Development of a predictive in vitro dissolution for clarithromycin granular suspension based on in vitro-in vivo correlations

The objective of this study was to evaluate the in vitro behavior of different clarithromycin granular suspensions based on a developed in vitro-in vivo correlation model, using one reference and two test formulations. In vitro release rate data were obtained for each product using the USP apparatus II, operated at 50?rpm under different pH conditions. The dissolution efficiency was used to analyze the dissolution data. In vivo study was performed on six healthy male volunteers under fasting condition. Correlation was made between in vitro release and in vivo absorption. A linear model was developed using percent absorbed data versus percent dissolved data from the three products. Dissolution condition of 0.1N HCl for 1?h and then phosphate buffer at pH 6.8 was found to be the most discriminating dissolution method. Rate of absorption for the reference as estimated by Wagner-Nelson deconvolution was correlated with in vitro release with a correlation coefficient of 0.99. The in vivo results for the two test products were compared to the predicted values using the reference model with a correlation coefficient of 0.94. Furthermore, multiple level C correlations were obtained for some pharmacokinetic parameters with the corresponding in vitro kinetic parameters with correlation coefficients exceeding 0.90. Moreover, the interpretation of the in vitro and in vivo data with reference to formulations was discussed.     

中药配方颗粒的发展现状及国际化对策探讨

近年来,世界各国对天然药物日益重视,而中药配方颗粒既能在中医理论指导下随证加减,又有服用便捷、适宜工业生产等优点,成为推动中药"走出去"的有力助力。通过回顾中药配方颗粒的发展历程、分析相关数据和国内外发展形势,对中药配方颗粒的研究现状、市场情况及国际化发展面临的主要挑战进行探讨,提出利用政府间交往推进中药国际贸易、充分发挥海外资源平台作用、帮助监管部门建立符合中药配方颗粒特点和审批国政策的合理化国际审批方案、争取国际标准主导权的建议,为推动中药配方颗粒产业在世界范围内高质量发展提供参考。     

Ultrastructural immunocytochemistry suggests that periderm granules in embryonic chick epidermis contain beta-defensins

The capability to express an innate antimicrobial action through the production of beta-defensins in the skin of chick embryos has been studied by immunocytochemistry. The immunolabeling of periderm granules present in the initial embryonic epidermis of the chick is obtained with a lizard anti-defensin antibody (Ac-BD-15) that recognizes a homologous peptide in the chick beta-defensin 9. Similar granules, termed honeycomb granules, are also stored in some basophilic granulocytes of adult and hatchling chicks, but did not show immunoreactivity to the antibody. It is unclear whether this morphology indicates different organelles, content or lack of available antigens due to organelle packaging. The remarkable ultrastructural similarity between periderm granules and the honeycomb granules present in basophil granulocytes further indicates that embryonic keratinocytes can synthesize antimicrobial peptides together with corneous proteins. These peptides may participate in the formation of an epidermal microbial barrier during ontogenesis or protect the embryo in case of damage to the amniotic-periderm barrier. These transient organelles, apart from the early keratinization of the epidermis that forms the initial barrier before hatching may also contribute to the formation of an efficient anti-microbial barrier against the penetration of microbes during embryonic life until hatching when the adaptive immunity system is still immature.     

Sustained release bioadhesive effervescent ketoconazole microcapsules tabletted for vaginal delivery

Microcapsules of ketoconazole with 1:1 and 1:2 core-wall ratios were prepared by means of the phase separation technique using sodium carboxymethylcellulose as a coating material. The microcapsules were mixed with effervescent granules and were tabletted. Dissolution studies of microcapsules, tabletted microcapsules and commercial ovules were carried out with a new basket method (horizontal rotating basket). A good sustained action was obtained with tablets. Micromeritic investigations were carried out on microcapsules in order to standardize the microcapsule product and to optimize the pilot production of the dosage forms prepared with these microcapsules. Bulk volume and weight, tapping volume and weight, fluidity, angle of repose, weight deviation, relative deviation, particle size distribution, density and porosity values of the microcapsules were determined. In addition, to evaluate whether some kind of glidant will be needed during tabletting of microcapsules, the Hausner ratio and consolidation index were also calculated and it may be concluded that microcapsules do not need any glidant.     

