吸入用乙酰半胱氨酸溶液雾化特性的体外评价

目的 研究吸入用乙酰半胱氨酸溶液的雾化特性,建立体外评价方法。方法 使用呼吸模拟装置对吸入用乙酰半胱氨酸溶液的递送速率和递送总量进行研究,使用新一代药用多级撞击器（NGI）测定空气动力学粒径分布。结果 不同雾化装置检测递送速率和递送总量数据存在明显差异,但使用同品牌雾化装置时吸入用乙酰半胱氨酸溶液自制样品和参比制剂的递送速率和递送总量无明显差异。不同雾化装置检测空气动力学粒径分布数据存在明显差异,但是使用同一品牌雾化装置,吸入用乙酰半胱氨酸溶液自制样品与参比制剂无明显差异。结论 所测定的体外数据描述了吸入用乙酰半胱氨酸溶液的体外特征,可为该制剂的体外评价提供参考。     

吸入用布地奈德混悬液的体外雾化特性

本文建立了吸入用布地奈德混悬液雾化特性的分析方法并分析其影响因素。通过将不同企业生产的吸入用布地奈德混悬液与不同型号的雾化装置联用,使用呼吸模拟器装置研究递送速率及递送总量;使用新一代撞击器与高效液相色谱法研究空气动力学粒径分布(aerodynamic particle size distribution, APSD)。相同企业样品与不同雾化装置联用后测得的微细粒子剂量(fine particle dose, FPD)、质量中值空气动力学粒径(mass median aerodynamic diameter, MMAD)、递送速率(delivery rate)及递送总量(total drug substance delivered, TDD)均存在差异(P <0.01),该差异是由于雾化装置设计参数不同导致。不同企业样品与相同雾化装置联用后测得的FPD存在差异(P <0.01),这可能是由于混悬液中混悬颗粒粒径等理化性质差异导致。本文方法可用于不同吸入液体制剂在临床上选择递送剂量与微细粒子剂量适宜的雾化装置,也可作为吸入液体制剂仿制药的研发与质量一致性评价研究时选择雾化装置...     

色甘酸钠滴眼液的质量评价研究

目的 从色甘酸钠滴眼液的溶液颜色、渗透压摩尔浓度、色甘酸钠含量和有关物质等方面开展一系列探索性研究,以期为色甘酸钠滴眼液的安全性和有效性作出更加合理的评价。方法 参照《中国药典》2015年版四部通则,对色甘酸钠滴眼液的溶液颜色进行目视法和色差计法检查,并测定其渗透压摩尔浓度;采用高效液相色谱法测定色甘酸钠滴眼液中色甘酸钠的含量,并与现行药典标准的紫外吸收系数法测定结果比较;在含量测定色谱条件下对13批次样品的有关物质相对含量进行测定。结果 色甘酸钠滴眼液的溶液颜色与性状描述的“无色或几乎无色”不符;渗透压摩尔浓度的测定结果显示,13批次样品中有10批次样品达不到等渗要求;含量测定结果表明,HPLC法测得的色甘酸钠含量略低于UV法所测含量;有关物质测定结果显示,色甘酸钠滴眼液的杂质相对含量总体较低,但随着贮藏时间的延长,杂质相对含量会增大。结论 色甘酸钠滴眼液现行质量标准性状描述不准确,缺乏渗透压摩尔浓度检查项,紫外吸收系数法测定色甘酸钠含量专属性差,易受干扰,不能有效地控制产品内在质量,建议修订质量标准。     

色甘酸钠滴鼻液的制备与质量控制

目的:建立自制色甘酸钠滴鼻液的质量控制方法.方法:以紫外分光光度法进行测定.结果:色甘酸钠在浓度为10～60μg/mL范围内线性良好,色甘酸钠的平均回收率为98.97%,RSD=0.94%.结论:紫外分光光度法简便、准确,适用于色甘酸钠滴鼻液的质量控制.     

