BACKGROUND & AIMS: BACKGROUND:Adherence to long-term chelation therapy in transfusion-dependent patients is critical to prevent iron overload-related complications. Once-daily deferasirox dispersible tablets (DT) have proven long-term efficacy and safety in patients ≥2 years old with chronic transfusional iron overload. However, barriers to optimal adherence remain, including palatability, preparation time, and requirements for fasting state. A new film-coated tablet (FCT) formulation was developed, swallowed once daily (whole/crushed) with/without a light meal. METHODS:The open-label, Phase II ECLIPSE study evaluated patient-reported outcomes (PROs) in transfusion-dependent thalassemia or lower-risk myelodysplastic syndromes patients randomized 1:1 to receive deferasirox DT or FCT over 24 weeks as a secondary outcome of the study. Three PRO questionnaires were developed to evaluate both deferasirox formulations: 1) Modified Satisfaction with Iron Chelation Therapy Questionnaire; 2) Palatability Questionnaire; 3) Gastrointestinal (GI) Symptom Diary. RESULTS:One hundred seventy three patients were enrolled; 87 received the FCT and 86 the DT formulation. FCT recipients consistently reported better adherence (easier to take medication, less bothered by time to prepare medication and waiting time before eating), greater satisfaction/preference (general satisfaction and with administration of medicine), and fewer concerns (less worry about not swallowing enough medication, fewer limitations in daily activities, less concern about side effects). FCT recipients reported no taste or aftertaste and could swallow all their medicine with an acceptable amount of liquid. GI summary scores were low for both formulations. CONCLUSIONS:These findings suggest a preference in favor of the deferasirox FCT formulation regardless of underlying disease or age group. Better patient satisfaction and adherence to chelation therapy may reduce iron overload-related complications. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014.

背景与目标： 背景：输血依赖型患者坚持长期螯合治疗对预防铁超载相关并发症至关重要。已证明每日一次地拉罗司分散片（DT）对于≥2岁的慢性输血铁超负荷患者具有长期疗效和安全性。但是，仍然存在妨碍最佳依从性的障碍，包括适口性，准备时间和对禁食状态的要求。开发了一种新的薄膜包衣片剂（FCT）制剂，每天（整顿或压碎）吞咽一次（含/不含便餐）。
方法：开放标签的II期ECLIPSE研究评估了输血依赖性地中海贫血或低危骨髓增生异常综合症患者的患者报告结局（PRO），这些患者在24周内按1：1的比例接受了Deferasirox DT或FCT作为继发性转归学习。开发了三份PRO问卷以评估两种Deferasirox制剂：1）对铁螯合疗法问卷的改良满意度； 2）可口性问卷； 3）胃肠道（GI）症状日记。
结果：173例患者入选。 87架接受了FCT，86架采用了DT配方。 FCT接受者持续报告出更好的依从性（更容易服药，更少的时间来准备药物和就餐前的等待时间），更高的满意度/偏好（总体满意度和药物管理）以及更少的担忧（更少担心没吞下足够的东西）药物治疗，日常活动限制较少，对副作用的担忧较少）。 FCT接收者报告没有味道或余味，可以用可接受量的液体吞服所有药物。两种配方的胃肠道摘要分数均较低。
结论：这些发现表明，无论基础疾病或年龄组如何，都倾向于使用地拉罗司FCT制剂。更好的患者满意度和对螯合疗法的依从性可以减少铁过载相关的并发症。
试用注册：ClinicalTrials.gov标识符：NCT02125877；于2014年4月26日注册。

BACKGROUND & AIMS: :The present study utilised a novel combination of eye movement and motion capture recordings to examine cognitive engagement during reading on a hand-held tablet computer. Participants read a multiple-page text with a specific task in mind and after reading recalled the main contents of text from memory. The results showed that head distance from screen was slightly shorter, and readers spent longer time reading task-relevant than irrelevant segments of text and had better memory for task-relevant than irrelevant text information, indicating that there are task-induced momentary changes in engagement during reading. Moreover, head motion and individual fixation durations decreased during the course of reading of relevant segments, and even though there was an overall increase in table motion during reading, the slope of this increase was steeper for irrelevant than relevant text segments. These results suggest that readers become more engaged with relevant and less engaged with irrelevant text segments across the text. The novel methodological combination of eye and postural movements seems to provide valuable information about cognitive engagement during reading in digital environments. The cumulation of evidence from this and previous studies suggests that reading on a tablet affords different interactions between the reader and the text than reading on a computer screen. Reading on a tablet might be more similar to reading on paper, and this may impact the attentional processes during reading.

