Preparation and in vitro release of dual-drug resinate complexes containing codeine and chlorpheniramine

Objective: To develop the dual-drug resinate complexes containing codeine and chlorpheniramine with a novel batch processing, characterize the dual-drug resinate complexes, and study its drug release behavior in vitro. Methods: A procedure of simultaneous dual-drug loading using combination solutions composed of different proportions of codeine phosphate and chlorpheniramine maleate was performed to achieve the specific resinate, and the dual-drug loading content was determined by high-performance liquid chromatography method. The dual-drug resinate complexes were characterized by a scanning electron microscope, and the formation mechanisms were confirmed with X-ray diffraction analyses and differential scanning calorimetric analyses. The release behavior of the two drugs from the dual-drug resinate complexes in vitro was studied in the media simulating in vivo environments (simulated gastric fluid: pH = 1.2 HCl, simulated in vivo ionic strength: 0.15 M NaCl, and simulated intestinal fluid: pH = 6.8 buffer solution containing KH2PO4–NaOH). Results: Scanning electron microscopic analyses proved that the dual-drug resinate complexes had the same appearance and characters as the initiative ion exchange resins (IERs). Via X-ray diffraction and differential scanning calorimetric analyses, it is found that the two drugs in dual-drug resinate complexes were combined with IERs by chemical bond. The drug-resinate complex, like IER, was in amorphous state. More than 90% of codeine phosphate was released in 15 minutes in three different media, whereas little amount of chlorpheniramine maleate was released in all the release time in the medium pH = 1.2 HCl, and the release equilibrium time was about 5 minutes, only 40% was released in the medium 0.15 M NaCl, and the equilibrium time was 40 minutes, and about 90% was released in the medium pH = 6.8 KH2PO4–NaOH. The increased ionic strength generally accelerated the release of the two drugs from the dual-drug resinate complexes. Conclusion: The dual-drug resinate complexes were formed through the reaction between the drugs and the IERs by chemical bond. The release behavior of the drug from the dual-drug resinate complexes in vitro was mainly correlated with the drug molecular structure, the eluting ionic strength, composition, and ionic strength of the release media. The novel dual-drug resinate complexes could be used to deliver two drugs in one therapeutic dose.     

累托石对水中扑尔敏的吸附性能

对累托石对水中扑尔敏的吸附性能进行了研究,系统地研究了吸附时间、溶液浓度、pH值对其吸附行为产生的影响。实验结果表明:累托石对扑尔敏的吸附速率先快速增大后趋于平缓,反应系统达到吸附平衡的时间约为22 h;在等温吸附研究中,室温下累托石对扑尔敏的最大吸附量为121.76 mg/g,吸附等温线方程符合Langmuir等温模型;吸附行为符合拟二级动力学方程;在pH值为2～8时,吸附量随pH值的升高而增大。     

扑尔敏对映体的毛细管电泳分离研究

本文采用毛细管电泳对扑尔敏对映体的分离进行了讨论。测定了不同pH值条下两对映体与β-环糊精相互作用的结合常数,讨论了结合常数与分离选择性的关系。针对理论计算出的两对映体淌度差达到最大时所需的β-环糊精最佳浓度理论值与达到最大分离度所需的β-环糊精实际浓度值之间存在一定偏差的现象,结合分离度的定义,推导了分离度与对映体淌度之间的关系并进行了验证。     

"Histamine H? receptors mediate morphine-induced locomotor hyperactivity of the C57BL/6J mouse": Correction to Mickley.

Reports an error in "Histamine H? receptors mediate morphine-induced locomotor hyperactivity of the C57BL/6J mouse" by G. Andrew Mickley (Behavioral Neuroscience, 1986[Feb], Vol 100[1], 79-84). An incorrect word was inadvertently printed. The last sentence of the introduction (p. 79) should read "This was accomplished by challenging the opiate-stimulated locomotion of the C57BL/6J mouse with injections of antihistamines into the nucleus accumbens/stria terminalis or lateral ventricles." (The following abstract of the original article appeared in record 1986-14026-001.) Locomotor hyperactivity induced in C57BL/6J male mice (N=43) by intraperitoneal morphine sulfate (30 mg/kg) was challenged with intracranial injections of antihistamines or the opiate antagonist naloxone HCl (2 μg). When 75 μg of cimetidine, an H? receptor blocker, was injected into the nucleus accumbens/stria terminalis, it significantly reduced opiate-stimulated locomotion. However, ventricular injections of cimetidine did not significantly alter hyperactivity induced by either morphine or dextroamphetamine sulfate (4 mg/kg), nor did cimetidine depress spontaneous locomotion. Although naloxone eliminated morphine-induced locomotion when injected into either the nucleus accumbens or the ventricles, chlorpheniramine (20 μg), an H? receptor blocker, failed to reduce this behavior. Data suggest that opiate-stimulated locomotion of the C57BL/6J mouse may be partially mediated by histamine H? receptors of the nucleus accumbens or closely adjacent structures. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