肺部吸入制剂评价方法研究进展

肺部吸入制剂在治疗肺炎、哮喘、慢性阻塞性肺病（COPD）等肺部疾病中的应用广泛。肺部吸入制剂主要包括吸入气雾剂、干粉吸入剂、吸入喷雾剂和吸入溶液,其体外评价方法主要包括递送剂量及递送剂量均一性,空气动力学粒径分布,喷雾模式和喷雾形态;体内评价方法主要包括药动学研究与放射性核素成像。就肺部吸入制剂的体内外评价方法的研究进展进行综述。     

格隆溴铵吸入喷雾剂的雾化特性研究

目的 考察格隆溴铵吸入喷雾剂的雾化特性。方法 采用激光成像系统和新一代撞击器等测定格隆溴铵吸入喷雾剂的喷雾模式、喷雾形态、递送剂量均一性和空气动力学粒径分布。结果 样品的椭圆度均符合美国食品药品管理局指导原则建议,不同样品喷雾模式和喷雾形态同一参数之间RSD值均小于7%,样品的罐间和罐内递送剂量均一性良好。格隆溴铵吸入喷雾剂与雾化吸入溶液的质量中值、几何标准偏差值基本一致,在肺内沉积方面上高于雾化吸入溶液。结论 格隆溴铵吸入喷雾剂具备良好的雾化特性。     

色甘酸钠霜的制备与临床观察

本文介绍了色甘酸钠霜的制备、质量控制、稳定性试验、刺激性试验和临床应用。该制剂使用结果表明，组方合理，质量稳定，疗效确切。     

无载体色甘酸钠粉雾剂的研究 Ⅱ.评价疗效的体外试验方法研究

采用喷雾干燥技术，经微粉化处理，制备粒径小、流动性好、吸入方便的色甘酸钠（ＳＣＧ）无载体粉雾剂。建立了评价粉雾剂疗效的体外试验方法，包括排空试验、吸入模拟试验和透粘膜试验。试验结果表明：无载体粉雾剂（Ｉ）排空率明显高于市售ＳＣＧ粉雾剂（Ｉ）；吸入模拟试验中，在具治疗意义的部位（第二级）其沉积量为Ｉ的３倍，提示Ｉ的临床疗效优于Ｉ。     

喜炎平注射液雾化吸入给药可行性探索研究

目的 通过雾化微细粒子空气动力学特性测定和小鼠经口鼻雾化吸入毒性研究,评估喜炎平注射液雾化吸入可行性,为其临床应用提供参考.方法 采用新一代级联撞击器和雾化器系统(采用2种雾化器,压缩空气雾化器和超声雾化器,测算药物雾化吸入空气动力学直径(MMAD)、几何标准偏差(GSD)、微细粒子分数(FPF),并采用呼吸模拟器测定...     

In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer

Most human tumours over-express receptors for growth factors and peptide hormones, which are being increasingly studied as a means to selectively deliver cytotoxic agents. An example being the transferrin receptor (TfR, CD71). Here, we studied expression levels and location of TfR in different lung epithelial cell types (i.e., bronchial and alveolar epithelial cells) by flow-cytometry and confocal laser scanning microscopy (CLSM). Furthermore, we assessed uptake levels and cytotoxicity of transferrin (Tf)-conjugated liposomes in vitro. TfR was found to be expressed at a significantly higher level in bronchial epithelial cells compared with their alveolar counterparts. Cells of cancerous origin (i.e., A549 cell line) showed a higher TfR expression level than healthy alveolar epithelial type II cells in primary culture. CLSM revealed TfR to be located primarily at the basolateral aspect of cells, with the exception of cells undergoing mitotic proliferation, which also showed TfR at their apical membranes, due to their loss of cell polarity. Higher expression levels of TfR correlated well with enhanced uptake of Tf-liposomes and increased levels of cytotoxicity. Liposome uptake was temperature-dependent and inhibitable by excess free Tf. Tf-conjugated liposomes appear as good candidates for an approach to deliver cytostatic drugs to sites of lung cancer by inhalation.     