正交试验法优选更年安舒颗粒提取工艺

摘 要 目的： 优选更年安舒颗粒的提取工艺。方法: 采用正交试验设计法,以松果菊苷及特女贞苷含量为指标综合评价,考察加水量、提取时间、提取次数对提取工艺的影响。结果: 最佳提取工艺为加水煎煮2次,每次2 h,每次加8倍量的水。结论: 优选的工艺合理可行、重复性良好、提取效率高,适合于工业化生产。     

清热解肌颗粒中挥发油的初步质量研究

目的 建立清热解肌颗粒中挥发油成分的质量标准.方法 采用薄层色谱法(TLC)对清热解肌颗粒中挥发油进行定性鉴别;采用气—质联用色谱仪(GC-MS)对挥发油提取物的成分进行鉴定;采用气相色谱法(GC)测定制剂中挥发油的含量.结果 薄层色谱斑点清晰,重现性好,阴性对照无干扰.GC-MS共检出13个色谱峰并鉴定出12个化合物.α-蒎烯、β-蒎烯、桉油精线性范围分别为1.89～605.00mg·L-1(r=1.000),1.25 ～99.60mg· L-1(r=1.000),2.32 ～185.81 mg·L-1(r=1.000),平均加样回收率分别为92.82％(RSD =4.83％)、94.29％(RSD=3.10％)和104.23％ (RSD =3.14％) (n =9).结论 所建立的方法准确、可靠、专属性强,可用于该制剂的质量控制.     

原料药粒径对头孢地尼颗粒体外溶出行为的影响

目的：考察原料药粒径对头孢地尼颗粒体外溶出度的影响。方法参照2010版中国药典第二法,以 pH ＝6．8磷酸盐缓冲液为溶出介质,转速为50 r·min －1,采用紫外分光光度法为分析方法,考察不同粒径的原料制备的头孢地尼颗粒与参比制剂溶出的一致性。结果粒径为 D90：142．90μm、D50：30．25μm、D10：3．47μm（100目筛）和 D90：51．21μm、D50：10．71μm、D10：2．25μm（200目筛）的头孢地尼原料制成的颗粒溶出行为与原研不相似;在不同溶出介质中,D90：35．62μm、D50：6．98μm、D10：1．66μm 的头孢地尼原料制成的颗粒,与参比制剂的溶出行为均相似。结论建立的分析方法简单可靠,原料微粉化能够有效提高难溶性药物的溶出度。     

康复新液保留灌肠治疗放射性肠炎的临床观察

目的：优选枇杷清肺颗粒的最佳醇提工艺。方法醇提工艺以盐酸小檗碱含量和浸膏得率为指标,采用正交试验优选枇杷清肺颗粒最佳醇提工艺。结果醇提最佳工艺条件为加10倍量70％乙醇,回流提取3次,每次2 h。结论优选出的提取工艺稳定,主要有效成分转移率高,为枇杷清肺颗粒的成型工艺研究奠定了基础。     

多指标综合评分法优选补正续骨颗粒最佳提取工艺

目的：优选补正续骨颗粒的提取工艺。方法采用 L9（34）正交试验法,以出膏率为考察指标,优选最佳水提取工艺,以川续断皂苷Ⅵ与柚皮苷总含量及出膏率综合评分为评价指标,优选最佳乙醇提取工艺。结果最佳水提取工艺为加6倍量水,提取2次,每次提取1 h。最佳乙醇提取工艺为加6倍量60％乙醇,提取3次,每次2 h。结论优选的提工艺稳定可行,适用于补正续骨颗粒的工业化生产。     

小儿双清颗粒治疗128例小儿急性上呼吸道感染的临床分析

目的：对小儿双清颗粒治疗小儿急性上呼吸道感染的临床效果进行分析。方法250例急性上呼吸道感染患儿,将其随机分为两组,治疗组128例,对照组122例,对照组采用西药治疗,即在0.9%氯化钠注射液中加入利巴韦林、青霉素钠氯化钠或头孢唑林钠静脉滴注,治疗组在对照组治疗基础上加用小儿双清颗粒治疗,疗效评定标准参照《中药新药临床研究指导原则》。结果治疗组治愈75例,占58.59%,显效32例,占25.00%,有效16例,占12.50%,无效5例,占3.91%,总有效率96.09%;对照组治愈55例,占45.08%;显效26例,占21.31%,有效22例,占18.03%,无效19例,占15.57%,总有效率84.43%,治疗组明显优于对照组,差异有统计学意义(P<0.05)。结论小儿双清颗粒治疗小儿急性上呼吸道感染较单独西药治疗效果好,安全性高,值得临床上应用推广。