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The environmental burden of inhalation 吸入造成的环境负担。
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.1016/j.ejps.2024.106893
A.H. de Boer
Inhalation systems, mostly metered dose inhalers (MDIs) and dry powder inhalers (DPIs), are currently submitted to a critical assessment for their carbon footprint (CF) and environmental impact. They are related to greenhouse gas (GHG) emissions and they produce waste of used devices with withheld drug residues and unused doses. However, with estimated contributions to anthropogenic GHG-emissions of 0.03 % for MDIs and 0.0012 % for DPIs globally, it may not be expected that mitigating the GHG emissions from inhalers will have a meaningful effect on the current climate change and global warming, notwithstanding that nationally these percentages may be somewhat higher, depending on the ratio of MDIs to DPIs and the total national CF. MDIs are particularly the preferred type of inhalers over DPIs in the USA and UK with ratios of 9: 1 and 7: 3 respectively. In such countries, a partial switch from MDIs to DPIs is to be recommended, providing that such a switch does not jeopardize the therapy. Using renewable energy only for the production and waste management of DPIs will make this type of inhaler almost climate neutral. A greater concern exists about inhaler waste, more particularly about the residual drug and unused doses in discarded devices. Inhalers contribute <0.02 % to global plastic waste annually and most plastic inhalers end in the domestic waste bin and not as litter polluting the environment with plastic. However, they do contain retained drug and unused doses, whereas even full inhalers are disposed. Because globally most municipal waste (70 %) ends up in dumps and landfills, leakage of the drugs into the soil and surface waters is a serious problem. It pollutes drinking water and endangers species and biodiversity. Therefore, a good collection system and an adequate waste management program for used inhalers seems to be the most meaningful measure to take for the environment, as this will stop inhalers and drugs from putting ecosystems at risk.
吸入系统,主要是计量吸入器(MDI)和干粉吸入器(DPI),目前正接受碳足迹(CF)和环境影响的严格评估。它们与温室气体(GHG)排放有关,并且会产生带有药物残留和未使用剂量的废旧设备。然而,据估计,计量吸入器和干粉吸入器分别占全球人为温室气体排放的 0.03% 和 0.0012%,因此,减少吸入器的温室气体排放可能不会对当前的气候变化和全球变暖产生有意义的影响,尽管根据计量吸入器和干粉吸入器的比例和国家总碳足迹,这些百分比在全国范围内可能会更高一些。在美国和英国,计量吸入器比干粉吸入器更受青睐,比例分别为 9:1 和 7:3。在这些国家,建议从计量吸入器部分转为干粉吸入器,前提是这种转换不会危及治疗。仅在干粉吸入器的生产和废物管理中使用可再生能源,将使这种吸入器几乎不影响气候。对于吸入器废物,尤其是废弃装置中的残留药物和未使用剂量,存在着更大的担忧。吸入器每年在全球塑料废物中所占的比例不到 0.02%,而且大多数塑料吸入器最终都会被扔进家庭垃圾桶,而不会成为污染环境的塑料垃圾。然而,吸入器中确实含有残留的药物和未使用的剂量,而即使是完整的吸入器也会被丢弃。由于全球大多数城市垃圾(70%)都被丢弃在垃圾场和填埋场,因此药物渗漏到土壤和地表水中是一个严重的问题。它污染饮用水,危害物种和生物多样性。因此,为使用过的吸入器建立良好的收集系统和适当的废物管理计划似乎是对环境最有意义的措施,因为这将阻止吸入器和药物危及生态系统。
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引用次数: 0
The cyclization of human salivary Histatin 1 via click chemistry for skin wound healing 人唾液组蛋白1环化对皮肤创面愈合的影响。
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.1016/j.ejps.2024.106978
Xiaoxuan Lei , Yu Yang , Judun Zheng , Liwen Liang , Liuhanghang Cheng , Yunqing Dong , Biying Qiu , Floris J. Bikker , Tymour Forouzanfar , Biao Cheng , Gang Wu , Bin Yang
Acute skin injuries can result in the breakdown of the skin barrier, heightening the risk of infections and complications. Histatin 1 (Hst1) promotes the adhesion, spreading, and migration of various skin-related cells, thus encouraging wound healing. However, Hst1 is extensively degraded upon exposure to wound exudates. Cyclized hst1 (Cyclic-hst1) has a much higher resistance to protease degradation than Hst1, thus increasing its stability and half-life. Herein, we synthesized Cyclic-hst1 via a click reaction and explored its efficacy in wound healing via cellular and animal experiments. Cyclic-hst1, at a 100-fold lower concentration than Hst1, effectively promoted acute skin wound healing. In addition, Cyclic-hst1 had a superior effect to Hst1 in terms of its anti-inflammatory, re-epithelialization, collagen deposition, and angiogenic effects, thus significantly promoting skin wound healing. Consequently, Cyclic-hst1 could represent a favorable treatment to manage acute skin wound healing, providing a promising experimental basis for clinical transformation and application.