特殊制剂体外群体生物等效性研究案例分析

目的：采用体外群体生物等效性评价方法评估4种特殊制剂的等效性。方法：对国内外指南中关于群体生物等效性的内容进行总结,选择混合标度法,针对不同制剂,主要考察粒径参数、给药装置等体外测量数据参数,将指南中的公式和方程运用于2种吸入制剂（吸入用布地奈德混悬液和左沙丁胺醇雾化吸入溶液）以及2种脂质纳米注射剂（阿扎胞苷注射剂和注射用白蛋白结合型紫杉醇）的等效性研究。结果：该文的体外群体生物等效性研究取得良好的实践结果,除了阿扎胞苷注射剂的受试制剂与参比制剂不等效,需要对粒径继续加以改进外,其他3种制剂有95%的把握度说明受试制剂与参比制剂等效。结论：该研究成功将指南中的公式运用在实际案例中,对特殊制剂体外群体生物等效性在制剂研发中的应用有指导意义。     

In vitro and in vivo characteristics of a thermogelling and bioadhesive delivery system intended for rectal administration of quinine in children

The aim of this work was to improve the rectal bioavailability of quinine hydrochloride by designing thermosensitive and mucoadhesive gels intended for rectal delivery. The rheological and mucoadhesive properties of poloxamer 407 solutions have been modulated by addition of hydroxypropylmethycellulose (HPMC) and propanediol-1,2. In vitro release and rectal absorption of quinine have been highlighted by a dialysis dissolution testing method and by the determination of bioavailability of the different formulations in rabbits. Increasing the proportions of HPMC and poloxamer in the formulations resulted in a prolonged release of quinine. Indeed, compared to the DT 50% of a rectal solution and a simple HPMC gel (27 and 65 min, respectively) the DT 50% of thermosensitive ternary systems was increased and ranged between 80 and 138 min, depending on the system composition. The release rate depended strongly on the elasticity of the gels after thermogelation. The absolute rectal bioavailability of quinine determined in rabbits was significantly improved with these thermosensitive and adhesive systems. It increased from 62% for the rectal solution to 98% for a ternary system 16/0.5/30 (poloxamer (16%)/HPMC (0.5%)/propanediol-1,2 (30%)). As a result of combined bioadhesion and prolonged release of quinine in vivo, higher average values of MRT and t_max (9.1 ± 0.2 h and 30 min, respectively) were obtained compared to the rectal solution (6.9 ± 0.9 h and 15 min, respectively). Moreover, these formulations presented a very good rectal tolerance.

Modulation by HPMC of the viscoelastic and mucoadhesive properties of poloxamer 407 thermogelling solutions allowed a prolonged release of quinine hydrochloride and an improvement of bioavailability in rabbit.     

In vitro and in vivo evaluation of tegaserod maleate pH-dependent tablets

The purpose of this study was to prepare tegaserod maleate (TM) pH-dependent tablets and evaluate their advantages as a sustained release delivery system. TM, insoluble in water and unstable in gastric milieu, was formulated into pH-dependent tablets coated with combinations of two methacrylic acid copolymers – Eudragit^® L100 and Eudragit^® S100. The influence of core tablet compositions, polymer combination ratios and coating levels on the in vitro release rate of TM from coated tablets was investigated. The optimum formulation was evaluated for in vitro release rate and in vivo bioavailability study on beagle dogs. In addition, physico-chemical properties of the drug, including solubility at different pH and temperatures, and dissociation constant were determined. The results showed that no drug was released in 0.1 mol/L hydrochloric acid within 2 h, and about 90% of the drug was released in the pH 6.8 phosphate buffer within 12 h in a sustained manner. The pharmacokinetic investigation showed that TM pH-dependent tablets exhibited a sustained plasma concentration, a lag time of approximately 2.3 h and a relative bioavailability of 159% compared to plain tablets. A close correlation existed between the in vitro release rate of the pH-dependent system and its in vivo absorption percentage. The results of the present study have demonstrated that the pH-dependent tablet system is a promising vehicle for preventing rapid hydrolysis in gastric milieu and improving oral bioavailability of TM for the treatment of irritable bowel syndrome.     

