吲哚美辛-泊洛沙姆188固体分散体的制备

目的制备吲哚美辛-泊洛沙姆188固体分散体,提高吲哚美辛的溶出度。方法以泊洛沙姆188为载体,采用溶剂-熔融法制备固体分散体。用差示热分析(DTA)、扫描电子显微镜(SEM)考察药物在载体中的存在状态,并进行体外溶出度研究。结果吲哚美辛以微晶或无定形分散在载体中,药物的溶出度随载体比例增加而增加。结论制备的固体分散体吲哚美辛的溶出度和溶出速率显著提高。     

吲哚美辛固体分散体的制备和理化性质的研究

目的:研究吲哚美辛(IMC)固体分散体的理化性质,提高IMC的溶出速度。方法:用溶剂法制备固体分散体,用粉末X射线衍射研究原型药物、载体、固体分散体(比例1∶1～1∶5)的物态性质,考察药物在分散体中溶出行为的改变。结果:制得的固体分散体大大提高了IMC的溶出速度,5min内溶出了将近100%的药物。结论:通过溶剂法,成功制备了IMC的固体分散体,药物在分散体中以无定型的状态存在,在溶出介质中药物能够迅速溶出。     

吲哚美辛脂质体滴眼液在家兔眼内的药动学

目的:研究吲哚美辛脂质体滴眼液在家兔眼内的药动学过程,为临床应用提供依据和参考.方法:以市售吲哚美辛滴眼液为参比制剂,采用高效液相色谱法(HPLC)测定两种制剂在用药后不同时间家兔房水中的药物浓度,按单剂量方案进行研究并计算药动学参数.结果:两药在家兔眼内均为一室模型,受试药物主要药动学参数为:Tmax=0.204 5 h;Cmax=1.518 7 mg·L-1:AUC=1.981 7 mg·L-1·h.参比药物为:Cmax=0.388 1 mg·L-1,Tmax=0.798 1 h,AUC=0.858 5 mg·L-1·h.结论:与吲哚美辛滴眼液相比吲哚美辛脂质体滴眼液眼内生物利用度提高2.3倍.     

吲哚美辛肠溶滴丸在比格犬体内的药动学研究

摘 要 目的：对吲哚美辛（IDM）肠溶滴丸的药动学进行考察。方法: 以比格犬为实验动物,以市售IDM肠溶片为对照,对同剂量IDM肠溶滴丸单剂量给药的药动学进行研究,用SPSS21.0软件进行模型拟合及参数计算,并进行生物等效性评价。结果: IDM肠溶滴丸及肠溶片均符合一室模型,Cmax、Tmax、AUC0-∞、Tlag等差异均有统计学意义（P<0.05）,Cmax及AUC0~∞均显著升高,Tmax及Tlag均显著缩短,肠溶滴丸的相对生物利用度为（121.0±7.7）%。结论:IDM肠溶滴丸相对于肠溶片而言,吸收显著增加,起效明显加快,值得进一步研发。     

西罗莫司固体分散体在Beagle犬体内的药动学研究

目的研究自制西罗莫司固体分散片在Beagle犬体内的药动学。方法6只Beagle犬分别按单剂量给药方案和多剂量给药方案口服西罗莫司受试制剂和参比制剂;采用UPLC-MS/MS法测定Beagle犬给药后不同时间的全血血样浓度。结果西罗莫司线性范围为0.50~20.00ng·mL^-1。Beagle犬单次口服西罗莫司受试制剂和参比制剂后的C max市售片>C max自制片,T max市售片C SSmax自制片,T max市售片相似文献   

吲哚美辛亚微乳胶药动学及体内外相关性研究

目的 研究吲哚美辛（indomethacin,IMC）亚微乳胶在兔体内的药动学,评价其生物利用度和经皮渗透性行为的体内外相关性。方法 采用改良Franz扩散池法,以SD大鼠腹部皮肤进行体外经皮渗透性实验。以家兔为实验动物,两侧腹部去毛涂抹亚微乳胶或市售普通乳膏10 g（相当于IMC 100 mg）,不同时间点心脏取血,用高效液相色谱法测定IMC的血药浓度。采用反卷积分法对体外经皮渗透数据和体内药动学数据进行体内外相关性研究。结果 IMC亚微乳胶体外24 h累积经皮渗透量是市售IMC普通乳膏的2倍;经皮给药后,与市售IMC普通乳膏相比,IMC亚微乳胶的T_max、C_max、T_1/2均无显著性差异;AUC_0-24和AUC_0-∞均为市售IMC普通乳膏的2倍。IMC亚微乳胶体内外相关性系数r=0.930。结论 与市售IMC普通乳膏相比,IMC亚微乳胶能够增加IMC渗透入血量,提高IMC的相对生物利用度,且其体内外经皮渗透行为具有良好的体内外相关性。     

