高效液相色谱法测定舒肝调气丸中厚朴酚含量

目的 :采用高效液相色谱法测定舒肝调气丸组方中厚朴酚的含量。方法 :应用色谱柱 PARRING KRO-MASIL C1 8(5μm ,2 5 0 mm× 4.6 mm ) ,流动相 :乙腈 -水 (6∶ 4) ,流速 :1ml/ min,检测波长 2 94nm,进样量 :2 0μl。结果 :厚朴酚在 0 .0 2～ 0 .10 mg/ ml范围内线性关系良好 ,样品中厚朴酚平均含量为 1.2 0 14mg/ g,平均加样回收率为 10 0 .4%,RSD为 1.2 7%。结论 :此法操作简便 ,精密度、重现性均较好 ,方法可行。     

HPLC测定龙胆泻肝丸中黄芩苷的含量

目的　用高效液相色谱法测定龙胆泻肝丸中黄芩苷的含量。方法　采用C18柱 ,以甲醇 水 冰醋酸 (5 0 ∶5 0 ∶1)为流动相 ,检测波长为 2 79nm测定。结果　对照品在 1.6 0～ 7.6 0 μg/ml内呈线性关系 ,r=0 .9998,加样回收率平均为 99.0 % ,RSD为2 .2 %。结论　本法准确、稳定、重复性好 ,可用于测定龙胆泻肝丸中黄芩苷的含量     

HPLC-ELSD法检测消癌平丸中通关藤苷H的含量及稳定性考察

目的:测定消癌平丸中通关藤苷H的含量,并考察其稳定性。方法:采用高效液相色谱-蒸发光散射检测器(HPLC-ELSD)法测定消癌平丸中通关藤苷H的含量;分别于下列条件测定消癌平丸中通关藤苷H的含量:(1)温度(25±2)℃、相对湿度(60±10)%,将3批消癌平丸放置0、3、6、9、12个月;(2)温度(30±2)℃、相对湿度(65±5)%,将3批消癌平丸放置0、1、2、3、6个月;(3)温度(40±2)℃、相对湿度(75±5)%,将3批消癌平丸放置0、1、2、3、6个月。结果:通关藤苷H的进样量在0.390 2³.902 0μg范围内与峰面积积分值呈良好线性关系(r=0.998 0);平均加样回收率为99.03%,RSD=1.75%。通关藤苷H在条件(1)下基本稳定,在条件(2)和(3)下不稳定,其RSD>3%。结论:采用HPLC-ELSD法测定消癌平丸中通关藤苷H的含量,样品中通关藤苷H与其他色谱峰完全分离,且峰形良好,可作为消癌平丸中通关藤苷H的含量测定方法。稳定性试验结果显示,通关藤苷H在消癌平丸中不稳定,不宜作为消癌平丸的质量控制指标。     

薄层扫描法测定参贝咳喘丸中人参皂苷Rg_1的含量

目的　采用薄层扫描法测定参贝咳喘丸中人参皂苷 Rg1 含量。方法　样品经适当提取、净化后点于硅胶 G薄层板上 ,以氯仿 -甲醇 -水 (1 3∶ 7∶ 2 ) 1 0℃以下放置的下层溶液为展开剂 ,1 0℃以下展开 ;喷以1 0 0 g· L-1 硫酸乙醇溶液 ,于 1 0 5℃烘至斑点清晰 ,检测波长为 λS=5 40 nm,λR=70 0 nm。结果　平均回收率为 99.2 % ,RSD =1 .4 %。结论　此方法重现性好、准确 ,可用于该制剂质量控制的指标之一     

海藻酸钙凝胶微丸作为口服缓释给药载体的研究

将海藻酸钠溶液滴入胶凝剂氯化钙溶液中制备了海藻酸钙凝胶微丸。以胶凝过程中凝胶微丸重量变化 (失水量 )研究了胶凝速率及不同浓度海藻酸钠溶液 ( 1 %～ 4 % )与氯化钙溶液 ( 0 0 5～0 2 0mol/L)对胶凝速率的影响 ,结果是 6h前胶凝速率快 ,随后减慢 ,约 70h胶凝完全 ,氯化钙溶液的浓度≥ 0 1mol/L对胶凝速率无明显影响。干燥的凝胶微丸在不同水性介质中溶胀试验结果表明 :在温度约 37℃时 ,微丸在蒸馏水和 0 1mol/L盐酸 ( pH1 0 )中几乎不溶胀 ,而在磷酸盐缓冲溶液( pH6 8)中1h溶胀 ,溶胀后的微丸直径是干燥前湿微丸直径的 1 80 %。海藻酸钙凝胶微丸这种溶胀的 pH敏感性 ,使它能成为口服药物缓释制剂的载体。以硝苯地平为模型药物制备的海藻酸钙凝胶微丸 ,其体外释放试验结果 ,2h累积释放量为 2 0 %～ 30 % ,6h为 6 0 %～ 80 % ,1 2h时大于85 %。药物从微丸中的释放是以扩散和骨架溶蚀相结合的方式。由此可见 ,硝苯地平的海藻酸钙凝胶微丸具有缓释作用     

