Extended tacrolimus release via the combination of lipid-based solid dispersion and HPMC hydrogel matrix tablets

The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacrolimus solid dispersion was prepared using glycerylbehenate(Compritol~?ATO888) and Pluronic F127 as the carrier materials with hot-melt method, which was then blended with hydrogel matrix materials, such as HPMC and lactose, the powders were directly compressed into tablets. In vitro drug release tests were carried out to evaluate the performance of the solid dispersions and the tablets. The dissolution rate of tacrolimus was significantly improved by the lipid-based solid dispersion, and the incorporation of HPC into the solid dispersion obviously improved its stability after storage. Extended release tablets loaded with tacrolimus solid dispersion showed prolonged drug release patterns over 24 h, the release patterns of the tablets can be tailored by the compositions of the matrix materials, including the types and content of HPMCs. A modified processing method that directly mixed the melted solid dispersion with HPMC powders improved the uniformity of the solid dispersion inside the tablet matrix and release profile. The release data of the extended release tablet fitted well to the Korsmeyer–Peppas model with n value of 0.85, which suggested diffusion-and erosion-controlled release mechanism. The combination of lipid-based solid dispersion and HPMC hydrogel matrix may find wide applications in the extended release dosage forms of high potent, water-insoluble drugs.

Rapid analysis of spatial distribution of PVPP and hardness of Yinhuang dispersible tablets by NIR-CI

The present study aimed at investigating the relationship between tablet hardness and homogeneity of different Yinhuang dispersible tablets by near-infrared chemical imaging(NIR-CI)technology.The regularity of best hardness was founded between tablet hardness and the spatial distribution uniformity of Yinhuang dispersible tablets.The ingredients homogeneity of Yinhuang dispersible tablets could be spatially determined using basic analysis of correlation between analysis(BACRA)method and binary image.Then different hardnesses of Yinhuang dispersible tablets were measured.Finally,the regularity between tablet hardness and the spatial distribution uniformity of Yinhuang dispersible tablets was illuminated by quantifying the agglomerate of polyvinyl poly pyrrolidone(PVPP).The result demonstrated that the distribution of PVPP was unstable when the hardness was too large or too small,while the agglomerate of PVPP was smaller and more stable when the best tablet hardness was 75 N.This paper provided a novel methodology for selecting the best hardness in the tabletting process of Chinese Medicine Tablet.

粉末压片-波长色散型X射线荧光光谱法测定废弃印刷线路板中10种金属元素的含量

测定废弃印刷线路板(WPCBs)中金属元素含量的方法均需对样品进行消解,操作复杂耗时;X射线荧光光谱法无需样品消解,但由于缺少相似基体的标准样品而定量不准确。基于此,以与WPCBs在元素组成上较为相似的地质类标准物质作为本底物,按不同比例添加环氧树脂及铜粉制备一系列校准样品并绘制校准曲线,提出了题示研究。取WPCBs研磨,过200目(0.074 mm)筛,于105℃烘干,取上述样品5 g置于不锈钢模具中,加入硼酸镶边,用压片机(压力200 kPa,保压时间20 s)制成直径40 mm圆片,采用波长色散型X射线荧光光谱法(WD-XRF)测定其中银、钡、铬、铜、铁、锰、镍、铅、硅、钛等10种金属元素的含量。结果表明:各元素的质量分数在一定范围内与响应强度呈线性关系;方法用于分析其他校准样品,测定值的相对误差的绝对值不大于20%;方法用于测定2个实际WPCBs样品分析,硅的测定结果与氟硅酸钾容量法的基本一致,其他元素测定结果与电感耦合等离子体原子发射光谱法(ICP-AES)的基本一致。

Study on the Clinical Efficacy of Megestrol Acetate Dispersible Tablets in Adjuvant Treatment of Acute Leukemia

Objective:To analyze the clinical efficacy of megestrol acetate dispersible tablets in the adjuvant treatment of acute leukemia.Methods:80 patients with acute leukemia admitted from December 2021 to December 2022 were randomly divided into two groups.The control group underwent chemotherapy,and the observation group took megestrol acetate dispersible tablets and underwent chemotherapy.The effect of the treatments were evaluated by analyzing the albumin(Alb)and prealbumin(Palb)indicators,and the adverse reactions were observed.Results:There was no significant difference in Alb and Palb indexes between the two groups before treatment(P>0.05).After treatment,Alb and Palb indexes in the observation group were greater than those in the control group(P<0.05).The incidence of adverse reactions in the control group was 20.00%,which was significantly higher than the observation group(5.00%),with P<0.05.Conclusion:The combination of megestrol acetate dispersible tablets and chemotherapy is more effective in treating patients with acute leukemia,and the Alb and Palb indexes can be optimized.Besides,there are fewer adverse reactions,which means that the treatment is relatively safe.