背景与目标： ：本研究利用眼睛运动和动作捕捉记录的新颖组合来检查在手持平板电脑上阅读时的认知参与度。参与者阅读多页文本时要牢记特定的任务，阅读后会从内存中调出文本的主要内容。结果显示，距屏幕的头部距离略短，并且与无关的文本段相比，读者花更长的时间阅读与任务相关的内容，并且与无关的文本信息相比，与任务相关的内容的记忆性更好，表明存在因任务而引起的瞬时变化在阅读过程中。而且，在阅读相关节段的过程中头部运动和个人注视的持续时间减少了，即使在阅读过程中桌子运动总体上有所增加，但与相关的文本节段相比，无关紧要的这种增加的斜率也更陡峭。这些结果表明，读者对文本的相关性越来越高，而对文本中无关紧要的文本则越不感兴趣。眼睛和姿势运动的新颖方法组合似乎为数字环境下阅读过程中的认知参与提供了有价值的信息。来自本研究和先前研究的证据表明，在平板电脑上阅读与在计算机屏幕上阅读相比，在阅读器和文本之间提供了不同的交互。在平板电脑上阅读可能与在纸上阅读更相似，并且这可能会影响阅读过程中的注意力过程。

BACKGROUND & AIMS: :SETTING: Treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) are poor. Due to drug toxicity and a long treatment duration, approximately half of patients are treated successfully. Medication is often crushed for patients who have difficulty swallowing whole tablets. Whether crushing tablets affects drug exposure in MDR-TB treatment is not known.OBJECTIVE AND DESIGN: We performed a sequential pharmacokinetic study in patients aged >18 years on MDR-TB treatment at two hospitals in Cape Town, South Africa. We compared the bioavailability of pyrazinamide, moxifloxacin, isoniazid (INH), ethambutol and terizidone when the tablets were crushed and mixed with water before administration vs. swallowed whole. We sampled blood at six time points over 10 h under each condition separated by 2 weeks. Non-compartmental analysis was used to derive the key pharmacokinetic measurements.RESULTS: Twenty participants completed the study: 15 were men, and the median age was 31.5 years. There was a 42% reduction in the area under the curve AUC0-10 of INH when the tablets were crushed compared with whole tablets (geometric mean ratio 58%; 90%CI 47-73). Crushing tablets of pyrazinamide, moxifloxacin, ethambutol and terizidone did not affect the bioavailability significantly.CONCLUSION: We recommend that crushing of INH tablets in the MDR-TB treatment regimen be avoided. Paediatric INH formulations may be a viable alternative if the crushing of INH tablets is indicated.

背景与目标： 地点：耐多药结核病（MDR-TB）的治疗效果不佳。由于药物毒性和较长的治疗持续时间，约有一半的患者得到了成功的治疗。对于吞咽整片药物有困难的患者，通常会压服药物。目的：我们在南非开普敦的两家医院对年龄> 18岁的患者进行了耐多药结核病治疗的序贯药代动力学研究。我们比较了将吡嗪酰胺，莫西沙星，异烟肼（INH），乙胺丁醇和特立西酮在给药前压碎并与水混合后的生物利用度与吞咽的整体生物利用度。在间隔2周的每种情况下，我们在10小时内的六个时间点对血液进行了采样。结果：二十名参与者完成了这项研究：15名男性，中位年龄为31.5岁。与整粒片剂相比，当将片剂压碎时，INH曲线AUC0-10下的面积减少了42％（几何平均比率58％； 90％CI 47-73）。吡嗪酰胺，莫西沙星，乙胺丁醇和特立西酮的压片对生物利用度没有显着影响。结论：我们建议避免在耐多药结核病治疗方案中压碎INH片。如果需要将INH片剂压碎，则小儿INH制剂可能是可行的选择。

BACKGROUND & AIMS: :In this study, compression-coated tablets were prepared and examined by real-time swelling/erosion analysis and dissolution studies. Of the coating materials, PVP showed no swelling behavior and had no impact on theophylline release. Polyox(®) exhibited swelling behavior of an entangled polymer, which was reflected in its > 14-hour delayed-release profile. Hydroxypropyl methylcellulose (HPMC), which revealed the characteristics of a disentangled polymer, caused a 2-h delay in theophylline release. Based on preliminary texture analysis data, Polyox(®)/PVP blends were used as coating materials to manipulate the onset of drug release from the compression-coated tablets. Of the blends, at a 1:1 ratio, for example, resulted in a burst release after 10 h, which demonstrated the feasibility of preparing delayed release dosage forms by compression coating. Furthermore, it was feasible to predict the dissolution behavior of polymers from their swelling/erosion data, which were generated from texture analysis.

背景与目标： ：在这项研究中，制备了压缩包衣片剂，并通过实时溶胀/侵蚀分析和溶出度研究进行了检查。在包衣材料中，PVP没有显示溶胀行为，对茶碱的释放没有影响。 Polyox®表现出缠结聚合物的溶胀行为，这反映在其> 14小时的延迟释放曲线中。羟丙基甲基纤维素（HPMC）揭示了缠结聚合物的特性，导致茶碱释放延迟了2小时。基于初步的质地分析数据，将Polyox®/ PVP掺合物用作包衣材料，以控制药物从压制包衣片中释放的开始。在这些混合物中，例如以1：1的比例导致10小时后爆发释放，这证明了通过压制包衣制备延迟释放剂型的可行性。此外，从由结构分析产生的溶胀/侵蚀数据预测聚合物的溶解行为是可行的。

