盐酸氨溴索干粉吸入剂的制备工艺

目的优化盐酸氨溴索干粉吸入剂的制备工艺。方法采用喷雾干燥法制备盐酸氨溴索干粉吸入剂,采用双层液体碰撞器测定盐酸氨溴索干粉吸入剂体外沉积率,扫描电镜观察粉粒的形态,激光粒度测定仪测定粒径大小,以产品收率、粉末的空气动力学径、休止角及体外沉积率为考察指标,通过正交设计结合多指标综合评价法优化最佳制备工艺。结果通过正交试验-多指标综合评价,最佳制备工艺为:进口温度110℃、喷液速度1.8 mL.min-1、泵压170 kPa、气流量0.7 m3.min-1。结论按最佳制备工艺制得的干粉收率的质量分数为62.10%,空气动力学径Da 3.05μm,休止角36.16°,沉积率32.05%。正交实验结合多指标综合评价法用于盐酸氨溴索干粉吸入剂制备工艺的优化实用有效。     

硫酸特布他林的HPLC测定法

以硫唑嘌呤为内标,采用 HPLC 法测定硫酸特布他林的含量。其色谱蜂面积与含量的线性关系良好,相关系数 r=0.9999,平均回收率为99.01%,平均偏差为0.48%。6个批号样品的测定结果与 BP 法无显著差异。     

布地奈德吸入剂联合特布他林治疗哮喘的临床效果分析

目的探讨布地奈德吸入剂与特布他林联合应用于哮喘中的临床意义。方法以2015年4月27日至2017年1月3日我院哮喘患者116例为研究对象,根据平均、完全随机原则,将其分为两组。对照组施以特布他林治疗,在此基础上,观察组联合布地奈德吸入剂。观察两组相关临床症状缓解以及不良事件发生情况。结果在症状缓解时间方面,观察组气喘、咳嗽、哮鸣音、呼吸困难数据分别为(3.23±1.50)d、(5.02±1.69)d、(3.44±0.91)d、(2.48±0.69)d,均较对照组数据更优,P值<0.05;观察组不良事件发生概率(3.45%)低于对照组,但二者对比价值不大,P值>0.05。结论布地奈德吸入剂与特布他林联合应用于哮喘治疗中,效果可靠,可有效控制病情,且安全性较高。     

硫酸特布他林片HPLC测定

采用Ｃ１８柱，以惭腈－０．００５ｍｏｌ／Ｌ樟脑磺酸溶液（２０：８０）为流动相，咖啡因为只标经ＨＰＬＣ法测定硫酸特布他林片的含量。平均回收率为１０１．５％（ＲＳＤ＝０．８６％）。     

硫酸特布他林的合成

以３,５－二羟基苯甲酸为起始原料,经酯化,苄基保护,水解,酰化,氧化,缩合、还原,脱苄制成硫酸特布他林,总收率２１％。     

硫酸特布他林脉冲控释片的制备与释放机理研究硫酸特布他林脉冲控释片的制备与释放机理研究

目的制备硫酸特布他林双层包衣脉冲片，考察处方及释放条件对体外释药行为的影响，解析其释放机理。方法粉末直接压片法制备含渗透活性物质的片芯，滚转包衣锅法分别包溶胀层和控释衣层。通过测定释放度研究脉冲片的制剂学特征，并研究脉冲片的吸水动力学和膨胀行为。结果双层包衣片以脉冲形式释放，释药时滞随控释衣层厚度增加而延长，释药速度减小；渗透活性物质和溶胀层可提高快速释放期的释药速率。溶出介质pH值和搅拌速度对释药行为无影响。释药机理包括扩散、溶胀和渗透泵原理。结论调整控释衣膜厚度和组成可获得理想的脉冲释药行为，满足时辰治疗的要求。     

均匀设计法优化硫酸特布他林微囊的处方

目的制备硫酸特布他林（TBS）缓释微囊。方法采用乳化-溶剂扩散法，并用均匀设计优化处方，以微囊外观、粒度分布和包封率为考察指标，优化硫酸特布他林缓释微囊的制备工艺。结果在优化条件下制备的TBS微囊，外形圆整光滑，分布均匀，不粘连，平均粒径为40-50μm，包封率达91．2％，8h体外释放百分率为82．3％。结论优化条件下可制备外观较好、包封率高的TBS微囊，且在体外具有缓释作用。     

硫酸特布他林治疗重症肺心病的临床观察

硫酸特布他林治疗重症肺心病的临床观察周红勤胡婵宋菊桂刘寅芝陈芬宝（湖南省邵阳市第一人民医院邵阳４２２００１）为探讨硫酸特布他林（ＴＢＴ）在慢性肺原性心脏病（ＣＰＨＤ）中的治疗价值，我们对６２例ＣＰＨＤ进行了临床和动脉血气监测，并随机对其中３０例加服Ｔ...     

