Liposomes with nifedipine and nifedipine-cyclodextrin complex: calorimetrical and plasma stability comparison

Inclusion complexes of nifedipine with 2-hydroxypropyl-ß-cyclodextrin (HPβCD) were formed by the spray- and freeze-drying methods. Nifedipine or its inclusion complexes (Nifedipine-CD complex I and II) were incorporated into liposomes prepared by the ethanol injection method. The highest entrapment value (77.7% of the starting material) was achieved for liposomes with N-CD complex II. The interaction of nifedipine with lipid bilayers was measured calorimetrically. DPPC liposomes mixed with nifedipine or N-CD complex II showed a slight shift of the transition temperature of DPPC towards lower temperatures compared to DPPC liposomes alone or mixed with HPßCD. However, with nifedipine, an additional transition peak was seen at lower temperatures in the second and all subsequent scans which could not be detected for the N-CD complex. Plasma stability studies showed that liposomes containing N-CD complex II are more stable than liposomes containing nifedipine. Encapsulation of drug-cyclodextrin complexes into liposomes can increase the entrapment of the lipophilic drug and reduce its release from the carrier.     

多相脂质体139注射液化学稳定性的研究

本文根据多相脂质体139注射液的处方组成及其主要有效成份的结构和性质,设计了利用碘量法测定139注射液中不饱和度(双键氧化)和电导滴定法测定酸度的变化规律,得出包封于脂质体中药物的氧化反应符合零级反应速度方程,载体主要成分的脂键水解反应也符合零级反应速度方程;并求得了多相脂质体139注射液中双键氧化反应与载体成分的水解反应的活化能和反应速度常数;预测了药物贮存期 t_(0.9)~(25℃)=2.63年。同时,本文提出了利用电导滴定曲线确定在缓冲溶液及多种化学成份的复杂体系中弱酸盐滴定终点的新方法。     

极谱测定锌与大分子配合物生成常数及分子量

本文采用常规极谱法测定了锌离子与几种蛋白质等大分手的配合物生成常数及大分子的分子量.在溶液中,简单金属离子和配离子的扩散系数不同,则扩散电流不同,扩散电流变化发生转折,由实验求出大分子溶液的浓度,就能求出大分子的分子量.在25℃,测得简单金属离子和配离子的扩散电流(id)s和(id)c及半波电位((E1)/2)s和(E(1/2))c,根据公式:logK=n·△((E1)/2)0.05915—log0.5—leg[MX]可以计算出金属离子与蛋白质等大分子配合物的生成常数K.     

Mivacurium in short to intermediate surgical procedures

Mivacurium, a new benzylisoquinoline muscle relaxant, appears to be close to the ideal for short to intermediate surgical procedures. Ideal properties of such an agent are discussed, in addition to indications for muscle relaxation in such procedures. Two studies are presented, showing the onset and offset times of mivacurium and its cardiovascular stability in both young and elderly patients. It is concluded that it is a well-tolerated and appropriate agent for use in short to intermediate surgical procedures in those patients with normal plasma cholinesterase function, despite a slight prolongation of action in the elderly.     

Analytical Approaches to the Study of Monoclonal Antibody Stability

The stability of two purified monoclonal antibodies, MN12 and WT31, was investigated. The monoclonal antibodies were incubated for 32 days at different pH values (ranging from 3.0 to 10.0) at 4 and 37°C. Various analytical methods were used to assess changes in physicochemical properties of the proteins. The monoclonal antibodies were more susceptible to degradation at 37°C than at 4°C. At low pH irreversible precipitation occurred. Decomposition of the proteins was enhanced at increasing pH values in the alkaline range. This was concluded from mouse IgG-specific and antigen-specific enzyme-linked immunosorbent assays, flow cytometry, analytical gel permeation chromatography, sodium dodecyl sulfate–polyacrylamide gel electrophoresis, isoelectric focusing, and immunoblotting. No substantial change in the apparent affinity constant of MN12 was observed, as determined by an affinity enzyme-linked immunosorbent assay. Fluorescence spectra, fluorescence polarization values, and fluorescence quenching parameters of MN12 and WT31 were not substantially affected, indicating that no major irreversible conformational changes had occurred. It was concluded that each of the techniques used has only limited value for stability assessment of monoclonal antibodies and, hence, that the application of several analytical techniques is essential to gain insight into monoclonal antibody stability.     

