BACKGROUND & AIMS: :The study demonstrates the application of QbD based on historical data for a product at a later development stage - retrospective QbD (rQbD). More specifically, it is investigated the root-cause for the observed slower drug release in Orodispersible Films (ODFs) during storage. Risk assessment tools were used to identify parameters affecting ODFs critical quality attributes, namely percent drug release and residual water content. The parameters room temperature, room relative humidity, drying temperature and mixing equipment were used in the statistical modeling of the available data. The estimated models were then used to define the feasible working region. Statistical modeling indicates that initial residual water content of the ODFs is mainly affected by 2nd order interactions of room temperature, room relative humidity and drying temperature, while the stability of drug release profile is mostly influenced by room temperature and an interaction between room relative humidity and drying temperature. Depending on the drying temperature employed the effect of room temperature and room relative humidity change significantly. This work shows that it is possible to apply rQbD to achieve a greater understanding of the manufacturing process of ODFs and to define a proper design space.

背景与目标： ：研究证明了基于历史数据的QbD在后期产品开发中的应用-回顾性QbD（rQbD）。更具体地说，研究了在储存过程中观察到的较慢的药物在口腔分散膜（ODF）中释放的根本原因。风险评估工具用于确定影响ODF关键质量属性的参数，即药物释放百分比和残留水分。在可用数据的统计模型中，使用了室温，室内相对湿度，干燥温度和混合设备等参数。然后，将估计的模型用于定义可行的工作区域。统计模型表明，ODFs的初始残留水含量主要受室温，室温相对湿度和干燥温度的二阶相互作用影响，而药物释放曲线的稳定性主要受室温以及室温相对湿度与干燥温度之间相互作用的影响。干燥温度。取决于所采用的干燥温度，室温和室内相对湿度的影响会明显变化。这项工作表明，有可能应用rQbD来更好地理解ODF的制造过程并定义适当的设计空间。

BACKGROUND & AIMS: :A three-way crossover study in 27 human volunteers was conducted to characterize the pharmacokinetics and to assess the dose proportionality of 100 mg, 200 mg and 300 mg strengths of a novel once-a-day tramadol controlled-release tablet (Tramadol Contramid OAD) following single-dose administration. Serial blood samples were collected at predefined timepoints over a 48 h period and racemic tramadol and O-desmethyltramadol concentrations in plasma were determined using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using noncompartmental methods. Following dose normalization and logarithmic transformation of concentration-dependent parameters, the results were compared using analysis of variance (ANOVA). The residual variability thereby obtained was used to construct 90% classical confidence intervals. The two one-sided tests procedure was used for all pairwise comparisons. Dose proportionality was concluded since the 90% CI for the ratio of geometric means was included in the acceptance range of 0.80-1.25 for all comparisons.

背景与目标： ：在27位人类志愿者中进行了三项交叉研究，以表征药代动力学并评估新型每日一次曲马多控释片剂（曲马多Contramid OAD）的100 mg，200 mg和300 mg强度的剂量比例）单次给药后。在48小时内的预定时间点采集系列血样，并使用经过验证的LC-MS / MS方法测定血浆中的外消旋曲马多和O-去甲基曲马多浓度。使用非房室方法得出药代动力学参数。剂量归一化和浓度依赖性参数的对数转换后，使用方差分析（ANOVA）比较结果。由此获得的残余变异性用于构建90％的经典置信区间。所有的成对比较均使用两个单面测试程序。由于所有比较的几何均数比率的90％CI都在0.80-1.25的接受范围内，因此得出剂量比例。

BACKGROUND & AIMS: :Cefpodoxime proxetil is a third generation cephalosporin antibiotic demonstrates pH dependent solubility and is highly soluble only in acidic pH. The purpose of this investigation was to design and develop immediate release tablets of cefpodoxime proxetil by direct compression method and determine the effect of different solid buffers (organic acids) such as fumaric acid (formulations F1-F4), maleic acid (formulations M1-M4) and citric acid (formulations C1-C4) by using cefpodoxime and acid in the ratios of 4:1, 2:1, 1:1 and 1:2 to achieve pH-independent release of the drug. Physical parameters and assay were found to be within the acceptable range as prescribed in USP 36 / NF 31. In vitro dissolution studies of each formulation were performed in distilled water, USP dissolution medium, HCl buffer solution of pH 1.2, phosphate buffer solutions of pH 4.5 and 6.8 to observe the drug release. The formulations F3, F4, M4 were selected for film coating on the basis of better drug release profile, to protect the drug from chemical degradation through hydrolysis. Film coated formulation F3, F4 and M4 showed a remarkable in vitro release of the drug (72.88±0.43 to 92.67±0.71%) within 30min of observation in all dissolution media and further evaluated by model independent and model dependent approaches. The drug release was found to be best fit to Weibull model as highest r2adjusted (0.924-0.998) and lowest AIC (18.416-54.710) values were obtained in all dissolution media. R Gui® applied for stability studies of F3 and F4 formulations, showing shelf lives of 28 & 27months at ambient and 33 months at accelerated temperatures. Formulation F4 was chosen as best formulation on the basis of physical properties, highest dissolution rate and stability studies.