急性皮肤损伤可导致皮肤屏障的破坏,增加感染和并发症的风险。组蛋白1 (Hst1)促进各种皮肤相关细胞的粘附、扩散和迁移,从而促进伤口愈合。然而,Hst1暴露于伤口渗出液后被广泛降解。环化hst1 (Cyclic-hst1)具有比hst1更高的蛋白酶降解抗性,从而提高了其稳定性和半衰期。本研究通过点击反应合成了Cyclic-hst1,并通过细胞和动物实验探讨了其在伤口愈合中的作用。Cyclic-hst1浓度比Hst1低100倍,可有效促进急性皮肤创面愈合。此外,Cyclic-hst1在抗炎、再上皮、胶原沉积、血管生成等方面均优于Hst1,显著促进皮肤创面愈合。因此,Cyclic-hst1可能是治疗急性皮肤创面愈合的良好药物,为临床转化和应用提供了良好的实验基础。
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引用次数: 0
Real-life dosing conditions in older adults and geriatric patients in Poland – An international questionnaire study to investigate the regional differences in drug intake behaviour in the older population 波兰老年人和老年患者的真实给药条件——一项调查老年人口药物摄入行为地区差异的国际问卷研究。
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-30 DOI: 10.1016/j.ejps.2024.107001
Dorota Sarwinska , Marta Miller , Jagoda Arendt , Michał Markiewicz , Katarzyna Michta , Michael Grimm , Łukasz Balwicki , Werner Weitschies
Older people represent approximately 20% of the Polish population and are the primary population using medications. Behaviours connected with drug intake (such as dosage form modifications, type and amount of fluid and/or food accompanying administration) are crucial for drug efficacy and avoidance of adverse effects. The presented study had three research aims; firstly, to investigate the real-life drug administration process among older adults and geriatric patients in Poland. Secondly, to compare data from Poland with data from a previous study performed in Germany, based on the same questionnaire. Thirdly, to discuss the potential influence of dosing conditions on the behaviour of orally administered medications (especially drug absorption) and identify potential problems with drug intake itself. This questionnaire-based study was conducted in the form of in-person interviews led by research team members. In this study, 174 participants, aged 65–94 years old were recruited from three settings in the Pomeranian region of Poland: home setting, nursing home and hospital. In Poland, the preferred method of medication intake was administration of all medications simultaneously. Patients were taking their medications most often directly after food ingestion, which commonly consisted of bread with butter, ham or cheese and black tea. The most common fluid for drug administration was either a few sips or 100 mL of non-carbonated water (mineral or tap water) as well as black tea. Dividing tablets (defined as splitting tablets in parts) was the most common modification. There were many similarities in the way of administering medications between the Polish and German older populations, specifically the use of non-carbonated water as the most common fluid for medication intake as well as bread as the main ingredient of breakfast and dinner. The biggest difference between populations was the choice of black tea as a medium for medication intake much more frequently in the Polish population than the German (who also preferred mint, herbal and fruit teas), and using a smaller volume of fluid. The presented study gives insight into the medication intake process in the older Polish population from the Pomeranian region in North Poland in comparison to the German population from the Pomeranian region in North East Germany. The results may help to identify factors that could decrease medication efficacy and safety, which is crucial, especially for the older population. Furthermore, the collected data may be useful for in vitro or in silico simulations to enhance drug development based on real-life data.
