A family of nanogel drug carriers has been designed to enhance the oral absorption of paclitaxel (PTX). The PAHy-based nanogels were prepared by the interpenetration of poly-α,β-polyasparthydrazide (PAHy) chains and dicarboxyl-poly (ethylene glycol) (CPEG), forming a smart chain network. The PAHy-based nanogels were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), dynamic light scattering (DLS), X-ray diffraction (XRD) and high performance liquid chromatography (HPLC). The adhesion and retention properties of fluorescein isothiocyanate (FITC)-nanogels in vivo were investigated using an in vivo imaging system and confocal laser scanning microscopy (CLSM). The smart nanogels had a particle size of -200 nm, increased the degree and rate of release, and spent over 12 h in the gastrointestinal tract. They also produced excellent adhesion, permeability and retention (APR) effects and increased oral absorption, confirming their use as potential sustained-release carriers for the oral delivery of the hydrophobic anticancer agent PTX.

Objective To establish a determination method for five residual solvents in Rifamycin sodium.Methods DB-5 capillary column was adopted with inlets temperature at 200 ℃;FID detector and programmable temperature was applied.The initial temperature was 40 ℃ and kept for 8 min,the temperature was then raised to 200 ℃ at the rate of 15 ℃·min-1 and lasted 2 min.Results Five residual solvents were completely separated with good linear relationships(r=0.9933-0.9999).The average recovery rates were in the range of 82.0%-102.0%(RSD=1.2%-5.3%,n=9).Conclusion The methods was proved to be accurate and sensitive,which can be used for the determination of residual solvents in Rifamycin sodium.

Objective To establish a HPLC method for the determination of cefoperazone impurity C in cefoperazone sodium and sulbactam sodium for injection.Methods The analytes were analyzed on a C_(18) column, using a mixture of 0.005mol/L tetrabutylammonium hydroxide solution-acetonitrile(75:25) as the mobile phase with a flow rate of l.0mL/min.Detection wavelength was 220nm,and the column temperature was maintained at 30℃. Results Cefoperazone impurity C was well separated from other impurities and both of cefoperazone and sulbactam were completely separated from their related substances.The calibration curve was linear in the range of 3.19~25.6μg/mL and the correlation coefficient was 0.9998.The average recovery was 97.45%and the RSD was 2.4%(n=9).Conclusion The established method is accurate,sensitive and specific.It is suitable to determinate cefoperazone impurity C in cefoperazone sodium and sulbactam sodium for injection and can be effectively used for quality control of the drug.

Objective:To compare the similarity of captopril tablets from the original drug enterprise and the other 6 enterprises to assess their quality difference and the quality controllability of current dissolution determination method.Method:The dissolution was determined on the basis of CP 2010 Edition.The RSD of each point in the dissolution curves was calculated in order to study the repeatability of each tablet.The similarity was compared by the calculation of f_1 and f_2 factors using the product from the original enterprise as the reference preparation.Result:The good repeatability of each tablet could be found.Single-point dissolution of the tablets from the 6 enterprises was all better than that from the original drug enterprise.The dissolution curve of the product from one enterprise was similar to that from the original drug enterprise evaluated by the method of f_1 and f_2 factors.Conclusion:It is promising to assess product intrinsic quality by f_1 and f_2 factors.

Objectives The aim of this study was to investigate the correlation between the growth behaviour and in-vitro dissolution rate of water-insoluble drugs prepared with high-shear wet granulation.Methods Granules containing nimodipine, microcrystalline cellulose, low-substituted hydroxypropylcellulose and aqueous solution of hydroxypropylcellulose were prepared and the effects of independent process variables, including impeller speed and liquid-to-solid ratio were taken into consideration. The mean granule size, granule-size distribution (GSD), porosity and surface properties were monitored at different kneading times to identify the granule-growth mechanisms simultaneously. A computer-based method was applied to simulate the dissolution behaviour of polydisperse granules based on the GSD data.Key findings The in-vitro dissolution rate of drug was high for the early stages of granulation and sharply decreased when coalescence and consolidation of granules started, approaching a flat and low level when granules were sufficiently consolidated. The simulated dissolution results were in agreement with experimental observations and were significantly affected by the GSD, porosity and surface properties of granules during the granulation process. Moreover the GSD was directly related to the granule-growth behaviour and mechanisms.Conclusions In general, it was concluded that the dissolution properties of nimodipine basically correlated with the growth behaviour of granules in a high-shear mixer. The simulation method based on GSD can be used as a convenient and rapid way to predict the dissolution properties for formulation development and granulation optimization.

目的 对玻璃酸钠的特性粘度进行测定研究.方法 以日本药局方、欧洲药典、中国药典方法 测定玻璃酸钠的特性粘度并比较.结果 日本药局方与欧洲药典的测定结果 分别为2407及2506 cm3/g,与中国药典一定浓度范围内供试品的测定结果 相近.结论 日本药局方与欧洲药典的测定方法 较为严谨,结果 相近,中国药典方法 在适宜的浓度范围内可较为简便的测定特性粘度.

The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature were taken into consideration. Two polymorphs of the model drugs and granules were characterized by X-ray powder diffraction analysis and quantitatively determined by differential scanning calorimetry. A theoretical kinetic method of ten kinetic models was applied to analyze the polymorphic transformation of model drugs. The results obtained revealed that both the transformation of modification I to modification II of NMD and the transformation of the α form to the γ form of IMC followed a two-dimensional nuclei growth mechanism. The activation energy of transformation was calculated to be 7.933 and 56.09 kJ·mol−1 from Arrhenius plot, respectively. Both the granulating temperature and the impeller speed affected the transformation rate of the drugs and, in particular, the high shear stress significantly accelerated the transformation process. By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high-shear mixer.