背景与目标： ：头孢泊肟酯是第三代头孢菌素抗生素，显示出pH依赖性溶解度，仅在酸性pH值下高度可溶。这项研究的目的是通过直接压缩方法设计和开发头孢泊肟肟酯的速释片，并确定不同的固体缓冲剂（有机酸）如富马酸（配方F1-F4），马来酸（配方M1-M4）的作用）和柠檬酸（配方C1-C4），使用头孢泊肟和酸的比例为4：1、2：1、1：1和1：2，以实现不依赖pH值的药物释放。发现物理参数和测定均在USP 36 / NF 31规定的可接受范围内。每种制剂的体外溶出度研究是在蒸馏水，USP溶出介质，pH 1.2的HCl缓冲溶液，pH 1.2的磷酸盐缓冲溶液中进行的。 4.5和6.8观察药物释放情况。基于更好的药物释放曲线，选择制剂F3，F4，M4进行薄膜包衣，以保护药物免受水解的化学降解。薄膜包衣的制剂F3，F4和M4在观察到的30分钟内在所有溶出介质中均显示出显着的药物体外释放（72.88±0.43至92.67±0.71％），并通过模型独立和模型依赖的方法进行了进一步评估。发现在所有溶出介质中均获得了最高的r2调整值（0.924-0.998）和最低的AIC值（18.416-54.710），从而使药物释放最适合于Weibull模型。 RGui®应用于F3和F4配方的稳定性研究，在室温下的保质期为28和27个月，在加速温度下的保质期为33个月。根据物理性能，最高的溶出速率和稳定性研究，选择配方F4作为最佳配方。

BACKGROUND & AIMS: BACKGROUND:Timothy grass sublingual immunotherapy (SLIT) tablets are indicated for children with allergic rhinitis with or without conjunctivitis. OBJECTIVE:To use pooled analyses to assess the short- and long-term tolerability and safety of timothy grass SLIT-tablet in children. METHODS:Data from 9 double-blinded, randomized European or North American trials that included children with allergic rhinitis with or without conjunctivitis treated up to 3 years with once-daily timothy grass SLIT-tablet or placebo were pooled. RESULTS:In all, 1818 (timothy grass SLIT-tablet, n = 923; placebo, n = 895) subjects were included in the analysis. The frequency of treatment-emergent adverse events (AEs) was 86% in the SLIT-tablet group and 83% in the placebo group, and the frequency of treatment-related AEs (TRAEs) was 59% and 23%, respectively. Most (98%) TRAEs were mild to moderate in severity. The 2 most common TRAEs with SLIT-tablet were oral pruritus (33%) and throat irritation (19%), which had a median onset of 1 day and recurrence of 14.5 and 5 days, respectively. In all, 8% of subjects in the SLIT-tablet group and 2% in the placebo group discontinued because of AEs. There were 7 serious AEs assessed as related to SLIT-tablet, 1 systemic allergic reaction (severe with a drop in blood pressure), 3 epinephrine administrations, no eosinophilic esophagitis events, and no serious airway obstructions. The safety profile was similar in subjects across geographic regions and with and without asthma. CONCLUSIONS:Pooled data indicate that short- and long-term timothy grass SLIT-tablet is well tolerated in children, regardless of geographic region. AEs were generally local, mild, and transient allergic reactions.

