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Searching for a long-acting injectable formulation for the antiretroviral dolutegravir 寻找抗逆转录病毒多替格拉韦的长效注射制剂
Pub Date : 2019-12-31 DOI: 10.5920/bjpharm.568
A. Marchi, C. Kobarg, Keity Margareth Doretto, Luis Gustavo Robello, M. Pigatto, M. Alves, R. Pereira
The aim of this study was to engineer a DTG particle size able to provide plasma drug concentration maintenance above PA-IC-90 and, based on such drug prolonged- exposure, to evaluate the 30 days-acting injectable DTG feasibility for anti-HIV therapy. Liquidantisolvent precipitation technology was used to engineer dolutegravir particles. As a strategy for controlling variations of the habit, particle size and polymorphs of Dolutegravir, process intensification was performed using acetone, methanol, and DMSO as solvents and a temperature range from 5oCto 30oC. Physical properties of particles were characterized and in vitro drug release was measured. As a pivotal characterization, in vivo pharmacokinetic analysis was conducted in Wistar male rats. Findings revealed that crystal habit and polymorph were solvent and temperature independents. Concerning solvents, particle sizes were not markedly different. However, results suggested that the higher the temperature the higher dolutegravir particle size. Particle size ranging from 6.48 µm to 17 µm (D50) shown an accelerated release rate and 93% of the drug were released up to 12th day. Results demonstrated thatDolutegravir particles of approximately 13 µm (D50) maintained plasma drug concentration above PA- IC90 for 26 days.
本研究的目的是设计一种DTG颗粒大小,能够使血浆药物浓度维持在PA-IC-90以上,并基于这种药物长时间暴露,评估30天可注射DTG抗hiv治疗的可行性。采用液相反溶剂沉淀法制备偏重颗粒。为了控制Dolutegravir的习性、粒径和多晶型的变化,采用丙酮、甲醇和DMSO作为溶剂,在50℃至30℃的温度范围内进行了工艺强化。对颗粒的物理性质进行了表征,并测定了其体外释放度。作为关键表征,在Wistar雄性大鼠体内进行了药代动力学分析。结果表明,晶体习性和晶型与溶剂和温度无关。溶剂的粒径差异不显著。然而,结果表明,温度越高,偏重粒子的粒径越大。粒径范围为6.48µm ~ 17µm (D50),释药速度加快,至第12天释药率为93%。结果表明,约13µm (D50)的多替替韦颗粒可使血浆药物浓度维持在PA- IC90以上26天。
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引用次数: 1
Inter-professional prescription safety workshop for non-medical prescribing and pharmacy students: A cross-sectional study. 非医疗处方和药学学生跨专业处方安全研讨会:一项横断面研究。
Pub Date : 2019-11-01 DOI: 10.5920/bjpharm.659
S. Hemingway, M. Culshaw, J. Stephenson
This article reports on an evaluation of a prescribing workshop to increase ‘sharedlearning’ between registered practitioners undertaking a non-medicalprescribing (NMP) course (midwifery, nursing, physiotherapy, and podiatry) andundergraduate pharmacy students to increase awareness of, and understanding of theroles.  The focus was on three domains ofsafe prescribing: Knowledge (of commonly prescribed medicines and theirsuitability for individual patients); Process (of legal requirements and supplyof medicines and associated patient information); and Relationships (betweenprescribers and pharmacists). A cross-sectional evaluation was utilized with6-point Likert-style items and a free text section, completed by 337participants.  Participants reported positivelyabout the workshop content and their learning experience, although somedifferences between pharmacy and NMP participants were noted in the knowledgedomain. Quantitative analysis revealed significant differences (p<0.001) oflow-to-moderate magnitude (partial-2=0.146) between NMP and Pharmacy studenton all 3 domains, with NMP students reporting slightly more positive outcomes(between 0.4 and 1.5 points higher) in all cases. However, both groups scoredpositively; with mean domain scores of 15.6 to 16.5 on scales with maximumscores of 18.