硫酸特布他林有关物质的合成

目的合成2个硫酸特布他林有关物质,为其质量研究提供杂质对照品。方法以硫酸特布他林为原料经曼尼希反应合成特布他林环化物(杂质A);以3,5-二甲氧基苯乙酸为原料,通过缩合、还原、脱保护、成盐得到特布他林氢化物(杂质B)。结果与结论 2种杂质的结构经过ESI-MS、NMR谱确证,HPLC测定纯度均在98%以上,本研究为制定硫酸特布他林的质量标准提供了借鉴,也为其原料药的进一步研究奠定了基础。     

Disposition kinetics of ketotifen from liposomal dry powder for inhalation in rat lung

1. The aim of the present study was to understand the benefit of liposomal dry powder for inhalation (LDPI) of ketotifen fumarate (KF) over plain drug dry powder for inhalation as a pulmonary targetted drug-delivery system. 2. The KF liposomes, composed of egg phosphatidyl choline and cholesterol, were prepared by the lipid film hydration technique. The liposomal dispersion was freeze dried and formulated to a dry powder for inhalation. Values of 89.0-65.3% drug entrapment of freeze-dried liposomes were estimated in prepared batches. 3. Rehydrated KF liposomes formed by the hydration of LDPI or the plain KF solution was delivered to rat lungs by intratracheal instillation. Simultaneous monitoring of drug levels in the bronchoalveolar lavage and lung tissue enabled assessment of pulmonary drug disposition. 4. Cumulative drug levels in lung tissue after intratracheal administration revealed that with liposomes targetting factors were between 1.36 and 1.54. The maximal drug concentration in lung homogenate for LDPI was 42.0 micro g compared with 73.6 micro g for plain drug solution. 5. Similarly, the time to reach maximum drug concentration in the lung homogenate for liposomal dry powder was 9-12 h compared with 3 h for plain drug. 6. Hence, the use of LDPI of KF was found to provide desired drug levels in the lung for a long time and thereby increased pulmonary targetting 7. This is expected to enhance the therapeutic index of the drug and probably reduce the dose administered and the cost of therapy.     

胰岛素吸入粉雾剂的制备及其体外沉积性质

目的采用喷雾干燥法制备胰岛素吸入粉雾剂,并对其体外沉积性质做出评价。方法以产品收率,粉末的空气动力学径、休止角及水分含量为考察指标,采用正交设计Z综合评价法优化喷雾干燥制备方法中各工艺参数,同时采用双层液体碰撞器测定该工艺所制备的胰岛素吸入粉雾剂的有效部位沉积量,并通过扫描电镜观察产品的形态。结果优选出的工艺参数为:气流量为0.6 m3.min-1,进口温度为100℃,喷液速度为5.0 mL.min-1,泵压为130 kPa,溶液质量分数为0.75%。体外有效部位沉积质量高达60%。结论采用本法制备胰岛素肺部吸入粉雾剂重现性好,所得粉雾剂的有效部位沉积量高,提示大部分粒子能够到达肺部。     

影响干粉吸入剂雾化和沉积性能的制剂因素

干粉吸入剂是近年来肺部给药制剂研发的热点。随着微粉化技术不断成熟,新型给药装置日益涌现,干粉吸入剂的应用范围越来越广。本文从微粉化的药物、载体和干粉吸入器等3个方面综述了干粉吸入剂的处方组成,并重点介绍了影响药物粉末雾化和沉积性能的几个关键因素。     

