蒙脱石散对部分喹诺酮类药物的体外吸附作用

目的:比较在人工胃液和水溶液中蒙脱石散对常用剂量的喹诺酮类药物吡哌酸、诺氟沙星、氧氟沙星、盐酸环丙沙星、甲磺酸培氟沙星、盐酸洛美沙星的吸附作用.方法:取蒙脱石散分别加入到上述药物的水溶液和人工胃液中,用紫外分光光度法测定药物含量,计算吸附率.结果:在水溶液中吡哌酸、诺氟沙星、氧氟沙星极微溶.在人工胃液中,药物质子化程度提高,表现为阳离子特性,蒙脱石对其吸附率达98.6%以上.盐酸环丙沙星、甲磺酸培氟沙星、盐酸洛美沙星已与酸成盐,无论在水溶液还是在人工胃液中,蒙脱石对其的吸附率达99%以上.结论:蒙脱石对常用剂量的喹诺酮类药物有强大的吸附作用,服用上述药物应在服用蒙脱石散之后1～2 h.     

蒙脱石对配伍药物体外吸附的影响

目的：比较在水溶液和人工胃液中蒙脱石散对常与其配伍的药物黄连素、雷尼替丁、甲硝唑、头孢氨苄、阿莫西林、磷霉素钙的体外吸附作用。方法：取蒙脱石散分别加入到上述药物的水溶液和人工胃液中，用紫外分光光度法、高碘酸法测定药物含量，计算吸附率。结果：对已成盐的黄连素、雷尼替丁、无论在水溶液还是在人工胃液中，蒙脱石对其吸附率达85．6％以上；甲硝唑、头孢氨苄、阿莫西林、磷霉素钙在人工胃液中质子化程度提高，表现为阳离子特征，蒙脱石对其吸附率达38．4％以上。结论：蒙脱石对上述药物有吸附作用。建议相隔2h服用。     

蒙脱石散对氧氟沙星体外吸附作用研究

目的:研究蒙脱石散对氧氟沙星的体外吸附作用。方法:取不同剂量的氧氟沙星与蒙脱石散分别混合于人工胃液和人工肠液中,(37±0.5)℃水浴恒温1h后过滤,采用紫外分光光度法测定氧氟沙星的含量变化。结果:在人工胃液和人工肠液中,蒙脱石散对氧氟沙星的吸附率分别为(99.76±0.01)%和(99.55±0.02)%。结论:蒙脱石散在人工胃液和人工肠液中对氧氟沙星有强大的吸附作用,应避免同时服用2药。     

果糖注射液与5种药物的配伍稳定性考察

目的:探讨果糖注射液与注射用头孢拉定、利巴韦林注射液、注射用阿昔洛韦、注射用盐酸左氧氟沙星、注射用青霉素钠的配伍稳定性。方法:考察果糖注射液与5种药物分别配伍后的外观、pH值、含量及不溶性微粒的变化,用紫外分光光度法进行光谱扫描。结果:果糖注射液与注射用头孢拉定、利巴韦林注射液、注射用阿昔洛韦、注射用青霉素钠配伍后,外观、含量和pH值均无明显变化,配伍后性质稳定。与注射用盐酸左氧氟沙星配伍后24h内含量显著下降,pH值略有下降,同时混合液出现浑浊现象。结论:果糖注射液与注射用头孢拉定、利巴韦林注射液、注射用阿昔洛韦、注射用青霉素钠在室温下可配伍使用;与注射用盐酸左氧氟沙星的配伍在临床上则应谨慎。     

清开灵注射液与6种药物配伍稳定性考察

目的考察清开灵注射液与注射用青霉素钠、氧氟沙星氯化钠注射液、注射用头孢拉定、注射用阿昔洛韦、注射用更昔洛韦和利巴韦林注射液配伍的稳定性。方法将清开灵注射液与上述6种药物分别配伍，观察配伍后溶液的外观、pH值和含量变化，采用紫外分光光度法进行光谱扫描测定。结果清开灵注射液与青霉素钠和头孢拉定配伍后产生沉淀，颜色加深；与阿昔洛韦配伍后含量显著下降；与阿昔洛韦配伍后2 h内性质稳定，24 h内含量显著下降；与利巴韦林注射液和氧氟沙星氯化钠注射液、更昔洛韦配伍后外观、含量和pH值均无明显变化，配伍后性质稳定。结论清开灵注射液可以和更昔洛韦、氧氟沙星氯化钠注射液、利巴韦林注射液联合使用；与青霉素钠、头孢拉定不能混合使用；与阿昔洛韦配伍应在2 h内滴完。     