背景与目标： 背景：蒂莫西草舌下免疫治疗（SLIT）片适用于患有或不患有结膜炎的过敏性鼻炎患儿。
目的：使用汇总分析来评估儿童提摩西草SLIT片剂的短期和长期耐受性和安全性。
方法：收集来自9项欧洲或北美双盲，随机试验的数据，该试验包括患有过敏性鼻炎的儿童（有或没有结膜炎），每天用一次速效草SLIT片剂或安慰剂治疗长达3年。
结果：总共纳入了1818名（蒂莫斯草SLIT片剂，n = 923;安慰剂，n = 895）受试者。 SLIT-片剂组出现治疗的不良事件（AEs）的频率为86％，安慰剂组为83％，与治疗相关的AEs（TRAEs）的频率分别为59％和23％。大多数（98％）TRAE的严重程度为轻度至中度。带有SLIT片剂的2种最常见的TRAE是口腔瘙痒（33％）和喉咙刺激（19％），它们的中位发作为1天，复发分别为14.5和5天。总之，SLAE片剂组中有8％的受试者和安慰剂组中有2％的受试者因AE停药。评估了与SLIT片剂相关的7种严重不良事件，1例全身性过敏反应（严重且血压下降），3次肾上腺素给药，无嗜酸性食管炎事件以及无严重气道阻塞。在有或没有哮喘的地区，受试者的安全性特征相似。
结论：汇总的数据表明，不论地理区域如何，儿童短期和长期食用提莫乐草SLIT片剂的耐受性都很好。 AE通常是局部，轻度和短暂的过敏反应。

BACKGROUND & AIMS: BACKGROUND:Posaconazole is approved for invasive fungal infection prophylaxis in patients with hematologic malignancies. Posaconazole suspension is plagued by poor oral absorption and dietary requirements that are difficult for patients to meet. The delayed-release tablet formulation of posaconazole may be taken without regards to meals and has significantly better oral absorption than posaconazole suspension. OBJECTIVES:We sought to determine if a switch to posaconazole tablets improved steady-state drug level attainment for invasive fungal infection prophylaxis in patients with acute myeloid leukemia. METHODS:All adult inpatients with acute myeloid leukemia undergoing chemotherapy, who received posaconazole for invasive fungal infection prophylaxis between 2012 and 2015, were included. The primary outcome was proportion of patients with first posaconazole level greater than 700 ng/mL. Secondary outcomes included proportion of patients with first posaconazole level greater than 1000 ng/mL, invasive fungal infection within 100 days, and adverse drug events. RESULTS:Forty patients received posaconazole tablets and 34 patients received suspension. Posaconazole levels were significantly higher at first measurement in patients receiving tablet than suspension (1296 ng/mL vs. 788 ng/mL, p < 0.01). Thirty-seven patients receiving tablets had a serum drug level greater than 700 ng/mL on first measurement versus 18 receiving suspension (p < 0.01). Patients receiving tablets were also more likely to have a serum drug level over 1000 ng/mL on first measurement (26 vs. 11, p < 0.01). Rates of invasive fungal infection and adverse events were not statistically different. CONCLUSIONS:Patients receiving posaconazole tablets attained significantly higher serum drug levels than those receiving suspension.

背景与目标： 背景：泊沙康唑被批准用于血液系统恶性肿瘤患者的侵入性真菌感染预防。泊沙康唑悬浮液的口服吸收不良和饮食需求使患者难以满足。泊沙康唑的缓释片剂可在不考虑进餐的情况下服用，并且口服吸收比泊沙康唑悬浮液要好得多。
目的：我们试图确定使用泊沙康唑片是否可以改善预防急性髓性白血病患者侵袭性真菌感染的稳态药物水平。
方法：纳入2012年至2015年期间接受泊沙康唑预防侵入性真菌感染的所有接受化疗的急性髓性白血病成人患者。主要结局是首次泊沙康唑水平高于700μng/ mL的患者比例。次要结果包括首次泊沙康唑水平大于1000µng / mL，100天内侵袭性真菌感染以及药物不良反应的患者比例。
结果：40例患者接受泊沙康唑片治疗； 34例患者接受悬浮液治疗。首次接受片剂的患者中，泊沙康唑的水平明显高于混悬液（1296 ng / mL vs. 788 ng / mL，p <0.01）。初次测量时有37例接受片剂治疗的患者血清药物水平高于700μng/ mL，而接受悬浮液的有18例患者（p <0.01）。首次服用片剂的患者血清药物水平也更有可能超过1000μng/ mL（26 vs. 11，p <0.01）。侵袭性真菌感染和不良事件的发生率在统计学上没有差异。
结论：接受泊沙康唑片剂的患者血清药物水平明显高于接受悬浮液治疗的患者。