马来酸氯苯那敏片健康人体药动学和相对生物利用度

目的: 研究马来酸氯苯那敏片剂在健康人体内的相对生物利用度。方法: 采用HPLC 法测定18名男性健康志愿者单剂量交叉口服马来酸氯苯那敏片参比制剂和被试制剂8 mg 后不同时间血浆药物浓度。用3P97 药动学软件进行药动学参数计算及生物等效性评价。结果: 参比和被试制剂的药-时曲线均符合一房室模型,两制剂的主要药动学参数如下:C_max 分别为(15.74±7.06)μg·L^-1 和(14.88±4.40)μg·L^-1;t_max 分别为(3.9±1.2) h 和(4.5±0.8) h;t_1/2ke 分别为(15.54±3.76) h 和(14.49±3.24) h;AUC_0-t 分别为(248.86±78.52)μg·h·L^-1和(245.09±90.77)μg·h·L^-1,AUC_0-∞分别为(292.64±99.21)μg·h·L^-1 和(282.04±98.64)μg·h·L^-1 。与标准参比制剂相比,被试制剂的相对生物利用度F_0-t为(1 04.1±36.1) %,F_0-∞为(103.2±35.6) %。结论: 方差分析与双单侧t 检验证明,两种制剂具有生物等效性。     

气相色谱-串联质谱法测定动植物源性食品中氯苯胺灵残留量

建立气相色谱-串联质谱测定动植物源食品中氯苯胺灵残留量的分析方法。样品采用优化QuEChERS及固相萃取法前处理，HP-5MS气相色谱柱进行分离，采用外标法进行定量。结果显示，本方法测定的香蕉样品在0.01～0.5 μg/mL范围内线性关系良好，测定的动物食品样品在0.03～1 μg/mL范围内线性关系良好，相关系数R2均大于0.999。在3 种基质中进行的加标回收实验测得回收率在80.6%～107.8%之间，相对标准偏差在2.3%～8.5%之间。本研究开发了动植物源食品中氯苯胺灵的检测方法，操作简便、重复性好，适用于批量样品检测，为评估氯苯胺灵的膳食摄入风险提供了理论依据。     

Facile fabrication of pH-responsive and swellable slow release microparticles of chlorpheniramine maleate with chitosan-starch matrices and their crosslinks

Abstract

We synthesized chitosan and modified same by blending with starch, crosslinking the matrices with sodium tripolyphosphate (TPP) and encapsulation with the drug chlorpheniramine maleate (CPM). These microparticles were characterized by FTIR, TGA, and SEM techniques. The amounts of CPM released from the microparticles generally decreased for the TPP-crosslinked beads but increased as the starch composition increased. Their release rates were best described by zero-order kinetics while their release mechanisms followed less-Fickian diffusional release. Our findings show that both the uncrosslinked and crosslinked chitosan-starch beads are promising carriers for the slow release of CPM.     

用毛细管电泳分离朴尔敏对映体

目的研究谷氨酸-β-CD和β-CD混合手性剂对扑尔敏对映体的分离. 方法谷氨酸-β-CD和β-CD混合,然后用作手性剂,重点考察β-CD和谷氨酸-β-CD的浓度、操作电压、背景电解质溶液pH值对β-CD和谷氨酸-β-CD混合体系分离扑尔敏对映体的影响. 结果混合手性剂的手性识别能力大于单一手性剂的手性识别能力;在pH 4以下,该混合体系对扑尔敏对映体的分离基本不受背景电解质溶液pH值的影响且具有较高的重现性. 结论采用β-CD和谷氨酸-β-CD混合体系作手性剂有利于扑尔敏的分离.     

Chiral Separation of Chlorpheniramine by Capillary Electrophoresis

目的研究谷氨酸βＣＤ和βＣＤ混合手性剂对扑尔敏对映体的分离．方法谷氨酸βＣＤ和βＣＤ混合，然后用作手性剂，重点考察βＣＤ和谷氨酸βＣＤ的浓度、操作电压、背景电解质溶液ｐＨ值对βＣＤ和谷氨酸βＣＤ混合体系分离扑尔敏对映体的影响．结果混合手性剂的手性识别能力大于单一手性剂的手性识别能力；在ｐＨ４以下，该混合体系对扑尔敏对映体的分离基本不受背景电解质溶液ｐＨ值的影响且具有较高的重现性．结论采用βＣＤ和谷氨酸βＣＤ混合体系作手性剂有利于扑尔敏的分离．     

盐酸氮卓斯汀对豚鼠实验性哮喘的作用及其机理研究

目的: 观察盐酸氮卓 斯汀(azelastine hydrochloride,AZ) 对豚鼠实验性哮喘的作用, 并探讨其作用机制。方法: 采用组胺和乙酰胆碱诱发在体豚鼠实验性哮喘模型, 观察AZ的整体作用;采用豚鼠离体气管螺旋条, 观察AZ对组胺所致的豚鼠离体气管螺旋条痉挛的拮抗作用。结果: AZ 能够剂量依赖性地拮抗组胺和乙酰胆碱的引喘作用, 明显延长引喘潜伏期, 显著减少抽搐动物发生率, 其ED50为0.216 mg·kg^-1,95 %可信限为0.214 ~ 0.219 mg·kg^-1 。AZ 可剂量依赖性地拮抗组胺对离体气管平滑肌的收缩作用, 使组胺量效曲线平行右移, 其pA2 值为8.99 。结论: 预先给予AZ能显著拮抗组胺和乙酰胆碱所诱发的在体豚鼠实验性哮喘, 抑制组胺所致的气管螺旋条收缩。