Hantzsch condensation reaction as a spectrofluorometric method for determination of alogliptin,an antidiabetic drug,in pure form,tablet form,and human and rat plasma

To analyze alogliptin in its pharmaceutical dosage forms and human plasma, a sensitive, inexpensive, simple, and precise spectrofluorimetric method was developed and tested. This method was also used to investigate the drug’s pharmacokinetic behaviour in the blood of rats. This was based on the Hantzsch reaction, which produces yellowish luminous products that can be detected spectrofluorometrically at 480 and 415 nm for emission and excitation, respectively, when the primary amine group in the examined drug reacts with acetylacetone and formaldehyde. Several experimental parameters that affect the reaction product's development and stability were explored and improved. The curve of fluorescence and concentration for alogliptin was linear in the concentration range 0.05–3.60 μg ml⁻¹. The proposed approach was validated according to International Council for Harmonization criteria. The method was successfully utilized to evaluate the examined drug in dose formulations and spiked human plasma with high accuracy.     

氧化锌软膏联合1%联苯苄唑乳膏对改善外阴阴道假丝酵母菌病患者外阴不适症状的疗效观察

目的:观察氧化锌软膏联合1%联苯苄唑乳膏局部外涂对改善外阴阴道假丝酵母菌病(VVC)患者外阴不适症状的疗效。方法:选择2017年1月至6月在本院妇科门诊就诊的VVC患者148例,根据外阴不适的轻、中、重程度随机分为研究组和对照组,每组各74例。两组患者均阴道内给予克霉唑阴道片1片(睡前),研究组在此基础上于外阴不适处联合外涂氧化锌软膏及1%联苯苄唑乳膏,早晚交替各1次;对照组仅每晚外涂1%联苯苄唑乳膏1次。3天后,比较两组的临床应用效果。结果:研究组和对照组有效率分别为87.84%(65/74)和71.62%(53/74),研究组显著高于对照组(P0.05);两组轻度外阴不适患者治疗后总有效率分别为97.14%(34/35)和94.59%(35/37),差异无统计学意义(P0.05);中度外阴不适患者总有效率分别为82.61%(19/23)和54.55%(12/22),研究组显著高于对照组(P0.05);重度外阴不适患者总有效率分别为75.00%(12/16)和40.00%(6/15),研究组显著高于对照组(P0.05)。结论:氧化锌软膏联合1%联苯苄唑乳膏局部交替外涂用于治疗伴中、重度外阴不适症状的VVC患者的临床疗效显著优于单用1%联苯苄唑乳膏局部外涂。     

酮洛芬缓释片人体药动学和生物等效性研究

目的:评价受试酮洛芬缓释片与参比酮洛芬片的生物等效性。方法:采用反相高效液相色谱法测定24名健康男性志愿受试者交叉单剂量口服受试酮洛芬缓释片与参比酮洛芬片150mg后血浆中酮洛芬的浓度,用3p97程序进行数据处理。结果:口服受试和参比酮洛芬制荆后的AUC_(0-(?))分别是38.94±9.15μg·h·ml~(-1)、38.04±6.90μg·h·ml~(-1);AUC_(0-(?))分别是44.50±8.09μg·h·ml~(-1)、42.99±8.36μg·h·ml~(-1);T_(max)分别是3.87±0.55 h、1.96±0.60h;C_(max)分别是5.78±1.11μg·ml~(-1)、11.62±2.10μg·ml~(-1);t_(1/2)(Ke)分别是5.88±1.16h、1.70±1.40h。结论:受试酮洛芬缓释片与参比酮洛芬片具有生物等效性。     

Compressed matrix core tablet as a quick/slow dual-component delivery system containing ibuprofen

The purpose of the present research was to produce a quick/slow biphasic delivery system for ibuprofen. A dual-component tablet made of a sustained release tableted core and an immediate release tableted coat was prepared by direct compression. Both the core and the coat contained a model drug (ibuprofen). The sustained release effect was achieved with a polymer (hydroxypropyl methylcellulose [HPMC] or ethylcellulose) to modulate the release of the drug. The in vitro drug release profile from these tablets showed the desired biphasic release behavior: the ibuprofen contained in the fast releasing component was dissolved within 2 minutes, whereas the drug in the core tablet was released at different times (⊂16 or >24 hours), depending on the composition of the matrix tablet. Based on the release kinetic parameters calculated, it can be concluded that the HPMC core was suitable for providing a constant and controlled release (zero order) for a long period of time. Published: September 21, 2007     