泮托拉唑钠肠溶微丸型片剂的制备

研究泮托拉唑钠肠溶微丸型片剂制备方法。采用流化床包衣法制备泮托拉唑钠肠溶微丸, 将肠溶微丸与适合的辅料混合采用直接压片法制备泮托拉唑钠微丸型片剂。用体外释放度法及扫描电镜法观察压片前后药物的体外累计释放量及微丸形态。结果表明, 优化处方: 衣膜增重55%, 增塑剂含量20%, Eudragit L30D-55/ NE30D为8∶2, 肠溶微丸/辅料 (MCC/PPVP/PEG 6000, 2∶1∶1) 为5∶5时, 肠溶片在0.1 mol·L⁻¹盐酸中2 h累积释放百分数<10%, pH 6.8磷酸盐缓冲液中1 h累积释放百分数>85%。制备的泮托拉唑钠肠溶微丸片的释药行为较好, 有望应用于工业生产。     

高效液相色谱法测定麝香抗栓丸中芍药苷的含量

目的建立HPLC测定麝香抗栓丸中芍药苷的含量。方法以芍药苷为对照品 ,乙腈 0 1 %磷酸溶液 ( 1 5∶85 ,mL/mL)为流动相 ,KromasilC18ODS色谱柱 ( 1 0 μm,2 5 0mm× 4 6mm)为固定相 ,流速为 0 8mL/min,检测波长为 2 30nm ;柱温为室温。结果芍药苷在 0 2 0～ 0 82mg/mL线性良好 ,r值为 0 9997,平均回收率 (x±RSD) %为 ( 1 0 0 5± 1 5 ) %。结论此法可较好地用于麝香抗栓丸的质量控制。     

娑罗子肠溶微丸胶囊的制备及质量评价

采用流化床底喷包衣法，对蔗糖丸芯依次包药物层、隔离层和肠溶衣层，制备娑罗子总皂苷提取物肠溶微丸。以微丸上药率、收率、工艺可行性、七叶总皂苷含量及2 h酸中释放量为评价指标，采用单因素试验结合多指标综合评价法优化肠溶微丸处方。照所得优化处方平行制备3批样品，并测得肠溶微丸的平均粒径为665.26μm，堆密度约为0.92 g/mL，脆碎度低于2.5%，总皂苷含量为(101.30±0.79)%。将所得肠溶微丸装入胶囊后进行体外释放度试验。结果显示，该肠溶微丸胶囊的2 h酸中释放量为(5.26±2.25)%，在磷酸盐缓冲液(pH 6.8)介质中45 min时基本释放完全。     

反相高效液相色谱法测定滋肾丸中芒果苷、盐酸小檗碱含量

目的采用反相高效液相色谱法测定滋肾丸中芒果苷、盐酸小檗碱的含量。方法色谱柱 :Hy persilC18柱 ;芒果苷流动相为甲醇 水 醋酸 (2 2∶78∶0 6,V∶V) ,检测波长 :3 2 0nm ;盐酸小檗碱流动相为甲醇 乙腈 水 三乙胺 (1 0∶2 3∶70∶0 2 ,V∶V) ,用磷酸调pH =4,检测波长 :3 40nm。结果芒果苷平均回收率为 97 3 % ,RSD =1 9% (n =5 ) ;盐酸小檗碱平均回收率为 1 0 0 8% ,RSD =2 8% (n =5 )。结论本法简便 ,准确 ,为滋肾丸的质量控制提供一定依据。     

RP-HPLC法测定参芍片中芍药苷的含量

目的　应用 RP-HPLC法对参芍片中芍药苷进行含量测定。方法　选用 Kromasil C1 8分析柱 ( 2 5 0 mm×4.6mm,1 0μm) ,以体积分数 5 0 %乙醇为提取溶剂 ,甲醇 -水 ( 3 5∶ 65 )为流动相 ,检测波长为 2 3 0 nm,流速为0 .8m L· min- 1。结果　线性范围 6.2 8～ 1 8.84mg· L- 1 ( r =0 .9999) ,平均回收率为 1 0 0 .1 2 % ,RSD为1 .48%。测定的 5批样品中芍药苷的平均含量为 6.1 3 % ,RSD为 1 .1 1 %。结论　本法可作为参芍片中芍药苷含量测定及有关制剂质量控制的一种准确、灵敏、可行的方法     