BACKGROUND & AIMS: BACKGROUND:Game-based training has been shown to improve behavioural motor learning in various medical fields including rehabilitation. OBJECTIVES:This study aimed to investigate the effects of a tablet PC (personal computer) game-based tongue training on tongue strength, thickness and compliance in healthy adults. METHODS:This study recruited 30 healthy volunteers. Subjects were randomly assigned to two groups (n = 15/group). Group 1 performed game-based tongue training, and group 2 performed tongue resistance training using the Iowa Oral Performance Instrument. Both groups performed the same tongue exercises as follows: frequency (isotonic = 30 times × 3, isometric = 20 seconds × 3), intensity (70% of 1-repeated maximum contraction) and intervention period (5 days for 6 weeks). The primary outcomes were tongue muscle strength and thickness. Secondary outcomes were assessed using a 0-to-10 numerical rating self-report scale that included motivation, interest/fun, physical effort and muscle fatigue/pain. RESULTS:Both groups showed significant improvement in tongue strength and thickness, but there were no significant differences between the groups after the intervention. The self-report scale numerical rating revealed that group 1 had significantly higher motivation and interest/fun after the exercise than group 2. Group 1 had expended a significantly lower physical effort than group 2. No significant differences were noted between the 2 groups for muscle fatigue/pain. CONCLUSION:This study showed that both exercises had similar effects on tongue strength and thickness increase in healthy adults, but game-based tongue training was more fun and physically less demanding.

背景与目标： 背景：基于游戏的训练已被证明可以改善包括康复在内的各个医学领域的行为运动学习。
目的：本研究旨在研究基于平板电脑（个人计算机）游戏的舌头训练对健康成年人舌头力量，厚度和顺应性的影响。
方法：本研究招募了30名健康志愿者。将受试者随机分为两组（n = 15 /组）。第一组进行基于游戏的舌头训练，第二组使用爱荷华州口腔表演仪进行舌头抵抗训练。两组进行以下相同的舌头练习：频率（等渗= 30次×3，等距= 20秒×3），强度（1次重复最大收缩的70％）和干预期（5天，共6周）。主要结局是舌头肌肉的力量和粗细。次要结局使用0到10的数字自我评估量表进行评估，该量表包括动机，兴趣/乐趣，体力劳动和肌肉疲劳/疼痛。
结果：两组患者的舌头力量和粗细程度均有显着改善，但干预后两组之间无显着差异。自我报告量表的数字评分显示，锻炼后的第1组的动机和兴趣/乐趣明显高于第2组。第1组的体力消耗明显低于第2组。两组的肌肉无明显差异。疲劳/疼痛。
结论：这项研究表明，两种锻炼对健康成年人的舌头力量和厚度增加都具有相似的效果，但基于游戏的舌头训练更有趣，对身体的要求也更低。

BACKGROUND & AIMS: :To overcome the poor dissolution of telmisartan (TMS) at weak acidic pH, amorphous alkalinized TMS (AAT) was prepared by introducing sodium hydroxide as a selective alkalizer. AAT-containing polymeric solid dispersions were prepared by a solvent evaporation method; these solid dispersions were AAT-PEG, AAT-PVP, AAT-POL, and AAT-SOL for the polymers of PEG 6000, PVP K30, Poloxamer 407, and Soluplus, respectively. The characteristics of the different formulations were observed by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. To compare the supersaturation behavior, a dissolution test was performed at 37 ± 0.5 °C either in 900 ml (plain condition) or 500 ml (limited condition) of pH 6.8-simulated intestinal fluid used as a medium. AAT-SOL exhibited enhanced dissolution, indicating the probability of extended supersaturation in the limited condition. AAT-SOL was further formulated into a tablet by introducing other excipients, Vivapur 105 and Croscarmellose, as a binder and superdisintegrant, respectively, using a direct compression method. The selected AAT-SOL tablet was superior to Micardis (the reference product) in the aspect of supersaturation maintenance during dissolution in the limited condition, suggesting that it is a promising candidate for practical development that can replace the commercial product in the future.