LC-MS/MS法测定吡非尼酮在大鼠体内的药动学参数

目的建立灵敏的液相色谱-串联质谱(LC-MS/MS)法测定大鼠血浆中吡非尼酮的浓度。方法血浆样品采用乙腈蛋白沉淀方法,色谱柱为Dikma Diamonsil C18;以0.1%甲酸-乙腈(45:55,v/v)为流动相;流速为0.4 m L·min-1;柱温为30℃。结果吡非尼酮血药浓度在5~2000 ng·m L-1内线性关系良好(r=0.9995),最低检测限为5 ng·m L-1;日内、日间RSD均≤10%,高、中、低3种浓度的回收率均在93%左右。6只SD大鼠单剂量口服给予吡非尼酮后药动学参数分别为:Cmax(1354.3±143.5)ng·m L-1;t1/2(2.21±0.24)h;AUC0~t(3474.6±982.5)h·ng·m L-1;AUC0~∞(3687.4±992.4)h·ng·m L-1。结论本方法简便、准确、灵敏、专属性强,同样适用于人血浆中吡非尼酮浓度的测定及其药动学研究,对于评价吡非尼酮疗效和安全性有重要意义。     

葛根素固体分散体的制备及体内药动学

目的研究葛根素固体分散体的制备及其在家兔体内药动学,以提高葛根素口服给药的生物利用度。方法采用溶出度法,确定葛根素固体分散体的最佳制备处方;采用HPLC法,测定家兔血浆中葛根素的含量,药动学参数经3P97药动学软件处理。结果葛根素固体分散体的最佳制备处方为葛根素:PEG6000:pluronicF-68=1:4:1(m/m/m);葛根素及葛根素固体分散体的血药浓度-时间过程均符合二室模型,主要药动学参数:α分别为(2.040±0.327)、(0.870±0.191)·h~(-1),β分别为(0.21 2±0.021)、(0.351±0.022)·h~(-1),AUC_(0-∞)分别为(11.966±1.370)、(91.419±3.531)mg·L~(-1)·h,t_(max)分别为(0.491±0.026)、(1.423±0.035)h,ρ_(max)分别为(3.917±0.066)、(20.416±1.870)mg·L~(-1)。葛根素固体分散体对葛根素的相对生物利用度为763.99%。结论葛根素固体分散体可提高葛根素口服给药在家兔体内的生物利用度。     

壳聚糖-吲哚美辛缓释微囊药动学研究

目的研究自制壳聚糖-吲哚美辛微囊的药动学。方法以市售普通吲哚美辛片剂为参比通过高效液相色谱测定模型动物家兔药时曲线。结果与普通片剂相比,兔口服壳聚糖-吲哚美辛微囊后,达峰时间明显推迟,且达峰浓度降低(P<0.05);同时药物在兔体内平均驻留时间明显长于普通片(P<0.05);但两制剂的AUC无差异(P>0.05)。结论研制的壳聚糖-吲哚美辛微囊具有较好的缓释效果,且吸收程度与普通吲哚美辛片剂等效。     

吲哚美辛锌的药物动力学研究

本文用ＵＶ法测定健康成人口服吲哚美辛锌、吲哚美辛胶囊剂后的尿药浓度，以酸－碱法提取尿中吲哚美辛原形药，在２６５ｎｍ处测定吸收度，在４～３２ｕｇ／ｍｌ范围内线性关系良好，平均回收率＞９９．０％，日内及日间ＲＳＤ＜０．９２％，对６名健康志愿者口服给药后的药物动力学研究结果：吲哚美辛锌及吲哚美辛的药动学参数分别为，Ｔｍａｘ＝３．３２，１．８７（Ｐ＜０．０１）；Ｋ＝０．１２７３，０．１５３１（Ｐ＜０．０５）；Ｔ１／２＝５．４７，４．６１（ｐ＜０．０５）；Ｘｕ（ｍｇ）＝１０．９１，１３．１４（Ｐ＞０．０５）吲哚美锌的相对生物利用度为８３．０３％。     

依普黄酮固体分散体在大鼠的药物动力学评价(英文)

