Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs

Nanocrystals, a carrier-free colloidal delivery system in nano-sized range, is an interesting approach for poorly soluble drugs. Nanocrystals provide special features including enhancement of saturation solubility, dissolution velocity and adhesiveness to surface/cell membranes. Several strategies are applied for nanocrystals production including precipitation, milling, high pressure homogenization and combination methods such as NanoEdge™, SmartCrystal and Precipitation-lyophilization-homogenization (PLH) technology. For oral administration, many publications reported useful advantages of nanocrystals to improve in vivo performances i.e. pharmacokinetics, pharmacodynamics, safety and targeted delivery which were discussed in this review. Additionally, transformation of nanocrystals to final formulations and future trends of nanocrystals were also described.     

HPLC法测定香丹注射液中丹参素、原儿茶醛、咖啡酸、迷迭香酸、丹酚酸B和丹酚酸A

目的 建立用高效液相色谱同时测定香丹注射液中丹参素、原儿茶醛、咖啡酸、迷迭香酸、丹酚酸B和丹酚酸A 6个水溶性成分的方法,并对20个生产厂家香丹注射液进行测定。方法 采用HPLC色谱系统,Alltima C₁₈(250 mm×4.6 mm, 5 μm);流动相为乙腈-0.026％磷酸,梯度洗脱;流速为1.0 mL/min;柱温25 ℃;检测波长为288 nm。结果 本方法6个成分色谱峰之间具有良好的分离度,它们的浓度和各自峰面积之间有着良好的线性关系,精密度、稳定性、重复性及加样回收率均符合要求。不同厂家香丹注射液中化学成分的含量存在较大差异, 其中丹酚酸A量差异最大,丹参素差异最小。结论 本方法能同时测定香丹注射液中6个主要化学成分,可为全面控制香丹注射液的质量提供参考。     

Autonomic nervous system mediates the cardiovascular effects of Rhodiola sacra radix in rats

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola sacra (Crassulaceae) exhibits cardiovascular bioactivities and is used in Tibetan medicine for promoting circulation and preventing hypertension. However, the underlying mechanisms of its cardiovascular effects are poorly understood. AIM OF THE STUDY: The aim of this study was therefore to evaluate the cardiovascular activity of water-soluble fraction (WtF) and n-butanol-soluble fraction (BtF) of Rhodiola sacra radix and to explore its mechanism of action in propofol anesthetized Sprague-Dawley rats. MATERIALS AND METHODS: The changes of blood pressure, heart rate and cardiac contractility after systemic administration of the extracts (10-75mg/kg) were examined for at least 40min. Different antagonists were used to evaluate the mechanisms of cardiovascular effects of the extracts. RESULTS: Intravenous injection of the WtF (10, 25, 35, 50 or 75mg/kg) exhibited dose-dependent hypotension and increases in heart rate and cardiac contractility. In contrast, mild alterations in the same cardiovascular parameters were detected only at high dose (75mg/kg) BtF. The WtF-induced hypotensive, positive inotropic and chronotropic effects were significantly abolished by pretreatment with hexamethonium (30mg/kg, i.v.) or reserpine (5mg/kg, i.v.), whereas the hypotensive, but not the positive inotropic or chronotropic effect was potentiated by captopril (2.5mg/kg, i.v.). Pretreatment with methylatropine (1mg/kg, i.v.), on the other hand, reversed the positive inotropic and chronotropic but not the hypotensive effects of WtF. The WtF-induced cardiovascular responses were not affected in rats pretreated with N(G)-nitro-l-arginine methyl ester (20mg/kg, i.v.). CONCLUSIONS: We conclude that systemic administration of the WtF of Rhodiola sacra radix elicited a potent hypotensive effect that was mediated by the withdrawal of sympathetic vasomotor tone and interaction with the circulatory angiotensin system. The positive inotropic and chronotropic effects of WtF may result from a direct vagal inhibition on the heart.     

米口袋化学成分的研究

从米口袋（Gueldenstae dtia multiflora Bge.）中分离得到11个化合物,应用光谱学和化学方法鉴定了其中7个化合物的结构,分别为黑麦草内酯、烈香杜鹃素Ⅰ、木栓醇、木栓酮、4-烯-3-酮豆甾烷、A’-Neogammacer-22（29）-en-3β-ol,acetate和β-谷甾醇。7个化合物均从该植物中首次分离得到,其中化合物Ⅰ是该植物中的水溶性成分。     

Cyrene™ as an Alternative Sustainable Solvent for the Preparation of Poly(lactic-co-glycolic acid) Nanoparticles