5-氨基水杨酸结肠定位给药时控微丸的制备与体外释放

目的　用水分散体包衣技术制备5-氨基水杨酸结肠定位微丸给药系统。方法　以低粘度HPMC为内层溶胀材料,乙基纤维素水分散体Aquacoat为外层控释包衣材料,柠檬酸三乙酯为增塑剂,使用流化床包衣设备,制备时间控制的微丸,用释放度测定法研究微丸在不同pH介质中的释放度。结果　溶胀层的加入对制备时控微丸是必要的,药物是通过外膜破裂释放的,溶胀层厚度增加,释药时滞有一定程度的缩短,外层厚度增加以及增塑剂用量增加,可显著延长释药时滞。微丸释药随介质pH增加而加快,在模拟胃肠道pH情况下延迟5 h释药,之后10 h内释药完全。结论　通过调整内外层的包衣厚度可制备5-氨基水杨酸结肠定位给药微丸。     

Investigation of the Gastrointestinal Transit and In Vivo Drug Release of Isosorbide-5-Nitrate Pellets

An oral formulation of controlled-release isosorbide-5-nitrate pellets has been used to investigate the location of pellets in the gastrointestinal (GI) tract and, in parallel, to measure the drug absorption from these locations. Using the method of gamma scintigraphy the transit times and spreading of pellets in the GI tract have been determined. The method of numeric deconvolution was applied to calculate the drug input into the systemic circulation. The results indicate that a well-absorbed substance such as isosorbide-5-nitrate is absorbed from the stomach and small intestinal in a manner that is controlled by the properties of the pellets. Drug absorption is reduced in the colon. The average transit time from mouth to colon is 6 to 8 hr, which represents the maximum acceptable time for drug release for this oral controlled-release preparation. Taking into account these relations an isosorbide-5-nitrate pellet formulation with a bioavailability of 84% has been developed that maintained the minimal therapeutic plasma level for more than 16 hr after application.     

Pectin-based oral drug delivery to the colon

This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.     

Pectin-based oral drug delivery to the colon

This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.     

Chitosan/Kollicoat SR 30D film-coated pellets of aminosalicylates for colonic drug delivery

The purpose of the study was to (i) prepare the chitosan/Kollicoat SR 30D film-coated pellets for colonic drug delivery, and (ii) evaluate the colonic delivery and efficacy of these coated pellets in the rat. The pellets were coated to different film thickness with chitosan/Kollicoat SR 30D formulations. In vitro drug release was assessed in simulated gastrointestinal (GI) tract conditions. Biodistribution of aminosalicylates (5-ASA) in GI tract and plasma was measured after oral administration of coated or uncoated 5-ASA pellets. Efficacy of the coated or uncoated 5-ASA pellets was tested in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat colitis model. Healing of induced colitis was assessed by measuring the myeloperoxidase activities, colon wet weight/body weight, and damage score. The coating was susceptible to bacteria digestion, resulting in an increase in the release of 5-ASA from the coated pellets. After administration of the coated pellets, the drug concentration in the large intestine was higher than those of uncoated pellets. In plasma, the observed mean C_max from the coated pellets was significantly lower than that of the uncoated pellets. Chitosan/Kollicoat SR 30D film-coated pellets could deliver the 5-ASA to the targeted site, providing effective treatment for inflammatory bowel disease. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:186–195, 2010     

In-vitro and in-vivo studies of pectin/ethylcellulosefilm-coated pellets of 5-fluorouracil for colonic targeting

The aim of the present study was to define in-vitro and in-vivo characteristics of pectin/ethylcellulose-film-coated pellets of 5-fluorouracil (5-FU) for colonic targeting. The pellet cores were coated to different film thicknesses with three different pectin/ethylcellulose formulations using a fluidized bed coater. The gastrointestinal (GI) transit of coated pellets was determined by counting the percentage of coated pellets in the GI lumen by celiotomy at certain times after oral administration. 5FU was administered to rats at a dose of 15 mg kg(-1). The toxicity of 5-FU in the GI tract was evaluated using histological examination. The 1:2 ratio pectin:ethylcellulose-coated pellets with 30% total weight gain (TWG-30%) produced more satisfactory drug-release profiles in the simulated gastric, intestinal and colonic fluids. Most of the coated pellets were eliminated from the stomach in 2 h, moved into the small intestine after 2-4 h, and reached the large intestine after 4 h. After oral administration of coated pellets, 5-FU started appearing in the plasma at 7 h, and reached peak plasma concentration (Cmax) of 3.21+/-2.01 microg mL(-1) at 16 h (Tmax); the Cmax for uncoated pellets was 22.21+/-2.60 microg mL(-1) at Tmax 0.75 h. The TWG-30% formulation showed delayed Tmax, decreased Cmax and prolonged mean residence time compared with uncoated pellets. Marked pathological features in the colon were seen in rats given coated pellets, but no injuries were observed in the upper GI tract. The formulation of TWG-30% could deliver 5-FU to the colon for local action.     