Tablet formulation studies on nimesulide and meloxicam-cyclodextrin binary systems

The objective of this work was to develop tablet formulations of nimesulide-β-cyclodextrin (NI-β-CD) and meloxicam-γ-cyclodextrin (ME-γ-CD) binary systems. In the case of nimesulide, 3 types of binary systems—physical mixtures, kneaded systems, and coevaporated systems—were studied. In the case of meloxicam, 2 types of binary systems—physical mixtures and kneaded systems—were investigated. Both drug-CD binary systems were prepared at 1∶1 and 1∶2 molar ratio (1∶1M and 1∶2M) and used in formulation studies. The tablet formulations containing drug-CD binary systems prepared by the wet granulation and direct compression methods showed superior dissolution properties when compared with the formulations of the corresponding pure drug formulations. Overall, the dissolution properties of tablet formulations prepared by the direct compression method were superior to those of tablets prepared by the wet granulation method. Selected tablet formulations showed good stability with regard to drug content, disintegration time, hardness, and in vitro dissolution properties over 6 months at 40°C±2°C and 75% relative humidity. Published: May 11, 2007     

坤复康片联合阿莫西林克拉维酸钾对慢性盆腔炎患者血液流变学、红细胞免疫功能和炎症因子的影响

摘要 目的：探讨坤复康片联合阿莫西林克拉维酸钾对慢性盆腔炎患者血液流变学、红细胞免疫功能和炎症因子的影响。方法：采用随机数字表法将我院2021年4月~2022年4月期间收治的98例慢性盆腔炎患者分为对照组（阿莫西林克拉维酸钾干混悬剂治疗,n=49）和研究组（坤复康片联合阿莫西林克拉维酸钾干混悬剂治疗,n=49）。对比两组症状好转时间、血液流变学、红细胞免疫功能和炎症因子水平,观察两种用药方案的安全性。结果：研究组的下腹疼痛、腰骶疼痛、白带量多、经期量多等临床症状好转时间均短于对照组（P<0.05）。研究组治疗14 d后全血高切黏度、全血低切黏度、血浆黏度、纤维蛋白原水平低于对照组（P<0.05）。研究组治疗14 d后血红细胞C3b受体花环率（RBC-C3bRR）高于对照组,免疫复合物花环率（RBC-ICR）低于对照组（P<0.05）。研究组治疗14 d后血清C反应蛋白（CRP）、白细胞介素-17（IL-17）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平低于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。结论：坤复康片联合阿莫西林克拉维酸钾可通过改善慢性盆腔炎患者的血液流变学、炎症因子、红细胞免疫功能来改善临床症状,具有较好的临床疗效。     

Process analytical technology case study part I: Feasibility studies for quantitative near-infrared method development

This article is the first of a series of articles detailing the development of near-infrared (NIR) methods for solid-dosage form analysis. Experiments were conducted at the Duquesne University Center for Pharmaceutical Technology to qualify the capabilities of instrumentation and sample handling systems, evaluate the potential effect of one source of a process signature on calibration development, and compare the utility of reflection and transmission data collection methods. A database of 572 production-scale sample spectra was used to evaluate the interbatch spectral variability of samples produced under routine manufacturing conditions. A second database of 540 spectra from samples produced under various compression conditions was analyzed to determine the feasibility of pooling spectral data acquired from samples produced at diverse scales. Instrument qualification tests were performed, and appropriate limits for instrument performance were established. To evaluate the repeatability of the sample positioning system, multiple measurements of a single tablet were collected. With the application of appropriate spectral preprocessing techniques, sample repositioning error was found to be insignificant with respect to NIR analyses of product quality attributes. Sample shielding was demonstrated to be unnecessary for transmission analyses. A process signature was identified in the reflection data. Additional tests demonstrated that the process signature was largely orthogonal to spectral variation because of hardness. Principal component analysis of the compression sample set data demonstrated the potential for quantitative model development. For the data sets studied, reflection analysis was demonstrated to be more robust than transmission analysis. Published: October 6, 2005 The views presented in this article do not necessarily reflect those of the Food and Drug Administration.     