Toxic and environmental harmful organic solvents are widely applied to prepare poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NP) in standard preparation methods. Alternative non-toxic solvents suffer from disadvantages like high viscosity and plasticizing effects. To overcome these hurdles, Cyrene? as a new sustainable, non-toxic and low viscous solvent was used to formulate PLGA NPs. A new preparation method was developed and optimized. Small sized blank NPs around 220 nm with a narrow size distribution and highly negative charge (<?23 mV) were obtained. To test the application for drug delivery, the lipophilic model drug atorvastatin was encapsulated in high drug loads with comparable physicochemical characteristics as the blank NPs, and a total drug release within 24 h. No changes of the crystallinity or plasticizing effects could be observed. Highly purified NPs were obtained with a residual Cyrene? content <2.5%. Finally, the biocompatibility of Cyrene? itself and of the NPs formed in the presence of Cyrene? was demonstrated in a hen's egg test. Conclusively, the use of Cyrene? as solvent offers a simple, fast and non-toxic procedure for preparation of PLGA NPs as drug delivery systems circumventing the downsides of standard methods.     

难溶性药物阿替洛尔单层芯渗透泵片的制备

 目的以阿替洛尔为模型药物,通过酸碱反应提高难溶性药物的溶解能力并制备单层芯渗透泵片。方法在处方中加入酒石酸使其与阿替洛尔的碱性基团反应从而增强药物的溶解性,用自行设计的带针冲头压制带孔片芯,以乙基纤维素为膜材包衣制备渗透泵片,采用相似因子作为指标筛选处方。结果在酒石酸溶液中阿替洛尔的溶解能力大幅度提高,制备的阿替洛尔单层芯渗透泵片能在24h内匀速释放药物,且释药行为不受桨转速和释放介质的影响。结论用酒石酸提高阿替洛尔的溶解能力并进而制备单层芯渗透泵片的方法是可行的。酸碱反应增溶药物的方法可望推广到其他难溶于水,但具有酸碱反应能力药物的增溶和渗透泵片的制备。     

药用红花生育期间可溶性糖和可溶性氨基酸含量动态的研究

在药用红花一生中,可溶性糖含量与可溶性氨基酸含量随生育进程而发生变化,与红花植株器官的发育密切相关。可溶性糖含量与可溶性氨基酸含量的比值随生育进程而增加.至生育后期其比值达最大。     

Dissolution Rate Enhancement by in Situ Micronization of Poorly Water-Soluble Drugs

Purpose. The purpose of this study was to evaluate a novel in situ micronization method avoiding any milling techniques to produce nano- or microsized drug particles by controlled crystallization to enhance the dissolution rate of poorly water-soluble drugs. Methods. Ibuprofen, itraconazole, and ketoconazole microcrystals were prepared by the association of the previously molecularly dispersed drug using a rapid solvent change process. The drug was precipitated in the presence of stabilizing agents, such as hydrocolloids. The obtained dispersion was spray-dried. Particle size, morphology, dissolution rate, specific surface area, and wettability were analyzed. Physicochemical properties were characterized using differential scanning calorimetry and X-ray diffractometry. Results. The obtained dispersions showed a homogeneous particle size distribution. Drugs are obtained in a mean particle size of approximately 2 m and below. A high specific surface area was created and in situ stabilized. Different stabilizers showed differences in protecting the precipitated drug from crystal growth. The surface was hydrophilized because of the adsorbed stabilizer. Thus, a drug powder with markedly enhanced dissolution rate was obtained. Conclusions. In situ micronization is a suitable method for the production of micro-sized drugs. This technique can be performed continuously or discontinuously and uses only common technical equipment. Compared to milled products drug properties are optimized as all particle surfaces are naturally grown, the particle size is more uniformly distributed and the powder is less cohesive.     

五味子水溶性成分的HPLC指纹图谱研究

目的:研究五味子水溶性成分高效液相指纹图谱的测定方法。方法:色谱柱:D iscovery SB-C18(150 mm×4.6 mm,5μm);流动相:水-乙腈,梯度洗脱;检测波长:203 nm;流速:1.0 mL/m in。结果:以五味子醇甲为参照物,标定五味子水溶性成分指纹图谱有8个共有峰,其稳定性、精密度、重复性均符合要求。结论:所选择的10批五味子药材水溶性成分的指纹图谱具有良好的相似性,该方法可靠、简便,可作为五味子质量控制的参考方法。     

新疆鼠尾草水溶性有效部位的筛选研究

目的:测定新疆鼠尾草水溶性各部位丹酚酸类的含量,寻找有效部位。方法:采用UV分光光度法,分别对各部位丹酚酸类进行含量测定和方法学研究。结果:新疆鼠尾草地上部分80%甲醇提取物经大孔树脂柱分离的10%EtOH-H2O部分中丹酚酸类的含量为53.144%,为有效部位。结论:UV分光光度法操作简便,结果准确,便于推广,为新疆鼠尾草水溶性有效部位的筛选提供了科学依据。