诺氟沙星—β—环糊精包合物的研究

采用中和法制备诺氟沙星－β－环糊精包合物并经差示扫描量热法证实。选择市售胶囊作对照进行体外溶出度及体内相对生物利用度测定，结果表明，制成包合物后，诺氟沙星的溶出度及生物利用度均有显著提高。     

诺氟沙星－β－环糊精包合物的研究

采用中和法制备诺氟沙星－β－环糊精包合物并经差示扫描量热法证实。选择市售胶囊作对照进行体外溶出度及体内相对生物利用度测定，结果表明，制成包含物后，诺氟沙星的溶出度及生物利用度均有显著提高。     

非诺贝特胶囊剂及家犬体内生物利用度

目的采用纳米分散技术制备非诺贝特胶囊剂,以提高其溶出度及生物利用度。方法用反溶剂沉淀法和高压匀质法制备非诺贝特纳米混悬剂,并通过喷雾干燥将其固化以制备胶囊剂,用差示扫描量热法(differential scanning calorimetry,DSC)和X-射线粉末衍射分析表征药物在胶囊剂中的存在状态,并测定药物的溶出度及家犬体内的生物利用度。结果非诺贝特以纳米晶体状态分散于胶囊剂中,自制胶囊溶出度为国产胶囊的3倍,相对生物利用度为国产胶囊的(274.5±15.6)%。结论自制非诺贝特胶囊剂可以通过增加非诺贝特的分散度来提高药物的溶出度与生物利用度。     

萘普生缓释胶囊与普通片在健康人的药物动力学和生物利用…

用肠溶性辅料将Ｎａｐ制成孔道骨架结构的缓释胶囊，与市售片进行溶出度比较，用ＨＰＬＣ测定健康受试者１次和多次服用本胶囊和片剂后的血药浓度，计算胶囊剂的生物利用度，结果：Ｎａｐ缓释胶囊具有缓释作用，缓释胶囊１次给药后，３～２４ｈ血药浓度在４０～８０μｇ／ｍｌ的有效浓度范围内，多次给药缓释胶囊能较快达到稳态，峰谷浓度波动小，与普通片生物利用度相当，具有生物等效性；体内吸收与体外溶出度有显著相关性，提示Ｎ     

头孢拉定片溶出度测定方法研究

中国药典收载了头孢拉定胶囊,但未收载头孢拉定片。本文根据头孢拉定片与头孢拉定胶囊同为口服胃溶片,用头孢拉定胶囊溶出度测定条件对头孢拉定片溶出度进行了检测,即采用转篮法,以0.1mol/L盐酸为溶剂,转速100rpm,时间为45分钟,测定波长为255nm,测定浓度为25μg/ml;依法测定头孢拉定片6批,溶出量均不少于85％,结果满意。     

尼莫地平片的溶出度和生物利用度的相关性研究

分别用部颁试标、部颁正标和以人工肠液为溶出介质的浆法测得尼莫地平片的溶出度,分别与其体内的生物利用度进行相关性研究。结果表明,按部颁试标测定的溶出度与生物利用度呈无显著性负相关,按部颁正标测定的溶出度与生物利用度呈无显著性正相关,而若采用人工肠液为溶出介质,则所得溶出度与生物利用度呈显著的正相关,即采用人工肠液为溶出介质最为合理。     

尼莫地平片的溶出度和生物利用度的相关性研究

分别用部颁试标、部颁正标和以人工肠液为溶出介质的浆法测得尼莫地平片的溶出度,分别与其体内的生物利用度进行相关性研究。结果表明,按部颁试标测定的溶出度与生物利用度呈无显著性负相关,按部颁正标测定的溶出度与生物利用度呈无显著性正相关,而若采用人工肠液为溶出介质,则所得溶出度与生物利用度呈显著的正相关,即采用人工肠液为溶出介质最为合理。     

