防风有效成分的提取工艺研究

目的：优化防风中有效成分的提取工艺。方法：以升麻素苷、5-O-甲基维斯阿米醇苷总含量为指标,分别考察超声提取法和乙醇提取法对防风有效成分提取率的影响,并优选提取工艺参数。结果：提取工艺以回流提取法最好,最佳提取工艺为：料液比为1：40（甲醇）,提取时间为1.5h,提取1次,防风中升麻素苷和5-O-甲基维斯阿米醇苷的总提取率达到0.46%。结论：该工艺合理可行,可用于防风有效成分的提取。     

RP-HPLC法同时测定不同产地及不同部位防风中4种有效成分的含量

目的建立防风药材中4种有效成分含量同时测定的方法,以比较不同产地防风药材及不同部位中有效成分的含量,为防风药材质量标准的制定及防风的资源开发提供科学依据。方法采用RP-HPLC法。色谱柱:Diamonsil C18柱(200 mm×4.6 mm,5μm);流动相:甲醇-水,梯度洗脱;流速:1.0 mL.min-1;检测波长:254 nm;柱温:30℃。结果升麻素、升麻素苷、5-O-甲基维斯阿米醇苷、亥茅酚苷能够达到基线分离;升麻素苷和5-O-甲基维斯阿米醇苷质量浓度在1.92~400 mg.L-1内与峰面积呈良好的线性关系(r=0.9999、0.9998,n=5),平均加样回收率分别为97.5%、97.7%,RSD分别为1.3%、2.8%(n=9);升麻素、亥茅酚苷质量浓度在0.96~200 mg.L-1内与峰面积呈良好的线性关系(r=0.9999、0.9999,n=5),平均加样回收率分别为99.3%、97.7%,RSD分别为2.0%、1.7%。结论本方法为防风药材的资源开发提供了参考,可用于防风药材的质量控制。     

正交试验法优选防风中升麻素苷和浸出物提取工艺

目的进行防风中升麻素苷和浸出物提取工艺研究。方法采用正交设计,以升麻素苷含量和浸出物为评价指标,考察乙醇浓度(A)、乙醇用量(B)、提取时间、提取次数(C)4个因素对防风中升麻素苷提取的影响,优化提取工艺。结果及结论最佳提取工艺为:用8倍量60%乙醇,提取2次,第1次2h,第2次1.5h。     

HPLC法测定防风中升麻苷、升麻素、5-O-甲基维斯阿米醇苷和亥茅酚苷的含量

目的建立高效液相色谱法测定防风中升麻苷、升麻素、5-O-甲基维斯阿米醇苷和亥茅酚苷的含量。方法采用Agilent Zorbax SB-C18（5μm,150 mm×4.6 mm id）柱,甲醇-水流动相体系梯度洗脱,检测波长254 nm,流速0.7 ml/min,柱温25℃,进样量5μl。结果成功建立了防风中4种主要成分的HPLC含量测定方法,且方法学考察结果良好。结论该方法简便可行,定量准确,可用于防风中4种主要成分的质量控制。     

超微粉碎对罗勒显微特征及总黄酮体外溶出的影响简

目的：对罗勒超微粉和常规粉中总黄酮的体外溶出、显微特征及粉体学性质进行考察.方法：采用比色法测定罗勒超微粉和常规粉中总黄酮体外溶出量和溶出速率,用生物显微镜进行显微特征观察,测定粉体休止角和堆密度.结果：罗勒超微粉和常规粉中总黄酮体外溶出量无显著性差异,超微粉体的溶出速率较常规粉体明显增加.罗勒超微粉颗粒均匀,基本无完整细胞存在.与常规粉相比,罗勒超微粉的休止角增大,堆密度减小.结论：超微粉碎不会影响总黄酮的体外溶出量,但可明显提高其溶出速率.植物细胞破壁率明显提高,但流动性和充填性变差,有待于在制剂生产中进行改进.     

