温敏性高分子材料对药物释放的研究

 目的合成一系列温度敏感性(温敏性)凝胶，测定其低临界溶液温度(相变温度)。筛选出具有与人体体温相近的相变温度的凝胶，并使其可以作为药物的载体。方法采用自由基水溶液聚合的方法合成共聚物，然后用聚合物承载药物并用高效液相色谱法测其不同温度下药物的释放情况。结果温敏性凝胶可以作为自控式或缓释药用辅料，但如果相变温度低于人体体温，则无实际应用意义。采用共聚合的方法，确可提高凝胶的相变温度。不同条件下合成的共聚物有着不同的相变温度，药物释放情况也不同。结论调整不同组成比例及交联剂的浓度，可使此类凝胶作为自控式或缓释药用辅料成为可能。     

海藻酸钠在药物制剂中的研究进展

海藻酸钠是从海带或海藻中提取的天然多糖类化合物，作为缓释制剂辅料广泛应用于片剂、微九、微蠢、脂质体、纳米粒等缓释制剂中，现综述近年来海藻酸钠作为辅料的影响因素及在缓释制剂中的应用研究进展。     

Beta-cyclodextrin as a suitable solubilizing agent for in situ absorption study of poorly water-soluble drugs

To evaluate the intestinal permeability of poorly water-soluble compounds, it is of importance to completely dissolve them in a medium and to avoid precipitation during experiments. This study was undertaken to find an agent possessing a high-solubilizing capacity and exhibiting minimal modulating impact on membrane integrity and absorption systems such as passive diffusion and carrier-mediated permeation. Phenytoin dissolution was compared in the presence of seven solubilizing agents at concentrations of 1, 2, or 5% using a centrifugation method. The capacity to dissolve phenytoin was great in β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin, followed by Tween 80. Those of methanol, dimethyl sulfoxide, dimethyl acetoamide, and polyethylene glycol 400 were much lower than expected. One percent β-CD did not alter the absorption of fluorescein isothiocyanate-dextran 4000 or the release of protein and lactate dehydrogenase into in situ loop contents, suggesting that 1% β-CD had no significant impact on the integrity of the intestinal membrane. One percent β-CD also did not alter the absorption of caffeine, ceftibuten, or rhodamine 123 from in situ jejunal loops, indicating no interference with passive diffusion and active transports mediated by a peptide transporter and P-glycoprotein. In conclusion, 1% β-CD is a suitable solubilizing agent for evaluating in situ intestinal absorption of poorly water-soluble compounds.     

差热分析法考察辅料对法莫替丁的影响

目的：考察制剂中法莫替丁与辅料之间的相溶情况,为辅料筛选的合理性提供科学依据。方法：通过差热分析法（DTA）分别进行了热图谱扫描及热谱特征的分析。结果：各种辅料之间以及法莫替丁与所有的4种辅料具有很好的可混溶性。结论：制剂中的法莫替丁与辅料间无物理或化学变化,辅料对药物无不利影响。     

Structural and Dynamic Properties of Crystalline and Amorphous Phases in Raffinose-Water Mixtures

Purpose. To obtain an improved characterisation of the raffinose-water solid-solid and solid-liquid state diagram, and to study the thermophysical behaviour of the solid amorphous phase. This information is expected to shed light on the potential of rafTinose as a pharmaceutical excipient, for stabilising labile preparations at high temperatures. Methods. X-ray diffraction, scanning electron microscopy, polarised-light microscopy, differential scanning calorimetry (DSC) and thermo-gravimetric analysis (TGA) were applied to study raffinose pentahydrate and its behaviour during progressive dehydration. Results. Isothermal dehydration of raffinose pentahydrate led to its gradual amorphisation, but also to minor changes in the diffractograms, suggesting the probability of lower stable hydrates. Their existence was confirmed by DSC. Anhydrous raffinose was found to be completely amorphous, and this was supported by the gradual disappearance of birefringence during dehydration. In contrast, electron micrographs, taken during the dehydration process, exhibited no changes in the original ultrastructural crystal morphology. The widths of the glass-to-fluid transitions and the absolute specific heats of crystalline and amorphous phases in the vitreous and fluid states were used to estimate some structural and relaxation characteristics of amorphous raffinose-water mixtures. Conclusions. Raffinose forms the most 'fragile' glass of those pharmaceutical excipients for which data are available. In its thermomechanical properties, it is superior to trehalose and should therefore be effective as a long-term stabiliser for dried biopharmaceutical preparations at temperatures up to 65°C.     