Anti-neuroexcitation peptide (ANEP) is a promising candidate for the treatment of neuroexcitation-associated diseases. N-Trimethyl chitosan (TMC) with different degrees of quaternization was synthesized, characterized and evaluated as a brain-targeting delivery vehicle for ANEP. ANEP-loaded TMC nanoparticles were prepared by ionic crosslinking of TMC with tripolyphosphate (TPP). The optimized formulation of nanoparticles consisted of TMC with a degree of quaternization (DQ) of 36.1% and TPP solution with a concentration of 0.6 mg/mL. The mean encapsulation efficiency and loading capacity of the optimum formulation was 80.63% and 185.4 μg/mL, respectively, while the mean particle size, zeta potential, and pH value were 255 nm, 32.0 mV and 6.61, respectively. ANEP was labeled with FITC for in vivo tissue distribution experiments. The results showed that the targetability of ANEP to brain was significantly increased by TMC nanoparticles. Absorptive-mediated transcytosis was believed to be the main pathway for the brain-targeting of FITC–ANEP–TMC/NPs. These findings demonstrate that TMC nanoparticles are potentially useful brain-targeting delivery systems for ANEP.

Purpose To establish an effective ELISA method for the determination of anti-neuroexcitation peptide(ANEP) and to investigate the stability of ANEP.Methods ANEP was determined by using two kinds of ELISA.After comparison,indirect ELISA was chosen and optimized for the research on stability of ANEP.The effects of temperature,pH value,freeze-thaw,and sonification on the stability of ANEP were investigated.Results The indirect ELISA showed better linearity and sensitivity than indirect competitive ELISA.A standard curve was obtained and the regression equation was y=1.026 6 x+0.044 3.The assay result was linear over a concentration range of 0.025-1.60 μg/mL with a limit of detection(LOD)of 10 ng/mL.ANEP didn′t degrade during 24 h incubation period at 37℃ and 60℃ and was found to be stable at the pH range from 5 to 11.ANEP obviously degraded after repeated freeze-thawing and sonification for more than 4 min.Conclusion The established indirect ELISA meets the requirements in determination of ANEP.ANEP is thermo-stable and sensitive to low pH value,repeated freeze-thawing and long time sonification.

This study compared the granulation processes for different formulations using a laboratory-scale high shear mixer. The effects of critical process parameters (impeller speed, chopper speed and kneading time) on granule characteristics were evaluated. The characteristics of the granules studied included the size distribution, friability and morphological properties. The flow profiles of the wet mass and material deposition during the process were also studied. The results obtained showed that the effect of the impeller speed was determined by the starting material system. On the other hand, chopper speeds from 1200 to 3600 rpm and kneading times from 120 to 240s had a consistent influence on all formulations. Moreover, it was found that the toroidal flow pattern of the wet mass could be maintained for a longer period and granules with a good spherical shape were obtained by removing the chopper during the last 120s of the granulation process. In addition, the use of the pregelatinized starch in the formulation also led to a reduction in the wall adhesion of the material. It was concluded that the effectiveness of high shear wet granulation could be improved by choosing a proper combination of starting material and process parameters and by monitoring the mass motion during the process.

Anti-neuroexcitation peptide (ANEP) is a novel recombinant peptide obtained from the venom of the Chinese scorpion Buthus martensii Karsch. However, the expression of recombinant ANEP in Escherichia coli results in the formation of insoluble aggregates known as inclusion bodies. Here, we describe a novel method for the preparation of ANEP which maximizes the yields of recombinant peptide in a soluble and active form. A non-fusion expression plasmid pNJUTRX-1-ANEP-His(6) encoding recombinant ANEP with a His(6)-tag at its C-terminus was constructed and transformed into E. coli strain BL21 (DE3). The expressed ANEP was almost in soluble form and accounted for about 12% of the total cellular proteins. The recombinant ANEP in the cell lysate was purified to homogeneity by His Bind affinity chromatography. This effective method solved the problem of a lack of sufficient active peptide which, until now, has hampered the further research and development. In order to develop an immunoassay method for ANEP, polyclonal rabbit antiserum was raised against the prepared ANEP and purified by protein A affinity chromatography. It was confirmed that the antibody reacted with recombinant ANEP by both Western blotting and ELISA results. Using purified antibody, the immunoassay method was developed.

综述了近年来有关制备蛋白质类药物微粒制剂的研究进展,包括溶剂挥发法、溶剂-非溶剂法、吸附法、喷雾干燥法、核芯包衣法制备微球和海藻酸钠/壳聚糖微球、脂质体微球、原位微球、水凝胶锚定脂囊泡系统的方法。

目的通过对凝胶剂的体外累计释放百分率的比较,优化伊曲康唑凝胶剂的处方。方法选用卡波姆-940作为凝胶剂的基质,用3种不同质量分数的伊曲康唑（ITZ）、甘油、PEG-400制备凝胶剂。采用Franz扩散池进行体外释放实验,正交设计优选处方。结果优选的凝胶剂最佳处方为:ITZ质量分数为1%、PEG-400质量分数为10%、甘油质量分数为5%。结论体外累积释放试验筛选伊曲康唑凝胶剂处方是可行的。