本文报告了一个处方研讨会的评估,以增加参加非医疗处方(NMP)课程(助产学,护理学,物理治疗和足病)的注册从业者和本科药学学生之间的“共享学习”,以提高对角色的认识和理解。重点是安全处方的三个领域:知识(常用处方药及其对个体患者的适用性);流程(法律要求和药品供应以及相关患者信息);以及关系(开处方者和药剂师之间)。横断面评估采用6点李克特式项目和自由文本部分,由337名参与者完成。参与者对研讨会的内容和他们的学习经历进行了积极的报告,尽管药学和NMP参与者在知识领域存在一些差异。定量分析显示,NMP和药学学生在所有三个领域之间存在中低量级(部分- 2=0.146)的显著差异(p<0.001), NMP学生在所有情况下报告的积极结果略高(高出0.4至1.5分)。然而,两组的得分都是正的;平均领域得分为15.6至16.5分,满分为18分。
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引用次数: 2
Differential effects of NSAIDs on amyloid β1-42 peptide aggregation 非甾体抗炎药对淀粉样蛋白β1-42肽聚集的不同影响
Pub Date : 2019-05-23 DOI: 10.5920/BJPHARM.628
A. Alzurfi, H. Aojula, J. Penny
Alzheimer’s disease (AD) is the most common cause of dementia and one of the great health-care challenges of the 21st century. The disease is characterised by extracellular aggregation of the amyloid beta (Aβ1-42) peptide within the brain, with subsequent formation of plaques leading to dementia. Currently, there is no cure for AD with only symptomatic therapies available which have demonstrated no, or limited, efficacy. Current pharmacologic studies into AD have focused principally on the development of disease-modifying therapies that can slow the progression of AD. Targets of these investigational agents include Aβ1-42 production, aggregation, and clearance. The ability of non-steroidal anti-inflammatory drugs (NSAIDs) to influence Aβ1-42 aggregation was assessed using the thioflavin-T spectrofluorimetric assay. Mefenamic acid and flufenamic acid both significantly reduced Aβ1-42 aggregation in vitro; however ibuprofen and naproxen had no significant effect on aggregation. These studies highlight that NSAIDs may have potential for helping manage or treat AD.
阿尔茨海默病(AD)是痴呆症最常见的病因,也是21世纪最大的卫生保健挑战之一。该疾病的特征是大脑内β淀粉样蛋白(Aβ1-42)肽的细胞外聚集,随后形成斑块,导致痴呆。目前,还没有治愈阿尔茨海默病的方法,只有对症治疗,但这些治疗没有或有限的疗效。目前对阿尔茨海默病的药理学研究主要集中在开发可以减缓阿尔茨海默病进展的疾病修饰疗法上。这些研究药物的靶点包括a - β1-42的产生、聚集和清除。非甾体抗炎药(NSAIDs)影响a - β1-42聚集的能力采用硫黄酮- t荧光光度法进行评估。甲非那明酸和氟非那明酸均能显著降低体外a - β1-42的聚集;而布洛芬和萘普生对凝集无明显影响。这些研究强调非甾体抗炎药可能有助于控制或治疗AD。
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引用次数: 1
Non-adherence to cardiovascular pharmacotherapy in Iraq assessed using 8-items Morisky questionnaire and analysis of dried blood spot samples 使用8项Morisky问卷和干血斑样本分析评估伊拉克心血管药物治疗的不依从性
Pub Date : 2019-05-23 DOI: 10.5920/BJPHARM.627
Ahmed Alalaqi, G. Lawson, Yaseen Obaid, S. Tanna
The study evaluated the non-adherence to selected cardiovascular medications, atenolol, atorvastatin, bisoprolol, diltiazem, lisinopril, simvastatin and valsartan in Iraqi patients by applying a standardized Morisky questionnaire (8-MMAS) and by measuring therapeutic drug concentrations in dried blood spots (DBS) analyzed by liquid chromatography - high resolution mass spectrometry (LC-HRMS). Sixty-nine patients, on continued use of one or more of the selected drugs, were evaluated. The questionnaire showed that 21.7% of participants were non-adherent whereas DBS analysis showed that 49.3% were non-adherent to their medications. No significant correlation between medication non-adherence and gender was detected, but adherence was negatively correlated with the number of medications in the regimen. The 8-items questionnaire was unable to differentiate non-adherence to multiple medications in the prescribed pharmacotherapy regimens. DBS is an alternative to conventional methods to monitor non-adherence objectively. Agreement between the two approaches was weak (Kappa =0.269, p-value 0.05).