ZIF-8泡腾辅助分散固相萃取结合高效液相色谱-串联质谱法测定人尿液中苯二氮卓类药物

发展了基于沸石咪唑酯骨架材料-8(ZIF-8)的泡腾辅助分散固相萃取(ET-DSPE)技术,结合高效液相色谱-串联质谱法(HPLC-MS/MS)对人尿液中艾司唑仑、阿普唑仑、地西泮、三唑仑和劳拉西泮5种苯二氮卓类药物(BZDs)进行分析。采用傅里叶变换红外光谱、X射线衍射仪、扫描电子显微镜和全自动比表面积及孔隙分析仪对ZIF-8进行表征,并考察了ZIF-8和Na_(2)CO_(3)用量、吸附时间、溶液pH值及离子强度、尿液稀释比例、洗脱溶剂、洗脱体积和时间对BZDs萃取效率的影响。在最佳条件下,艾司唑仑在0.002~100 ng/mL,其余4种BZDs在0.001~100 ng/mL范围内线性关系良好(r≥0.999),检出限和定量下限分别为0.0003~0.0006 ng/mL和0.001~0.002 ng/mL,3个加标水平下的回收率为81.6%~108%,日内和日间相对标准偏差分别为1.4%~5.6%和1.4%~9.9%。该方法不仅能够直接处理原始尿液,无需稀释和去蛋白操作,而且通过泡腾辅助分散,对BZDs的富集倍数达40.8~54.0倍,实现了尿液中5种BZDs的准确、简便和灵敏分析。

参芪降糖颗粒联合羟苯磺酸钙分散片治疗非增殖期糖尿病视网膜病变的效果及对PDGF、BMP-2水平的影响

目的探讨参芪降糖颗粒联合羟苯磺酸钙分散片治疗非增殖期糖尿病视网膜病变的效果及对血小板源性生长因子(PDGF)、骨形成蛋白-2(BMP-2)水平的影响。方法选取2020年2月至2023年1月收治的100例非增殖期糖尿病视网膜病变患者作为研究对象,按随机数字表法将其分为对照组和观察组,每组50例。对照组在常规治疗基础上加羟苯磺酸钙分散片治疗,观察组在对照组基础上采用参芪降糖颗粒治疗。比较两组的治疗效果。结果观察组的治疗总有效率明显高于对照组(P<0.05)。治疗后,观察组的空腹血糖(FBG)、餐后2 h血糖(2 h PG)水平及糖化血红蛋白(HbA1c)均低于对照组(P<0.05)。治疗后,观察组的最佳矫正视力高于对照组,黄斑中心凹视网膜厚度低于对照组(P<0.05)。治疗后,观察组的PDGF、BMP-2水平均低于对照组(P<0.05)。结论参芪降糖颗粒联合羟苯磺酸钙分散片治疗非增殖期糖尿病视网膜病变的效果确切,可有效降低血糖水平,改善患者视力,降低黄斑中心凹视网膜厚度,抑制PDGF、BMP-2表达。

瓜蒌薤白半夏汤联合银杏酮酯分散片对冠心病心绞痛患者心电图、MMP-9、EMPs水平的影响分析

目的观察瓜蒌薤白半夏汤联合银杏酮酯分散片对冠心病心绞痛患者心电图、MMP-9、EMPs水平的影响分析。方法纳入120例冠心病稳定型心绞痛痰浊闭阻证患者,按随机数表法随机分为观察组及对照组各60例。两组均给予冠心病稳定型心绞痛治疗常规用药,对照组给予银杏酮酯分散片,观察组在对照组基础上联合瓜蒌薤白半夏汤治疗,两组均治疗8周。治疗结束后观察两组治疗前后临床疗效、心绞痛发作情况、中医临床症状积分、心电图疗效、血脂水平及血管性血友病因子(von willebrand Factor,vWF)、基质金属蛋白酶-9(matrix metallopeptidase-9,MMP-9)、内皮细胞微粒(endothelial microparticles,EMPs)水平的变化情况。结果治疗8周后,观察组总有效率为88.33%(53/60),显著高于对照组的71.67%(43/60)(P<0.05);两组患者心绞痛发作次数及持续时间均较治疗前有显著改善(P<0.05),且观察组显著优于对照组(P<0.05);治疗后两组中医临床症状积分均有显著改善,观察组在胸闷、胸痛、气短喘促、痰多纳呆、身体困重症状积分显著优于对照组(P<0.05);观察组心电图总有效率为85.00%(51/60),显著高于对照组的60.00%(36/60)(P<0.05);同时两组患者治疗后总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白(low-density lipoprotein cholesterol,LDL-C)水平也明显改善(P<0.05),观察组TG、TC及LDL-C显著低于对照组(P<0.05),HDL-C则高于对照组(P<0.05);对照组及观察组经治疗后vWF、MMP-9、EMPs水平均较治疗前提升降低(P<0.05),同时观察组改善显著优于对照组(P<0.05)。结论冠心病稳定型心绞痛在常规治疗基础上采用瓜蒌薤白半夏汤联合银杏酮酯分散片治疗可有效减少患者心绞痛发作,改善临床症状及心电图情况,调节血脂水平,降低患者vWF、MMP-9、EMPs水平,提高临床治疗效果。