老年人约占波兰人口的20%,是使用药物的主要人群。与药物摄入有关的行为(如剂型改变、随服液体和/或食物的种类和数量)对药物疗效和避免不良反应至关重要。本研究有三个研究目的;首先,调查波兰老年人和老年患者的现实用药过程。其次,将波兰的数据与先前在德国进行的基于相同问卷的研究的数据进行比较。第三,讨论给药条件对口服药物行为(特别是药物吸收)的潜在影响,并确定药物摄入本身的潜在问题。本研究以问卷调查为基础,由研究小组成员带领进行面对面访谈。在这项研究中,174名年龄在65-94岁的参与者从波兰波美拉尼亚地区的三个环境中招募:家庭环境、养老院和医院。在波兰,首选的药物摄入方法是同时服用所有药物。患者通常在食物摄入后直接服药,通常包括黄油面包、火腿或奶酪和红茶。最常见的给药液体是几口或100毫升的非碳酸水(矿泉水或自来水)以及红茶。将片剂分开(定义为将片剂分成几部分)是最常见的修改。波兰和德国老年人口的用药方式有许多相似之处,特别是使用非碳酸水作为最常见的药物摄入液体,以及面包作为早餐和晚餐的主要食材。人群之间最大的差异是,波兰人群比德国人更频繁地选择红茶作为药物摄入的媒介(德国人也喜欢薄荷茶、草药茶和水果茶),而且使用的液体量更小。本研究对波兰北部波美拉尼亚地区的老年波兰人口与德国东北部波美拉尼亚地区的德国人口的药物摄入过程进行了比较。研究结果可能有助于确定可能降低药物疗效和安全性的因素,这一点至关重要,尤其是对老年人而言。此外,收集的数据可能对体外或计算机模拟有用,以增强基于真实数据的药物开发。
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引用次数: 0
Novel thermosensitive small multilamellar lipid nanoparticles with promising release characteristics made by dual centrifugation 双离心法制备具有良好释放特性的新型热敏小多层脂质纳米颗粒。
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-25 DOI: 10.1016/j.ejps.2024.106999
Jonas K. Koehler , Stefanie Schmager , Johannes Schnur , Lars Gedda , Katarina Edwards , Heiko Heerklotz , Ulrich Massing
Thermosensitive liposomes (TSLs) have great potential for the selective delivery of cytostatic drugs to the tumor site with greatly reduced side effects. Here we report the discovery and characterization of new thermosensitive small multilamellar lipid nanoparticles (tSMLPs) with unusually high temperature selectivity. Furthermore, the temperature-dependent release of the fluorescent marker calcein from tSMLPs is enhanced by human serum albumin. tSMLPs can easily be prepared through dual centrifugation (DC) at very high lipid concentrations using dipalmitoyl and distearoyl phosphatidylcholine (DPPC, DSPC) and the phospholipid dipalmitoyl-sn-glycero-phosphatidyldiglycerol (DPPG2). The new particles have a hydrodynamic diameter of about 175 nm and a narrow size distribution (PDI 0.02). tSMLPs consist of multiple lipid membranes, which become increasingly closer packed towards the particle center, and have no visible aqueous core. The particles are highly stable due to strong hydrogen bond-based membrane interactions mediated by DPPG2. tSMLPs can be used as carriers for water-soluble drugs (EE 25 %) entrapped within the interlamellar spaces. Based on biophysical (DSC, DLS and ITC) and morphological (cryo-EM) studies, a hypothesis is presented to explain the structural basis underlying the high temperature selectivity, as well as the unusual morphology of the new thermosensitive lipid nanoparticles.
