玳玳黄酮自微乳化微丸含量测定及HPLC特征图谱分析

目的:建立玳玳黄酮自微乳化微丸中柚皮苷、新橙皮苷HPLC含量测定方法和HPLC特征图谱,为玳玳黄酮自微乳化微丸的质量控制提供有效的方法。方法:含量测定采用Agilent-C18色谱柱(250 mm×4.6 mm,5μm),流动相为乙腈-0.1%磷酸水溶液(22∶78),流速为1.0 mL.min-1,柱温为室温。HPLC特征图谱测定采用250-4 Lichrocart C18色谱柱(250 mm×4.0mm,5μm),流动相为甲醇-乙腈-0.1%的磷酸水溶液,梯度洗脱,流速1.0 mL.min-1,柱温30℃。检测波长均为283 nm。结果:柚皮苷浓度在4.48～17.92μg.mL-1范围内线性关系良好(r=0.9998),平均加样回收率为97.5%(RSD=1.0%);新橙皮苷浓度在5.92～23.68μg.mL-1范围内线性关系良好(r=0.9997),平均加样回收率为98.8%(RSD=0.82%)。在此条件下所建立的特征图谱中各成分得到有效分离,各批玳玳黄酮自微乳化微丸的相似度在0.900～1.000间。结论:HPLC法同时测定玳玳黄酮自微乳化微丸中柚皮苷和新橙皮苷含量的方法简便、准确,建立的HPLC特征图谱可用于评价微丸的物质组成及有效物质群的质量变化,可作为玳玳黄酮自微乳化微丸质量控制的依据。     

玳玳果黄酮滴丸的溶出度及速释机制

目的:评价玳玳果黄酮滴丸的溶出度并初步探讨其速释机制。方法:在多种pH值溶出介质中采用多条溶出曲线评价玳玳果黄酮滴丸的体外溶出度,以柚皮苷为指标成分,运用HPLC法考察玳玳果黄酮滴丸在不同时间的累积溶出百分数,并通过差示扫描热分析研究滴丸的速释机制。结果:4种释放介质中柚皮苷在2.12～53.00mg.L-1范围内线性关系良好,玳玳果黄酮滴丸中柚皮苷在20 min时累积溶出度可达85%。差示扫描量热分析结果显示,玳玳果黄酮在PEG4000-PEG6000中形成了某种形式的固体分散体。结论:玳玳果黄酮滴丸具有良好的溶出度,玳玳果黄酮有效部位在滴丸内形成了良好的固体分散体,使药物在基质中的分散度增加而达到速释。     

玳玳黄酮自微乳化软胶囊制备过程药效成分转移率考察

目的 针对玳玳总黄酮有效部位多组分特性,基于HPLC特征图谱研究玳玳黄酮自微乳化软胶囊制备过程中的药效成分转移率。方法 采用HPLC特征图谱法,色谱柱为Lichrocart C₁₈(250 mm×4.0 mm,5 μm);流动相为甲醇-0.1%的磷酸水溶液(梯度洗脱);流速1.0 mL·min^-1;检测波长284 nm;柱温30 ℃。结果 玳玳黄酮自微乳化软胶囊制备工艺过程中8个共有峰的转移率为80.55%~95.93%,其中主要特征成分柚皮苷和新橙皮苷迁移率均>95%,各药效成分群整体迁移相似度>0.999。结论　玳玳黄酮自微乳化软胶囊制备工艺能够比较完整的保留玳玳总黄酮提取物的整体药效部位成分群。     

玳玳果黄酮降脂滴丸的肠吸收动力学特性

目的：考察玳玳果黄酮降脂滴丸的肠吸收特性并探讨其作用机制。方法：采用大鼠外翻肠囊模型,建立同时测定大鼠肠吸收液中玳玳果黄酮降脂滴丸特征药效成分新橙皮苷和柚皮苷含量的液-质联用（UPLC-MS）分析法,比较玳玳果黄酮降脂滴丸与原料玳玳果黄酮降脂提取物在大鼠不同肠段的累积吸收量,分析不同质量浓度大鼠空肠段的吸收过程,探讨其肠吸收部位及机制。结果：玳玳果黄酮降脂滴丸特征药效成分新橙皮苷和柚皮苷90 min时的累积吸收量由多到少依次是空肠、十二指肠、回肠和结肠;玳玳果黄酮降脂滴丸在高、中、低剂量下空肠的累积吸收量随时间的增加而增加,相关系数r>0.95,且随着药液质量浓度的增加新橙皮苷和柚皮苷的Ka均增加,符合一级药动学过程;在等剂量给药下,玳玳果黄酮降脂滴丸中新橙皮苷和柚皮苷的累积吸收量约是玳玳果黄酮降脂提取物的1.6倍。结论：玳玳果黄酮降脂滴丸在全肠道均有吸收,小肠的上中段为最佳吸收部位,新橙皮苷和柚皮苷吸收可能为被动吸收循环入体,制成的玳玳果黄酮降脂滴丸可显著改善提取物在肠道的吸收,提高其口服生物利用度。     