Simulation on dissolute and dust dispersion in comprehensive mechanized heading face with forced-exhaust ventilation

According to the characteristics of comprehensive mechanized heading face, established the mathematical model of single-phase air flow with κ-ε two equations model, and have established κ-ε-θ-κp mathematic model to solve two-phase flow of gas and particles in dust space with eulerian-eulerian method and eulerian-lagrangian method. Numerical solution of gas-particle two-phase flow was put forward based on collocated grid SIMPLE algorithm. Moreover, numerical simulation of dust concentration in fully mechanized caving face was carded out by using Fluent software. Finally, when in forced-exhaust ventilation circumstance, drawer type fan drum have less dust absorption, and most of dust spread to the other site; the dust concentration is inversely proportional to the distance from tunneling head, and the dust concentration has already diffused to decrease below 102 mg/m3 at the position ofx=12 m. Dust are more focused on relative side（in the range about y from 0 to 2 meter） of roadway space of press-ventilated fan drum, especially between tunneling place and drawer type fan drum; the roadway with road header have a higher dust concentration. These conclusions provide reliable theory basis for the dust prevention in comprehensive mechanized heading face.

Matrix Solid-phase Dispersion Extraction of Alkaloids from the Roots of Aconitum kusnezoffii Reichb

Matrix solid-phase dispersion（MSPD） was developed for the extraction of four alkaloids, including aconitine, mesaconitine, hypaconitine and deoxyaconitine, from the roots ofAconitum kusnezoffii Reichb. The determination of the analyte was carried out by high performance liquid chromatography with UV detection. The alkaline alumina was used as sorbent. The mixture of acetonitrile and water was used as elution solvent. Several extraction parameters, such as type of sorbent, the ratio of sample to solid support material, type of the elution solvent and the volume of the elution solvent were tested. Mean recoveries ranged from 93.16% to 102.73%, with relative standard deviations from 0.27% to 4.17%. With the extraction efficiency and time expenditure taken into account, MSPD extraction should be a comparatively good method.

双氯芬酸钠-β-环糊精包合物分散片的研制

目的：制备双氯芬酸钠－β－环糊精包合物分散片。方法：以交联聚乙烯吡咯烷酮为崩解及分散剂制备分散片并对其进行体外质量评价。结果：所制分散片具有快速崩解、分散及溶出度。结论：本品完全符合《英国药典》中有关分散片的质量标准，是一种值得开发的剂型。

RP-HPLC法测定人血浆中厄多司坦浓度及其药代动力学研究

目的:建立厄多司坦血浓度反相高效液相色谱测定方法,进行其人体药代动力学研究。方法:采用单剂两周期交叉试验设计,20名健康男性志愿者随机单剂量口服厄多司坦分散片或胶囊600 mg,按设定时间采集肘静脉血,以 Luna C_(18)(2)(150mm×4.6 mm,5 μm)为固定相,甲醇-醋酸钠(冰醋酸调 pH 至6.8)(5:95)为流动相,流速0.7 mL·min^(-1),检测波长236 nm,测定厄多司坦血浓度,计算其药代动力学参数,评价两制剂的生物等效性。结果:本方法最低定量限为0.01μg·mL^(-1),在0.01～3μg·mL^(-1)(r=0.9991)范围内线性关系良好,高、中、低浓度日内、日间 RSD 均小于5%。厄多司坦分散片和胶囊主要药代动力学参数 t_(1/2)分别为(2.478±1.206)h 和(2.603±1.282)h,T_(max)分别为(1.163±0.424)h 和(1.413±0.424)h,C_(max)分别为(1.419±0.385)μg·mL^(-1)和(1.594±0.558)μg·mL^(-1),AUC_(0～12)分别为(3.416±1.037)μg·mL^(-1)·h 和(3.433±0.910)μg·mL^(-1)·h,AUC_(0～∞)分别为(3.492±1.044)μg·mL^(-1)·h 和(3.523±0.912)μg·mL^(-1)·h。结论:测定方法准确、灵敏、快速,适用于厄多司坦人体药代动力学研究。厄多司坦两制剂主要药代动力学参数无显著性差异,为生物等效制剂。