蒙脱石散在人工肠液中对盐酸左氧氟沙星的吸附考察

目的探讨蒙脱石散在人工肠液中对盐酸左氧氟沙星片的体外吸附作用。方法不同剂量的盐酸左氧氟沙星与蒙脱石散混合于人工肠液中,在(37±0.5)℃水浴恒温1h后采用紫外分光光度法测定左氧氟沙星的含量变化。结果在人工肠液中,蒙脱石散对左氧氟沙星的吸附率为(99.57±0.01)%。结论蒙脱石散在人工肠液中对左氧氟沙星有较强吸附作用,应避免两药同时服用。     

蒙脱石散在人工肠液中对盐酸左氧氟沙星片的吸附作用观察

目的探讨蒙脱石散在人工肠液中对盐酸左氧氟沙星的体外吸附作用。方法不同剂量的盐酸左氧氟沙星与1小袋蒙脱石散混合于人工肠液中,在(37±0.5)℃水浴恒温1h后过滤,采用紫外分光光度法测定左氧氟沙星的含量变化。结果在人工肠液中蒙脱石散对左氧氟沙星的吸附率为(99.56±0.01)%。结论蒙脱石散在人工肠液中对左氧氟沙星有强大的吸附作用,因此临床应避免将两药同时服用。     

利巴韦林注射液与盐酸雷尼替丁注射液配伍的稳定性考察

目的考察利巴韦林注射液与盐酸雷尼替丁注射液配伍的稳定性。方法在室温下将利巴韦林注射液与盐酸雷尼替丁注射液按1∶1（V/V）的比例配伍，考察24 h内配伍液的外观和pH值变化，用紫外分光光度法和旋光法分别测定配伍液中盐酸雷尼替丁与利巴韦林的含量。结果 室温下，24 h内配伍液的外观、pH值及含量均无明显变化。结论利巴韦林注射液与盐酸雷尼替丁注射液可配伍使用。     

蒙脱石散对6种喹诺酮类药物体外吸附的作用分析

目的：研究蒙脱石散对几种常见喹诺酮类药物体外的吸附作用。方法将临床常用的几种喹诺酮类药物融入水及人工胃液中加入蒙脱石散,用紫外分光光度法进行测定比较。结果氧氟沙星、诺氟沙星、吡哌酸在水溶液中难溶,而在人工胃液中蒙脱石的吸附率均在98％以上;盐酸洛美沙星、盐酸环丙沙星、甲磺酸培氟沙星无论是在水溶液中还是在人工胃液中,蒙脱石散的吸附率均超过99％。结论蒙脱石散对于常用的几种喹诺酮类药物均具有明显的吸附作用,在实际操作中应严格控制两者的使用间隔时间。     

鱼腥草注射液与6种药物配伍的稳定性

目的：探讨中药鱼腥草注射液与青霉素钠、氧氟沙星氯化钠注射液、头孢拉定注射液和阿昔洛韦、更昔洛韦和利巴韦林注射液的配伍稳定性。方法：观察鱼腥草注射液与6种药物分别配伍后的外观，pH和含量变化，用紫外分光光度法进行光谱扫描。结果：鱼腥草注射液与青霉素钠和更昔洛韦配伍后产生沉淀，与阿昔洛韦配伍后含量显著下降，与头孢拉定配伍后2h内性质稳定，24h内含量显著下降，与利巴韦林注射液和氧氟沙星氯化钠注射液配伍后外观，含量和pH均无明显变化，配伍后性质稳定。结论：鱼腥草注射液与氧氟沙星氯化钠注射液、利巴韦林注射液联合使用，呈阴性结果；与青霉素钠、阿昔洛韦、更昔洛韦不能混合使用，呈阳性结果；与头孢拉定配伍应在2h内滴完。     

Effect of antacid on the pharmacokinetics of extended-release formulations of tolterodine and oxybutynin

