。方法以崩解时间为指标比较不同崩解剂的作用,以正交试验设计确定最佳处方,按照工艺制备并进行了体外溶出度、脆碎度、崩解度、硬度等数据的测定。结果工艺简单、稳定性良好,分散片崩解时间小于3min,其崩解时间、分散均匀度、硬度和溶出度均达到中国药典2005年版二部要求。结论研制的对乙酰氨基酚分散片能够快速溶出。     

盐酸曲马多分散片的溶出度考察

目的 考察盐酸曲马多分散片的溶出度,评价其内在质量。方法 采用紫外法测定含量,测定波长：271nm,以水为溶出介质,采用转篮法对盐酸曲马多分散片进行溶出度考察。求出溶出参数。结果 分散片溶出速度明显快于普通片,分散片20min即溶出83.6%,溶出较好。结论 盐酸曲马多分散片溶出度考察符合卫生部部颁标准及中国药典2000版二部标准之规定。     

复方盐酸曲马多片裂片问题的探讨

复方盐酸曲马多是一个新型的解热镇痛药，每片含对乙酰氨基酚325mg，盐酸曲马多37．5mg，预胶化淀粉为填充剂，十二烷基硫酸钠为表面活性剂及润滑剂，质量分数10％PVP K30和质量分数8％ PVPK90为混合黏合剂。由于对乙酰氨基酚为疏水性药物，成型性差，易出现裂片。笔者在该产品的工艺     

均匀设计实验考察对乙酰氨基酚分散片的处方

目的:用均匀设计实验考察对乙酰氨基酚分散片的处方.方法:通过均匀设计考察分散片的崩解时间、在水中分散均匀性和溶出度等指标,综合评价对乙酰氨基酚分散片的质量,初步进行处方筛选.结果:2%立崩、10%MCC和10%PVPK30%醇溶液组成的处方效果较好.     

HPLC法测定复方对乙酰氨基酚分散片的含量

目的:采用高效液相色谱法测定复方对乙酰氨基酚分散片的含量.方法:选用Spherisob-CN色谱柱,乙腈-水-冰醋酸(30 : 70:1),检测波长为280nm,流速为1.0ml·min-1.结果:对乙酰氨基酚在1.267～5.069μg范围内呈线性关系;氯唑沙宗在0.978～3.910μg范围内呈线性关系.结论:该法具有准确、简便、快速、灵敏等特点.     

高效液相色谱法测定对乙酰氨基酚的血药浓度及其生物利用度

目的 :建立高效液相色谱 (HPLC)法测定对乙酰氨基酚血药浓度的方法并对其分散片的生物利用度进行研究。方法 :以HPLC外标法测定人血浆中对乙酰氨基酚的浓度 ,流动相为甲醇 /乙腈 /水 (5∶5∶90 ) ,紫外吸收波长为 2 37nm。 12名健康志愿者服药后 ,依据对乙酰氨基酚分散片和对照片经时血药浓度 ,研究了 2种制剂相对生物利用度。结果 :本法对血浆中药物的最低检测浓度为 0 1μg·mL-1,线性范围为 0 2～ 18 0 μg·mL-1,回收率 >90 % ,日内RSD为 0 71%～ 1 6 5 % ,日间RSD为0 77%～ 4 41%。按AUC0→∞ 计算出对乙酰氨基酚分散片的相对生物利用度为 (10 7 8± 14 3) %。结论 :本法简便快速 ,可用于临床血药浓度测定。 2种对乙酰氨基酚制剂具有生物等效性。     

对乙酰氨基酚注射剂的工艺及质量研究

目的:对低浓度的对乙酰氨基酚注射剂进行改进。方法:以对比实验的方法,得出溶解对乙酰氨基酚最佳混合溶媒,并对其进行含量测定和稳定性的研究。结果:本实验通过对乙酰氨基酚的工艺研究生产出了25%的对乙酰氨基酚注射剂。结论:该工艺研究科学合理,可行性强,值得推广。     

对乙酰氨基酚分散片中辅料的初步筛选

目的利用新型辅料,筛选对乙酰氨基酚分散片中的辅料。方法通过考察辅料自身崩解性能、主药(对乙酰氨基酚APAP)与微晶纤维素(MCC)混合后稳定性、分散片制备工艺、在水中分散均匀性等,选择处方和工艺。结果选择MCC作为处方的填充剂(稀释剂);立崩、L-HPC、PVPP为混合型崩解剂;80g·L-1PVP醇溶液作黏合剂。结论根据该处方可以制得符合要求的对乙酰氨基酚分散片。     

External scintigraphy in monitoring the behavior of pharmaceutical formulations in vivo I: technique for acquiring high-resolution images of tablets