该研究通过标准化Morisky问卷(8-MMAS)和测定干血斑(DBS)中治疗药物的浓度,通过液相色谱-高分辨率质谱(LC-HRMS)分析,评估了伊拉克患者对选定的心血管药物阿替洛尔、阿托伐他汀、比索洛尔、地尔硫卓、赖诺普利、辛伐他汀和缬沙坦的不依从性。对69名继续使用一种或多种选定药物的患者进行了评估。问卷调查显示21.7%的参与者不坚持服药,而DBS分析显示49.3%的参与者不坚持服药。药物依从性与性别之间无显著相关,但依从性与方案中药物的数量呈负相关。8项调查问卷无法区分处方药物治疗方案中多种药物的不依从性。DBS是传统方法的替代方案,可以客观地监测不依从性。两种方法的一致性较弱(Kappa =0.269, p值0.05)。
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引用次数: 2
Medicine Manipulation for Paediatric Use: Dispersible aspirin tablets and dose uniformity. 小儿用药手法:阿司匹林分散片和剂量均匀性。
Pub Date : 2019-05-01 DOI: 10.5920/BJPHARM.623
Ahmed A Lahiq, H. Batchelor
Concerns about uniformityand the accuracy of the doses resulting from tablet manipulation havepreviously been reported.  When aspirinis required to treat children, an oral liquid is not readily available,therefore health care providers or parents are required to manipulate aspirintablets to produce the appropriate dose. In this work, aspirin 75mg dispersible tablets were dispersed in a rangeof waters (room temperature and warm deionized and tap water and sparklingwater) and the dose accuracy was measured. The impact of temperature on the dose accuracy for the tap water wasless pronounced yet there was overall lower accuracy compared to the deionisedwater. Dispersion of the tablet in sparkling water does not give an accuratedose.  Heatingfluid used in dispersion is practically achievable yet deionized water in thehome or a ward is impractical.  Sparklingwater should be avoided when dispersing aspirin tablet.  Thereis a need to evaluate the apparatus and methods used to manipulate medicinesfor children as both the water used and the tools to undertake the manipulationhave significant effects on the accuracy of the dose obtained.
此前曾报道过对药片操作导致的剂量均匀性和准确性的担忧。当需要阿斯匹林治疗儿童时,口服液不容易获得,因此卫生保健提供者或家长需要操纵阿斯匹林片以产生适当的剂量。本研究将阿司匹林75mg分散片分散在不同的水(常温、温去离子水、自来水、苏打水)中,并测定剂量的准确性。温度对自来水剂量准确性的影响不太明显,但与去离子水相比,总体准确性较低。片剂在气泡水中的分散不能给出准确的剂量。在分散中使用的加热流体实际上是可以实现的,但在家庭或病房中使用去离子水是不切实际的。分散阿司匹林片剂时应避免使用苏打水。有必要评估用于儿童药物操作的设备和方法,因为所使用的水和进行操作的工具对所获得剂量的准确性有重大影响。
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引用次数: 0
The Science of Differentiated Medicines: The 9th APS PharmSci Conference @FIP 2018 差异化药物的科学:第九届美国医学科学院药学科学会议@FIP 2018
Pub Date : 2019-04-17 DOI: 10.5920/BJPHARM.610
J. Wahlich
The Academy ofPharmaceutical Sciences (APSGB) hosts the annual Pharm Sci Conference, the UK’spremier pharmaceutical sciences event championing ‘The Science of Medicines’.In 2018 the 9th conference was linked to the FIP Conference held inGlasgow and consequently was a shorter meeting. The theme of APS Pharm Sci 2018was ‘The Science of Differentiated Medicines’
药学科学院(APSGB)主办一年一度的药学科学会议,这是英国倡导“医学科学”的最重要的药学科学活动。2018年,第9次会议与在格拉斯哥举行的FIP会议联系在一起,因此会议时间较短。2018年APS药学科学大会的主题是“差异化药物的科学”。
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引用次数: 0
