In Vitro System to Evaluate Oral Absorption of Poorly Water-Soluble Drugs: Simultaneous Analysis on Dissolution and Permeation of Drugs

Purpose. The aim of the present work was to develop a new in vitro system to evaluate oral absorption of poorly water-soluble drugs by utilizing Caco-2 monolayers. Methods. Caco-2 monolayer was mounted between side-by-side chambers, which enabled the simultaneous assay of dissolution and permeation of drugs (dissolution/permeation system; D/P system). Apical and basal sides of the chamber were filled with buffer solutions. Drugs were applied to the apical side as powder, suspension, or solution, and then, the permeated amounts into the basal side were monitored for 2 h. At the same time, dissolved amounts of drugs at the apical side were detected. The amount of drug applied to the D/P system was based on its in vivo clinical dose. Results. Sodium taurocholate (5 mM, apical side) and bovine serum albumin (4.5% w/v, basal side) increased the permeated amount of poorly water-soluble drugs. Both additives were considered to be effective at mimicking in vivo conditions of intestinal drug absorption. From the correlation between the permeated amount of 13 drugs (% dose/2 h) in the D/P system and their percentage dose absorbed in humans in vivo, this system was found to be useful in evaluating oral absorption of poorly water-soluble drugs. Conclusions. With attempts made to mimic the physiologic conditions of the human GI tract, in vivo oral absorption of drugs was quantitatively assessed in the D/P system in vitro. This system is quite useful to predict the oral absorption of poorly water-soluble drugs after administration as solid dosage forms.     

The action of cisapride on gastric emptying and the pharmacodynamics and pharmacokinetics of oral diazepam

Summary The effects of the benzamide cisapride (C) (8 mg) i.v. have been compared to placebo (P) in a double blind randomised study. The effects on gastric emptying, the absorption and effects of oral diazepam, and BP and pulse were observed.Cisapride increased the rate of gastric emptying of 500 ml liquid containing diazepam 10 mg (t_1/2 C: 7.4 min, P: 14.9 min). The initial rate of absorption of diazepam contained in the drink was increased by C (AUC 0–1 h C: 328 µg h 1^–1, P: 253 µg h 1^–1, but there was no change in overall bioavailability. This change in diazepam kinetics was associated with a significantly greater impairment in reaction time in the first 45 min after drinking but not in self rated sedation. Cisapride produced a significant tachycardia (e.g. after 10 min C: 82 beats/min, P: 69 beats/min) which probably reflects a peripheral vasodilator action. Cisapride may therefore alter the pharmacokinetics and dynamics of concurrently administered drugs.     

Ultrafast Studies of ZrTe3 by Transient Absorption Spectrometer

Two-dimensional (2D) tri-TMDCs carrier dynamics provide a platform for studying excitons through Ultrafast Pump-Probe Transient Absorption Spectroscopy. Here we studied the ZrTe₃ nanosheets (NTs) exciton dynamics by transient absorption (TA) spectrometer. We observed different carrier dynamics in the ZrTe₃ NTs sample at different pump powers and with many wavelengths in the transient absorption spectrometer. The shorter life decay constant is associated with electron-phonon relaxation. Similarly, the longer-life decay constant represents the long live process that is associated with charge separation. The interactions between carrier-phonons at nanoscale materials can be changed by phonons quantum confinements. The hot carrier lifetime determined the strength of carrier phonon interactions. The value of fast decay in the conduction band is due to carrier relaxation or the carrier gets trapped due to surface states or localized defects. The value of slow decay is due to the recombination of surface state and localized defects processes. The lifetime declines for long wavelengths as size decreases. Whereas, during short wavelength-independent decay, carrier characteristics have been observed. TA spectroscopy is employed to investigate insight information of the carrier’s dynamical processes such as carrier lifetime, cooling dynamics, carrier diffusion, and carrier excitations. The absorption enhanced along excitons density with the increase of pump power, which caused a greater number of carriers in the excited state than in the ground state. The TA signals consist of trap carriers and (electron-hole) constituents, which can be increased by TA changes that rely on photoexcitation and carrier properties.     

养正胶囊制备工艺研究

目的研究养正胶囊适宜辅料及制备工艺。方法以颗粒的休止角、粒度、堆密度以及颗粒的吸湿性曲线和颗粒的CRH为考察指标,筛选出合适的辅料及最佳制备工艺。结果颗粒的CRH为62.5%,颗粒质量适合生产。结论该工艺切实可行,适于工业化大生产。     

复方骨质增生贴剂体外透皮速率测定和体外释放研究

目的研究复方骨质增生贴剂(CPH)的经皮吸收的可行性.方法采用高效液相色谱法测定透皮接受液和释放接受液中指标成分-阿魏酸的浓度.结果体外透皮实验和体外释放实验结果表明阿魏酸在24h内以一定的速率0.2142μg·cm-2·h-1恒速渗透,其释放符合Higuchi方程.此外,该贴剂的体外释放速率为14.53μg·cm-2·h-1/2.结论复方骨质增生贴剂为皮肤限速型的骨架控释系统.     