A new method for monitoring tablet disintegration in vivo was developed. In this method, the tablets were labeled with a short-lived radionuclide, technetium 99m, and monitored by a gamma camera. Several innovations were introduced with this method. First, computer reconstruction algorithms were used to enhance the scintigraphic images of the disintegrating tablet in vivo. Second, the use of a four-pinhole collimator to acquire multiple views of the tablet resulted in high count rates and reduced acquisition times of the scintigraphic images. Third, the magnification of the scintigraphic images achieved by pinhole collimation led to significant improvement in resolution. Fourth, the radioinuclide was incorporated into the granulation so that the whole mass of the tablet was uniformly labeled with high levels of activity. This technique allowed the continuous monitoring of the disintegration process of tablets in vivo in experimental animals. Multiple pinhole collimation and the labeling process permitted the acquisition of quality scintigraphic images of the labeled tablet every 30 sec. The resolution of the method was tested in vitro and in vivo.     

Evaluation of critical process parameters for intra-tablet coating uniformity using terahertz pulsed imaging

The purpose of this study was to evaluate the intra-tablet coating uniformity and the identification of critical process parameters in an active pan coating process using terahertz pulsed imaging (TPI). A design of experiments (DoE) was performed with drum load, drum speed, spray rate, run duration and spray pressure as factors. Different measures of intra-tablet uniformity were investigated: the average thickness on the individual tablet faces, spatial variation in layer thickness over the tablet surface, and the coefficient of variation (CV_intra). Data analysis revealed that the process parameters in the investigated parameter space had hardly any influence on the difference in layer thickness of the tablet faces and centre band. No increase or decrease in layer thickness – as described in the literature – was found towards the edges of the tablet face. In overwetted process conditions a higher layer thickness at the centre band edges could be observed. Still, the highest variability in coating thickness was found along the circumference of the centre band rather than the height. In general, higher CV_intra of layer thickness were found on the centre bands in comparison with the tablet faces. The analysis of the DoE model revealed that the run duration had the highest influence on the CV_intra on the tablet faces. TPI showed high potential in the assessment of intra-tablet uniformity and layer thickness distributions over the whole tablet surface. It was successfully used to identify critical process parameters regarding intra-tablet coating uniformity.     

住院患者服用分劈药片的利弊

目的 :探讨住院患者服用分劈药片的利弊。方法 :收集我院由药师分劈、住院患者常用的13种处方药片 ,每种10片 ,共260个分劈片 ,采用《美国药典》剂量单位一致性测试方法分析分劈药片的重量变异性。结果 :药片分劈后均未通过剂量单位一致性测试。药片分劈效果与外形有关 ,带有刻线的相对好一些。在分劈过程中都存在一定的剂量损耗。结论 :药片分劈导致高比率的重量变异 ,故为节省开支而分劈药片的做法仅适合于那些低毒和剂量 -反应效应曲线相对平坦的药物 ,对于那些毒性较大和剂量 -反应效应曲线陡直的药物则不宜采用     

加替沙星分散片处方及制备工艺研究

目的:考察及筛选加替沙星分散片的制备工艺和最优处方。方法:通过系列试验筛选崩解剂等辅料,确定处方及制备工艺;测定并比较了分散片及普通片剂中主药的溶出度。结果:确定了以羧甲基淀粉钠、交联聚乙烯吡咯烷酮作为崩解剂的分散片处方;分散片溶出速度较普通片更快。结论:研制的加替沙星分散片处方合理、工艺可行,符合分散片的质量要求。     

正交试验优选丹参片片芯制备工艺

目的:选择适宜的制粒工艺,提高丹参片的片芯质量,利于薄膜包衣进行。方法:采用正交试验,以片芯硬度、脆碎度和外观为考察指标,以预胶化淀粉用量、聚乙烯吡咯烷酮(PVP)-30用量、乙醇用量、乙醇浓度为考察因素,优选丹参片片芯制备工艺。结果:以20g·kg-1PVP-30为黏合剂,以40mL·kg-175%乙醇为湿润剂,预胶化淀粉用量为50g·kg-1,通过高效湿法混合制粒机制粒,可使压制的片芯外表光洁,硬度达到(46.6±21.8)N,脆碎度为(0.72±0.19)%。结论:该工艺制得的片芯可达到薄膜包衣的要求,有利于该制剂的进一步研究。     

Microstructural investigation to the controlled release kinetics of monolith osmotic pump tablets via synchrotron radiation X-ray microtomography

Tomographic imaging techniques are attractive tools for the visualization of the internal structural characteristics of pharmaceutical solid dosage forms. In this paper, the internal structure of the tablet core for a monolith osmotic drug delivery system, felodipine sustained-release tablet, was visualized via synchrotron radiation X-ray computed microtomography during the drug release process. The surface areas and three dimensional parameters of the tablet core were calculated based on the three dimensional reconstruction of the images. At different stages of the drug release process, the surface morphology, the hydration, the swelling, and the structure changing of the tablet, were visualized from the two dimensional monochrome X-ray images. The three dimensional volumes of the remaining tablet core correlated well with the percentages of felodipine (R=0.9988). Also, the three dimensional surface area almost unchanged during the drug release process, which clearly demonstrated the intrinsic drug release mechanism of the osmotic drug delivery system. In conclusion, the synchrotron radiation X-ray computed microtomography, with rapid acquisition, high intensity and micro-scale spatial resolution, was found to be a useful tool for the quantitative elucidation of the intrinsic drug release kinetics and the three dimensional parameters such as surface areas of the remained core obtained by the synchrotron radiation. Thus, X-ray computed microtomography can be considered as a new and complimentary analytical tool to standard compendial pharmaceutical tests for quality control of osmotic drug delivery systems.     