热敏脂质体(Thermosensitive liposomes, TSLs)具有将细胞抑制药物选择性递送至肿瘤部位的巨大潜力,且副作用大大降低。在这里,我们报道了具有异常高温选择性的新型热敏小多层脂质纳米颗粒(tSMLPs)的发现和表征。此外,tSMLPs中荧光标记物钙黄蛋白的温度依赖性释放被人血清白蛋白增强。利用双棕榈酰和二硬脂酰磷脂酰胆碱(DPPC, DSPC)和磷脂双棕榈酰-sn-甘油-磷脂酰二甘油酯(DPPG2),可以在非常高的脂质浓度下通过双离心(DC)制备tSMLPs。新颗粒的水动力直径约为175 nm,尺寸分布较窄(PDI为0.02)。tSMLPs由多个脂质膜组成,这些脂质膜越来越靠近颗粒中心,并且没有可见的水核。由于DPPG2介导的强氢键基膜相互作用,颗粒高度稳定。tsmlp可作为层间空间内水溶性药物(EE 25%)的载体。基于生物物理(DSC, DLS和ITC)和形态学(cro - em)研究,提出了一种假设来解释高温选择性的结构基础,以及新的热敏脂质纳米颗粒的不同寻常的形态。
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引用次数: 0
3D printed extended-release hydrochlorothiazide tablets 3D打印氢氯噻嗪缓释片。
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-24 DOI: 10.1016/j.ejps.2024.106998
Teodora Tasevska , Ivana Adamov , Nikola Geskovski , Svetlana Ibrić , Katerina Goracinova , Maja Simonoska Crcarevska
In this study 3D printed tablets (printlets) with extended release of hydrochlorothiazide (HHT) as model active ingredient were designed and developed. Four formulations, F0.1SSE, F1SSE, F0.1DLP and F1DLP, have been manufactured and characterized, using non-typical semi-solid extrusion (SSE) with UV light solidification and digital light processing (DLP) techniques. Obtained rheological studies pointed out to F1SSE and F1DLP as more suitable for SSE and DLP printing, respectively. Photopolymerization process between photopolymer (PEGDA) and photoinitiator (DPPO; 0.1% and 1%) was investigated using FTIR, with PCA modeling utilized to analyze spectral variations over time and estimate crosslinking kinetics. SSE printlets averaged ∼6.5 mm in diameter, ∼3 mm in height and ∼110 mg in mass, while DLP printlets averaged ∼8.5 mm in diameter, ∼2.5 mm in height, with masses of ∼170 mg (F0.1DLP) and ∼220 mg (F1DLP). All four formulations complied to the requirements of European pharmacopeia for uniformity of dosage units of single dose preparations. In vitro release studies indicated extended-release profiles in both 0.1M Hydrochloric acid (HCl) and phosphate buffer pH 6.8 for SSE and DLP printlets. The release kinetics of HHT from the printlets were modeled to fit First order, Higuchi, Korsmeyer-Peppas and Hixson-Crowell equations and the most probable ones were determined based on the R2 values and Akaike information criterion. FTIR and Raman spectroscopic analyses of printlets confirmed the presence of characteristic peaks from both, HHT and excipients, as well as modifications in bonds due to the photopolymeric reaction.
本研究以氢氯噻嗪(HHT)缓释为模型有效成分,设计并开发了3D打印片剂。采用紫外光固化非典型半固态挤压(SSE)和数字光处理(DLP)技术制备了F0.1SSE、F1SSE、F0.1DLP和F1DLP四种配方,并对其进行了表征。得到的流变学研究表明,F1SSE和F1DLP分别更适合于SSE和DLP印刷。光聚合物(PEGDA)与光引发剂(DPPO)的光聚合过程0.1%和1%)进行了FTIR研究,利用PCA模型分析了光谱随时间的变化并估计了交联动力学。SSE打印件的平均直径为~ 6.5 mm,高度为~ 3 mm,质量为~ 110 mg,而DLP打印件的平均直径为~ 8.5 mm,高度为~ 2.5 mm,质量为~ 170 mg (F0.1DLP)和~ 220 mg (F1DLP)。四种制剂均符合欧洲药典对单剂量制剂剂量单位均匀性的要求。体外释放研究表明,SSE和DLP在0.1M盐酸(HCl)和pH为6.8的磷酸盐缓冲液中均有缓释。采用一阶方程、Higuchi方程、Korsmeyer-Peppas方程和Hixson-Crowell方程建立HHT的释放动力学模型,并根据R2值和Akaike信息准则确定最可能的HHT释放动力学。FTIR和拉曼光谱分析证实了HHT和赋形剂的特征峰的存在,以及由于光聚合反应引起的键的修饰。
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引用次数: 0
The impact of active substance on the adhesiveness of medicated patches containing liquid additives 活性物质对含液体添加剂药贴黏附性的影响。
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-23 DOI: 10.1016/j.ejps.2024.106997
Bartosz Maciejewski , Barbara Mikolaszek , Joanna Dłabiszewska , Małgorzata Sznitowska
Adhesiveness of dermal patches can be modified in the presence of active substances. The effect is more complex when liquid components are also present in the matrix. Commercial grade pressure sensitive adhesive (PSA) polyacrylates (three types) and silicones (two types) were used to prepare adhesive matrices and liquid additives were propylene glycol, polyoxyethylene glycol, isopropyl myristate, triacetin, triethyl citrate or low viscosity silicone oil. Drug-in-adhesive patches were prepared with model active substances (5% w/w): indomethacin or cytisine. The effect of the suspended or dissolved drug on adhesiveness was evaluated with probe tack test and 90° peel test. Most of the acrylate patches loaded with dissolved indomethacin showed acceptable level of adhesiveness. In case of cytisine, suspension type patches were often formed and only in some patches sufficient adhesiveness was retained. Adhesion of silicone based matrices was altered profoundly by the simultaneous drug and excipient addition. Only one matrix with indomethacin and silicone oil showed acceptable quality in both tack and peel tests (S1, Bio-PSA MD7–4502). In the course of the data analysis of the adhesiveness, the relevance of film formation mechanism was noted. It was observed, that if the film formation occurs by solvent evaporation in patches where drug particles are suspended, the impact of the particles on adhesion might be greater than in the case of patches with the dissolved drug. It was concluded, that a choice of a suitable polymer-liquid mixture for a particular active substance requires an experimental work in case of an adhesive properties adjustment. Due to complex physicochemical interaction between the components reliable theoretical predictions are considered as questionable.