玳玳黄酮滴丸质量分析

目的 建立玳玳黄酮滴丸质量评价方法。方法 采用薄层色谱法鉴别玳玳黄酮滴丸,并对玳玳黄酮滴丸进行重金属及砷盐的检查;建立高效液相色谱法同时测定玳玳黄酮滴丸主要药效成分柚皮苷和新橙皮苷含量的方法。结果 薄层色谱主要成分斑点清晰可见,阴性对照无干扰;玳玳黄酮滴丸重金属及砷盐的限量均小于百万分之十;新橙皮苷在4.088--16.352μg.mL 1内呈良好线性关系,柚皮苷在4.084--16.336μg.mL 1内呈良好线性关系,3批玳玳黄酮滴丸新橙皮苷平均含量分别为75.32,74.82,73.76 mg·g-1,柚皮苷平均含量分别为63.05,63.21,62.07mg·g-1。结论 所建立的鉴别、检查、含量测定方法稳定简便,可有效控制玳玳黄酮滴丸质量。     

玳玳黄酮提取物的质量标准研究

目的：建立玳玳黄酮提取物的质量标准。方法：采用薄层色谱法鉴别玳玳黄酮提取物中的柚皮苷和新橙皮苷;采用紫外分光光度法测定玳玳黄酮提取物中总黄酮含量;采用高效液相色谱法同时检测玳玳黄酮提取物中柚皮苷和新橙皮苷的含量。结果：薄层色谱斑点清晰,易于识别,专属性强;紫外分光光度法新橙皮苷在4．44～26．64μg·mL-1范围内呈良好线性关系,平均加样回收率为99．92％（RSD=1．65％）;HPLC法柚皮苷在1.988—13．916μg·mL-1范围内呈良好线性关系,平均加样回收率为99．73％（RSD=1．56％）,新橙皮苷在1．992～13．944μg·mL-1范围内呈良好线性关系,平均加样回收率为99．58％（RsD=1．89％）。结论：所建方法操作简便,结果准确,可有效控制玳玳黄酮提取物的质量。     

玳玳果黄酮降脂提取物体内效应组分排泄动力学研究

目的 建立同时测定大鼠尿液及粪便中提取物效应组分新橙皮苷和柚皮苷含量方法,研究大鼠口服玳玳果黄酮降脂提取物后的尿药排泄动力学及排泄特征。方法 采用UPLC-MS/MS建立效应组分新橙皮苷及柚皮苷在大鼠尿液及粪便的定量分析方法,计算口服玳玳果黄酮降脂提取物后不同时间点新橙皮苷及柚皮苷在尿液及粪便中的排泄率,并以亏量法计算尿液中的消除半衰期及消除速率常数,评价大鼠口服玳玳果黄酮降脂提取物后尿药排泄动力学及排泄特征。结果 所建立的UPLC-MS/MS定量分析方法专属性良好、标准曲线及线性范围良好,方法准确度与精密度、定量下限均符合有关规定,该方法能够满足大鼠尿液及粪便中效应组分的定量检测需要;口服72 h后,大鼠尿液中新橙皮苷、柚皮苷的平均累计排泄率分别为（1.76±0.76）‰和（1.39±0.57）‰;大鼠粪便中新橙皮苷、柚皮苷的平均累计排泄率分别为（52.45±6.30）%和（51.57±4.80）%;口服后效应组分新橙皮苷及柚皮苷在尿液及粪便中的排泄量分别在24~36 h和4~8 h达到峰值;72 h后仍有药物经尿液排泄,给药后24 h粪便累计排泄率便达坪值;亏量法计算得新橙皮苷消除速率常数为（0.080±0.021）·h^-1,消除半衰期为（9.41±3.22）h,柚皮苷消除速率常数为（0.077±0.017）·h^-1,消除半衰期为（9.51±2.97）h,新橙皮苷及柚皮苷的动力学参数间差异无统计学意义。结论 口服给药后效应组分原形即通过粪便较快地排出体外,粪便排泄是效应组分排出体外的主要途径,新橙皮苷及柚皮苷经尿液排泄的特征无明显差异。     