BACKGROUND & AIMS: Background & objectives:Iron supplementation is widely used public health measure to manage iron deficiency anaemia. In India, enteric-coated iron tablets are administered to adolescent boys and girls to avoid adverse effects such as gastritis, which reduces compliance, but this may result in poor iron absorption. Data on the absorption of iron from enteric-coated ferrous sulphate tablets are lacking. The present study using stable isotopic approach was aimed to measure iron absorption in iron deficient women. Methods:Iron absorption was measured from stable isotope-labelled enteric-coated ferrous sulphate ([57]Fe, ECFS) and uncoated ferrous sulphate ([58]Fe, UCFS) tablets in iron-deficient (n=9) women, aged 18-40 yr with no infection or inflammation. The two types of tablets (ECFS and UCFS) were administered on consecutive days, 60 min after breakfast, and the sequence being random. Blood samples were collected before dosing, and on day 15, to measure iron absorption from the shift in iron isotopic ratios in haemoglobin. Results:Eight women completed the iron absorption study. Iron absorption was found to be significantly lower in ECFS compared to UCFS (3.5 vs. 12%, P <0.05) consumption. Interpretation & conclusions:Our study showed poor iron bioavailability from ECFS, and supplementation programmes may consider UCFS tablets for better haematological outcomes.

背景与目标： 背景与目的：补铁被广泛用于控制缺铁性贫血的公共卫生措施。在印度，对青少年男孩和女孩服用肠溶铁片可避免诸如胃炎等不良反应，这会降低依从性，但这可能会导致铁吸收不良。缺乏从肠溶性硫酸亚铁片剂中吸收铁的数据。目前使用稳定同位素方法的研究旨在测量缺铁妇女的铁吸收。
方法：在年龄为18岁的缺铁女性中，采用稳定同位素标记的肠溶性硫酸亚铁（[57] Fe，ECFS）和未涂覆的硫酸亚铁（[58] Fe，UCFS）片剂测量铁的吸收。 -40年，无感染或发炎。早餐后60分钟连续两天服用两种类型的片剂（ECFS和UCFS），顺序是随机的。在给药前和第15天收集血样，以从血红蛋白中铁同位素比的变化来测量铁吸收。
结果：八名妇女完成了铁吸收研究。与UCFS消耗量相比，ECFS中的铁吸收量显着降低（3.5％vs. 12％，P <0.05）。
解释与结论：我们的研究表明ECFS的铁生物利用度较差，补充计划可能会考虑使用UCFS片剂来获得更好的血液学结果。

BACKGROUND & AIMS: :Powdered cellulose (PC) and microcrystalline cellulose (MCC) are common excipients in pharmaceuticals. Recent investigations imply that particle size is the most critical parameter for the different performance in many processes. High-pressure homogenization (HPH) was used to reduce fiber size of both grades. The effect of the homogenization parameters on suspension viscosity, particle size, and mechanical properties of casted films was investigated. PC suspensions showed higher apparent viscosities and yield stresses under the same process conditions than MCC. SLS reduced shear viscosity and thixotropic behavior of both cellulose grades probably due to increased electrostatic repulsion. Homogenization reduced cellulose particle sizes, but re-agglomeration was too strong to analyze the particle size correctly. MCC films showed a tensile strength of up to 16.0 MPa and PC films up to 4.1 MPa. PC films disintegrated within 30 s whereas MCC films did not. Mixtures of MCC and PC led to more stable films than PC alone, but these films did not disintegrate anymore. Diclofenac sodium was incorporated in therapeutic dose with drug load of 47% into orodispersible PC films. The content uniformity of these films fulfilled requirements of Ph.Eur and the films disintegrated in 12 s. In summary, PC and MCC showed comparable results after HPH and most differences could be explained by the smaller particle size of MCC suspensions. These results confirm the hypothesis that mainly the fiber size during processing is responsible for the existing differences of MCC and PC in pharmaceutical process, e.g., wet-extrusion/spheronization.

背景与目标： ：粉状纤维素（PC）和微晶纤维素（MCC）是药物中的常见赋形剂。最近的研究表明，粒径是许多工艺中不同性能的最关键参数。高压均质化（HPH）用于减小两种等级的纤维尺寸。研究了均质化参数对流延膜的悬浮液粘度，粒度和机械性能的影响。与MCC相比，在相同的工艺条件下，PC悬浮液表现出更高的表观粘度和屈服应力。 SLS降低了两种纤维素等级的剪切粘度和触变性，这可能是由于静电排斥力增加所致。均质化降低了纤维素的粒径，但是再聚结太强而无法正确分析粒径。 MCC膜的拉伸强度高达16.0 MPa，PC膜的拉伸强度高达4.1 MPa。 PC薄膜在30秒钟内崩解，而MCC薄膜则没有。 MCC和PC的混合物比单独的PC产生更稳定的薄膜，但这些薄膜不再崩解。将双氯芬酸钠以治疗剂量并以47％的载药量掺入可口分散的PC膜中。这些薄膜的含量均匀性满足Ph.Eur的要求，并且薄膜在12秒内崩解。总之，PCH和MCC在HPH后显示出可比的结果，并且大多数差异可以通过MCC悬浮液的较小粒径来解释。这些结果证实了以下假设：在加工过程中，主要的纤维尺寸是造成制药过程中MCC和PC存在差异的原因，例如湿法挤出/滚圆。