目的:评价依普黄酮固体分散体在大鼠体内的药物动力学行为。方法:测定它的药物动力学参数和相对生物利用度,采用高压液相色谱法测定大鼠血浆中依普黄酮的浓度。结果:大鼠灌胃依普黄酮固体分散体250mg·kg~(-1),其血药浓度-时间曲线符合一室模型,药物动力学参数为:K_e=0.21h~(-1),T_(1/2K_e)=5.19h,K_a=1.71h~(-1),T_(1/2K_a)=0.41h,T_(max)=0.67h,C_(max)=429μg·L~(-1),AUC=3916μg·h·L~(-1),相对生物利用度是323％。结论:依普黄酮固体分散体与依普黄酮的物理混合物比较,在大鼠体内有更多被吸收。     

依普黄酮固体分散体在大鼠的药物动力学评价

AIM: To evaluate pharmacokinetic behavior of ipriflavone solid dispersion in rats. METHODS: The plasma concentrations of ipriflavone in rats were determined by HPLC with UV detector. RESULTS: Plasma concentration-time curves after ig ipriflavone solid dispersion 250 mg.kg-1 in rats were fitted with one-compartment model. Pharmacokinetic parameters were as follows: Ke = 0.21 h-1, T1/2Ke = 5.19 h, Ka = 1.71 h-1, T1/2Ka = 0.41 h, Tmax = 0.67 h, Cmax = 429 micrograms.L-1, AUC = 3916 micrograms.h.L-1; The relative bioavailability of ipriflavone solid dispersion was 323%. CONCLUSION: Ipriflavone in solid dispersion was absorbed more effectively than that in physical mixture in rats.     

姜黄素固体分散体在小鼠体内的药代动力学

目的以姜黄素混悬液为对照,研究姜黄素-聚维酮固体分散体灌胃给药后在小鼠体内的药代动力学。方法按300mg·kg-1的剂量小鼠灌胃姜黄素固体分散体溶液或姜黄素混悬液,采用高效液相色谱法测定血浆中姜黄素含量,用DAS软件拟合房室模型,计算药动学参数。并测定了给药3h时药物的吸收率。结果姜黄素-聚维酮固体分散体在小鼠体内的药代动力学符合二室开放模型,主要药动学参数如下:T12α和T12β分别为16.4和266min,AUC为89.6mg·mL-1.min-1,Vd为763.9L,V1为51.0L,CL为1.99L·min-1。姜黄素-聚维酮固体分散体在胃肠道的吸收率是姜黄素混悬液的6.75倍。结论姜黄素固体分散体灌胃可显著增加姜黄素的生物利用度,血药浓度较高。     

Comparison between polyvinylpyrrolidone and silica nanoparticles as carriers for indomethacin in a solid state dispersion

States of interaction between indomethacin (IM) and polyvinylpyrrolidone (PVP) in an amorphous solid dispersion prepared by co-grinding were compared with those between IM and silica nanoparticles. Changes in the carbon chemical states of the solid dispersions were evaluated based on the chemical shift in the 13C-CP/MAS-NMR. Hydrogen bonds between the amide carbonyl of PVP particles and the carboxyl groups of IM molecules were formed by co-grinding. Despite the wide difference in carrier properties, the apparent equilibrium solubility (AES) of IM in the ground IM-PVP mixture was predicted by solid state NMR on the basis of the relationship previously established for IM with SiO(2). This indicates that AES is affected solely by the state of IM, irrespective of the carrier species, and despite carrier-dependent chemical interactions.     

拉西地平固体分散体在Beagle犬体内的药动学和生物等效性研究

目的研究不同拉西地平固体分散体在Beagle犬体内的药动学和生物等效性。方法采用Thermo C_(18)色谱柱(50 mm32.1 mm,2.6μm);流动相:0.2%甲酸水溶液–乙腈(17∶83);体积流量:0.2 mL/min;柱温:30℃;进样室温度:15℃;进样量:10μL。采用电喷雾离子源(ESI),多反应监测(MRM)方式扫描,以正离子方式进行检测;用于定量分析的离子对分别为拉西地平m/z 473.47(母离子)→354.28(子离子),内标尼莫地平m/z 419.25(母离子)→343.18(子离子)。6只健康Beagle犬分别给予4 mg参比制剂拉西地平片(R)、拉西地平-HPMC E5固体分散体(T_1)和拉西地平-Soluplus固体分散体(T_2),绘制血药浓度–时间曲线,采用DAS 2.1.1软件非隔室模型计算主要药动学参数,并进行生物等效性分析。结果拉西地平在0.25~100 ng/mL线性关系良好,定量下限为0.25 ng/mL。在0.5、5.0、80.0 ng/mL的提取回收率和基质效应分别为100.92%~102.89%和100.71%~102.89%,RSD值11%。T_1、T_2和R的主要动力学参数分别为峰浓度(C_(max))为(24.45±6.53)、(28.80±11.89)、(26.647±4.44)ng/mL;达峰时间(t_(max))为(1.13±0.70)、(1.29±0.64)、(1.79±1.36)h;t_(1/2)分别为(8.39±4.60)、(7.10±6.73)、(5.20±6.16)h。受试制剂相对生物利用度为(112.2±57.8)%、(110.6±51.6)%。生物等效性分析两组受试制剂与参比制剂均不具备生物等效性。结论该方法准确、灵敏度高、专属性强,可用于拉西地平制剂的药动学和生物等效性研究。自制拉西地平固体分散体与市售拉西地平片生物等效性不一致。     