中心复合设计法优化丹七有效部位缓释微丸

目的:应用挤出滚圆法制备丹七提取物缓释微丸,研究微丸制备的最佳工艺和处方.方法:用挤出滚圆机制备丹七提取物缓释微丸;采用单因素考察和中心复合设计筛选最优处方和工艺条件;考察了微丸粉体学性质、收率和体外溶出度.结果:用挤出滚圆法制备的微丸圆整度好,大小均匀,收率高,药物体外溶出具有明显的缓释作用,体外释放曲线符合Peppas和Higuchi方程.结论:该工艺简便易行.     

醒脑静不同口服固体制剂的溶出度对比研究

目的:对醒脑静不同口服固体制剂进行溶出度考察,对比其有效成分的体外溶出特点,为优选醒脑静口服剂型提供依据。方法:采用小杯法,转速100r·min-1,以蒸馏水为溶出介质。采用高效液相色谱法测定不同口服固体制剂中有效成分栀子苷和龙脑的溶出度,计算累积溶出度,用相似因子进行释放曲线的相似性比较,对溶出曲线进行多种数学模型拟合。结果:不同口服固体制剂中,除水溶性包衣片和胶囊中栀子苷溶出曲线有一定相似性外,各制剂中栀子苷溶出曲线、龙脑溶出曲线均有较大差异,各剂型有效成分溶出曲线基本符合一级动力学方程。结论:醒脑静不同口服固体制剂中有效成分溶出度15min之内均可达到90%以上;栀子苷在胶囊中溶出最快,龙脑在水溶性包衣片中溶出最快。     

溃结康微丸的制备和体外溶出度考察

目的:制备渍结康微丸并进行处方优化,考察微丸的体外溶出度.方法:用挤出滚圆造粒机制备溃结康微丸,优化制剂处方组成;采用高效液相色谱法以黄芩苷和芍药苷为指标,对其体外溶出度进行考察.结果:制得微丸圆整度好.大小均匀,收率在75%以上.黄芩苷和芍药苷的溶出度45 min内均达80%以上.结论:本法研制的溃结康微丸,处方合理,工艺可行.     

柚皮苷固体脂质纳米粒包封率及体外释放度测定

目的：建立柚皮苷固体脂质纳米粒（solid lipid nanoparticles,SLN）的包封率和体外释放度的测定方法。方法：采用超滤法和高效液相色谱法测定柚皮苷SLN包封率。通过透析袋法测定柚皮苷SLN的体外释放度。结果：柚皮苷在2．5—160．0μg·ml^-1范围内,线性关系良好（r=0．9999）。平均回收率为99．9％,RSD为1．1％。透析袋对柚皮苷没有吸附作用。柚皮苷SLN包封率为61．3％,体外释药曲线符合一级动力学方程。结论：所建立的方法简单可靠。     

Preparation and in vitro evaluation of a novel combined multiparticulate delayed-onset sustained-release formulation of diltiazem hydrochloride

A combined delivery system, containing two kinds of diltiazem hydrochloride multi-layer coated pellets with different release characteristics, was developed to meet chronotherapeutic requirements. The dissolution studies in vitro indicated that the combined system could constantly release drug at a predetermined time in synchrony with the biologic rhythm of disease activity. These two kinds of pellets were mixed at the ratio 1:1. Pellet 2 could provide drug during the later phase of drug release from pellet 1, because the amount released was insufficient in the later phase (about 14-24 h after administration) for pellet 1. Addition of Tween 20 in the HPMC swelling layer was able to modify the hydration rate of HPMC layer which controlled the delayed time of the release system. It was found that the drug release kinetics followed Hixson-Crowell equation and this indicated that the main drug-transport mechanism inside the pellets was an erosion mechanism. The drug release rate was independent of the hydrodynamic conditions and pH of the external environment, and showed a decrease with increasing of osmotic pressure of the dissolution medium. These release characteristics indicated that the drug release from this system was driven by osmotic-pressure gradient.     