Potential Improvement in Shelf Life Using the Prodrug Approach. II. A Systematic Examination of Kinetic Requirements

The utilization time (UT) for a solution of a prodrug that is rapidly and completely converted to drug in the blood may be longer than the time for 10% loss of the initial concentration. The UT for an intravenous prodrug solution is the period during which the total prodrug and drug concentration exceeds 90% of the initial concentration. The influence of the rate of prodrug degradation (k _nc), its conversion (k _c) to drug, and the subsequent drug degradation (k _h) on the UT of a stored solution was examined by simulating the prodrug and drug concentration–time courses. The ratio of the shelf life of a prodrug solution to that of the parent drug (UT_ratio) was calculated using a wide range of values for the three rate constants. Three-dimensional plots relating the UT_ratio to the k _c, k _nc, and k _h values provide a basis for making a priori assessments of kinetic requirements for designing a prodrug to increase storage time. A parenteral prodrug intended to increase storage time may have a larger overall rate of loss than the parent drug, but it must have a smaller degradation rate (k _nc < k _h) to be successful. The UT for an oral prodrug solution depends upon the bioavailability of the prodrug relative to the drug in addition to the values for k_nc, k _c, and k _h. Two ampicillin prodrugs were used as models to calculate actual UT_ratio versus pH profiles. Intravenous solutions showed modest gains in the UT_ratio in the acid region, whereas oral solutions reached a UT_ratio as high as 22 by combining favorable rate constants with increased bioavailability. These actual UT_ratio versus pH profiles were interpreted in terms of the theory established using the simulations.     

动态市场经济行为模型及其分歧、浑沌现象之分析

根据市场经济的行为特点,结合考虑人的心理因素等影响,提出了一种新的市场动态行为模型,并讨论了它的几种扩展形式,随后对其解的稳定性做了分析。通过仿真实验,发现此系统中存在着非线性动态系统所特有的分歧、浑沌现象。     

Stability of bupivacaine hydrochloride with diamorphine hydrochloride in an epidural infusion

The stability of diamorphine (0.02 mg/ml as the hydrochloride) in 250 ml bupivacaine hydrochloride (0.15% wt/vol infusion) was studied by high pressure liquid chromatography at temperatures in the range 7 to 45°C. Diamorphine hydrochloride was degraded by approximately 0.13% per day at 7°C. No bupivacaine hydrochloride degradation was detectable during the study. The storage life of the combination at 7°C, based on the lower 95% confidence limit of the time to 5% diamorphine hydrochloride degradation, was 14 days. The stability at 25°C was adequate to allow transport and administration over 24 h at ambient temperature. Stability was also maintained for at least 24 h at 32 and 45°C. Infusion of the mixture with an ambulatory infusion pump which uses a standard polyvinyl chloride infusion bag is therefore possible. A study of its compatibility with different infusion pump medication reservoirs was not undertaken. The drugs were also stable on frozen storage at –18°C for up to 6 months.     

硫酸长春新碱在0.9%氯化钠注射液中的稳定性研究

本文用紫外分光光度法对硫酸长春新碱在０．９％氯化钠注射液中的稳定性，按经典恒温加速试验法进行了动力学实验研究，结果表明，硫酸长春新碱的降解为一级反应。２５℃，３２℃时硫酸长春新碱的有效期ｔ０．９分别为１２．５１ｈ，８．８６ｈ。为临床合理用药提供了确切的数据。