在活性物质的存在下,皮肤贴片的粘附性可以被改变。当基质中也存在液体成分时,效果更为复杂。采用工业级压敏胶(PSA)聚丙烯酸酯(三种类型)和有机硅(两种类型)制备胶粘剂基质,液体添加剂为丙二醇、聚氧乙烯醇、肉豆酸异丙酯、三乙酸酯、柠檬酸三乙酯或低粘度硅油。以吲哚美辛或胞氨酸为模型活性物质(5% w/w)制备药物贴。用探针粘连试验和90°剥离试验评价悬浮剂和溶解剂对粘连性的影响。大多数丙烯酸酯贴片加载溶解吲哚美辛显示出可接受的粘附水平。在胞氨酸的情况下,经常形成悬浮型贴片,只有部分贴片保留了足够的粘附性。药物和赋形剂的同时加入使硅基基质的粘附性发生了深刻的变化。只有一种含有吲哚美辛和硅油的基质在粘接和剥离试验中均表现出可接受的质量(S1, Bio-PSA MD7-4502)。在黏附性的数据分析过程中,注意到成膜机理的相关性。我们观察到,如果在药物颗粒悬浮的贴片中通过溶剂蒸发形成薄膜,那么颗粒对粘附的影响可能比溶解药物的贴片更大。结论是,在粘合剂性能调整的情况下,为特定活性物质选择合适的聚合物-液体混合物需要进行实验工作。由于组分之间复杂的物理化学相互作用,可靠的理论预测被认为是有问题的。
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引用次数: 0
Modular self-emulsifying drug delivery platform to enhance cellular uptake activity in triple-negative breast cancer 模块化自乳化给药平台增强三阴性乳腺癌细胞摄取活性。
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-20 DOI: 10.1016/j.ejps.2024.106993
Nandini Gandhi, Shail Modi, Shailvi Soni, Terrick Andey
Triple-negative breast cancer (TNBC) presents with resistance phenotypes to certain therapies, such as cisplatin, often requiring higher dosing, with associated acquired tumor resistance, renal toxicity, and variable patient responses. A self-emulsifying drug delivery (SEDD) formulation approach was proposed to overcome the limitations of cisplatin in TNBC, focusing on improving intracellular cisplatin and control siRNA uptake as a proof-of-principle of dual drug delivery. Four SEDD formulations were prepared and optimized for cisplatin (o/w) emulsion and FITC-siRNA (w/o) emulsion using pseudo-ternary phase diagrams to facilitate the formation of water-in-oil-water (w/o/w) emulsions. Formulations were characterized by size, polydispersity (PDI), and surface charge and tested in vitro. Cellular uptake via triplex staining of drug-loaded SEDDs was investigated. SEDDs showed enhanced internalization and promoted selective TNBC cellular uptake. The current study is a proof-of-principle for the successful co-delivery of cisplatin (small molecule) and siRNA (large molecule) via the SEDDs platform.