pH依赖—缓释型美沙拉秦结肠靶向小丸的制备与体外评价

以肠溶型和渗透型丙烯酸树脂为包衣材料制备ｐＨ依赖－缓释型美沙拉秦结肠靶向小丸,评价其体外释放特性。结果表明,包衣小丸在０．１ｍｏｌ／ＬＨＣｌ中２ｈ几乎不释放药物,在ｐＨ７．５缓冲液中具有较好的缓释作用。在模拟胃肠道各区段最高的和最低的ｐ变化的释放度试验中,均在对应小肠区段时开始缓慢释药。分别有４０％和７０％的药物进入结肠后释放。优于单独的肠溶或缓释制剂。     

Preparation and gamma scintigraphic evaluation of colon specific pellets of ketoprofen prepared by powder layering technology

BACKGROUND AND THE PURPOSE OF THE STUDY: Multiparticulates by powder layering process have advantages of the uniform distribution of the binder solution, easy-to-clean pan and the possibility of applying the successive functional film coating using the same equipment. This study relates to a multiparticulate formulation comprising pellets with a multilayer of pectin-ethyl cellulose on non pareil seeds by powder layering technology. The pellets were prepared to target ketoprofen in colon based on the microbial enzyme dependent drug release mechanism. METHODS: Multiparticulate formulation by powder layering technology was prepared by conventional pan coating process to evaluate the effect of 59% methoxylated pectin and 45 cps ethyl cellulose on coating label. The formulations were tagged with (99m)Tc-DTPA, a tracer in gamma scintigraphy study to evaluate the transit behavior of drug loaded pellets and compared with uncoated pellets to evaluate its specific release. RESULTS: The transit behavior and scintigraphy image clearly indicates that the formulation can delay the drug release prior to colon. In albino rabbit, the coated pellets released drug in the colon indicating that site specificity has been achieved with pectin/ethyl cellulose coating at 1:2 ratio with 20% coating label. MAJOR CONCLUSION: Formulation containing pectin and ethyl cellulose with suitable coating label may be suitable as a coating formulation for colon delivery of ketoprofen and can be successfully evaluated by gamma scintigraphy method.     

口服结肠定位甲硝唑微球的部分因子设计与体外释放

口服结肠定位给药系统 (ｏｒａｌｃｏｌｏｎ ｓｐｅｃｉｆｉｃｄｒｕｇｄｅｌｉｖｅｒｙｓｙｓｔｅｍ ,ＯＣＤＤＳ)有利于治疗多种结肠疾病 ,如结肠炎、结肠癌、结肠性寄生虫病。ＯＣＤＤＳ可避免因大剂量用药而引起的全身副作用[1] 。甲硝唑用于厌氧菌引起的结肠炎有效 ,但其口服吸收良好(>80 % ) ,在结肠部位难于达到有效治疗浓度[2 ] 。目前临床上治疗结肠炎的主要给药途径是将甲硝唑长期灌肠 ,病人顺应性差。本文拟设计甲硝唑ＯＣＤＤＳ微球 ,有利于给药系统在结肠快速释药 ,有重要的临床意义。国内外未见报道。材料和方法　　材料与仪…     

Characterization and evaluation of self-microemulsifying sustained-release pellet formulation of puerarin for oral delivery

The present study aims to develop self-microemulsifying drug delivery systems (SMEDDS) in sustained-release pellets of puerarin to enhance the oral bioavailability of puerarin. The performances of puerarin-SMEDDS including oils, emulsifiers, and co-emulsifiers were evaluated. Pseudo-ternary phase diagrams shows that the optimized formulation consisted of castor oil as the oil phase, Cremophor EL as the emulsifier, and 1,2-propanediol as the co-emulsifier. SMEDDS sustained-release pellets were prepared via extrusion-spheronization. The particle size distributions of the formulations were determined using transmission electron microscopy and scanning electronic microscopy. The mean particle size was 50 ± 8 nm. The pharmacokinetics and bioavailability of the puerarin-SMEDDS sustained-release pellets and puerarin tablets were evaluated and compared in beagle dogs. The absolute bioavailability of the puerarin-SMEDDS sustained-release pellets was enhanced by approximately 2.6-fold compared with that of the puerarin tablet. The relative bioavailability (F(rel)) of the SMEDDS pellets was 259.7% compared with the tablet group. The results demonstrated that the puerarin-SMEDDS sustained-release pellets had a sustained-release effect, and could remarkably improve the oral bioavailability of puerarin.