Globule-size distribution in injectable 20% lipid emulsions: Compliance with USP requirements.

PURPOSE: The compliance of injectable 20% lipid emulsions with the globule-size limits in chapter 729 of the U.S. Pharmacopeia (USP) was examined. METHODS: As established in chapter 729, dynamic light scattering was applied to determine mean droplet diameter (MDD), with an upper limit of 500 nm. Light obscuration was used to determine the size of fat globules found in the large-diameter tail, expressed as the volume-weighted percent fat exceeding 5 microm (PFAT(5)), with an upper limit of 0.05%. Compliance of seven different emulsions, six of which were stored in plastic bags, with USP limits was assessed. To avoid reaching coincidence limits during the application of method II from overly concentrated emulsion samples, a variable dilution scheme was used to optimize the globule-size measurements for each emulsion. One-way analysis of variance of globule-size distribution (GSD) data was conducted if any results of method I or II exceeded the respective upper limits. RESULTS: Most injectable lipid emulsions complied with limits established by USP chapter 729, with the exception of those of one manufacturer, which failed limits as proposed for to meet the PFAT(5) three of the emulsions tested. In contrast, all others studied (one packaged in glass and three packaged in plastic) met both criteria. CONCLUSION: Among seven injectable lipid emulsions tested for GSD, all met USP chapter 729 MDD requirements and three, all from the same manufacturer and packaged in plastic, did not meet PFAT(5) requirements.     

FDA对生物类似药说明书的要求

美国食品药品监督管理局（FDA）于2018年7月发布了"供企业用生物类似药说明书指导原则"。该指导原则提出了起草生物类似药说明书的一般原则，并对生物类似药说明书的内容提出了许多具体建议。而我国目前尚无类似的指导原则。详细介绍FDA的该指导原则主要内容，对我国撰写、阅读和监管生物类似药说明书有重要的参考价值。     

FDA处方药说明书要求三则

本文简要介绍FDA对处方药说明书要点和目录的要求以及对抗高血压药适应症有关心血管最终疗效描述的要求,并列举实例。希望对我国说明书的管理和撰写有所启迪。     

FDA对抗菌药说明书有关微生物学的要求

目前我国抗菌药说明书有关微生物学的内容和形式参差不齐,问题不少,而我国至今尚无这方面的管理规章和指导原则,本文介绍美国食品药品监督管理局有关规章和指导原则中对抗菌药说明书有关微生物学的一些要求.期望对改进我国抗菌药说明书有帮助.     

Compliance with drug therapy.

Although no single method is ideal for measuring compliance the methods now available allow accurate assessment of compliance in most settings. Studies using new and more accurate methods of measuring compliance have shown poor compliance to be an even greater problem than was previously thought. Using these methods, efforts in the future should be directed at relating compliance to treatment outcome, and investigating whether manoeuvres aimed at improving compliance actually improve patient outcome.     

FDA对阿片类镇痛药说明书的两则新要求

为了更合理地使用阿片类镇痛药,2013年1月美国食品药品监督管理局（FDA）公布了“防滥用的阿片类药物——评价和说明书”指导原则（草案）,2014年4月FDA发布了给缓释/长效（ER/LA）阿片类药物申请书持有者的公开信。概要介绍这两个文件中对防滥用阿片类药物说明书的防滥用性质描述的要求,对ER/LA阿片类药物安全性资料更新的要求,希望通过这两个文件对我国药品生产企业相应说明书的起草和更新有所启发和帮助,防止药物滥用及不良反应。     

益气活血通络方下调TGF-β/ERK信号通路对蛛网膜下腔出血大鼠的神经保护作用

目的探讨益气活血通络方对蛛网膜下腔出血大鼠TGF-β/ERK信号通路的影响及神经保护作用。方法 SD大鼠随机分为假手术组,模型组,益气活血通络方5、10、15 g/kg组和尼莫地平组,除假手术组外,其余各组建立蛛网膜下腔出血模型大鼠,分组处理后,各组大鼠进行神经功能缺损评分;以伊文思蓝染料外渗实验检测大鼠血脑屏障通透性;以TUNEL染色检测大鼠脑皮质神经细胞凋亡情况;以酶联免疫吸附法(ELISA)检测大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平;以蛋白免疫印迹法检测大鼠脑皮质组织TGF-β/ERK通路相关蛋白TGF-β1、p-ERK/ERK表达情况。结果与假手术组相比,模型组大鼠神经功能缺损评分、伊文思蓝渗出量、TUNEL阳性细胞比例、血清IL-6、TNF-α水平、TGF-β1表达、p-ERK/ERK明显升高(P0.05)。与模型组相比,益气活血通络方5、10、15 g/kg组和尼莫地平组大鼠神经功能缺损评分、伊文思蓝渗出量、TUNEL阳性细胞比例、血清IL-6、TNF-α水平、TGF-β1表达和p-ERK/ERK水平明显降低(P0.05),且益气活血通络方各组呈剂量相关性,益气活血通络方15 g/kg组与尼莫地平组相比,各指标比较差异无统计学意义。结论益气活血通络方可下调TGF-β/ERK信号,保护蛛网膜下腔出血大鼠神经功能。     

FDA对处方药说明书临床药理学项目的要求

美国食品药品管理局（FDA）于2016年12月发布了“人用处方药和生物制品说明书临床药理学项目——内容和形式供企业用的指导原则”（正式版本）。该指导原则规定药品说明书临床药理学项目必须包括作用机制、药效学和药动学3个小项;如果需要,可加设微生物学和药物基因组学等小项并说明了各小项应包括的内容,还阐述了该项目撰写的一般原则和格式。介绍该指导原则的主要内容,希望对我国处方药说明书的撰写和监管有所帮助。     

FDA对药品说明书适应症项目的要求

美国食品药品管理局（FDA）于2018年7月发布了“人用处方药和生物制品说明书的适应症和应用项目——内容和格式供企业用指导原则（草案）”。该指导原则指出适应症和应用项目一般由适应症和使用限制两部分组成,并详细介绍了该项目应包括的内容和格式,同时告诫不应出现的内容和格式。介绍该指导原则的主要内容,期望对我国药品说明书适应症项目的撰写和监管有益。     

Osmolality/osmolarity data and calculations.