Preparation, characterization, and tableting of a solid dispersion of indomethacin with crospovidone

A significant problem with solid dispersion (SD) systems is the difficulty in preparing dosage forms. This difficulty can be overcome using crospovidone (CrosPVP) as a carrier. A powder SD of indomethacin (IM) with CrosPVP was prepared using mechanical mixing followed by heating to temperatures below the melting point. IM and CrosPVP interacted to produce IM in an amorphous state when its concentration was <40%. The solubility of IM was improved about fourfold compared to IM crystal. The SD had good fluidity, and tablets were prepared by direct compression. Tablets with small weight variation and acceptable hardness were obtained using only 1% of magnesium stearate as excipient. The dissolution of IM from tablets was similar to that of SD powder because CrosPVP, a disintegration agent, caused the tablets to break up rapidly.     

复合载体齐墩果酸固体分散体的制备及评价

目的：制备复合载体齐墩果酸固体分散体,提高齐墩果酸的溶出度。方法：采用溶剂法,以聚乙烯吡咯烷酮（PVP VA64）和聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物（Soluplus）为复合载体,制备齐墩果酸固体分散体,以累积溶出度为评价指标,考察不同载体比例,药物与载体比例,筛选最佳工艺。通过差式扫描量热法（DSC）、扫描电镜（SEM）、傅里叶红外光谱（FTIR）、粉末X 射线衍射（XRPD）等技术手段对其表征,并考察其溶出度。结果：Soluplus和PVP VA64复合载体比例为3∶2,药物与载体比例为1∶7,制备固体分散体,在45 min时累积溶出度为92.43%,DSC、SEM、XRPD、FTIR等表征结果显示药物以无定形状态存在于固体分散体中,且药物与载体之间存在氢键相互作用。结论：Soluplus和PVP VA64作为复合载体材料,联合应用可显著提高齐墩果酸的体外溶出度。     

Raman and thermal analysis of indomethacin/PVP solid dispersion enteric microparticles

Indomethacin (IMC) and three types of poly-(vinylpyrrolidone) (PVP 12PF, PVP K30 and PVP K90) were studied in the form of solid dispersion, prepared with the solvent evaporation method, by spectroscopic (Raman, FT-IR, X-ray diffraction), thermal (differential scanning calorimetry, thermogravimetry, hot-stage microscopy), fractal and image analysis. Raman and FT-IR micro-spectroscopy indicated the occurrence of drug/polymer interaction and the presence of an amorphous form of IMC, as also resulting from X-ray diffractometry. Hot-stage microscopy suggested that the interaction between IMC and the polymer occurring on heating of a physical mixture, is common to other acidic compounds and causes a depression of the temperature of the appearance of a molten phase. Co-evaporated particles were coated by spray-congealing process with molten stearic acid for gastroprotection, but also for stabilization of the amorphous structure of the drug: the final particles were spherically shaped. Dissolution tests carried out on the final microparticles showed that the coating with stearic acid prevents IMC release at acidic pH and also protects against recovery of the IMC crystallinity, at least after 9 months of aging: the extent and mode of the release, before and after aging, overlap perfectly. The test revealed a notable improvement of the drug release rate from the solid dispersion at suitable pH, with respect to pure IMC. The comparison of the present solid dispersion with IMC/PVP (surface) solid dispersion obtained by freeze-drying of an aqueous suspension, where IMC maintained its crystalline state, revealed that there was no difference concerning the release rate, but suggested a superior quality of this last process as a mean of improving IMC availability for the easiness of preparation and stability, due to the absence of the amorphous state of the drug, as a possible instability source of the system. Finally, the coating with stearic acid is discussed as a determining process for the practical application of solid dispersions.