BACKGROUND & AIMS: :This randomized, six-treatment, six-period, six sequence, single dose, crossover pharmacokinetic study assessed the effect of different types of food on the bioavailability of 500-mg cefaclor extended release tablet in 23 healthy male volunteers. A single dose of cefaclor extended release 500-mg tablet was administered at six occasions: after overnight fasting, after two vegetarian (high-fat and low-fat), two non-vegetarian (high-fat and low-fat) and rice diets. Serial blood samples were collected up to 12 h after dose. Serum cefaclor concentrations were determined by a validated HPLC method. An almost equivalent increase in both Cmax and AUC was observed with both high-fat non-vegetarian and low-fat vegetarian breakfasts. However, when MIC90 values, a pharmacodynamic end-point were compared, the low-fat vegetarian diet fared better than the high-fat non-vegetarian diet. The results obtained favor low-fat vegetarian diet (breakfast) to be taken with cefaclor extended release tablet to achieve maximum benefit in terms of clinical efficacy.

背景与目标： ：这项随机，六次治疗，六次治疗，六次治疗，六次治疗，单次剂量，交叉药代动力学研究评估了23种健康男性志愿者中不同类型食物对500 mg头孢克洛缓释片生物利用度的影响。单剂量头孢克洛500毫克头孢克洛缓释片分六次服用：禁食过夜后，两次素食（高脂和低脂），两次非素食（高脂和低脂）和大米饮食后。给药后直至12 h收集系列血样。血清头孢克洛浓度通过有效的HPLC方法测定。高脂非素食早餐和低脂素食早餐的Cmax和AUC均几乎增加。但是，当比较MIC90值（药效学终点）时，低脂素食饮食的表现要好于高脂非素食饮食。获得的结果有利于低脂素食饮食（早餐），与头孢克洛缓释片一起服用可在临床疗效方面获得最大收益。

BACKGROUND & AIMS: BACKGROUND:This study aims to systematically explore the efficacy of sacubitril valsartan sodium tablet (SVST) for the treatment of chronic heart failure (CHF). METHODS:Nine electronic databases, including PUBMED, Cochrane Library, EMBASE, PsycINFO, Web of Science, Allied and Complementary Medicine Database, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched. Randomized controlled trials on SVST in the treatment of CHF will be collected. The search time limit will be from the establishment of each electronic database until June 1, 2019. Two authors will independently select the literature, carry out the data, and assess the methodological quality. RESULTS:This study will systematically investigate the efficacy and safety of SVST for CHF. The outcomes consist of all-cause mortality, change in body weight, urine output, change in serum sodium; and incidence of any expected and unexpected adverse events. CONCLUSION:The findings of this study will summarize from evidence-based medicine and a scientific basis for the efficacy and safety of SVST in the clinical treatment of CHF. PROSPERO REGISTRATION NUMBER:PROSPERO CRD42019138882.

背景与目标： 背景：本研究旨在系统地研究沙比特比缬沙坦钠片（SVST）在治疗慢性心力衰竭（CHF）中的疗效。
方法：将检索9个电子数据库，包括PUBMED，Cochrane图书馆，EMBASE，PsycINFO，Web of Science，联合和补充医学数据库，WANGFANG，中国生物医学文献数据库以及中国国家知识基础设施。将收集关于SVST治疗CHF的随机对照试验。搜索时间限制是从每个电子数据库的建立到2019年6月1日。两位作者将独立选择文献，进行数据研究并评估方法学质量。
结果：本研究将系统地研究SVST治疗CHF的有效性和安全性。结果包括全因死亡率，体重变化，尿量变化，血清钠变化；以及任何预期和意外的不良事件的发生率。
结论：本研究的结果将从循证医学和SVST在CHF临床治疗中的有效性和安全性的科学基础中总结。
PROSPERO注册号：PROSPERO CRD42019138882。

BACKGROUND & AIMS: :Particle characteristics, chemical substitution, compaction behavior, and tablet properties of hydroxypropyl methylcellulose powders from two different suppliers were related using multivariate data analysis. By Principal Component Analysis it was shown that the the degree of substitution of the HPMC powders did not correlate to the particle and compaction properties as strongly as anticipated. Particle shape and powder surface area seem to be more important for the compaction behaviour of the powders than the degree of substitution. In addition, particle and tablet properties were predicted from infrared spectral data. Fourier transform infrared (FTIR) and near infrared (NIR) spectral data of the powders were combined with measured values of the particle characteristics, compaction behavior, and tablet properties using the multivariate data analysis program SIMCA 7.1. Properties like density, particle shape, tablet tensile strength, and drug release characteristics of the HPMC powders and corresponding tablets in this study could be predicted using Partial Least Squares models. In conclusion, the particle shape and powder surface area of HPMC powders seem to be important factors for the quality of tablet attained. Further, this study confirms that NIR and FTIR analysis used in combination with multivariate analysis are powerful tools for predicting the properties of materials and the quality of the end product.

