肠吸收促进剂的研究进展

肠吸收促进剂可改善肠粘膜透过能力低药物的口服生物利用度。本文综述了肠吸收促进剂研究的实验方法、制剂及生理因素对其促吸收作用的影响、安全性问题以及近年重点研究的促进剂类型。     

金耳多糖浸膏喷雾干燥工艺研究

目的对全耳多糖浸膏的喷雾干燥工艺进行优选。方法采用正交试验法，以含水量为考察指标，对影响喷雾干燥的因素进行考察，确定最佳喷雾干燥工艺。结果喷雾干燥机进风温度和输液泵开裂对试验结果有影响，浸膏相对密度对试验结果无影响。结论金耳多糖浸膏的最佳干燥工艺条件为浸膏相对密度1．04。进口温度180℃，输液泵开裂70％。     

促渗剂对司来吉兰贴片透皮性能的影响

目的:考察不同质量分数的氮酮、油酸和肉豆蔻酸异丙酯3种促渗剂对司来吉兰贴片经离体豚鼠皮渗透性的影响。方法:采用Franz扩散池进行体外经皮渗透试验,利用高效液相色谱法为浓度测定方法,以不含促渗剂的司来吉兰贴片为对照计算氮酮、油酸和肉豆蔻酸异丙酯的增渗比及表观扩散系数比较促渗剂渗透效果。结果:与对照组比较,质量分数为3%的3种促渗剂增渗倍数分别为1.53、1.37和1.26,表观扩散系数分别增至2.37、1.65、1.13倍。结论:3种促渗剂均可提高司来吉兰贴片的透皮性能,其中以3%氮酮的促渗效果较好。     

4种透皮吸收促进剂对盐酸苯海拉明透皮性能的影响

目的:研究油酸、1,3-丙二醇、月桂氮酮、丙三醇4种透皮吸收促进剂对盐酸苯海拉明透皮性能的影响。方法:在一定量的盐酸苯海拉明溶液中分别加入4种不同浓度的透皮吸收促进剂,采用改良Franz扩散池进行体外透皮吸收试验,测定不同浓度下不同透皮吸收促进剂的24h累积透过量(Q)。结果:以Q为指标,促透作用油酸>1,3-丙二醇>月桂氮酮>丙三醇,且前三者分别以0.5%、0.5%、0.2%为最佳促透浓度,丙三醇未见有明显的促透作用。结论:4种透皮吸收促进剂在一定浓度下均可增强盐酸苯海拉明局部给药制剂的透皮吸收作用。     

喷雾与减压干燥的秦香止泻干膏粉吸湿性及流动性比较

目的比较喷雾干燥法与减压干燥法对秦香止泻干浸膏粉吸湿性及流动性的影响,为确定秦香止泻浓缩液（或稠浸膏）合理的干燥方法提供依据。方法通过测定秦香止泻干浸膏粉的吸湿速度,吸湿量达2％时的相对湿度（relative humidit,RH）,建立其动力学模型,提取吸湿速度参数并比较大小;通过测定秦香止泻干浸膏粉的休止角比较流动性优劣。结果两种干燥方法制成的干浸膏粉吸湿动力学模型皆符合对数正态分布模型,减压干燥比啧雾干燥吸湿速度快,吸湿量随RH变化的函数关系,喷雾干燥粉符合逻辑斯蒂模型;减压干燥粉符合修正指数函数曲线,吸湿量达2％时的RH,喷雾干燥粉为90．12％;减压干燥85．81％,减压干燥法比喷雾干燥法制成的干浸膏粉休止角大,流动性差。结论喷雾干燥制成的干浸膏粉不易吸湿,稳定性好,流动性好。     

Producing Amorphous Solid Dispersions via Co-Precipitation and Spray Drying: Impact to Physicochemical and Biopharmaceutical Properties