百乐眠胶囊联合艾司西酞普兰片对失眠伴抑郁焦虑患者睡眠质量、不良情绪以及神经递质水平的影响

摘要 目的：探讨百乐眠胶囊联合艾司西酞普兰片对失眠伴抑郁焦虑患者睡眠质量、不良情绪以及神经递质水平的影响。方法：选取2017年7月~2019年12月期间我院收治的失眠伴抑郁焦虑患者117例,将上述患者根据随机数字表法分为对照组（n=58,艾司西酞普兰片治疗）和研究组（n=59,百乐眠胶囊联合艾司西酞普兰片治疗）,比较两组患者睡眠质量、不良情绪、多导睡眠图（PSG）参数、神经递质水平及不良反应。结果：研究组治疗2个月后的临床总有效率为93.22%（55/59）,高于对照组的79.31%（46/58）（P<0.05）。两组治疗2个月后汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）以及匹兹堡睡眠质量指数（PSQI）评分、睡眠潜伏期、P物质（SP）均较治疗前降低,且研究组低于对照组（P<0.05）。两组治疗2个月后睡眠总时间、睡眠效率、神经肽Y（NPY）、5-羟色胺（5-HT）升高,且研究组高于对照组（P<0.05）。治疗期间研究组不良反应发生率较对照组降低（P<0.05）。结论：失眠伴抑郁焦虑患者经百乐眠胶囊联合艾司西酞普兰片治疗后,睡眠质量、不良情绪得到显著改善,同时还可有效改善血清神经递质水平,减少不良反应,临床应用效果确切。     

Effect of Tacrolimus on the pharmacokinetics of bioactive lignans of Wuzhi tablet (Schisandra sphenanthera extract) and the potential roles of CYP3A and P-gp

We recently reported that Wuzhi tablet (WZ), a preparation of the ethanol extract of Wuweizi (Schisandra sphenanthera), had significant effects on blood concentrations of Tacrolimus (FK506) in renal transplant recipients and rats. The active lignans in WZ are schisandrin A, schisandrin B, schisandrin C, schisandrol A, schisandrol B, schisantherin A, and schisantherin B. Until now, whether the pharmacokinetics of these lignans in WZ would be affected by FK506 remained unknown. Therefore, this study aimed to investigate whether and how FK506 affected pharmacokinetics of lignans in WZ in rats and the potential roles of CYP3A and P-gp. After a single oral co-administration of FK506 and WZ, the blood concentration of lignans in WZ was decreased by FK506; furthermore, the AUC of schisantherin A, schisandrin A, schisandrol A and schisandrol B was only 64.5%, 47.2%, 55.1% and 57.4% of that of WZ alone group, respectively. Transport study in Caco-2 cells showed that these lignans were not substrates of P-gp, suggesting decreased blood concentration of lignans by FK506 was not via P-gp pathway. Metabolism study in the human recombinant CYP 3A showed that these lignans had higher affinity to CYP3A than that of FK506, and thus had a stronger CYP3A-mediated metabolism. It was concluded that the blood concentrations of these lignans were decreased and their CYP3A-mediated metabolisms were increased in the presence of FK506 since these lignans had higher affinity to CYP3A.     

硝苯地平- 海藻酸钠骨架缓释片的制备及处方工艺优化

目的：研制硝苯地平- 海藻酸钠骨架缓释片并优化处方工艺。方法：以海藻酸钠为缓释骨架材料,乳糖为填充剂,硬脂酸镁为润滑剂,乙醇为黏合剂,湿法制粒并制备硝苯地平骨架缓释片。在处方单因素考察的基础上,选择对缓释片释放行为影响较大的3 个处方因素——海藻酸钠用量、磷酸氢钙用量和海藻酸钠黏度,以累积释放度为指标,利用正交实验设计L9(34) 对缓释片处方进行优化。考察制备的硝苯地平骨架缓释片的释放机制。将自制缓释片的体外释放行为和大鼠体内药动学与市售缓释片进行比较。结果：在3 个处方因素中,磷酸氢钙用量对硝苯地平- 海藻酸钠骨架缓释片的体外释放度影响最大,最佳处方组成为45% 海藻酸钠、20% 磷酸氢钙和黏度为105 mPa ? s的海藻酸钠。处方优化的硝苯地平骨架缓释片体外释放行为符合一级动力学方程,属于Baker-Lonsdale 球形扩散机制。与市售产品相比,自制缓释片的缓释效果更好;其经口给予大鼠后,硝苯地平的t max 明显延长,药物作用时间延长及生物利用度提高。结论：自制的硝苯地平-海藻酸钠骨架缓释片具有明显的缓释效果,并优于市售产品。