β环糊精对甘草酸二铵胶囊体外溶出度和体内生物利用度的影响

建立了测定体外溶出介质中甘草酸二铵（ＤＧ）及血浆中ＤＧ的反相高效液相色谱法，并对含有β－环状糊精（ＣＤ）的ＤＧ胶囊（Ａ）与不含ＣＤ的ＤＧ胶囊（Ｂ）进行了体外港出度和动物体内生物利用度的研究。体外溶出度试验表明：两种胶囊的Ｔ＿（５０）差异非常显著（Ｐ＜０．０１），胶囊Ａ主药的溶出比Ｂ快。生物利用度试验表明：胶囊Ｂ相对于Ａ的口服吸收分数为０．７７．口服胶囊后主药（ＤＧ）的体内过程符合表现一级吸收和一级消除的二室模型。     

7厂家头孢拉定胶囊体外溶出度考察

目的:考察不同厂家生产的头孢拉定胶囊的体外溶出度,为临床选用提供参考。方法:采用转篮法进行体外溶出度试验,以紫外分光光度法测定头孢拉定的含量,计算累积溶出百分率,以双指数模型拟合溶出参数a、b、Td、T80,并用方差分析对组间参数进行统计处理。结果:7厂家头孢拉定胶囊的体外溶出度均符合2005年版《中国药典》中的相关规定,但各厂家产品a、b、Td、T80间均有显著性差异(P<0·01)。结论:不同厂家头孢拉定胶囊的溶出参数存在差异,临床选用时应加以注意。     

萘普生缓释胶囊与普通片在健康人的药物动力学和生物利用度比较

用肠溶性辅料将Nap制成孔道型骨架结构的缓释胶囊,与市售片进行溶出度比较;用HPLC测定健康受试者1次和多次服用本胶囊和片剂后的血药浓度,计算胶囊剂的生物利用度.结果:Nap缓释胶囊具有缓释作用,缓释胶囊1次给药后3～24h血药浓度在40～80μg/ml的有效浓度范围内,多次给药缓释胶囊能较快达到稳态,峰谷浓度波动小,与普通片生物利用度相当,具有生物等效性;体内吸收与体外溶出度有显著相关性.提示Nap能动释胶囊是一种1d眼药1次能够维持有效治疗浓度的新的缓释制剂.     

Preparation of evodiamine solid dispersions and its pharmacokinetics

In order to increase the dissolution rate and bioavailability, solid dispersions of evodiamine in PVP K(30) with different enriched samples of evodiamine to PVP K(30) ratios were prepared by solvent method. Our studies showed that the dissolution rate of evodiamine was significantly higher in the solid dispersion system in comparison with that in enriched samples of evodiamine or physical mixtures. The increase of the dissolution rate was evidently related to the ratio of evodiamine to PVP K(30). The solid dispersion system (enriched samples of evodiamine/PVP K(30)= 1/6, w/w) gave the highest dissolution rate: about 27.7-fold higher than that of enriched samples of evodiamine in hard capsules. Powder X-ray diffraction studies showed that enriched samples of evodiamine presented a total chemical stability after its preparation as solid dispersions. In vivo administration studies indicated that solid dispersions of evodiamine in hard capsules had a higher C(max) and a shorter T(max) than those of physical mixture in hard capsules, and the differences of C(max) and T(max) between them were significant. These results suggest that solid dispersions of evodiamine in hard capsules has a notably faster and greater absorption rate than enriched samples of evodiamine in physical mixture hard capsule and corresponds with the in vitro dissolution.     