鲑鱼降钙素肺部干粉吸入剂的制备及含量影响因素的考察

目的喷雾干燥法制备鲑鱼降钙素(salmon calcitonin,sCT)肺部干粉吸入剂;考察溶液pH值、喷干温度和处方中泊洛沙姆(F68)的用量对鲑鱼降钙素含量的影响。方法分别制备不同pH值和不同F68用量的鲑鱼降钙素溶液,在不同温度下喷雾干燥制备鲑鱼降钙素干粉吸入剂粉末,用高效液相色谱仪对所制备的粉末进行含量测定。采用TSI装置测定粉末沉积率,用LS320激光粒度测定仪测定粒径大小,用扫描电子显微镜观察粉末的表面形态。结果制备的鲑鱼降钙素吸入粉末的平均粒径为2.1μm,沉积率在45.42%左右。在pH小于3.3的冰醋酸溶液中,F68的用量超过固型物总量的1%时,喷干温度低于120℃时,鲑鱼降钙素喷雾干燥后的含量均在80%以上。结论在较低的pH环境中,选用适量的蛋白保护剂F68,采用较低的喷干温度,均可有效的降低喷干过程中鲑鱼降钙素的变性几率。     

特普他林对大鼠烟雾吸入伤后肺泡液体清除功能的影响

目的　观察特普他林对大鼠烟雾吸入伤后肺泡上皮液体清除能力变化的影响。方法　采用大鼠烟雾吸入性损伤模型。伤后 2 4h经气管滴注特普他林 ( 10 -4 mol·L-1)溶液 5ml·kg-1;1h后检测肺泡内液体清除率 (ALC)、总肺水量 (TLW )、肺血管外肺水量 (EVLW)和动脉血气指标。结果　大鼠伤后 2 4hALC降低 46 8% ,TLW和EVLW明显增加 ,出现严重的低氧血症。特普他林组ALC增高 5 7 6 % ,TLW和EVLW显著减少 ,低氧血症明显改善。钠转运特异性抑制剂阿咪洛利或哇巴因能部分抑制特普他林刺激肺泡内液体清除的作用。结论　特普他林通过上调钠主动转运机能 ,促进肺水肿液的吸收 ,从而改善换气功能 ,对吸入伤后肺水肿有一定的治疗作用     

Relative bioavailability of terbutaline to the lung following inhalation, using urinary excretion

AIMS

The aim of the study was to determine the relative lung and systemic bioavailability of terbutaline.

METHODS

On separate days healthy volunteers received 500 µg terbutaline study doses either inhaled from a metered dose inhaler or swallowed as a solution with and without oral charcoal. Urine samples were provided at timed intervals post dosing.

RESULTS

Mean (SD) urinary terbutaline 0.5 h post inhalation, in 12 volunteers, with (IC) and without (I) oral charcoal and oral (O) dosing was 7.4 (2.2), 6.5 (2.1) and 0.2 (0.2) µg. I and IC were similar and both significantly greater than O (P < 0.001). Urinary 24 h terbutaline post I was similar to IC + O. The method was linear and reproducible, similar to that of the urinary salbutamol method.

CONCLUSIONS

The urinary salbutamol pharmacokinetic method post inhalation applies to terbutaline. Terbutaline study doses can replace routine salbutamol during these studies when patients are studied.     

Development,characterisation and pharmacoscintigraphic evaluation of nano-fluticasone propionate dry powder inhalation as potential antidote against inhaled toxic gases

Acute lung injuries caused due to inhalation of toxic irritant gases such as ammonia, chlorine, hot smoke and burning plastic fumes predominantly affect the airways, causing tracheitis, bronchitis, and other inflammatory responses. The purpose was to develop and characterise nanoparticle based fluticasone propionate (FP) DPI formulation and assess its in vitro and in vivo pulmonary deposition using pharmacoscintigraphy. FP nanoparticles were prepared by nanoprecipitation method. Optimisation was carried out with the help of Box–Behnken statistical design. Nanoparticles were characterised with the help of SEM, FT-IR, DSC and XRD. Anderson cascade impaction showed that nano-FP exhibited significantly higher respirable fraction of 60.3?±?2.41 as compared to 16.4?±?0.66 for micronised form. Ventilation lung scintigraphy in human volunteers confirmed significant increase in drug delivery till alveolar region with nano-FP in comparison to micronised drug. Results indicate that the developed formulation may have a potential prophylactic/therapeutic role against toxic, irritant gas inhalation.     

干粉吸入剂的粉末定量分装设备浅析

干粉吸入剂是一种新兴呼吸道给药剂型,其吸入粉末的分装装置不同于常见的口服固体粉末分装装置。本文综述国际上常用的干粉吸入剂的粉末定量分装装置,包括标准定量器装置装置、真空滚筒分装装置、Xcelodose精确粉末微定量装置等,同时介绍几种较新的、处于研发阶段的粉末分装装置。