Effects of formulation and operating variables on Zanamivir dry powder inhalation characteristics and aerosolization performance

Abstract

The objective of this study was to investigate the influence of formulation and operating variables on the physical characteristics and aerosolization performance of zanamivir spary-dried powders for inhalation. Spray-dried samples of zanamivir, zanamivir/mannitol and zanamivir/mannitol/leucine were prepared from their corresponding aqueous solutions under the same conditions to study the influence of the composition, and zanamivir/mannitol/leucine (1/1/3 by weight) formulation was used for investigation of the effect of the preparation process. Dry powders were characterized afterwards for different physical properties, including morphology, particle size, flowability, density and moisture absorption. The in vitro deposition was also evaluated after the aerosolization of powders at 100?L?min^?1 via the Aerolizer® into a Next Generation Impactor (NGI). The highest FPF of 41.40?±?1.1% was obtained with a zanamivir/mannitol/leucine ratio of 1/1/3, which had an average D_g of 3.11?±?0.13?μm and an angle of repose of 36°^?±?1. It was found that the influence of the preparation process on zanamivir spary-dried powders characteristics and aerosolization properties was relatively small, but the influence of the composition was relatively large. Optimization of DPI can be achieved by selecting the most appropriate formulation and preparation process.     

Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms

Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the “magic bullets” concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know‐how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products.     

利用海带渣制备药用辅料微晶纤维素的研究

目的为了高效利用海洋生物资源,降低环境污染,以海带加工废弃海带渣为原料制备药用辅料微晶纤维素。方法利用海带渣纤维素与HCl进行水解反应制备微晶纤维素,并研究反应时间对微晶纤维素制备的影响。利用扫描电子显微镜观察微晶纤维素的形貌,利用X射线衍射仪分析微晶纤维素的物相组成的表征。测定产品和市售样品的溶胀性,并将产品和市售样品以阿司匹林为主药进行压片,按照中国药典的规定对其进行硬度、崩解度、溶出度对比考察。结果在酸料比为1∶10,,盐酸浓度为2mol.L-1,水解温度为100℃的条件下,最佳水解时间为40min。海带渣微晶纤维素呈不规则的颗粒状,结晶度为79%,晶粒尺寸为3.9nm。与市售样品相比较,产品压片后崩解时限短、溶出速度快。结论以海带渣为原料用于药用辅料微晶纤维素的制备是可行的,所制备的微晶纤维素性能良好。     

不同辅料对健胃消食片质量参数的影响

目的:研究不同辅料对健胃消食片质量参数的影响,为实际生产工艺的优化提供科学依据.方法:采用湿法制粒压片,改用不同辅料研制4种健胃消食片,采用小杯法测定累积溶出度,进行溶出曲线相似因子拟合,溶出机制模型拟合.结果:4种不同辅料制得健胃消食片中,样品Ⅰ与Ⅱ,Ⅲ,Ⅳ中橙皮苷溶出曲线存在显著性差异,样品Ⅱ,Ⅲ,Ⅳ相互间不存在显著性差异;样品Ⅱ中橙皮苷溶出最快,累积溶出度最高;橙皮苷溶出行为都最接近一级动力学方程.结论:采用糊精、蔗糖和硬脂酸镁等辅料制备的健胃消食片质量最佳.     

EMA对说明书中辅料聚山梨酯安全性资料的最新要求

欧洲药品局（EMA）于2018年11月发布了"人用药品辅料聚山梨酯的包装说明书资料（草案）"文件，详细评价了聚山梨酯的安全性。介绍该文件中有关药品说明书中辅料聚山梨酯安全性资料撰写的新要求，期望我国相关的药品生产厂家借鉴EMA的做法，在含有辅料聚山梨酯的药品说明书中提供聚山梨酯的安全性信息，确保用药者的安全。