背景与目标： ：为克服替米沙坦（TMS）在弱酸性pH下的不良溶解，通过引入氢氧化钠作为选择性碱化剂来制备无定形碱化TMS（AAT）。含AAT的聚合物固体分散体是通过溶剂蒸发法制备的。这些固体分散体分别是PEG 6000，PVP K30，泊洛沙姆407和Soluplus的聚合物的AAT-PEG，AAT-PVP，AAT-POL和AAT-SOL。通过差示扫描量热法，粉末X射线衍射，傅里叶变换红外光谱和扫描电子显微镜观察了不同制剂的特性。为了比较过饱和行为，在37±0.5°C的900毫升（纯条件）或500毫升（有限条件）的pH 6.8模拟肠液作为介质中进行了溶出度测试。 AAT-SOL表现出增强的溶解性，表明在有限条件下扩展过饱和的可能性。通过使用直接压片法分别引入其他赋形剂Vivapur 105和Croscarmellose，分别将AAT-SOL和AVI-SOL分别制成粘合剂和超崩解剂，制成片剂。所选的AAT-SOL片剂在有限条件下溶解过程中的过饱和维持方面优于Micardis（参考产品），这表明它是可以在将来替代商业产品的实际开发中有希望的候选者。

BACKGROUND & AIMS: BACKGROUND:Ancylostomatids ('hookworms') are among the most important zoonotic nematode parasites infecting dogs worldwide. Ancylostoma caninum and Uncinaria stenocephala are two of the most common hookworm species that infect dogs. Both immature and adult stages of hookworms are voracious blood feeders and can cause death in young dogs before infection can be detected by routine fecal examination. Hence, treatment of both immature and adult stages of hookworms will decrease the risk of important clinical disease in the dog as well as the environmental contamination caused by egg-laying adults, which should reduce the risk of infection for both dogs and humans. The studies presented here were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), against induced larval (L4), immature adult (L5) and adult A. caninum, and adult U. stenocephala infections in dogs. METHODS:Eight negative-controlled, masked, randomized laboratory studies were conducted. Two separate studies were conducted against each of the target parasites and stages. Sixteen or 18 purpose bred dogs, 8 or 9 in each of the two treatment groups, were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Timing of dosing relative to parasite inoculation allowed for efficacy to be evaluated primarily against the target parasite stage. Worm counts were conducted 7 or 8 days after treatments during necropsy. Efficacy was based on the number of worms recovered at necropsy compared to placebo control. RESULTS:Based on geometric mean worm counts, efficacy of Simparica Trio™ was ≥ 98.4% against L4 larval stage of A. caninum, ≥ 99.8% against immature adult (L5) A. caninum, and 100% against adult A. caninum and adult U. stenocephala. CONCLUSIONS:These studies confirm the efficacy of a single oral dose of a novel, chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against L4 larval and immature adult (L5) A. caninum, and adult A. caninum and U. stenocephala infections in dogs.

背景与目标： 背景技术：钩虫（钩虫）是全世界感染犬的最重要的人畜共患线虫寄生虫。犬十二指肠瘤和钩头畸形犬是感染狗的两种最常见的钩虫。钩虫的未成熟阶段和成年阶段都是贪食者，它们可以使幼犬死亡，然后才能通过常规粪便检查发现感染。因此，对钩虫的未成熟阶段和成年阶段的治疗都将降低犬中发生重要临床疾病的风险以及成虫产卵所造成的环境污染，这将降低犬和人的感染风险。此处进行的研究旨在评估含有sarolaner，moxidectin和pyrantel（Simparica Trio™）的新型口服咀嚼片对诱导幼虫（L4），成年幼虫（L5）和成年犬链霉菌以及成年U的功效。狗的头颅感染。
方法：进行了八项阴性对照，隐蔽，随机实验室研究。针对每个目标寄生虫和阶段进行了两个单独的研究。每项研究均包括16只或18只目的犬，两个治疗组分别为8只或9只。实验上感染目标寄生虫的狗在第0天用安慰剂片剂或Simparica Trio™片剂给药一次，以提供最低剂量1.2毫克/千克sarolaner，24微克/千克莫昔克丁和5.0毫克/千克吡喃酮（作为pamoate盐）。相对于寄生虫接种的给药时间允许主要针对目标寄生虫阶段评估功效。尸检后7或8天进行蠕虫计数。功效是基于尸检时与安慰剂对照相比发现的蠕虫数量。
结果：基于蠕虫的几何平均数，Simparica Trio™对抗犬链球菌L4幼虫期的效率≥98.4％，针对未成年犬（L5）犬链球菌的≥99.8％，对成年犬链球菌和成虫的功效为100％头颅单胞菌。
结论：这些研究证实了单次口服的含有sarolaner，moxidectin和pyrantel（Simparica Trio™）的新型可咀嚼片剂对L4幼虫和未成年成年犬L. A. caninum以及成年成年犬A. caninum和U的功效。狗的头颅感染。

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。