Preparation, characterisation and cell transfection of cationic liposomes in gene therapy 基因治疗中阳离子脂质体的制备、表征及细胞转染
Pub Date : 2019-04-17 DOI: 10.5920/BJPHARM.618
Hassan Elsana, J. Carr-wilkinson, A. Faheem, A. Elkordy
Cationic lipid-mediated gene transfer is one of the most commonly used non-viralvectors. It has been shown to be a safe and effective carrier. However, its use ingene delivery was hampered by its low transfection efficiency and stability.DOTAP, DOPE, cholesterol (CHO) and carboxymethyl-β-cyclodextrin (CD) wereused to prepare cationic liposomes. Cationic liposomes were prepared using both,thin film hydration and a microfluidic method. Formulation stability wasevaluated using liposome size, zeta potential and polydispersity index (PDI).Promega QuantiFluor® ONE dsDNA System was used to investigate theencapsulation efficiency. COS7 and SH-SY5Y cell lines were used to determinetransfection efficiency. Results show that carboxymethyl-β-cyclodextrin increasedencapsulation efficiency by 15.5% and 8% using NanoAssemblr® and rotaryevaporator, respectively compared to liposomes without CD. The addition ofcarboxymethyl-β-cyclodextrin to cationic liposomes resulted in an increase intransfection efficiency in both cell lines.B
阳离子脂质介导的基因转移是最常用的非病毒载体之一。它已被证明是一种安全有效的载体。然而,其转染效率和稳定性较低,阻碍了其在基因传递中的应用。用DOTAP、dopo、胆固醇(CHO)和羧甲基β-环糊精(CD)制备阳离子脂质体。采用薄膜水合和微流控两种方法制备阳离子脂质体。通过脂质体大小、zeta电位和多分散性指数(PDI)评价制剂的稳定性。采用Promega QuantiFluor®ONE dsDNA系统考察包封效率。以COS7和SH-SY5Y细胞株检测转染效率。结果表明,与不含CD的脂质体相比,在nanoassembly®和旋转汽化器中,羧甲基β-环糊精的包封效率分别提高了15.5%和8%。在阳离子脂质体中添加羧甲基β-环糊精可以提高两种细胞系的感染效率。B
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引用次数: 1
Effects of preparation methods on the characteristics of niosomes 制备方法对纳米体特性的影响
Pub Date : 2019-04-17 DOI: 10.5920/BJPHARM.616
A. Elkordy, C. Chaw, L. Yeo
Niosomes are colloidal vesicles that capable of encapsulating drugs as a carrier for drug delivery system. They are formed by self-assembly of a non-ionic surfactant with cholesterol and co-surfactant. In this work, cinnarizine-containing niosomes comprised of sorbitan monostearate (Span® 60), cholesterol and co-surfactant (Cremophor® ELP, Cremophor® RH40 or Solutol® HS15) were prepared using conventional thin film hydration and microfluidic methods. Effects on characteristics of niosomes with the presence of poorly water-soluble drug, cinnarizine in the niosomal formulations prepared using different methods and incorporation of different co-surfactants were studied and compared for their particle size, polydispersity index (PDI) and encapsulation efficiency. Dynamic light scattering was employed for particle size measurements and drug loading studies were analysed using high performance liquid chromatography (HPLC). The morphology of niosomes was characterized using optical light microscopy.