背景与目标： ：使用多变量数据分析，对来自两个不同供应商的羟丙基甲基纤维素粉的颗粒特征，化学取代，压实行为和片剂性质进行了关联。通过主成分分析表明，HPMC粉末的取代度与预期的强烈颗粒与压实度不相关。颗粒形状和粉末表面积对于粉末的压实行为似乎比取代度更为重要。另外，根据红外光谱数据预测了颗粒和片剂的性质。使用多元数据分析程序SIMCA 7.1，将粉末的傅立叶变换红外（FTIR）和近红外（NIR）光谱数据与颗粒特性，压实行为和片剂特性的测量值结合在一起。可以使用偏最小二乘模型预测本研究中HPMC粉末和相应片剂的密度，颗粒形状，片剂拉伸强度和药物释放特性等特性。总之，HPMC粉末的颗粒形状和粉末表面积似乎是获得片剂质量的重要因素。此外，这项研究还证实，将近红外和FTIR分析与多变量分析结合使用是预测材料性能和最终产品质量的有力工具。

BACKGROUND & AIMS: PURPOSE:To test for bioequivalence of 200 mg lacosamide oral tablet and syrup formulations. Additional objectives were to compare the pharmacokinetic profile of lacosamide in saliva and plasma, and to evaluate its tolerability. METHODS:This open-label, randomized, two-way crossover trial was conducted in 16 healthy Caucasian male participants in Germany. The bioequivalence of 200 mg lacosamide tablet and syrup was evaluated using plasma to determine maximum measured concentration (C(max)) and area under the curve from zero to the last time point (AUC)(0-tz). Plasma and saliva samples for evaluation of pharmacokinetic parameters of lacosamide and the major metabolite O-desmethyl lacosamide (SPM 12809) were taken over 15 time points (0.5-72 h) and used to statistically compare bioavailability of the two. Urine samples were collected predose and over five time points (0-48 h) to evaluate the cumulative amount of unchanged drug and metabolite. KEY FINDINGS:Lacosamide median time to reach C(max) (t(max)) was 1 h for tablet and 0.5 h for syrup in plasma and saliva. Mean terminal half life (t(½)) for tablet and syrup was 12.5 and 12.4 h in plasma, and 13.1 and 13.3 h in saliva, respectively. Tablet and syrup mean plasma AUC(0-tz) was 84.5 and 83.3 μg/mL*h, respectively. Mean AUC(0-tz) in saliva was 93.2 μg/mL*h for tablet and syrup. Mean C(max) for tablet was 5.26 μg/mL in plasma and 5.63 μg/mL in saliva. Syrup mean C(max) was 5.14 and 8.32 μg/mL in plasma and saliva, respectively. Within 2 h of syrup administration, elevated lacosamide concentration in saliva compared to plasma was observed. The ratio of lacosamide syrup to tablet was 0.98 for C(max) and 0.99 for AUC(0-tz) in plasma, and 1.00 for AUC((0-tz)) in saliva; the 90% confidence intervals (CIs) for these parameters were within the range of 0.80-1.25, which meets accepted bioequivalence criteria. The syrup-to-tablet ratio for C(max) in saliva was 1.48, and the 90% CIs exceeded the accepted upper boundary for bioequivalence (1.32-1.66). Both formulations were well tolerated. Metabolite concentration versus time profiles for saliva were similar to plasma following tablet and syrup administration. SIGNIFICANCE:The tablet and syrup formulations of lacosamide 200 mg were bioequivalent and well tolerated. Saliva samples were demonstrated to be a suitable surrogate to evaluate lacosamide tablet pharmacokinetics in the central compartment. Due to residual syrup in the buccal cavity, limitations exist when using saliva to evaluate the pharmacokinetics of lacosamide syrup <2 h after administration.

背景与目标： 目的：测试200毫克拉考酰胺口服片剂和糖浆制剂的生物等效性。其他目标是比较拉可酰胺在唾液和血浆中的药代动力学特征，并评估其耐受性。
方法：这项开放标签，随机，双向交叉试验是在德国的16位健康的白种人男性参与者中进行的。使用血浆评估200 mg拉考酰胺片和糖浆的生物等效性，以确定最大测量浓度（C（max））和从零到最后一个时间点的曲线下面积（AUC）（0-tz）。在15个时间点（0.5-72 h）采集血浆和唾液样品以评估拉可酰胺和主要代谢产物O-去甲基拉可酰胺（SPM 12809）的药代动力学参数，并用于统计学比较两者的生物利用度。在给药前和五个时间点（0-48小时）内收集尿液样品，以评估未改变药物和代谢物的累积量。
主要发现：血浆和唾液中Lacosamide达到C（max）（t（max））的中位时间为1小时，糖浆为0.5小时。片剂和糖浆的平均终末半衰期（t（1/2））在血浆中分别为12.5和12.4 h，在唾液中分别为13.1和13.3 h。片剂和糖浆的平均血浆AUC（0-tz）分别为84.5和83.3μg/ mL * h。片剂和糖浆中唾液的平均AUC（0-tz）为93.2μg/ mL * h。片剂的平均C（max）在血浆中为5.26μg/ mL，在唾液中为5.63μg/ mL。血浆和唾液中糖浆的平均C（max）分别为5.14和8.32μg/ mL。在给予糖浆的2小时内，观察到唾液中拉考酰胺的浓度与血浆相比有所升高。血浆中拉考酰胺糖浆与片剂的比例在血浆中C（max）为0.98，在AUC（0-tz）中为0.99，在唾液中AUC（（0-tz））中为1.00。这些参数的90％置信区间（CIs）在0.80-1.25的范围内，符合公认的生物等效性标准。唾液中C（max）的糖浆与片剂之比为1.48，并且90％的CI超过了生物等效性的可接受上限（1.32-1.66）。两种制剂均具有良好的耐受性。片剂和糖浆给药后，唾液的代谢物浓度与时间的关系与血浆相似。
重要性：200毫克拉考酰胺的片剂和糖浆制剂具有生物等效性，并具有良好的耐受性。唾液样品被证明是评估中隔室中拉考酰胺片药代动力学的合适替代品。由于颊腔中残留糖浆，使用唾液评估给药后2小时内的拉考酰胺糖浆的药代动力学存在局限性。