基质固相分散-超快速液相色谱测定山楂片中的4种苏丹红染料

采用基质固相分散-超快速液相色谱法测定了山楂片中的苏丹红染料,基质固相分散萃取的最佳条件为：0.45 g硅胶分散剂,6 mL乙酸乙酯作为洗脱剂,样品与分散剂质量比为1：3.乙腈-水为流动相,流速：0.3 mL/min,进样量：10 μL,柱温：30℃,梯度洗脱,4种苏丹红化合物回收率在86.1％ ～ 108.3％之间;RSD在2.3％ ～9.8％之间.测定苏丹红的线性范围为0.01～ 2.5 mg/kg（苏丹红Ⅰ,Ⅱ和Ⅲ）,0.025 ～ 2.5 mg/kg（苏丹红Ⅳ）,检出限为4.2～8.9μg/kg,检出限优于国标方法,可满足实际样品分析的要求.

RP-HPLC测定桂利嗪分散片的含量及检查有关物质

目的采用HPLC法测定桂利嗪分散片的含量及有关物质。方法用Kromasil C18色谱柱(250 mm×4.6 mm,5μm);流动相为甲醇-0.2%三乙醇胺-三乙胺(85:15:0.03,盐酸调pH6.5);流速1.0 ml.min-1;检测波长254 nm;柱温为室温。结果桂利嗪的线性范围为20~200μg.ml-1(r=0.9999),最低检测限为0.2 ng.ml-1;样品溶液至少在8 h内稳定,回收率99.4%,RSD=0.92%(n=9)。结论所建方法简便、快速,专属性好,可用于桂利嗪分散片的含量测定和有关物质检查。

基于UFLC-Q-TOF-MS/MS技术的盐酸克林霉素棕榈酸酯分散片杂质的研究

采用UFLC-Q-TOF-MS/MS技术,在正离子模式下,根据各物质的质谱裂解规律,研究鉴定出盐酸克林霉素棕榈酸酯分散片中16种杂质,其中克林霉素九酸酯、克林霉素十酸酯、克林霉素十一酸酯、克林霉素十三酸酯为首次检到,本研究为其质量监控提供了实验依据。

HPLC法测定氯沙坦钾-氢氯噻嗪复方分散片中药物及有关物质的含量

目的建立测定氯沙坦钾—氢氯噻嗪复方分散片中药物及有关物质含量的HPLC法。方法将2种主药与适宜的辅料混合制备成分散片，采用Kromasil C8柱（150mm×4．6mm，5μm），磷酸盐缓冲液（20mmol·L^-1磷酸氢二钠1000mL与20mmol·L^-1磷酸二氢钾600mL混合，pH值7．2）为流动相A，乙腈为流动相B进行梯度洗脱，流速1．0mL·min^-1，柱温40℃，检测波长280nm。结果2种主药及5种有关物质能够完全分离，氯沙坦钾质量浓度在100—600mg·L^-1内、氢氯噻嗪质量浓度在25～150mg·L^-1内与峰面积呈良好的线性关系，精密度RSD分别为0．16％、0．34％，重复性RSD分别为1．5％、2．6％。样品在12h内稳定，回收率分别为101．8％（RSD=1．8％）、101．1％（RSD=1．3％），该方法能准确定量主药成分。结论该方法专属性强、稳定可靠，适用于氯沙坦钾-氢氯噻嗪复方分散片的药物含量测定及有关物质检查。

酮洛芬羟丙基-β-环糊精分散片的处方研究和溶出度考察

目的:制备酮洛芬羟丙基-β-环糊精包合物(KP-HP-β-CD)分散片并考察体外溶出度。方法:以崩解时间为指标,采用正交设计方法对处方进行筛选和优化,转篮法考察分散片的体外溶出度。结果:分散片优化处方的崩解剂为羧甲基淀粉钠(CMS-Na),用量12%,表面活性剂十二烷基硫酸钠(SLS)用量1%,分散片崩解时间为(112.7±5.0)s。体外溶出参数分别为:T50=3.0 min,Td=5.4 min。结论:该分散片符合中华人民共和国药典2005年版的规定,溶出速度明显快于普通片。