In view of the increasing interest in the osmolarity of parenteral solutions, an extensive compilation of pertinent numerical data is described. This compilation tabulates values of density, molar concentration, freezing point lowering,real osmolality, and molar concentration of the isotonic sodium chloride solution for 99 compounds, two-thirds of which are of use in pharmacy. A wide range of concentrations is covered for each compound, the values being listed in increments of 0.50, 1.00, or 2.00 percent w/w. Simple equations to convert molar into molal concentrations and to correlate freezing point lowering, osmotic pressure, osmolality and molality are presented. The practical use and theoretical meaning of the osmotic coefficient are discussed. As an example of a solution with several solutes, the real osmolality and osmolarity of Ringer's Solution is computed from the tabulated values of the freezing point depressions of the component salts.     

不符合指导原则要求的抗菌药说明书实例讨论

国家药品监督管理局于2018年5月发布了“抗菌药说明书撰写技术指导原则”。该指导原则极其详细地说明了抗菌药说明书各个项目应包含的内容及其撰写格式,为提高这类药品说明书的质量提供了保障。通过阿奇霉素片等4个实例,以该指导原则为准绳,与美国食品药品管理局（FDA）核准的同品种说明书进行比较,分析我国药品说明书存在的问题,期望对理解和落实指导原则,起草或修订抗菌药品说明书有所帮助。     

Compliance of scored tablet halves produced by Palestinian Pharmaceutical Companies with the new European Pharmacopoeia requirements

The aim of this study was to evaluate the weight uniformity of commonly divided tablets produced by Palestinian Pharmaceutical Companies and to evaluate the importance of both patient- and formulation-related variables on the splitting results. Eighty-four volunteers were enrolled in this study; their age, gender and occupation were documented in order, and the effect of these variables on the tablet splitting results was evaluated. Each volunteer was asked to divide six scored tablets of each product tested and was given clear instructions on how to conduct the splitting process. The split units were individually weighed and the RSD for each product was calculated as instructed in the European Pharmacopoeia (Ph. Eur. 5.5). Only one scored tablet product passed the Ph. Eur. test of mass uniformity, while the remaining 13 products failed; this indicates that the splitting of these tablet products is not a reliable means for the provision of accurate doses to patients. Age, gender and occupation of volunteers were not found to be predictive of any variability noted in the splitting results. The only factors that were suspected to be linked to passing the splitting test, as per the European Pharmacopoeia, were the shape, friability and hardness of the tablets. As a result of this study, we believe that the practice of dividing tablets, which should provide therapeutic and economic benefits for the patient, may potentially cause significant problems, especially in drugs with low therapeutic indices. Tablets produced by Palestinian Pharmaceutical Companies should comply with the new Ph. Eur. splitting regulations to reduce this potential for complications.     

美国食品药品管理局（FDA）对药品说明书中老年用药信息的要求及启示

美国食品药品管理局（FDA）于2020年9月发布了供企业用"处方药和生物制品说明书中的老年用药信息"指导原则。该指导原则主要介绍对说明书中老年用药信息位置和内容的要求并给出描述的示例。内容极其详细、具体，便于操作。而我国尚无类似指导原则，详细介绍该指导原则，期望对我国相关指导原则的起草及其上位法规的修订有帮助，对药品说明书老年用药信息的撰写也有益。     

FDA对处方药说明书中药物不良反应部分的要求

美国FDA现行的"人用处方药和生物制品说明书的不良反应部分指导原则",对说明书不良反应部分的内容和形式有详尽的要求.而我国还没有相关法规对此作详细规定,也没有相应指导原则.本文介绍FDA该指导原则的主要内容,期望对在我国上市的处方药说明书的撰写和监管有所启迪.     

Drug Compliance Scale. I. Development of the Drug Compliance Scale

The failure of patients to comply with treatment regimens recommended by their physicians is a significant clinical problem. Researches on the assessment of compliance have, however, been precluded by methodological difficulties such as lack of adequate measures. The purpose of this study was to develop a self-administered questionnaire to evaluate drug compliance. First, questionnaire containing a 52-items complied by two doctors, a pharmacist and a nurse, was tested on 81 outpatients, all volunteers, attending the departments of psychosomatic medicine and internal medicine. Four items were temporarily removed for later analysis because they directly inquired about drug compliance (drug compliance items). The other 48 items were analyzed and three factors consisting of 26 items were further studied: expectation on taking medicine, rejection to taking medicine and seeking knowledge of drugs. Chronback's alpha coefficients representing internal consistency of the three factors were sufficiently high (ranging from .75 to .84). Furthermore, we preformed a simplified pill count to validate the 4 drug compliance items. There was a weak to moderate correlation between the result of pill count and each of 4 drug compliance items. A new self-administered questionnaire of 30 items was thus developed and named the Drug Compliance Scale.