BACKGROUND & AIMS: :The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24 healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt). A randomized, crossover design with a 2-week wash-out period between each dose was applied. Serum samples, obtained before dosing and at various appropriate time points up to 192 hours, were analyzed for fluoxetine and norfluoxetine content by a simple, accurate and precise HPLC method. ANOVA, power analysis, 90% confidence intervals (CI), and two one-sided tests were used for the statistical analysis of pharmacokinetic parameters. The tolerability of the preparations was good. The respective point estimates of the ratios of the geometric means of log-Cmax and log-AUC(0-infinity) of fluoxetine were 0.912 and 0.935 with 90% of 0.838-0.992 and 0.857-1.020. The corresponding point estimates of norfluoxetine were 0.952 (90% CI = 0.843-1.075) and 0.904 (90% CI = 0.807-1.013), respectively. Since both 90% CI for the AUC(0-infinity). and Cmax geometric mean ratios of fluoxetine and norfluoxetine were included in the 80% to 125% interval proposed by the FDA the test drug (fluoxetine tablets) was considered bioequivalent to the reference one (Prozac capsules) according both to the rate and extent of absorption.

背景与目标： ：在单次口服20 mg氟西汀（作为盐酸盐）后，在24位男女健康受试者中比较了氟西汀胶囊（参考）和片剂（测试）的药代动力学和相对生物利用度。采用随机，交叉设计，每个剂量之间有2周的清除期。通过简单，准确和精确的HPLC方法分析给药前和至多192小时的各个适当时间点获得的血清样品的氟西汀和去甲氟西汀含量。方差分析，功效分析，90％置信区间（CI）和两个单方面试验用于药代动力学参数的统计分析。制剂的耐受性良好。氟西汀的log-Cmax和log-AUC（0-无穷大）的几何平均值之比的点估计分别为0.912和0.935，其中90％为0.838-0.992和0.857-1.020。去甲氟西汀的相应点估计分别为0.952（90％CI = 0.843-1.075）和0.904（90％CI = 0.807-1.013）。因为两个90％CI均为AUC（0-无穷大）。 FDA提议的80％至125％区间中包括氟西汀和去氟西汀的Cmax和Cmax几何平均比值，根据吸收率和吸收程度，认为测试药物（氟西汀片）与参考药（百忧解胶囊）具有生物等效性。

BACKGROUND & AIMS: :The present study investigates the use of nimodipine-polyethylene glycol solid dispersions for the development of effervescent controlled release floating tablet formulations. The physical state of the dispersed nimodipine in the polymer matrix was characterized by differential scanning calorimetry, powder X-ray diffraction, FT-IR spectroscopy and polarized light microscopy, and the mixture proportions of polyethylene glycol (PEG), polyvinyl-pyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), effervescent agents (EFF) and nimodipine were optimized in relation to drug release (% release at 60 min, and time at which the 90% of the drug was dissolved) and floating properties (tablet's floating strength and duration), employing a 25-run D-optimal mixture design combined with artificial neural networks (ANNs) and genetic programming (GP). It was found that nimodipine exists as mod I microcrystals in the solid dispersions and is stable for at least a three-month period. The tablets showed good floating properties and controlled release profiles, with drug release proceeding via the concomitant operation of swelling and erosion of the polymer matrix. ANNs and GP both proved to be efficient tools in the optimization of the tablet formulation, and the global optimum formulation suggested by the GP equations consisted of PEG=9%, PVP=30%, HPMC=36%, EFF=11%, nimodipine=14%.

背景与目标： ：本研究调查了尼莫地平-聚乙二醇固体分散体在泡腾控释浮动片剂配方开发中的应用。通过差示扫描量热法，粉末X射线衍射，FT-IR光谱和偏振光显微镜以及聚乙二醇（PEG），聚乙烯吡咯烷酮（PVP）的混合比例来表征分散的尼莫地平在聚合物基质中的物理状态。 ，羟丙基甲基纤维素（HPMC），泡腾剂（EFF）和尼莫地平针对药物释放（60分钟时的释放百分比以及90％的药物溶解时间）和漂浮特性（片剂的漂浮强度和持续时间）进行了优化，采用了25次D-最优混合设计，并结合了人工神经网络（ANN）和遗传编程（GP）。已发现尼莫地平以mod I微晶形式存在于固体分散体中，并且稳定至少三个月。片剂表现出良好的漂浮性和控释特性，同时伴随着聚合物基质的溶胀和侵蚀而进行药物释放。人工神经网络和GP均被证明是优化片剂配方的有效工具，GP方程建议的全局最优配方包括PEG = 9％，PVP = 30％，HPMC = 36％，EFF = 11％，尼莫地平= 14％。