番泻叶超微饮片与不同粉体溶出度的比较研究

目的:比较番泻叶超微饮片与不同粉体的体外溶出特性。方法:采用桨法进行体外溶出试验,高效液相色谱法测定番泻叶超微饮片与不同粉体不同时间点番泻苷A和番泻苷B的溶出量,计算累积溶出百分率,并对其进行威布尔分布函数拟合。结果:番泻叶中粉、细粉、超微粉与超微饮片之间的溶出速度具有明显差异,超微饮片中番泻苷A和番泻苷B的溶出量最大,累积溶出70%的时间明显小于其他粉体。结论:番泻叶超微饮片具有快速溶出、高效溶出有效成分的特点。     

大黄细粉和超微粉的理化性质比较

目的:比较研究大黄粉体的理化性质,确定大黄粉体的超微粉碎程度。方法:分别考察3种大黄粉体的流动性、吸湿行为、有效成分含量、体外溶出行为等理化性质。结果:超微粉碎对大黄粉体的流动性有显著性影响,使其黏着力变大,流动性变差。大黄微粉的吸湿曲线与细粉相似。大黄各有效成分的含量不随粉体粒度的减小而减小。大黄粉体中5种有效成分的溶出程度大小顺序为大黄微粉Ⅱ>大黄细粉>大黄微粉Ⅰ。结论:微粉化有利于大黄中有效成分的溶出。     

超微粉碎对血竭、红花及其混合粉体性质的影响

目的：研究超微粉碎之后,血竭、红花单味药材粉体及其混合粉体的性质差异。方法：采用振动式超微粉碎机制备不同粒度的血竭、红花单味药材粉体及其混合粉体,根据药物引湿性试验指导原则考察各粉体的吸湿性,采用视频光学接触角测定仪测定各粉体的水接触角,采用高效液相色谱方法测定各粉体的有效成分含量及其体外溶出行为。结果：混合粉体的吸湿性较红花粉体大大降低;随着粒径的降低,混合粉体和血竭粉体中血竭素的含量变化不存在显著性差异,但混合粉体中羟基红花黄色素A（HSYA）的含量降幅小于红花粉体;混合粉体接触角与血竭粉体相近,与红花粉体相比接触角均显示出显著性差异;与单味药材粉体相比,混合粉体有利于血竭素的溶出,且随着混合粉体粒径的降低而增加,混合粉体细粉不利于HSYA的溶出,混合粉体微粉则对HSYA的溶出没有显著性影响。结论：混合粉体中由于血竭粉体的存在而可能对红花中不稳定成分HSYA产生保护作用。超微粉碎使得混合粉体可能接近或具有类似固体分散体的性质,难溶性药物血竭分散在易溶载体红花中,有利于难溶性成分血竭素的溶出。     

中络面瘫丸中防风薄层色谱鉴别研究

目的:建立中络面瘫丸中防风的薄层色谱鉴别方法,为制定其质量标准提供依据。方法:采用薄层色谱法鉴别中络面瘫丸主要药物防风中升麻素苷,以三氯甲烷-甲醇(4:1)为展开剂,展开,取出,晾干。结果:置紫外光灯(254nm)下检视,供试品色谱中,在与对照药材色谱和对照品色谱相应的位置上,分别显相同颜色的荧光斑点。结论:该方法操作简便,专属性强,重现性好,阴性无干扰,可用于中络面瘫丸防风中升麻素苷的定性定量控制。     

HPLC切换波长法同时测定升麻中5种成分的含量

目的:建立以切换波长的方法同时测定升麻中咖啡酸、升麻素苷、阿魏酸、异阿魏酸、升麻素5种成分含量的方法。方法:采用反相高效液相色谱法,Agilent Eclipse XDB-C18(4.6 mm×150 mm,5μm)色谱柱;流动相:乙腈-0.1%磷酸水溶液(13:87);检测波长:0～7 min,323 nm;7～12 min,254 nm;12～17 min,316 nm;17～20 min,254 nm;柱温:40℃;流速:1.0 mL.min-1;进样量:10μL。结果:不同商品地的升麻中5种成分的含量差异显著,升麻素苷和升麻素在部分样品中未检出。结论:切换波长法可用于升麻中5种成分含量的同时测定,为升麻质量评价提供了科学依据。     