Many small-molecule active pharmaceutical ingredients (APIs) exhibit low aqueous solubility and benefit from generation of amorphous dispersions of the API and polymer to improve their dissolution properties. Spray drying and hot-melt extrusion are 2 common methods to produce these dispersions; however, for some systems, these approaches may not be optimal, and it would be beneficial to have an alternative route. Herein, amorphous solid dispersions of compound A, a low-solubility weak acid, and copovidone were made by conventional spray drying and co-precipitation. The physicochemical properties of the 2 materials were assessed via X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, and scanning electron microscopy. The amorphous dispersions were then formulated and tableted, and the performance was assessed in vivo and in vitro. In human dissolution studies, the co-precipitation tablets had slightly slower dissolution than the spray-dried dispersion, but both reached full release of compound A. In canine in vitro dissolution studies, the tablets showed comparable dissolution profiles. Finally, canine pharmacokinetic studies showed that the materials had comparable values for the area under the curve, bioavailability, and C_max. Based on the summarized data, we conclude that for some APIs, co-precipitation is a viable alternative to spray drying to make solid amorphous dispersions while maintaining desirable physicochemical and biopharmaceutical characteristics.     

正交试验法优选甲基橙皮苷的喷雾工艺

目的 优选甲基橙皮苷喷雾干燥的最佳工艺。方法 采用正交试验法,以溶剂残留量和收率为考察指标,考察进风温度、出风温度和塔内压力的影响。结果 甲基橙皮苷喷雾干燥的最佳工艺为进风温度170℃,出风温度85℃,塔内压力-7 Pa。干燥所得的甲基橙皮苷的平均溶剂残留量为3 050 mg/kg,平均收率为93.6%。结论 该试验优选的工艺稳定,能有效控制产品的质量。     

喷雾干燥法制备前体脂质体的基础研究

研究了喷雾干燥法制备前体脂质体（ＰｒｏＬｉｐｏｓｏｍｅ，ＰＬ）的处方工艺，及将ＰＬ水合成重建脂质体（ＲＬ）的可行性，ＲＬ的粒径及影响因素．用丙二醛监测法、碘值法、酸度法考查了脂质体膜材在喷干过程中经受瞬间高温的稳定性．实验结果证明用简单振摇的方法即可将ＰＬ水合为ＲＬ，在通常范围内振摇时间及温度对ＲＬ的粒径无显著影响．制备脂质体所用豆磷脂可以经受喷干的瞬间高温，未有氧化水解等显著破坏，稳定性良好．实验证明，利用制备前体脂质体的方法可以解决脂质体以水溶液形式储存的氧化、水解、聚集、分层等问题，这是脂质体走向工业化生产的关键．与冻干法比，喷干法成本低，生产周期短．喷干法也可适用有机溶媒，这里将更降低喷干的时间和温度，更适于不稳定的药物．此法也可制备无菌制剂．     

雪荔颗粒喷雾干燥法制备的工艺优化

采用正交试验法，选定药液密度、进液速度和进风温度3因素，筛选雪荔颗粒喷雾干燥的最佳工艺。最佳工艺为药液密度1．07mg／ml(热测法)，进液速度9ml／min，进风温度176℃。     

不同促渗剂对蛇床子软膏透皮吸收特性的影响

目的考察不同促渗剂对蛇床子软膏透皮吸收的影响。方法采用改良Franz扩散池,以离体裸鼠皮肤为屏障,考察氮酮、油酸和高良姜油等不同种类的促渗剂对蛇床子软膏的累积渗透量、渗透吸收速率、增渗倍数等参数的影响。结果几种促渗剂对蛇床子软膏的透皮吸收均有较好的促进作用,其中以3%高良姜油效果最佳。结论高良姜油对蛇床子素经皮吸收具有显著的促进作用,为蛇床子经皮给药制剂处方设计和新药开发提供了依据。     

Gastropods as an Evaluation Tool for Screening the Irritating Potency of Absorption Enhancers and Drugs