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:GRAZAX(®) (Phleum Pratense, 75,000 SQ-T/2,800 BAU, ALK, Denmark), an SQ-standardized grass allergy sublingual immunotherapy tablet for the desensitization of grass pollen-induced rhinoconjunctivitis, has been developed to facilitate patient access to specific immunotherapy (SIT), while minimizing the risk of serious treatment-related adverse events. As a minimum duration of 3 years is recommended for SIT treatment, the GRAAL trial aimed to assess the safety profile of GRAZAX(®) in real-world conditions during long-term treatment of patients with grass pollen-induced allergic rhinoconjunctivitis (ARC). METHODS:A multicentre, prospective, open-label, observational trial was conducted over three consecutive grass pollen seasons from November 2007 to October 2010 in France. A total of 130 physicians included 628 patients with previously documented ARC. Patients received one tablet daily (no up-titration) for at least 4 months before the expected start of the pollen season (pre-season), which was then maintained throughout the entire season (co-season). The primary endpoint was safety and tolerability (immediate, i.e. each year at first tablet administration, and long-term) after pre- and co-seasonal exposure to GRAZAX(®). RESULTS:Patients were treated for an average of 5.5 months per year. After administration of the first tablet, immediate tolerable reactions (defined as benign, local, of short duration [<30 minutes] and not requiring any symptomatic treatment) were experienced by 54.6%, 38.4% and 33.6% of the patients during the first, second and third years of treatment, respectively. Immediate intolerable reactions (required study discontinuation, symptomatic medication or lasted >30 minutes) occurred in 14 patients (2.2%) during GRAZAX(®) initiation, and one patient (0.3%) at treatment reintroduction during the second year. Adverse events considered to be related to GRAZAX(®) were reported by 46.2%, 14.4% and 1.8% of patients, during the first, second and third years of treatment, respectively. The most frequently reported adverse events were mild-to-moderate local events (at the oral and pharyngeal mucosa levels). These symptoms mainly occurred within the first month of treatment initiation and subsequent tablet reintroduction. CONCLUSION:Daily administration of GRAZAX(®) for three consecutive years was generally safe and well tolerated. An improvement in the incidence of adverse events related to treatment was observed at reintroduction of GRAZAX(®) and during the course of treatment. TRIAL REGISTRATION:http://clinicaltrials.gov (NCT01433510).

背景与目标： 背景和目的：已经开发了GRAZAX（®）（Phleum Pratense，75,000 SQ-T / 2,800 BAU，ALK，丹麦），一种用于草粉引起的鼻结膜炎脱敏的SQ标准化草过敏性舌下免疫治疗片。获得特定的免疫疗法（SIT），同时将与治疗相关的严重不良事件的风险降至最低。由于建议对SIT治疗至少持续3年，因此GRAAL试验旨在评估GRAZAX（®）在花粉诱导的变应性鼻结膜炎（ARC）患者长期治疗期间在现实条件下的安全性。
方法：从2007年11月至2010年10月，在法国连续三个季节进行了一项多中心，前瞻性，开放标签的观察性试验。总共130位医生包括628名先前记录过ARC的患者。患者在预期的花粉季节开始前（淡季前）至少每天服用4片（不滴定），然后在整个季节内均保持一整天（共同季节）。主要终点是在季节前和季节性共同暴露于GRAZAX®之后的安全性和耐受性（即立即，即每年首次服用片剂，每年一次）。
结果：患者平均每年接受5.5个月的治疗。服用第一片后，在第一片中，有54.6％，38.4％和33.6％的患者立即发生了可耐受的反应（定义为短时间[<30分钟]的良性，局部性，不需要任何对症治疗），第二年和第三年。在启动GRAZAX®的过程中，立即发生了无法忍受的反应（要求中止研究，对症药物治疗或持续> 30分钟），其中14例患者（2.2％）在第二年的重新治疗中发生了1例患者（0.3％）。在治疗的第一年，第二年和第三年，分别有46.2％，14.4％和1.8％的患者报告了与GRAZAX®相关的不良事件。最常见的不良事件是轻度至中度的局部事件（在口腔和咽粘膜水平）。这些症状主要发生在治疗开始的第一个月和随后的片剂重新引入内。
结论：GRAZAX（®）连续三年每日给药通常是安全的，并且耐受性良好。在重新引入GRAZAX®和治疗过程中，观察到了与治疗相关的不良事件发生率的改善。
试用注册：http：//clinicaltrials.gov（NCT01433510）。