超微粉碎对白术中内酯成分体外溶出的影响

目的:考察白术经超微粉碎后的粒度和体外溶出变化。方法:用粒度分析仪分析白术超微粉碎前后的粒径差异;以白术内酯Ⅲ、白术内酯Ⅰ含量为指标,采用高效液相色谱法测定其含量,以此反映溶出情况。结果:超微粉碎后样品粒径明显变小,约为白术细粉的30%;与白术细粉比较,白术内酯Ⅲ、白术内酯Ⅰ的含量提高约27%。结论:超微粉碎可以明显降低粒径,增加比表面积,有助于白术药材中白术内酯Ⅲ、白术内酯Ⅰ的溶出。     

不同粉碎度野生西洋参人参皂苷Rb_1的体外溶出度研究

目的采用体外溶出法考察野生西洋参细粉、极细粉与超微粉人参皂苷Rb1的溶出速率与溶出度。方法按2010年版《中国药典》规定进行不同粉碎度野生西洋参粉体外溶出度试验,绘制溶出曲线,考察不同粉碎度粉末的体外溶出行为及释药机制。结果前10 min,野生西洋参中人参皂苷Rb1的溶出速率为极细粉〉细粉〉超微粉,10 min后超微粉的溶出率最大,极细粉的溶出次之,而细粉溶出最慢。结论野生西洋参粉中人参皂苷Rb1的溶出速率与粉末本身的粒径和浸润有关,在粉末浸润后,超微粉的溶出最快。     

An investigation of the relationship between particle size and compression during capsule filling with an instrumented mG2 simulator

An instrumented mG2 capsule filling machine simulator has been employed to study the effects of the amount of compression (compression ratio) on the capsule fill weight uniformity and measured compression and ejection stresses. Four size fractions of lactose were studied (mean particle sizes 15.6, 17.8, 37.5 and 155.2 micron). The range of compression over which satisfactory filling could be achieved was large for fine, cohesive powders but decreased with increasing particle size. The lower limit of filling ability was the ability to retain the powder and the amount of compression needed to achieve retention increased with increasing particle size. The upper limit on compression, was the compaction of the powder which prevented the piston acting to cause retention. Large particle sizes were able to undergo only a small change in volume before compaction occurred whilst fine, cohesive powders were considerably more compressible and hence could be filled satisfactorily at higher compression settings.     

Preparation and in vitro/in vivo evaluation of revaprazan hydrochloride nanosuspension

Revaprazan hydrochloride (RH) is a new reversible proton pump inhibitor. However, due to poor water solubility, oral bioavailability of the drug was relatively low. To investigate the particle size reduction effect of RH on dissolution and absorption, three suspensions that containing different sized particles were prepared by high pressure homogenization and in vitro/in vivo evaluations were carried out. DSC and powder X-ray diffraction were used to study crystalline state of freeze dried powder of RH suspensions and the results showed that particles of RH microsuspension and nanosuspension remained in the same crystalline state as coarse suspension, but had lower lattice energy. In the in vitro dissolution test, both microsuspension and nanosuspension showed increased dissolution rate. In the in vivo evaluation, compared to coarse suspension, RH nanosuspension exhibited significant increase in AUC(0-t), C(max) and decrease in T(max), MRT. Nevertheless, RH microsuspension did not display any significant differences in these pharmacokinetic parameters compared to the coarse suspension. The findings revealed that particle size reduction can influence RH absorption in gastrointestinal tract and nanosuspension can enhance oral bioavailability of RH in rats.     

Direct estimation of the in vivo dissolution of spironolactone, in two particle size ranges, using the single-pass perfusion technique (Loc-I-Gut) in humans.

AIM: The objective of this in vivo dissolution study was to investigate the usefulness of the Loc-I-Gut technique for differentiating between the in vivo dissolution rate of two particle sizes of spironolactone, and to compare these in vivo results with corresponding in vitro data. METHODS: The study included six volunteers, and consisted of three sequential parts (I, II, III). In parts I and III the in vivo dissolution was measured directly by perfusing a semi-open segment in the proximal jejunum. In part II, a solution of spironolactone was administered orally, and the plasma concentration time profile was followed for 48 h. The in vitro dissolution was measured using flow-through cells and different dissolution media simulating human gastrointestinal fluids. RESULTS: A difference in in vivo dissolution rate of the two different particle sizes was observed, based on perfusion data. This difference was not pronounced in the relative bioavailability of spironolactone administered in two different particle sizes. The relative bioavailability was dependent on the bile acid concentration in vivo. In vitro, dissolution rate of the smaller particles was improved at fasted state bile acid concentrations, while the larger particles were only significantly affected at fed state bile acid concentrations. CONCLUSION: In vivo dissolution studies discriminated between the dissolution rate of the two different particle sizes of spironolactone, based on the perfusate samples. The lack of difference in relative bioavailability, might be explained by the insufficient wash-out of particles after ending the perfusion, reabsorption of surface active ingredients along the GI tract, relatively small difference in particle size and the large inter- and intra-individual differences in pharmacokinetic variables.     