Correlation between dissolution rate and bioavailability of different commercial mefenamic acid capsules

A dissolution test was performed with five brands of 250 mg mefenamic acid capsule products available on the market. Three of them, the fast dissolving A and the slow dissolving D and E were subjected to a bioavailability study using a commercially available suspension as the reference. The products were administered orally in a cross-over design to 6 healthy men, and then parameters for the bioavailability were calculated from the plasma concentration-time curve. Analysis of variance indicated several significant differences among the products with respect to C_max, T_max and AUC. The relative availabilities of A, D and E were 86, 81 and 28%, respectively, with the AUC value (0-7 h) for the suspension as 100%.No correlation was observed between the in vitro dissolution rate of the drug from the capsules and the in vivo data, because the dispersing behavior of the capsule exerted a marked influence on its in vitro dissolution rate. To eliminate the influence of the capsule disintegrating process, a dissolution test was done on the contents of the capsules. A good correlation was found between the bioavailability and the dissolution rate of the drug from the capsule contents.Product E with the lowest bioavailability was passed through a 200-mesh sieve, placed in a new capsule, and tested for its bioavailabilky in humans. The AUC value was greater than that of the original product and the bioavailability was about equal to that of the suspension. The in vitro dissolution rate of the drug from the pulverized product E was also markedly increased.     

尼群地平胶丸的研制

采用聚乙二醇４００制备了尼群地平软胶丸,其体外溶出度高于市售片剂。９名健康受试者交叉口服胶丸剂和片剂,胶丸剂的达峰时间（Ｔｍａｘ）提前,峰浓度（Ｃｍａｘ）增高,药时曲线下面积（ＡＵＣ）值增加,经统计学分析,两制剂的生物利用度有显著性差异。     

The pharmacokinetics and bioavailability of urapidil. In vitro/in vivo correlations of different experimental formulations

The pharmacokinetic parameters, including the relative bioavailabilities of two experimental batches of a 60-mg urapidil slow release-capsule and a 30-mg urapidil drinking ampoule (Ebrantil) had to be evaluated in a randomized, three-period change-over study with 12 healthy volunteers after single dosing. The appropriate parameters for the capsule formulations were compared with their dissolution rates obtained by different in vitro models. The capsules showed different half-change, but comparable single-fluid dissolution profiles. Both batches of the capsules showed equivalence with respect to the extent of absorption, in connection with 100% relative bioavailability on average. A correlation of the in vivo parameters Tmax and Cmax with the half-change model can be assumed.     

双氯芬酸钠缓释胶囊的制备及药代动力学

研制了双氯芬酸钠缓释胶囊．结果表明：本品的体外溶出符合一级动力学方程（相关系数ｒ＞０９８），体内血药浓度经时曲线平缓持久，达到良好的缓释效果；生物利用度为９１３％；多剂量口服３天后血药浓度达到稳态；体内吸收分数与体外累积释放分数具有良好的相关性，ｒ＝０９７５（Ｐ＜００１）．     

Preparation and in vitro characterization of a semi-solid dispersion of flurbiprofen with Gelucire 44/14 and Labrasol

Flurbiprofen is characterized by low solubility in water and has been implicated in causing gastro intestinal ulceration. The purpose of this study was to increase the dissolution characteristics of flurbiprofen by preparing a semi-solid dispersion with Gelucire 44/14 and Labrasol (F1) in hard gelatin capsules. The results were evaluated by comparing several in vitro parameters with powdered drug filled into hard gelatin capsules. The in vitro dissolution testing of the dosage forms was performed in different media (simulated gastric fluid, pH 1.2; citrate buffer pH 4.5; phosphate buffers pH 6.8 and 7.2, and water). Characterization of semi-solid dispersions and physical mixtures was performed using Fourier transform-infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), particle size analysis and turbidity measurement. The results suggest that all semi-solid dispersions of flurbiprofen showed a remarkable improvement in the rate and extent of drug dissolution. The dissolution of F1 exhibited significant improvement in all dissolution media at different pH. The dissolution of flurbiprofen within 30 min in pH 1.2 was (55%), in pH 4.5 67%, pH 6.8 96%, pH 7.2 98% and in water 88%. FT-IR indicated no strong drug: excipient interactions, and DSC studies indicated a loss of crystalline nature of the drug. The particle size analysis revealed an average size diameter from 194 to 278 nm. Therefore, a semi-solid dispersion of flurbiprofen with Gelucire and Labrasol may have the potential of improved bioavailability because of the enhanced in vitro properties.     