BACKGROUND: In general, extended-release (ER) formulations are designed to prolong the duration of efficacy and reduce the adverse effects of a drug. These formulations often contain the entire daily dose in a single tablet. Therefore, failure of the ER mechanism not only diminishes the desired benefits, but may temporarily expose the patient to drug concentrations higher than those released from a conventional tablet. In this study we determined whether pH has an effect on drug release from the ER formulations of oxybutynin (OROS technology) and tolterodine (membrane coated beads) in vitro and in vivo. STUDY DESIGN: In vitro studies were based on standardised dissolution experiments for each drug in media of different pH (artificial gastric fluid at pH 1.2, artificial intestinal fluid at pH 7.5, and water). In the two separate, identically designed in vivo studies, single doses of each drug were administered alone and with an antacid to male and female healthy volunteers aged 18-45 years. The randomised, crossover, open-label in vivo studies employed a validated assay to determine plasma concentrations of tolterodine and its metabolite 5-hydroxymethyl tolterodine (5-HM), or oxybutynin and its metabolite N-desethyloxybutynin. RESULTS: The in vitro study showed similar slow and steady drug release from ER-oxybutynin in each pH medium, with 64-71% released after 12 hours. Drug release from ER-tolterodine was steady and slow in artificial gastric fluid, with 72.5% of drug released after 12 hours. However, drug release was much faster in artificial intestinal fluid and water, where 69.8% and 69.1%, respectively, of the drug was released within 4 hours. These in vitro results were consistent with the findings of the in vivo studies. In vivo, the pharmacokinetic profile (peak plasma concentration [C(max)] and area under the concentration-time curve) of ER-oxybutynin was similar after administration with or without antacid, whereas C(max) values of both tolterodine and 5-HM increased significantly when ER-tolterodine was administered with antacid (p < or = 0.017 vs ER-tolterodine alone). CONCLUSIONS: Changes in pH affected the release of tolterodine from ER-tolterodine, while they had no effect on the release of oxybutynin from the proprietary ER technology used in ER-oxybutynin. The technology employed in ER formulations thus determines sensitivity of drug release to external factors.     

Synthetic Zeolites as Controlled‐Release Delivery Systems for Anti‐Inflammatory Drugs

Scientists have always been trying to use artificial zeolites to make modified‐release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10–20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment.     

pH对芸香苷纳米乳的体外释放和稳定性的影响

目的：考察不同pH芸香苷纳米乳的体外释放以及在水及胃肠液中的稳定性。方法：采用HPLC测定芸香苷的含量,以透析法进行芸香苷纳米乳的体外释放实验,利用药物释放模型方程拟合释放曲线。结果：pH6.5、pH 5、pH3.5 3种芸香苷纳米乳在释放介质pH6.863的磷酸盐缓冲液中的释放速率均较芸香苷减缓,释放行为均符合Higuchi模型,降解行为在水和人工胃液中相似,但与在人工肠液中显著不同。纳米乳的降解速率小于对照溶液或基本相同。结论：芸香苷纳米乳具有一定的缓释作用。不同pH纳米乳均可以提高芸香苷的稳定性。     

血管活性肠肽化学及生物学稳定性研究

目的:考察血管活性肠肽(vasoactive intestinal peptide,VIP)的化学及生物学的稳定性,为VIP的制剂学研究提供依据。方法:考察VIP在不同pH值(2.0,4.0,7.0,9.0,11.0,13.0)、不同离子强度溶液、不同温度以及人工胃液和人工肠液中的稳定性,用HPLC法检测VIP含量变化。结果:VIP的稳定性具有pH依赖性,VIP在酸性及中性条件下稳定,pH≤7时几乎无降解,但VIP在碱性条件下不稳定,pH=13时30min已完全降解;离子强度对其稳定性无影响;VIP在冷冻条件下稳定性良好,在冷藏条件下低浓度存在降解;VIP在人工胃液和人工肠液中降解迅速,0 min即完全降解,无法检测到主药峰。结论:VIP化学及生物学的稳定性差,口服无效。     

In vitro evaluation of drug release from self micro-emulsifying drug delivery systems using a biodegradable homolipid from Capra hircus

Self micro-emulsifying drug delivery systems (SMEDDS) are specialized form of delivery systems in which drugs are encapsulated in a lipid base with or without a pharmaceutically acceptable surfactant. In this work, SMEDDS were formulated with a biodegradable homolipid from Capra hircus and Tween 65, and contained lipophilic drug-piroxicam, hydrophilic drug-chlorpheniramine maleate and hydrolipophilic drug-metronidazole. The SMEDDS formulated were evaluated for their drug release and drug content. The drug release studies were conducted in simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and distilled water, representing different pH values. Particle size of the SMEDDS was determined by light microscopy. The results of this study indicated that drug release was affected by the particle size of the SMEDDS. It was found that piroxicam release from the SMEDDS formulated with homolipids from Capra hircus was highest in SIF compared to the other drugs. This method of drug delivery could prove to be a versatile and reliable alternative to conventional drug delivery approaches.     