三阴性乳腺癌(TNBC)表现出对某些治疗(如顺铂)的耐药表型,通常需要更高的剂量,并伴有获得性肿瘤耐药、肾毒性和不同的患者反应。提出了一种自乳化给药(SEDD)配方方法来克服顺铂在TNBC中的局限性,重点是改善细胞内顺铂和控制siRNA摄取,作为双重给药的原理证明。采用拟三元相图对顺铂(o/w)乳化液和FITC-siRNA (w/o)乳化液制备了四种SEDD配方,并对其进行了优化,以促进油包水(w/o/w)乳化液的形成。采用粒径、多分散性(PDI)、表面电荷等指标对其进行表征,并进行体外实验。通过三重染色研究了载药SEDDs的细胞摄取。SEDDs显示增强内化和促进选择性TNBC细胞摄取。目前的研究是通过SEDDs平台成功共递送顺铂(小分子)和siRNA(大分子)的原理证明。
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引用次数: 0
A non-linear modelling approach to predict the dissolution profile of extended-release tablets 用非线性模型方法预测缓释片的溶出度
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-28 DOI: 10.1016/j.ejps.2024.106976
Ana Sofia Lourenço , Tobias Schuster , João Almeida Lopes , Annette Kirsch
This study proposes a novel non-linear modelling approach to predict the dissolution profiles of extended-release tablets, by combining a full-factorial design, curve fitting to the dissolution profiles, and artificial neural networks (ANN), with linear regression methods, partial least squares (PLS) and multiple linear regression (MLR) as benchmarks.
Hydroxypropylmethylcellulose (HPMC) and carboxymethylcellulose (CMC) grades, active pharmaceutical ingredient (API) lubrication, and compression force were chosen as DoE factors. The resulting batches were tested to obtain their corresponding dissolution profile, and a first-order dissolution equation was fitted to each profile. ANN, PLS and MLR were used to model and predict the tablet-specific constant k which then served to simulate dissolution profiles.
This study demonstrates how non-linear methods, specifically ANN, outperform traditional linear models in predicting the complex interactions affecting drug release from extended-release formulations.
本研究提出了一种新的非线性建模方法来预测缓释片的释放度分布,该方法结合全因子设计、曲线拟合和人工神经网络(ANN),以线性回归方法、偏最小二乘法(PLS)和多元线性回归(MLR)为基准。选择羟丙基甲基纤维素(HPMC)和羧甲基纤维素(CMC)等级、活性药物成分(API)、润滑和压缩力作为DoE因素。对所得批次进行测试,得到相应的溶出谱,并对每个谱拟合一阶溶出方程。利用人工神经网络、PLS和MLR模型预测片剂特异性常数k,然后用于模拟溶出曲线。本研究展示了非线性方法,特别是人工神经网络,如何在预测影响缓释制剂药物释放的复杂相互作用方面优于传统的线性模型。
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引用次数: 0
Interaction of preservatives with contact materials during filling and storage of parenteral liquid formulations 肠外液体制剂在灌装和储存过程中防腐剂与接触材料的相互作用。
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-26 DOI: 10.1016/j.ejps.2024.106971
Paul Gottschalk , Patrick Schlossbauer , Lucas Schleicher, Katrin Lindner, Ingo Presser, Maximilian Wittmann
Silicone tubing is a frequently used material in pharmaceutical filling processes for parenteral formulations, as its characteristics like flexibility, chemical resistance and easy handling make it particularly suitable for these purposes. This study investigated the time-dependent interaction of phenol and m-cresol with silicone tubing and other broadly applied contact materials used during the filling and transport processes of parenteral formulations. Phenol losses could be observed after incubation in silicone tubing, depending on the inner diameter (ID). This has been demonstrated for process interruptions of up to 120 min. A loss of 40 % could be observed for a small ID of 3.2 mm which can be found close to filling needles, and up to 12 % for larger tubes with an ID of 9.5 mm commonly used for sterile filtration and transport processes. Analysis of tubes with varying ID revealed a linear relationship between the decrease of phenol and the surface-to-volume ratio. m-cresol showed an even more pronounced loss in silicone tubing. Fluorinated polymers and thermoplastic elastomers were also analyzed, and no loss of phenol and m-cresol was observed. Pumping tests revealed that shear forces in peristaltic pumps led to strong particle formation in selected tubing. A strong increase in particle concentration was observed in thermoplastic elastomers, particularly in PharMed® BPT tubing. In contrast, the C-Flex® tubing demonstrated minimal particle formation. Fluorinated polymers are not compatible with peristaltic pumps, which is why they were not analyzed regarding pumpability. Although silicone tubes are not impervious to preservatives such as phenol, they did not generate particles when pumped.
