Exact Power Function of Compendial Test Requirements for Content Uniformity

Abstract

The exact distributions associated with the current compendial test requirements are generated by resorting to the well known Computer Intensive Algorithm method to establish the exact percentage point (limit) for RSD, corresponding to each selected cut-off probability level (confidence level) for each of the four possible experimental outcomes based on the USP-NF test requirements. A table is constructed to present the two-dimensional power function. The similarities between these tabular values and the current compendial RSD limits for 10 and 30 dosage units are extremely remarkable.

Minor differences exist, however. It is suggested that both the theoretical as well as the numerical approaches should be carried out to arrive at a comprehensive solution.     

Detection of Discordant Content Uniformity Observations and Compendial Compliance

A discordant observation is a data point whose value is drastically different from that of the rest of the members in the data set. In the context of content uniformity experiments, however, a discordant observation arises in two ways: (i) when the value of an observation is markedly distant from that of the other data points even though it is within the required compendial range, and (ii) when the value of an observation is outside the permissible compendial range. Several statistical tests for detecting one or more discordant observations are presented. Since discordancy distorts the symmetricity of the data, several tests of symmetricity are provided. Tests for detection of group discordancy induced by discordant samples are also included. The compendial requirements are explained in statistical terms. The impact of discordant observations on compendial compliance requirements is assessed. The statistical basis of the construction of compendial limits as well as the assumptions implicit in the construction is elaborated. The results of the statistical analysis of three content uniformity studies are appropriately interpreted.     

Detection of Discordant Content Uniformity Observations and Compendial Compliance

Abstract

A discordant observation is a data point whose value is drastically different from that of the rest of the members in the data set. In the context of content uniformity experiments, however, a discordant observation arises in two ways: (i) when the value of an observation is markedly distant from that of the other data points even though it is within the required compendial range, and (ii) when the value of an observation is outside the permissible compendial range. Several statistical tests for detecting one or more discordant observations are presented. Since discordancy distorts the symmetricity of the data, several tests of symmetricity are provided. Tests for detection of group discordancy induced by discordant samples are also included. The compendial requirements are explained in statistical terms. The impact of discordant observations on compendial compliance requirements is assessed. The statistical basis of the construction of compendial limits as well as the assumptions implicit in the construction is elaborated. The results of the statistical analysis of three content uniformity studies are appropriately interpreted.     

Content Uniformity of a Low Dose Pharmaceutical Product

ABSTRACT

Optimum homogeneity and physical stability for a Roche compound (RO) low dose formulations (0,125 and 0.250 mg Tablets i.e. 0.07 to 0.14% w/w drug load, respectively) were achieved. Direct compression powder formulations were prepared by mixing the active drug substance with Starch 1500 (ST) to form an active pre-mix. Other ingredients were added subsequently. The final powder mix was subjected to a vibration of 4 Hz frequency using a specially designed segregation unit and content uniformity was assessed for these formulations. ST was considered superior to both lactose anhydrous and Avicel PH 102 in preparing homogeneous and physically stable mixes. Production-size batches of the product were successfully manufactured (Mean Drug content = 98 100%, RSV = 2%).     

多元红外探测器均匀性自动化测试

针对光导型多元红外探测器特性,研制了红外探测器均匀性自动化测试系统.本文介绍了测试系统的组成及相应的软件,阐述了工作原理、控制策略及数据处理技术.测试结果表明系统设计合理、工作稳定,具有精确控制和抗干扰能力.     

磁共振成像系统图像均匀性的检测

医用磁共振成像(MRI)系统是大型医用影像诊断设备,如何对磁共振影像进行评价,图像均匀性是一项重要指标.本文根据医用磁共振成像(MRI)系统的技术特性,参考国际标准和国家标准,验证、推荐了一种图像均匀性检测方法,该方法科学性、适用性强,可作为计量检测、医院质量控制的技术依据.     

Content Uniformity: Separation and quantitation of sources of dose variation

Abstract

A propagation of error formula is presented which describes a mathematical relationship between uniformity of dosage units (dose variation) and the individual sources of variability. Using this propagation of error formula and a minor modification of the USP Content Uniformity test procedure, one can assign dose variation to weight variation, blend heterogeneity and assay imprecision without compromising the information required by the USP XXII. This formula separates and quantitates the sources of dose variation and defines the manner in which weight variation, blend heterogeneity and assay imprecision are propagated. By knowing how the dose variation is propagated, specific measures can be taken to improve the uniformity of dosage units.