25例小儿支气管哮喘并肺部感染的治疗体会

目的观察顺尔宁联用普米克令舒＋博利康尼氧驱动雾化吸入治疗小儿支气管哮喘的疗效。方法对收住的25例支气管哮喘并肺部感染患儿的临床资料进行回顾性分析。结果顺尔宁联用普米克令舒＋博利康尼雾化吸入治疗小儿支气管哮喘并肺部感染的半年复发率为0,单纯用普米克令舒＋博利康尼氧驱动雾化吸入治疗小儿支气管哮喘并肺部感染的半年复发率为46．7％。结论顺尔宁联用普米克令舒＋博利康尼氧驱动雾化吸人治疗小儿支气管哮喘并肺部感染疗效显著,值得临床推广应用。     

In vitro and cell uptake studies for targeting of ligand anchored nanoparticles for colon tumors

Hyaluronic acid (HA) coupled chitosan nanoparticles (HACTNP) bearing 5-flurouracil (5FU) were prepared, by ionotropic gelation method, for the effective delivery of drug to the colon tumors. HACTNP appeared to be spherical in shape and mean size was found to be around 150+/-3.4nm with low polydispersity index. The in vitro drug release was investigated using USP dissolution test (paddle type) apparatus in different simulated GIT fluids. The biocompatibility of NPs formulations were evaluated for in vitro cytotoxicity by MTT assay using HT-29 cell lines and cell uptake was assessed by fluorescent microscopy. Cellular uptake of HACTNP was determined by incorporating calcein as a fluorescent marker. The cellular uptake of fluorescent HACTNP was clearly evidenced by fluorescence microscopy. HACTNP nanoparticles showed significant higher uptake by cancer cells as compared to uncoupled nanoparticles and the uptake of HA coupled CTNPs by HT-29 colon cancer cells were observed to be 7.9 times more as compared to uncoupled CTNPs at the end of 4h. The cytotoxicity of 5FU incorporated in HACTNP was higher compared to the conventional 5FU solution, even at the lower concentrations. 5FU in HACTNP was about 2.60-folds more effective than free 5FU on HT-29 cells.     

注射用炎琥宁联合乙酰半胱氨酸治疗肺部感染的临床研究

目的探讨注射用炎琥宁联合吸入用乙酰半胱氨酸溶液治疗肺部感染的临床疗效。方法选择2016年1月—2017年1月西宁市第三人民医院收治的肺部感染患者153例为研究对象,随机分为对照组(76例)和治疗组(77例)。对照组雾化吸入吸入用乙酰半胱氨酸溶液,3 m L/次,2次/d。治疗组在对照组治疗基础上静脉滴注注射用炎琥宁,160 mg加入到5%葡萄糖注射液250 m L中,1次/d。两组患者均连续治疗7 d。观察两组的临床疗效,比较两组的临床肺部感染评分(CPIS)、白细胞计数、临床症状、肺部X片恢复时间和炎症因子水平。结果治疗后,对照组和治疗组的总有效率分别为85.53%、97.40%,两组比较差异有统计学意义(P0.05)。治疗后,两组CPIS和白细胞计数均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组体温恢复时间、咳痰消失时间、肺部X片恢复正常时间短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组超敏C反应蛋白(hs-CRP)和降钙素(PCT)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组炎症因子水平明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论注射用炎琥宁联合吸入用乙酰半胱氨酸溶液治疗肺部感染具有较好的临床疗效,可改善临床症状,降低炎症反应,安全性好,具有一定的临床推广应用价值。