Development of sensor elements to control drug release from capsular drug delivery systems

The objective of this study was to develop a capsular drug delivery system, which releases the drug when a sensor element is activated by gastrointestinal fluids. The sensor element consists of a microswitch and a control membrane. After disintegration or dissolution of the control membrane the gastrointestinal fluid switches on an electric circuit. Via a gas producing cell the drug reservoir of the capsule is emptied within 6 min.

In vitro experiments with pH-sensitive polymethacrylic sensor membranes (Eudragit S 100) show that prednisolone dihydrogenphosphate is released within a few minutes when the capsule is transferred from gastric juice to artificial intestinal fluid of pH 6.8. Experiments with sensor elements prove that the membrane thickness influences the response time of the sensor. When 32 μm membranes are used, the electric circuit is switched on with a delay of about 70–80 min at pH 6.8. The developed systems are intended to be used as pump systems to deliver drugs into specific areas of the gastrointestinal (GI) tract.     

Studies of chitosan/organic acid/Eudragit RS/RL-coated system for colonic delivery

Prednisolone (PDS) beads were coated sequentially with (i) innermost hydrophobic layer of Eudragit RS/RL, (ii) middle drug release-triggering layer of chitosan, organic acid and Eudragit RS/RL, and (iii) outermost enteric coating layer. Continuous dissolution studies were carried out in artificial gastric fluid (pH 1.2), followed by intestinal fluid (pH 6.8), and finally in colonic fluid (pH 4 and 6) with and without beta-glucosidase. While drug release was prevented in the gastric and small-intestinal fluids, a continuous release was observed in the colonic fluid. Succinic acid provided the fastest rate of release in the colonic fluid compared to citric, tartaric or malic acid. A combined mechanism of drug release is proposed, which considers the swelling of chitosan and Eudragit RS/RL in the presence of succinic acid possibly via electrostatic interaction between the amine groups of chitosan/quaternary ammonium groups of Eudragit RS/RL and the carboxyl groups of succinic acid in aqueous medium. The results of plasma pharmacokinetic studies in Sprague-Dawley rats showed that the developed system provided a significant delay (T(max) 9.3 h) in the absorption profile of PDS compared with simple enteric-coated (T(max) 4 h) or powder (T(max) 1 h) formulation that was taken as proof for the colon-targeted delivery.     

Enhancement of dissolution rate of piroxicam using liquisolid compacts

Piroxicam is a poorly soluble, highly permeable drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal. The poor dissolution rate of water-insoluble drugs is still a major problem confronting the pharmaceutical industry. There are several techniques to enhance the dissolution of poorly soluble drugs. Among them, the technique of liquisolid compacts is a promising technique towards such a novel aim. In this study, the dissolution behaviour of piroxicam from liquisolid compacts was investigated in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). To this end, several liquisolid tablets formulations containing various ratios of drug:Tween 80 (ranging from 10% to 50% w/w) were prepared. The ratio of microcrystalline cellulose (carrier) to silica (coating powder material) was kept constant in all formulations. The results showed that liquisolid compacts demonstrated significantly higher drug release rates than those of conventionally made (capsules and directly compressed tablets containing micronized piroxicam). This was due to an increase in wetting properties and surface of drug available for dissolution.     

乳酸菌在体外模拟胃肠环境中的抗性研究及其发酵特性

目的筛选耐酸、耐胆盐能力强,能耐受人体胃肠环境在肠道中存活生长的乳酸菌菌株.方法对2株链球菌和6株乳杆菌进行耐酸、耐胆盐能力试验,并接种在人工胃液和人工肠液中,在不同时间段取样,活菌计数.结果菌株BLL26在pH值为1.5的培养液中1h,活菌数为107 CFU.mL-1,存活率为5.38%;在猪胆盐浓度0.3%的培养液中,活菌数为108 CFU.mL-1,存活率为58.9%;在人工胃液中3h,活菌数为106 CFU.mL-1;在人工肠液中6h,活菌数没有变化.结论菌株BLL26是能够耐受人体胃肠环境的菌株,其发酵特性适宜酸乳发酵.