Bioavailability and in vitro oesophageal sticking tendency of hydroxypropyl methylcellulose capsule formulations and corresponding gelatine capsule formulations

The overall aim of the present study was to widen our knowledge about the biopharmaceutical behaviour of novel hydroxypropyl methylcellulose (HPMC)-based two-piece capsules by comparing them with the classic hard gelatine capsules. Firstly, the tendency of the HPMC capsules to stick to isolated porcine oesophageal preparation was evaluated. The force needed to detach the HPMC capsules from the oesophagus was significantly lower than that for the gelatine capsules (P<0.001), which is evidently an advantage of this new dosage form. The second aim was to investigate the possibility of preparing sustained-release capsules using different powdered HPMCs as diluents (K100, K4M and K15M) and the effect of the molecular weight of HPMC powder on the in vitro and in vivo behaviour of the capsules. In addition to peroral drug administration also rectal dosing was applied. Two groups of eight healthy volunteers participated in randomised, cross-over, single-dose studies. One group was administered capsules orally and the other rectally. There were no marked differences in the bioavailability properties of either the oral or rectal HPMC capsules containing ibuprofen as model drug as compared with corresponding gelatine capsule formulations. Using different viscosity grades of HPMC powders as diluents it was possible to control the absorption rate of the model drug both from gelatine and HPMC capsules as far as the oral route was concerned. After rectal administration there were no statistically significant differences between the formulations containing different grades of HPMC powder. Only partial correlation was observed between the results of the bioavailability studies and the in vitro dissolution studies. From a biopharmaceutical point of view these two shell materials can be regarded as interchangeable.     

The Dissolution and Bioavailability of Etodolac from Capsules Exposed to Conditions of High Relative Humidity and Temperatures

The dissolution and bioavailability of etodolac from capsules exposed to high relative humidity and temperature were compared to those from capsules stored at room temperature (RT). Dissolution of stressed and control capsules was evaluated using a USP basket apparatus at 100 rpm with 900 mL pH 7.5 phosphate buffer (0.05 M) at 37°C. The dissolution of etodolac from capsules exposed to stressed conditions was also evaluated with enzymes (pancreatin, 1%, w/v) added to the dissolution medium. The bioavailability of etodolac from capsules exposed to stressed conditions was compared in both dogs and humans to capsules stored at RT conditions. Capsules, 200 and 300 mg, exposed to stressed conditions failed the dissolution (without enzymes) specification [not less than 85% released (80% Q) in 30 min]. However, upon enzyme addition, all capsules met the specification. The rate and extent of absorption from these 200 and 300 mg etodolac capsules in dogs were equivalent to those from capsules stored at RT conditions that passed the dissolution specification. Similarly, the bioavailability of etodolac from 300 mg capsules that failed the dissolution specification upon exposure to stressed conditions was equivalent to that of control capsules in 24 adult male volunteers. Thus, an in vitro dissolution test with enzymes provides a better indication of stressed capsule performance in vivo.     

消炎痛缓释胶囊的生物利用度研究

消炎痛普通制剂口服吸收迅速,可出现不必要的高血药浓度,导致不良反应。为此我们对三种消炎痛缓释胶囊(A,B,C)和一种常用片剂(D)作了体外溶出试验和体内生物利用度比较。胶囊制剂由丙烯酸类树脂材料E_(30)D包衣的药物小丸制成,其体外溶出行为显示缓慢释放图象。在8名成年男性交叉实验中,不同胶囊制剂和普通片剂之间的Tmax,Cmax和AUC_(0～124)经方差分析无统计学差异,但是在给药后4至12小时的血清浓度—时间曲线,均比普通片剂高而平滑。在第12小时,三种胶囊产生的血清浓度显著高于普通片剂(P<0.1)。根据体外溶出行为和体内生物利用度发现T_(50)或Tmax和包衣厚度呈良好线性关系。