Studies on zinc sulphate microcapsules (1): Microencapsulation and in vitro dissolution kinetics

Microcapsules of zinc sulphate with core: wall ratios of 1:1 and 2:1 were prepared by the coacervation method, using ethylcellulose as the coating material. The prepared microcapsules were separated into batches of 250 and 500 micron in size by sieving. The effects of particle size, the amount of zinc sulphate, and the core: wall ratio on the dissolution kinetics were studied, and evaluated kinetically by the Rosin-Rammler-Sperling-Bennet-Weillbull (RRSBW) distribution.     

Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder

The effect of particle size on the dissolution behavior of the particles of amorphous solid dispersions (ASDs) of griseofulvin (GF), with 0%-50% Kollidon^® VA 64 as a crystallization inhibitor is investigated. Both the final dissolved GF concentration and the dissolution rate of GF ASDs were found to be inversely proportional to the particle size. The solution concentrations for the smallest (45-75 μm) size group with different polymer loadings were significantly higher than those for the largest (250-355 μm) group regardless of the initial GF amount. Specifically, the dissolution rate of GF ASDs with 50% polymer loading for the finest group was 2.7 times higher than for the largest group under supersaturating conditions. The rates of dissolution and recrystallization were assessed through surface concentration (C_s) and Avrami recrystallization rate kinetics, where the solid-state recrystallization was confirmed using Raman spectroscopy. Outcomes indicated that particle size reduction enhanced ASD drug loading by reducing the amount of polymer necessary as finest size ASDs initially dissolve faster, negating their higher recrystallization rate. Kollidon® VA 64 at 30% loading was sufficient to inhibit the GF recrystallization. Overall, the combination of particle size reduction and recrystallization inhibition is effective for improved dissolution behavior of GF ASDs.     

Effect of particle size on the available surface area of nifedipine from nifedipine-polyethylene glycol 6000 solid dispersions

Solid dispersions containing 5%, 10%, 20%, 30% and 50% of nifedipine were prepared with polyethylene glycol (PEG) 6000 as carrier, respectively, by the fusion method. Drug release from four different size fractions of nifedipine-polyethylene glycol 6000 solid dispersions were examined. The probability parameters of Weibull distribution or log-normal distribution could be obtained from linear regression of the dissolution data. The effects of particle size on the dissolution rate of nifedipine were evaluated in terms of the time course of the available surface area (S(t)). The X-ray diffraction patterns showed that nifedipine was dispersed homogeneously in an amorphous state in the solid dispersions with nifedipine concentration up to 10%. The initial values and faster rate of decrease of S(t) during the dissolution process were markedly enhanced in the solid dispersions with lower contents of nifedipine (5% and 10%) due to the formation of high energy metastable (amorphous) states of the drug and differences in the particle sizes had little effect on the values of the available surface area and the dissolution of the drug. Values of available surface area were particle size dependent for the solid dispersions with higher contents of nifedipine (20%, 30% and 50%) and the rate of decrease of S(t) was enhanced as the particle size reduced.     

珍珠粉颗粒粒度与氨基酸体外溶出效果的关系

目的：测定不同粒度的珍珠粉氨基酸体外溶出量和溶出速率，考察氨基酸体外溶出效果。方法：选取不同粒度的珍珠粉体，以氨基酸为溶出指标，利用分光光度法测定其在一定时间内的溶出量和溶出速率，并对结果进行分析。结果：随着珍珠粉颗粒粒度的减少，氨基酸的溶出量增大，溶出速率加快，超细珍珠粉与未超细珍珠粉相比，表现得更加明显。结论：珍珠经超微细化后，可以大大提高珍珠粉氨基酸的溶出效果。