The propagation of error formula can also be used to calculate a priori estimates of dose variation by choosing reasonable or expected variances for weight variation, blend heterogeneity and assay imprecision. Such calculations can save hours of fruitless effort which attempt to improve the content uniformity without considering how dose variation is propagated and to what extent the expected dose variation can be improved.     

Content Uniformity: Separation and quantitation of sources of dose variation

A propagation of error formula is presented which describes a mathematical relationship between uniformity of dosage units (dose variation) and the individual sources of variability. Using this propagation of error formula and a minor modification of the USP Content Uniformity test procedure, one can assign dose variation to weight variation, blend heterogeneity and assay imprecision without compromising the information required by the USP XXII. This formula separates and quantitates the sources of dose variation and defines the manner in which weight variation, blend heterogeneity and assay imprecision are propagated. By knowing how the dose variation is propagated, specific measures can be taken to improve the uniformity of dosage units.

The propagation of error formula can also be used to calculate a priori estimates of dose variation by choosing reasonable or expected variances for weight variation, blend heterogeneity and assay imprecision. Such calculations can save hours of fruitless effort which attempt to improve the content uniformity without considering how dose variation is propagated and to what extent the expected dose variation can be improved.     

对具有电子枪装置的试验方法和特殊要求

BackgroundAs two tasks of project Development of International Standards for Chinese advantage Technologies,a National Science and Technology Major Project during China's 11th Five-Year Plan Period,two international standards IEC 60703:2008 Test Methods of Electric Heating Devices with Electron Gun and IEC 60519-7:2008 Safety of Electric Heating Devices Part: 7 Special Requirements for Electric Heating Devices with Electron Gun are based on Chinese advantage technologies,highly recognized by IEC/TC27 for its technological and conceptual innovations in the high-quality,high-level and high-efficiency way.     

关于战术导弹防护包装设计与试验要求的探讨

根据战术导弹的产品特征、寿命期剖面、寿命期环境剖面以及作战使用要求,在分析和对比国内外战术导弹防护包装特点的基础上,提出了我国战术导弹防护包装设计与试验要求,供战术导弹产品设计、包装研制以及标准化研究人员参考,也可供其他通用弹药产品设计和包装改进人员参考。     

Analysis of Content Uniformity Data of Tablets with two Active Ingredients

A method based on scatter plots of content uniformity data of tablets containing two active ingredients was utilized to gauge the degree of segregation in the finished product. The difference of semi-axes of the tolerance ellipse imposed on the content uniformity data and the covariance of data were found to be useful in estimating degree of segregation. Direct compression formula of a specific case was found to have slightly more segregation than a wet granulated product.     

Blending Validation and Content Uniformity of Low-Content,Noncohesive Powder Blends

Abstract

Blending validation has become mandatory, partly through good manufacturing practice (GMP), partly through a court action (the Barr decision) in 1993. Although feasibly carried out with existing technology, there are situations where the methodology for sampling causes a suspected bias in the figures, and one such case is where the drug content (expressed as fraction in the following) is low. In particular, this dilemma is predominant where the blended materials are not cohesive. Possible explanations for this are voiced, as are suggestions on how to proceed rationally in such cases.     

Blending Validation and Content Uniformity of Low-Content, Noncohesive Powder Blends

Blending validation has become mandatory, partly through good manufacturing practice (GMP), partly through a court action (the Barr decision) in 1993. Although feasibly carried out with existing technology, there are situations where the methodology for sampling causes a suspected bias in the figures, and one such case is where the drug content (expressed as fraction in the following) is low. In particular, this dilemma is predominant where the blended materials are not cohesive. Possible explanations for this are voiced, as are suggestions on how to proceed rationally in such cases.     