硅胶管是肠外制剂灌装过程中经常使用的一种材料,因为它具有柔韧性、耐化学腐蚀性和易于处理等特点,特别适用于这些用途。本研究调查了苯酚和间甲酚与硅胶管及其他广泛应用于肠外制剂灌装和运输过程的接触材料之间随时间变化的相互作用。根据硅胶管的内径(ID),在硅胶管中培养后可观察到苯酚的损失。这已在长达 120 分钟的工艺中断中得到证实。内径为 3.2 毫米的小硅胶管(可在灌装针头附近找到)的苯酚损失率为 40%,而内径为 9.5 毫米的大硅胶管(常用于无菌过滤和运输过程)的苯酚损失率则高达 12%。对不同内径的管子进行的分析表明,苯酚的减少量与表面体积比之间呈线性关系。对含氟聚合物和热塑性弹性体也进行了分析,没有发现苯酚和间甲酚的损失。泵送测试表明,蠕动泵中的剪切力导致选定管材中形成大量颗粒。在热塑性弹性体中,尤其是在 PharMed® BPT 管材中,观察到颗粒浓度大幅增加。相比之下,C-Flex® 管中的颗粒形成极少。含氟聚合物与蠕动泵不兼容,因此没有对它们的泵送性进行分析。虽然硅胶管不耐受苯酚等防腐剂,但在泵送时也不会产生颗粒。
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引用次数: 0
Exploiting a type III interferon response to improve chemotherapeutic safety and efficacy 利用III型干扰素反应提高化疗安全性和有效性。
IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-26 DOI: 10.1016/j.ejps.2024.106974
Scott G. Tilden , Madison H. Ricco , Emily A. Hemann , Thomas J. Anchordoquy
Immune reactions to nanomedicines can be detrimental to the patient and compromise efficacy. However, our recent study characterizing the effects of a type III interferon (IFN-λ) response to lipid nanoparticles complexed with nucleic acids (lipoplexes) suggests that an IFN-λ pretreatment can increase tumor accumulation while decreasing off-target distribution of chemotherapeutic nanomedicines. This project provides a direct follow-up to our previously published works by clarifying 1) which cell type(s) can produce IFN-λ in response to lipoplexes and how the effects of IFN-λ may be propagated in humans. Additionally, we demonstrate 2) that an IFN-λ pretreatment is also capable of altering the accumulation profile of chemotherapeutic small molecules like doxorubicin. Finally, we determined 3) that the subcutaneous administration route for an IFN-λ pretreatment is the most efficacious, and 4) that an IFN-λ pretreatment can significantly increase the survival time of mice receiving Doxil® in a murine CT26 tumor model. With several chemotherapeutic nanomedicines available in the clinic and an IFN-λ product recently completing late phase clinical trials, this study provides the model for a novel anti-cancer treatment regime that can be rapidly translated to the clinic and improve the efficacy of contemporary treatment protocols.
对纳米药物的免疫反应可能对患者有害并影响疗效。然而,我们最近的研究表征了III型干扰素(IFN-λ)对脂质纳米颗粒与核酸(脂质复合物)的反应,表明IFN-λ预处理可以增加肿瘤积累,同时减少化疗纳米药物的脱靶分布。该项目为我们之前发表的工作提供了直接的后续研究,阐明了1)哪种细胞类型可以产生IFN-λ以响应脂肪丛,以及IFN-λ的作用如何在人类中传播。此外,我们证明了2)IFN-λ预处理也能够改变化疗小分子(如阿霉素)的积累谱。最后,我们确定了3)IFN-λ预处理的皮下给药途径是最有效的,4)IFN-λ预处理可以显著增加Doxil®小鼠在小鼠CT26肿瘤模型中的存活时间。随着几种化疗纳米药物在临床上可用,IFN-λ产品最近完成了后期临床试验,本研究为一种新的抗癌治疗方案提供了模型,该方案可以快速转化为临床并提高当代治疗方案的疗效。
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European Journal of Pharmaceutical Sciences
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