Purpose. The objective of this study was to develop a simple alternative test using naked snails (slugs) for screening the irritating potency of chemicals on mucosal surfaces. Methods. The effect of various absorption enhancers and two -blocking agents on the mucosal tissue was determined from the total protein and lactate dehydrogenase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs caused by the treatment were measured. Results. According to the effects on the mucosal epithelium of the slugs the following rank order of increasing toxicity was established: PBS, HP--CD (5%), -CD (1.8%) and oxprenolol hydrochloride (1 %) < DDPC (l%) < STDHF (l%) < BAC (l%), SDC (l%) and propranolol hydrochloride (1 %). The results of the present study are in agreement with other studies using the same compounds on other models. Conclusions. The results of this study indicated the mucosa of slugs can serve as a primary screening tool for the evaluation of chemicals on mucosal surfaces. By simply measuring mucus production and weight loss reliable toxicity information can be obtained. This demonstrates rapid screening tests can be carried out using simple toxicity endpoints.     

血栓康胶囊喷雾干燥工艺研究

目的:选择血栓康胶囊喷雾干燥的最佳工艺条件。方法:应用正交实验法,以每小时药粉产量为考察指标,同时兼顾药粉中的有效成分,对影响血栓康胶囊喷雾干燥过程的因素进行考察。结果:正交实验设计的三个因素中,浸膏的相对密度影响最显著,入塔风压的影响较显著。结论:最佳工艺条件:入塔风温165℃,入塔风压-1550Pa,浸膏相对密度为1.28,采用喷雾干燥的工艺生产出的血栓康胶囊,有效成分黄芪甲甙的含量明显高于湿法制粒的含量。     

舒肝散结片干燥工艺研究

目的 优选舒肝散结片的干燥工艺.方法 比较减压干燥和喷雾干燥对舒肝散结片的干燥效果,并采用正交试验设计,优选喷雾干燥的条件.结果 进风温度为(190±2)℃,排风温度为(90±2)℃,提取液浓缩至相对密度为1.15～1.20(60℃测定)时喷雾效果最好.结论 喷雾干燥适合作为舒肝散结片的干燥工艺.     

计算流体力学在喷雾干燥中的应用

计算流体力学是利用计算机求解流体流动的动量、能量和质量等方程,从而获得流体流动状态和各种热力学参数分布的一种数值模拟技术,该技术已成为研究流体流动和传质传热的重要工具.本文就计算流体力学在设计喷雾干燥仪结构、优化工艺参数、减少喷雾干燥过程塔壁沉积等方面的应用现状进行了综述.     

Conversion of Nanosuspensions into Dry Powders by Spray Drying: A Case Study

Purpose  Drying of nanosuspensions can cause destabilization of the particles, leading to irreversible aggregation. In order to prepare an effective solid dosage form for a nanosuspension, it is imperative that the spray-dried nanoparticles should go back to their original particle size when reconstituted in an aqueous system. This case study examines impact of various formulation and processing parameters on redispersibility of the spray dried nanoparticles. Methods  Nanosuspensions were prepared using the microprecipitation–homogenization process. Spray drying of nanosuspensions was achieved using a lab-scale Buchi spray dryer. Results  Formulation components appeared to have the most significant impact on redispersibility of spray dried particles. Absence of surface charge led to particles that could not be redispersed. On the other hand, charged particles stabilized with an appropriate sugar led to spray dried powders that were flowable and easily redispersible. Dissolution testing showed the presence of two phases—a lag phase that represented dispersion of the loose aggregates, and dissolution of the dispersed nanoparticles. Conclusions  Nanosuspensions of a poorly soluble drug could be spray dried to obtain flowable powders that could be easily redispersed. These optimized powders also showed significantly improved dissolution rates as compared to the micronized drug, or unoptimized nanosuspensions.     