莲子心总碱缓释片体外释放度试验

目的　考察莲子心总碱缓释片体外释放度。方法　模拟人体体内环境,用紫外分光光度法测定莲子心总碱的体外释放度。结果　莲子心总碱释药方程:log(1 0 0 -Rn) =2 . 1 1 2 - 0 . 1 2 8t(F =2 1 9 . 31 0 ,P <0 0 0 1 ) ,r =- 0 . 982 (P <0 . 0 0 1 ) ,T50 =3 . 2 33h ,Td=4 . 2 74h ,Kr=0 . 1 2 8h-1 。结论　莲子心总碱缓释片体外释药符合一级释药模式,具有缓释特点。     

坎地沙坦酯自微乳软胶囊的制备和溶出度评价

目的研制坎地沙坦酯自微乳软胶囊,并对其溶出度进行评价。方法制备坎地沙坦酯自微乳软胶囊,并按药典方法考察自微乳软胶囊与普通胶囊在三种不同溶出介质（水、0.1mol/L盐酸和pH6.8的缓冲溶液）中的溶出度。结果坎地沙坦酯自微乳释药系统处方为乙酸乙酯：聚氧乙烯氢化蓖麻油RH40：聚乙二醇400为9∶14∶7。坎地沙坦酯自微乳受溶出介质的影响小,且溶出速率高于普通胶囊。结论自微乳软胶囊能显著提高坎地沙坦酯的体外溶出。     

In vitro dissolution kinetic study of theophylline from hydrophilic and hydrophobic matrices

Oral dosage forms containing 300 mg theophylline in matrix type tablets, were prepared by direct compression method using two kinds of matrices, glycerylbehenate (hydrophobic), and (hydroxypropyl)methyl cellulose (hydrophilic). The in vitro release kinetics of these formulations were studied at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process were studied by analyzing the dissolution data using four kinetic equations, the zero-order equation, the first-order equation, the Higuchi square root equation and the Hixson-Crowell cube root law. The analysis of the dissolution kinetic data for the theophylline preparations in this study shows that it follows the first order kinetics and the release process involves erosion / diffusion and an alteration in the surface area and diameter of the matrix system, as well as in the diffusion path length from the matrix drug load during the dissolution process. This relation is best described by the use of both the first-order equation and the Hixson-Crowell cube root law.     

香青兰总黄酮渗透泵片的体外释放

目的:研究香青兰总黄酮渗透泵片的体外释放度。方法:采用相似因子(f2)法对香青兰中总黄酮释放曲线的相似性进行比较评价,考察不同溶出方法、溶出介质的种类和桨叶转速对香青兰总黄酮渗透泵片体外释放的影响。结果:采用桨法的小杯法,溶出介质为0.8%十二烷基硫酸钠溶液,桨叶转速为100r.min-1时,香青兰总黄酮渗透泵片的体外释药行为没有受到显著性影响。结论:香青兰总黄酮渗透泵片体外释药稳定,重复性好,控制释放特征明显     

Release Behaviour of Single Pellets and Internal Fine 3D Structural Features Co-define the In Vitro Drug Release Profile

Multi-pellet formulations are advantageous for the controlled release of drugs over single-unit dosage forms. To understand the diffusion controlled drug release mechanism, the pellet structure and drug release from a single pellet (not at dose level) were studied using synchrotron radiation X-ray computed microtomography (SR-μCT) and a sensitive LC/MS/MS method. The purpose of this article is to introduce a powerful, non-invasive and quantitative technique for studying individual pellet microstructures and to investigate the relationship between the microstructure and drug release from single pellets. The data from the single pellet dissolution measurements demonstrated that the release profile of capsules containing approximately 1,000 pellets per unit dose was the summation of the release profiles of the individual pellets. The release profiles of single tamsulosin hydrochloride (TSH) pellets formed three groups when a cluster analysis was performed, and the dissolution rate of the individual pellets correlated well with the combined effects of the drug loading, volume and surface area of the pellets (R² = 0.9429). In addition, the void microstructures within the pellet were critical during drug release. Therefore, SR-μCT is a powerful tool for quantitatively elucidating the three-dimensional microstructure of the individual pellets; because the microstructure controls drug release, it is an important parameter in the quality control of multi-pellet formulations.KEY WORDS: microstructure, release kinetics, single pellet, synchrotron radiation X-ray computed microtomography