与设备包装有关的冲击试验要求的探讨

根据国内的相关实际现状 ,对 GJB1 50 .1 8冲击试验中与设备包装有关的铁路车辆撞击试验、运输跌落试验、粗暴装卸试验、易损性试验的某些试验要求进行了分析 ,提出了相应的修改建议     

Investigating a New Approach to Film Casting for Enhanced Drug Content Uniformity in Polymeric Films

Films prepared by conventional casting onto trays such as teflon-coated perspex trays (TCPTs) suffer from poor drug content uniformity. The aim of this study was to prepare a silicone-molded tray (SMT) with individual wells for film casting and to evaluate it in terms of enhancing drug content uniformity. Films were prepared by solvent evaporation or emulsification and cast onto TCPT and SMT. Preparation of films by the SMT method was superior in terms of meeting drug content uniformity requirements. As compared with the TCPT method, the SMT casting method also reduced the variability in mucoadhesivity, drug release, and film thickness. Reproducibility of the SMT method was demonstrated in terms of drug content, mucoadhesion, and drug release.     

纳米压入测试中面积函数测量方法综述

在纳米压入法材料力学性能测试中,面积函数的准确测量对保证测量结果的准确性非常重要。本文对纳米压入测试中常用的面积函数确定方法进行了分类介绍,并对各种方法的特点进行了分析,指出了为提高纳米硬度和弹性模量等力学性能参数的测量准确性对面积函数进行校准的必要性。     

气动噪声预测中非紧致格林函数的数值计算方法

采用声模拟理论预测非紧致结构与非定常流动相互作用诱发的气动噪声时,为考虑边界对声场的散射影响,需要应用非紧致格林函数。为此,发展了一种基于边界元思想的非紧致格林函数数值计算方法,该方法适用于任意外形结构,能直接计算非紧致格林函数及其偏导数。以二维圆柱边界为算例,采用理论解析方法推导了非紧致格林函数及其偏导数的正确表达式,并将数值计算方法结果与理论解析方法结果相比较,验证了数值方法的正确性。     

Exact Critical Values for Mood's Distribution-Free Test Statistic for Dispersion and Its Normal Approximation

In this paper we produce a table of critical values of Mood's test statistic which may be used in the distribution-free comparison of the dispersions of two independent samples. As far as we know the main drawback in using this test statistic, developed more than 14 years ago, lies in the fact that its distribution has never been tabulated except for a few isolated cases. We also discuss a normal distribution approximation which may be used when the sample sizes fall outside the scope of our present table. A uniform correction for continuity cannot be suggested since Mood's statistic does not take on equi-spaced values. However, we do attempt such a correction. Our investigations indicate that this suggestion may not be worthwhile, especially for sample sizes the sum of which exceed about 30.     

Validation of the Content Uniformity Testing of USP XXI (1985) for Tablets Containing Potent Drugs

Abstract

The content uniformity of tablets containing high potency, low dosage drugs can only be successfully maintained by application of GMP at all stages of the total manufacturing process including both formulation and quality control. This requires both understanding of the pharmaceutical technology involved and appropriate designing of content uniformity test.

The USP XXI (1985) has made the content uniformity test more stringent by applying both tests by attributes and variables, In this study the test has been challenged by using 27 batches of ethinyloestradiol 10 μg tablets having different degrees of homogeneity in powder mixes and tablets.

The results indicate that the test has a weak potential in determining the content uniformity of batches prepared from cohesive drug powders and characterised by skewed distribution of drug content in tablets. It is the same drawback of the USP XX (1980) content uniformity test. This defect is due to the small sample size of 10 unit doses in the first step which is not sufficient to detect the presence of unit dosages containing high drug content in a batch of tablets hawing skewed distribution. Statistical analysis of the results using coefficient of skBwness and nonparametric Lilliefors test has shown that some batches which have passed the USP XXI (1985) content uniformity test are pharmaceutically unacceptable. This indicates the importance of incorporating within the official specifications a test which includes an examination of the type of distribution and hence, increasing sample size is required.     

信息资源标准一致性测评需求及指标——以农产品安全流通信息化平台为例

为解决目前农产品物流领域现存的质量安全问题多、信息集成度低、协同性差、溯源力弱等问题而建立的农产品安全流通信息化平台,需要基础信息资源类标准为信息化平台建设提供支撑。本文针对农产品安全流通信息化平台建设过程中的代码和数据元等信息资源标准,探讨数据质量测评的需求和原则,并在测评需求分析的基础上提出信息资源标准一致性测评的指标评价体系。本文针对信息资源类标准的一致性测试的需求和指标进行探索和分析,对信息化系统建设过程中的数据标准一致性测试具有较高的参考价值和实践意义。