BACKGROUND & AIMS: INTRODUCTION AND AIMS:The medical complications of injecting preparations from crushed tablets can be severe, and most can be attributed to the injection of insoluble particles and micro-organisms. Previously we have shown that most of the particles can be removed by filtration, but it was not known whether bacteria could also be filtered in the presence of a high particle load. This study aims to determine the feasibility of filtration to remove bacteria from injections prepared from tablets. DESIGN AND METHODS:Injections were prepared from crushed slow-release morphine tablets, in mixed bacterial suspensions of Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa. The injection suspensions were passed through syringe filters of porosity 0.45 or 0.20 μm, or combined 0.8 then 0.2 μm, and the bacterial load was counted. RESULTS:Bacterial concentrations in unfiltered injections were 2.5-4.3 × 10(6) colony forming units mL(-1) . Both the 0.20 and 0.45 μm filters blocked unless a prefilter (cigarette filter) was used first. The 0.2 μm filter and the combined 0.8/0.2 μm filter reduced the bacteria to the limit of detection (10 colony forming units mL(-1) ) or below. Filtration through a 0.45 μm filter was slightly less effective. DISCUSSION AND CONCLUSIONS:Use of a 0.2 μm filter, together with other injection hygiene measures, offers the prospect of greatly reducing the medical complications of injecting crushed tablets and should be considered as a highly effective harm reduction method. It is very likely that these benefits would also apply to other illicit drug injections, although validation studies are needed.

背景与目标： 简介和目的：从压碎的片剂中注射制剂的医学并发症可能很严重，并且大多数归因于注射了不溶性颗粒和微生物。以前我们已经表明，大多数颗粒可以通过过滤除去，但是尚不清楚在高颗粒负载下是否也可以过滤细菌。这项研究旨在确定从片剂制备的注射剂中过滤去除细菌的可行性。
设计与方法：从粉碎的缓释吗啡片剂中，在金黄色葡萄球菌，化脓性链球菌和铜绿假单胞菌的混合细菌悬液中制备注射剂。使注射悬浮液通过孔隙率为0.45或0.20μm或组合为0.8然后为0.2μm的注射器过滤器，并对细菌负荷进行计数。
结果：未经过滤的注射液中细菌浓度为2.5-4.3×10（6）菌落形成单位mL（-1）。除非首先使用预过滤器（香烟过滤器），否则0.20和0.45μm的过滤器都会堵塞。 0.2μm的过滤器和组合的0.8 /0.2μm的过滤器将细菌减少到检测极限（10个菌落形成单位mL（-1））或以下。通过0.45μm的过滤器进行过滤的效果稍差。
讨论与结论：使用0.2μm的过滤器以及其他注射卫生措施，可以大大减少注射压碎片剂的医疗并发症，因此应被视为一种有效的减少危害的方法。尽管需要进行验证研究，但这些好处也很有可能也适用于其他非法药物注射。

BACKGROUND & AIMS: BACKGROUND:Fentanyl buccal tablet (FBT), a rapid onset opioid used to treat breakthrough cancer pain, must be titrated to an effective dose that provides adequate analgesia and minimizes undesirable events. This open-label, randomized study compared the percentage of patients achieving an effective dose of FBT when starting titration at 100 or 200 μg. METHODS:Opioid-tolerant patients with chronic cancer-related pain who experienced up to four breakthrough pain episodes daily were randomized to a starting dose of 100 or 200 μg for the titration period. The dose was increased until an effective dose (100, 200, 400, 600 or 800 μg) providing adequate analgesia with acceptable adverse events was achieved. Patients achieving an effective dose entered a treatment period during which they treated up to eight breakthrough pain episodes with their effective dose. RESULTS:A total of 442 patients from 135 sites in seven European countries were screened. Non-inferiority was established with the percentage of patients achieving an effective dose starting titration at 200 μg (81.4%) compared with the 100-μg (75.2%) starting dose. The most common effective doses of FBT were 200 μg (39.6%) and 400 μg (26.9%). No new safety concerns were identified with use of FBT at doses up to 800 μg per episode. CONCLUSIONS:This study involving a real clinical practice setting showed a similar percentage of patients safely achieving an effective dose by titration starting with 100 versus 200 μg of FBT.

背景与目标： 背景：芬太尼颊片剂（FBT）是一种用于治疗突破性癌症疼痛的快速发作的阿片类药物，必须滴定至有效剂量，以提供足够的镇痛作用并最大程度地减少不良事件的发生。这项开放标签的随机研究比较了以100或200μg开始滴定时达到有效剂量的FBT的患者百分比。
方法：每天经历多达四次突破性疼痛发作的耐受阿片类药物的慢性癌症相关疼痛患者，在滴定期间随机分配至起始剂量100或200μg。增加剂量直至达到有效剂量（100、200、400、600或800μg），可提供足够的镇痛作用并具有可接受的不良事件。达到有效剂量的患者进入治疗期，在此期间，他们以有效剂量治疗了多达八次突破性疼痛发作。
结果：筛选了来自七个欧洲国家135个站点的442名患者。非劣效性是指以200μg（81.4％）的有效剂量开始滴定，而100μg（75.2％）的开始剂量达到有效剂量的患者百分比。 FBT最常见的有效剂量是200μg（39.6％）和400μg（26.9％）。每次发作使用FBT的剂量最高至800μg，未发现新的安全隐患。
结论：这项涉及实际临床实践的研究表明，从100μg对200μgFBT开始，通过滴定安全地获得有效剂量的患者百分比相似。