蛇床子素β-环糊精包合物分散片的制备及大鼠体内药动学研究

目的制备蛇床子素β-环糊精包合物以提高蛇床子素的水溶性,并考察体外释药特性及大鼠体内的药动学行为。方法采用逆向混合搅拌法制备蛇床子素β-环糊精包合物,以崩解时限、硬度及溶出度为综合指标L9(34)正交实验,高效液相色谱法测定大鼠体内的血药浓度。结果最终确定优选处方的辅料比例为10%微晶纤维素(MCC),6%低取代羟丙基纤维素(L-HPC)和12%交联聚维酮(PVPP);所制备的包合物分散片的崩解时间(52.7±2.4)s,硬度(5.13±0.47)kg,1 h内的累积溶出度(93.1±1.2)%;大鼠体内原料药组的Tmax为2.65 h,Cmax为2.87μg/mL,AUC0-24为21.32μg.h/mL,包合物分散片组的Tmax为2.14 h,Cmax为36.64μg/mL,AUC0-24为272.41μg.h/mL,经配对t检验,Tmax、Cmax、AUC0-24差异均有显著性(P<0.05)。结论蛇床子素包合物分散片具有溶散快,分散均匀,有效成分溶出速率快的特性,并能提高其大鼠体内生物利用度。

阿莫西林/克拉维酸分散片对产β-内酰胺酶菌的体外抗菌作用

目的 了解 β-内酰胺类抗生素与酶抑制剂的联合药物新型剂 -阿莫西林 /克拉维酸分散片 (AMC)的体外抗菌活性。方法 采用稀释法将该药对临床 2 34株产 β-内酰胺酶菌进行体外抗菌活性的测定 ,并与原片剂作比较 ;同时对 AMC分散片在不同的 p H值、细菌接种量及血清浓度等条件影响下的最小抑菌浓度 (MIC)分别做了检测。结果 AMC分散片与原片剂具有相似的抗菌谱和抗菌活性 ,但杀菌曲线实验显示 :分散片能在 2 4h内有效地杀灭金葡菌和大肠埃希菌 ,而原片剂则在 2 4h后细菌活菌数有恢复的现象 ;p H偏酸或偏碱及细菌接种量的增加对该药的杀菌效果均有一定的减弱作用。结论 AMC制成分散片后 ,使其服用方便、吸收快。

HPLC-ELSD法测定银杏叶分散片中萜类内酯的溶出度

目的:建立测定银杏叶分散片中萜类内酯的溶出度测定方法。方法:用HPLC-ELSD法测定溶出液中萜类内酯的含量,用Hypersil ODS C18柱(200 mm×4．6 mm,5μm),正丙醇-四氢呋喃-水(1:15:84)为流动相,流速1．0 ml·min-1,用ELSD检测,溶出度测定方法用《中国药典》2005年版二部附录XC第三法,以0．1 mol·L-1盐酸溶液为溶剂。结果:白果内酯、银杏内酯A、银杏内酯B及银杏内酯C的线性范围分别为0．92-3．66,0．51-2．04,0．52-2．08μg和0．45-1．78μg,平均回收率分别为100．1％(RSD 0．7％),97．7％(RSD为1．1％),97．6％(RSD为1．1％),101．0％(RSD0．9％)。3批样品溶出度(限度)分别为97％,96％和98％％。结论:该方法简便、重复性好,可作为银杏分散片中萜类内酯的溶出度的测定。

RP-HPLC法同时测定山葛降脂分散片中葛根素和牡荆素鼠李糖苷的含量

目的:建立反相高效液相色谱法同时测定山葛降脂分散片中葛根素和牡荆素鼠李糖苷的含量测定方法。方法:色谱柱为Diamonsil C185μm(200mm×4.6mm),流动相为乙腈-0.5%冰醋酸,以流速1.0mL.min-1进行梯度洗脱;柱温:35℃;检测波长为268nm。结果:葛根素在0.076125～0.380625μg(r=0.9993)、牡荆素鼠李糖苷在0.055～0.275μg(r=0.9998)的范围内呈现良好线性关系,平均加样回收率为分别98.08%和98.82%,RSD分别为2.2%和2.2%。结论:本方法简便、快速、准确,可用于山葛降脂分散片的质量控制。