超声波喷雾干燥优化药物制剂特性的研究

目的 选用BÜCHI超声波控制器为主要设备,以疏水性药物HNN为模型药物进行超声波喷雾干燥改善药物的制剂特性,从粉体学性质、晶型以及化学稳定性3个方面比较超声喷雾干燥前后药物的主要性质变化。方法 测定药物粒径分布、密度、休止角等主要的粉体学性质,并以扫描电镜考察其微观形态;采用DSC、IR、XRPD、Raman分析技术对药物晶型进行表征;采用HPLC按照自身对照法计算药物有关物质含量。结果 原料药粒径分布在4.44~1 710 μm,分布宽且不均匀,喷雾干燥后粒径分布在50~300 μm间,分布更窄,更均匀,且呈现正态分布;堆密度由0.054 5 g·cm^-3增加到0.515 4 g·cm^-3,提高到原料药的9.5倍;休止角由57.26°降至37.21°,已经接近粉末直接压片的要求;扫描电镜原料药的微观形态为针状,杂乱无章,而喷雾干燥后为球状圆整颗粒,粒径均一;DSC结果显示喷雾干燥前后熔点没有改变,IR、XRPD、Raman结果表明药物特征峰前后一致,药物晶型无变化;有关物质化学稳定试验结果表明喷雾干燥工艺对药物稳定性没有影响。结论 超声波喷雾干燥的颗粒圆整均一,极大地优化了HNN药物的制剂特性,这种依靠超声波能量雾化的低剪切方式,最大程度的保护了药物的晶型及稳定性,可以作为类似药物处方前研究的一个可选方式进行药物制剂相关特性的优化。     

喷雾干燥法制备麦冬皂苷肠溶微球的影响因素

以丙烯酸树脂Ⅱ为囊材、微粉硅胶为抗黏剂、蓖麻油为增塑剂、95%乙醇为溶剂,采用喷雾干燥法制得麦冬皂苷肠溶微球.以外观形态、粒径、包封率、释放度等为指标,对进风温度、雾化速度、增塑剂种类、药物与囊材比例、囊材浓度等因素进行考察.结果表明,按优化条件制得的微球表面光滑,平均粒径(20.6±5.2)μm,包封率(94.8±2.7)%,载药量(54.8±2.1) mg/g.在pH 6.8磷酸盐缓冲液中的释放度较好.     

Effect of Absorption Enhancers on Ciliated Epithelium: A Novel In Vivo Toxicity Screening Method Using Rotifers

Pharmaceutical Research -     

Low-Voltage Electrohydrodynamic (EHD) Spray Drying of Respirable Particles

Spray drying is a widely used process to produce pharmaceutical powders. In traditional spray drying, the particle size distribution is wide and not well controlled. Using EHD atomization for spray drying offers a possibility to tailor the particle size and morphology. In conventional EHD spray drying, the generated particles are charged and need to be discharged to avoid Rayleigh breakup. Discharging adds complexity to the process and eliminates the possibility to collect the powder using an electric field. The present work describes a novel EHD spray drying setup based on a low-voltage nozzle. The low-voltage nozzle imparts moderate charge to the droplets, which makes discharging unnecessary. The charged particles can be controlled and collected by using an auxiliary electric field. The EHD spray dryer has been characterized in terms of particle size, particle morphology, process output, and yield. The size distribution of the generated particles is very narrow. Both porous and completely spherical particles can be produced. The yield of small-scale bench-top equipment was 20%, which is similar to the yield of a small-scale conventional spray dryer. The effective output with five nozzles was 75 mg/hr of dry powder. Because of the repelling forces associated with the unipolarly charged droplets, the number of nozzles can be increased without risking coalescence.     

天仙口服液中麝香、斑蝥、蟾酥的薄层色谱鉴别

天仙口服液是由30种中药组成的复方制剂。名贵药材麝香及剧毒药材斑蝥、蟾酥,在处方中量较少,只占0.3%～0.7%。薄层色谱鉴别未见报导。本文进行薄层色谱鉴别,斑点清晰,结果满意。1　麝香、斑蝥的薄层色谱鉴别取本品1支,充分摇匀,吸取10ｍｌ,加石油醚(30～60℃)20ｍｌ,超声20ｍｉｎ,分取石油醚液,滤过,滤液于60℃以下水浴蒸干,加2,4-二硝基苯肼试液1ｍｌ溶解,作为供试品溶液。取麝香、斑蝥对照药材各0.1ｇ,分别加石油醚(30～60℃)10ｍｌ,超声20ｍｉｎ,滤过,滤液在60℃以下水浴蒸干,各加2,4-二硝基苯肼试液1ｍｌ溶解,作为对照药材溶液。再分别…