乳小体是一种能够包封药物的胶状囊泡,是药物递送系统的载体。它们是由非离子表面活性剂与胆固醇和助表面活性剂的自组装形成的。本研究采用传统的薄膜水合和微流控方法制备了由山山糖单硬脂酸酯(Span®60)、胆固醇和辅助表面活性剂(Cremophor®ELP、Cremophor®RH40或Solutol®HS15)组成的含肉桂碱的纳米体。研究了不同制备方法及不同表面活性剂掺入量对乳质体性能的影响,并比较了其粒径、多分散性指数(PDI)和包封效率。采用动态光散射法测定颗粒大小,并采用高效液相色谱法分析载药量。光镜下观察了纳米体的形态。
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引用次数: 2
Fabrication and physicochemical characterisation of novel pimozide loaded PLGA nanoparticles 新型吡莫胺负载PLGA纳米颗粒的制备及物理化学表征
Pub Date : 2019-04-17 DOI: 10.5920/BJPHARM.615
N. Uddin, A. Elkordy, A. Faheem
Cancer has always been a big concern for human health. There is always an increased need for fabrication of newer drugs or repurposing the existing drugs to treat cancer. Apart from being an antipsychotic agent, pimozide has already shown its anticancer activity against various cancers in several studies. The aim of the present study was to fabricate pimozide loaded PLGA nanoparticles and hence characterize them. Single emulsion and microfluidic techniques were used to prepare nanoparticles. Physicochemical properties such as particles size, shape, surface charge, and encapsulation efficiency were investigated. Results showed that the nanoparticles were in average size distribution of 200-300 nm, spherical in shape and negatively charged. Additionally, high encapsulation efficiency (50-89%) makes these nanoparticles potential drug delivery systems to target cancer cells.
癌症一直是人类健康的一大问题。制造新药或重新利用现有药物来治疗癌症的需求总是在增加。除了作为一种抗精神病药物,吡莫齐在几项研究中已经显示出对各种癌症的抗癌活性。本研究的目的是制备吡莫胺负载的PLGA纳米颗粒,并对其进行表征。采用单乳液和微流控技术制备纳米颗粒。研究了颗粒大小、形状、表面电荷和包封效率等理化性质。结果表明,纳米颗粒的平均粒径分布在200 ~ 300 nm之间,呈球形,带负电荷。此外,高封装效率(50-89%)使这些纳米颗粒成为靶向癌细胞的潜在药物递送系统。
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引用次数: 0
EPTRI – European Paediatric Translational Research Infrastructure. Bridging the gaps of the paediatric excellence medicine EPTRI -欧洲儿科转化研究基础设施。弥合儿科卓越医学的差距
Pub Date : 2019-04-17 DOI: 10.5920/BJPHARM.614
D. Bonifazi, Mariangela Lupo, Valeria Pignataro, I. Toni, H. Kubová, C. Tuleu, M. Lavitrano, A. Ceci
Development of age appropriate medicines for children is one of the major challenge of our century. Historically, research of new paediatric drugs has been neglected due to poor industrial interest and limited public and private investments. The ID-EPTRI project is aimed to bridge the existing gaps in the paediatric medicine that stop the progress, from the early stage drug development phases to be translated into paediatric use of medicines, through a new paediatric Research Infrastructure. To reach this goal, EPTRI has developed and disseminated a survey in order to identify the gaps and map the competences of the excellence of the paediatric research in pan-European countries that will be the potential service providers of the new Research Infrastructure. EPTRI will network all the available competences and technologies useful to the paediatric research, creating an open science space allowing top-level researchers to work together.
开发适合儿童年龄的药物是本世纪的主要挑战之一。从历史上看,由于工业兴趣差和公共和私人投资有限,新的儿科药物的研究一直被忽视。ID-EPTRI项目旨在通过新的儿科研究基础设施弥合儿科医学中现有的差距,这些差距阻碍了从早期药物开发阶段转化为儿科药物使用的进展。为了实现这一目标,EPTRI制定并传播了一项调查,以确定差距,并绘制泛欧国家儿科研究卓越能力的地图,这些国家将成为新的研究基础设施的潜在服务提供者。EPTRI将把所有对儿科研究有用的能力和技术联网,创造一个开放的科学空间,允许顶级研究人员一起工作。
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引用次数: 2
期刊
British Journal of Pharmacy
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