消瘤止痛巴布剂中苦参碱的体外透皮吸收实验

目的测定消瘤止痛巴布剂和消瘤止痛软膏中苦参碱的体外经皮渗透性.方法采用高效液相色谱法和Franz扩展池法以小鼠皮为透过屏障进行观察.结果消瘤止痛巴布剂中苦参碱能透过小鼠皮.结论且巴布剂优于软膏剂(P＜0.05).     

Percutaneous Absorption of Nicardipine and Ketorolac in Rhesus Monkeys

Vehicle effects on the percutaneous absorption of nicardipine base, nicardipine hydrochloride, ketorolac acid, and ketorolac tromethamine were determined using the rhesus monkey as an in vivo model for human skin penetration. Vehicles investigated included blends of propylene glycol, trimethylene glycol, ethanol, Azone, Tween 20, water, and long-chain fatty acids. Formulations were prepared such that the compound dose, application area, and percentage saturation of the compound in the vehicle were held constant. Variations in absorption of the compounds were therefore attributable to vehicle effects. Each formulation was applied to three monkeys for a period of 24 hr using 10 Hill Top Chambers. Plasma samples were taken at appropriate intervals for 36 to 48 hr. The results indicated that trimethylene glycol and Tween 20 did not enhance absorption of the test compounds despite claims by other investigators. Azone and ethanol provided moderate enhancement of both the rate and the extent of absorption, while long-chain fatty acids in combination with propylene glycol significantly enhanced penetration. In general, higher fluxes were observed with the more lipophilic compounds nicardipine base and ketorolac acid as compared to the hydrochloride and tromethamine salts.     

分子吸收光度法测定万寿菊中代森锰锌残留量

目的:采用分子吸收光度法测定万寿菊中代森锰锌残留。方法:通过蒸馏和溶液吸收实验装置,氯化亚锡催化,二乙基二硫代氨基甲酸钠分解定量产生二硫化碳气体,通过浓硫酸脱氧脱水,氢氧化钾的甲醇液吸收,用分光光度法在304 nm波长处测定其标准曲线。代森锰锌以平均相对分子质量333计,可通过平均相对分子质量计算出代谢锰锌的含量。结果:万寿菊中添加浓度为10 mg.kg-1和20 mg.kg-1(以二硫化碳计)的回收率(n=5)分别为95.9%和93.2%,RSD分别为4.8%和3.7%;最低检测限为2 mg.kg-1。结论:该方法操作简单,灵敏度高,适合大批量样品的检测。     

Pharmacokinetics of ampicillin and its prodrugs bacampicillin and pivampicillin in man

Five healthy fasting male subjects were each given single doses of intravenous ampicillin (471 mg), oral ampicillin tablets (495 mg), oral bacampicillin hydrochloride tablets (562 mg ampicillin equivalent), and oral pivampicillin hydrochloride capsules (491 mg ampicillin equivalent) in a crossover experiment. The resulting concentrations of ampicillin were determined in plasma and urine. The pharmacokinetic analysis was made according to a two-compartment open model. The total distribution volume of unbound ampicillin during the disposition phase was 0.247 ± 0.045 (sd) liter/kg, which is only slightly more than the extracellular fluid, suggesting that tissue binding and intracellular distribution of ampicillin are limited. The bioavailability of the esters bacampicillin (86 ± 11%) and pivampicillin (92± 18%) was significantly greater than that of ampicillin (62 ± 17%); however, the difference between the esters was not statistically significant. The absorption for all drugs given orally proceeded at a constant rate, suggesting zero-order release rates from the products. The absorption rate was highest for bacampicillin (0.89 ± 0.39% of dose absorbed per minute), followed by pivampicillin (0.64 ± 0.19) and ampicillin (0.58 ± 0.16). Bacampicillin also had the shortest lag time for the start of absorption (7.0 ± 0.9 min) under the present conditions. Thus, in comparison with ampicillin, the esters have a higher bioavailability, which, in fact, is close to the theoretically highest possible value by clearance concepts. The higher bioavailability in connection with higher absorption rates may be clinically important in ampicillin treatment by the oral route.This work was supported by the Swedish Medical Research Council, Project No. 522 (L. O. B.).     

原发性高血压红细胞膜结合钙的测定

用火焰原子吸收法测定红细胞膜结合钙含量。测定健康者35例,D为4.68±1.37μg/mg膜蛋白;原发性高血压患者34例。D为2.00±0.26μg/mg膜蛋白。测定结果表明,原发性高血压细胞膜结合钙含量明显低于对照组(P<0.01)。该测定方法的回收率为98.23％～104.68％,相对标准偏差小于3.18％。