Drug tablet thickness estimations using air-coupled acoustics

A non-contact/non-destructive acoustic technique for predicting the coating layer thickness of a drug tablet is presented. Quality of tablet coatings can play a major role in the effectiveness of drug delivery. Many pharmaceutical tablets consist of a tablet core and a coated outer cover. Variations in the tablet coating can be indicative of various process problems and, therefore, is of a concern for quality assurance. In the current non-contact measurement system, an air-coupled excitation and laser interferometric detection for predicting the coating layer thickness of a drug tablet is introduced. Drug tablets with different coating thicknesses are vibrated via an acoustic field generated by an air-coupled transducer in a frequency range sufficiently high to excite their several vibrational modes. The tablet surface vibrational responses are acquired at a number of measurement points by a laser interferometer in a non-contact manner. An iterative computational procedure, based on the FE method and Newton's method, was developed and demonstrated to extract the coating layer thicknesses of the tablets from a subset of the measured resonance frequencies.     

Evaluation of Small-Scale Powder Flow Characterization Tests in the Prediction of Large-Scale Process Failures

In pharmaceutical development, powder flow characteristics are notoriously difficult to predict. Although tests exist that aim to determine the flowability of powders, many have not been definitively correlated with a powder’s performance in downstream processes. Part of the challenge is that powder flow must occur over a broad range of consolidating stresses, including low-stress flow regimes such as the filling of a die cavity in a tablet press and high-stress flow regimes such as the deformation associated with tablet compression. The objective of this work was to characterize several placebo formulations utilizing a variety of standardized and non-standardized experiments and contrasting those results with downstream tablet compression performance. Angle of repose, bulk and tap density, Hausner ratio, Carr’s compressibility index, a visual powder flow assessment, a mass flow rate test, Flodex, and powder shear testing were evaluated on several different blends of placebo powders to determine a predictive test for downstream process performance. The placebo powders consisted of a standard base unit formula, mixed with various levels of four different “pseudo-active pharmaceutical ingredients (APIs)” (i.e., excipients that mimic poorly flowing active pharmaceutical ingredients). All formulations were evaluated by the individual flow tests and then compressed on a rotary tablet press. Formulations were deemed failures if the relative standard deviation of tablet weight was >2 %, material stuck to punches (low lubrication), or exhibited ejection forces high enough to trigger automatic shutdown of tablet press. The 2 % RSD limit is based on internally developed best practices for transferring tablet compression processes from development into manufacturing. The results of the tablet compression process were then compared to the results of the flowability tests to detect any correlations. The Hausner ratio and powder shear test results discriminated marginally between successful and failed batches and were highly correlated with each other.     

对乙酰氨基酚口腔崩解片的研制

目的 以对乙酰氨基酚（扑热息痛）为模型药物制备新型口服速释剂型口腔崩解片。方法 以崩解时间为指标，采用正交试验筛选片剂的处方组成，并优化制备工艺。结果 以MCC／L-HPC 50：15作为崩解剂，部分制粒压片工艺制得的扑热息痛口腔崩解片，体外平均崩解时间为35s，置于口腔40s内可崩解，无砂砾感，片剂体外溶出度1min可达95％。结论 扑热息痛口腔崩解片于口腔内可迅速崩解，制备工艺简单可行，有效地改善了药物粉末的流动性，适宜于大生产。     

马来酸氨氯地平分散片处方及制备工艺研究分析

目的探讨马来酸氨氯地平分散片的处方以及制备工艺。方法通过实验对马来酸氨氯地平分散片的处方以及制备工艺进行研究。结果使用交联聚维酮和低取代羟并纤维素为崩解剂,预胶化淀粉和微晶纤维素作为填充剂,使用聚维酮-K30作为粘合剂以及二氧化硅和硬脂酸镁为润滑剂制成的马来酸氨氯地平分散片,可以在3min内崩解,并且能够通过2号筛,硬度适中,成型性好,外观光洁,可以迅速的分散,符合《中国药典》对分散片的要求。结论马来酸氨氯地平分散片符合分散片的制剂要求,溶出度比较高,崩解迅速,制备工艺简单,符合大规模生产要求。