反应条件对脂肪酶酯化活性和对映选择性的影响

分别测定了２－萘基丙酸类药物萘普生Ｒ－,Ｓ－对映体在有机溶剂中的酶促酯化反应初速度,并研究了反应温度,酰基受体和有机溶剂等反应条件对脂肪酶的反应活性和对映选择性的影响。在一定范围内,酶反应活性随温度升高而增加,温度过高易使酶失活;酶选择性则随温度升高而下降;反应温度以３５￣４０℃为佳。     

萘普生中间体的薄层色谱分析

用薄层色谱法定性分析萘普生合成中的１０ 种中间体, 使用乙酸乙酯∶环己烷＝ １∶４（ Ｖ／ Ｖ） 作展开剂, 在萘普生合成工艺中可用于丙酰基化、溴代和缩酮化等反应进行程度的监测,分析效果好。     

Preparation of molecularly imprinted polymer films on monodisperse macromolecular beads

A new and facile technique for preparing homogeneous and highly selective molecularly imprinted polymers (MIPs) films on porous monodisperse poly‐(glycidyl methacrylate‐co‐ethylene glycol dimethacrylate) beads (P_GMA‐EDMA beads) has been described: before polymerization, initiator was immobilized on the P_GMA‐EDMA beads' surface by chemical reactivity; then functional monomers and crosslinkers were initiated by the surface‐bound initiator and copolymerized to form MIPs films on the P_GMA‐EDMA beads' surface in the presence of template molecules. The resulting beads were analyzed by FTIR spectroscopy and X‐ray photoelectron spectra. The effects of the initiator amount and copolymerization time on the content of MIPs, and MIPs contents on morphologies and pore properties of the resulting beads were investigated. The results show that the content of MIPs can be adjusted by changing initiator amount or by controlling copolymerization time. The binding experiments indicate that, at lower grafting level, with the increase of MIPs content, the adsorption and recognition capabilities of the resulting beads enhance. When MIPs content increase to 16.75%, the highest adsorption and recognition capabilities are obtained. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Flocculation of Polymer Stabilized Nanocrystal Suspensions to Produce Redispersible Powders

Aqueous suspensions of crystalline naproxen nanoparticles, formed by antisolvent precipitation, were flocculated with sodium sulfate, filtered, and dried to form redispersible powders for oral delivery. The particles were stabilized with polyvinylpyrrolidone (PVP K-15) and/or poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) (poloxamer 407). The yield of the drug in the powder was typically 92–99%, and the drug loading was reproducible to within 1–2%. The filtration process increased the drug loading by up to 61% relative to the initial value, as unbound surfactant was removed with the filtrate. Upon redispersion of the dried powder, the average particle size measured by light scattering was comparable to the original value in the aqueous suspension prior to flocculation, and consistent with primary particle sizes observed by scanning electron microscopy (SEM). For 300-nm particles, up to 95% of the drug dissolved in 2 min. The dissolution rate was correlated linearly with the specific surface area calculated from the average particle diameter after redispersion. The redispersion of dried powders was examined as a function of the salt concentration used for flocculation and the surfactant composition and concentration. Flocculation followed by filtration and drying is an efficient and highly reproducible process for the rapid recovery of drug nanoparticles to produce wettable powders with high drug loading and rapid dissolution.     

P(HEMA-co-NVP)/CMC的制备及对药物的控制释放

用N,N-亚甲基双丙烯酰胺(Bis)为交联剂,过硫酸铵(APS)为引发剂,羧甲基纤维素(CMC)为助剂,合成了N-乙烯基吡咯烷酮与甲基丙烯酸-β羟基乙酯共聚物[P(NVP-co-HEMA)]/CMC半互穿网络水凝胶,并在模拟人体环境的条件下,以非水溶性药物萘普生为模拟药物,考察了水凝胶在不同温度及酸度下的药物释放。非水溶性药物萘普生在P(HE-MA-co-NVP)/CMC半互穿网络水凝胶载体体系中pH为2.00时,药物释放率受温度的影响较少,而在pH为7.40时,药物释放率受温度的影响较大。     

Novel naproxen/esomeprazole magnesium compound pellets based on acid-independent mechanism: in vitro and in vivo evaluation

The purpose of this study was to develop the novel naproxen/esomeprazole magnesium compound pellets (novel-NAP/EMZ) depending on EMZ acid-independent mechanism which has been proved to be predominate in the mechanism of co-therapy with nonsteroidal anti-inflammatory drug. The novel-NAP/EMZ compound pellets, composed of NAP colon-specific pellets (NAP-CSPs) and EMZ modified-release pellets (EMZ-MRPs), were prepared by fluid-bed coating technology with desired in vitro release profiles. The resulting pellets were filled into hard gelatin capsules for in vivo evaluation in rats and compared with the reference compound pellets, consisted of NAP enteric-coated pellets (NAP-ECPs) and EMZ immediate-release pellets (EMZ-IRPs). The reference compound pellets were prepared simulating the drug delivery system of VIMOVO^®. In vivo pharmacokinetics, EMZ-MRPs had significantly larger AUC_0–t (p?0–_t. Compared to the reference compound pellets, the novel-NAP/EMZ compound pellets did not show distinct differences in histological mucosal morphology. However, biochemical tests exhibited enhanced total antioxidant capacity, increased nitric oxide content and reduced malondialdehyde level for novel-NAP/EMZ compound pellets, indicating that the acid-independent action took effect. The gastric pH values of novel-NAP/EMZ compound pellets were at a low and stable level, which could ensure normal physiological range of human gastric pH. As a result, the novel-NAP/EMZ compound pellets may be a more suitable formulation with potential advantages by improving bioavailability of drug and further reducing undesirable gastrointestinal damages.     

Improved compaction and packing properties of naproxen agglomerated crystals obtained by spherical crystallization technique

Naproxen was crystallized from acetone-water in the presence of different concentrations of hydroxypropylcellulose (HPC). Naproxen particles recrystallized in the presence of HPC exhibited an obvious improvement in their packing, flow, and mechanical properties compared to naproxen recrystallized in the absence of the polymer (control particles). The results showed that the particle size distributions of the treated samples were broader than those obtained when HPC was absent. The agglomerates produced in the presence of 0.25% HPC displayed superior flow characteristics (displaying both a low angle of repose and Carr index) in comparison to samples produced in the presence of other concentrations of HPC. This was attributed to the spherical shape and smooth surface, since the area of contact in the powder bed for spherical agglomerates was smaller than that for other crystal shapes. However it was found that the tensile strength of tablets with the particles isolated in the presence of 1% HPC was increased to a greater extent than tablets produced using the spherical particles. Generally, the tensile strengths of the tablets increased with increasing concentrations of HPC present in the crystallization medium. Differential scanning calorimetry (DSC) and X-ray powder diffraction studies showed that naproxen particles, crystallized in the presence of HPC did not undergo structural modifications.     

乳化-溶剂挥发法制备乙基纤维素/萘普生复合微球

以乙基纤维素（EC）为载体材料,萘普生为包埋药物,采用O/W型乳化-溶剂挥发法制备了包封率较高的EC/萘普生复合载药微球,利用正交试验优化制备工艺,得出当EC与萘普生的质量比为3：1,EC用量2.5%,聚乙烯醇用量0.8%,吐温-80用量0.4%时是复合微球的最佳制备工艺,在该工艺条件下药物包封率达到88.97%。通过扫描电子显微镜（SEM）、激光粒度分析、傅里叶变换红外光谱（FT-IR）对复合微球的形态和结构进行了分析表征。SEM显示复合微球的形态顺滑,激光粒度分析表明复合微球平均粒径为14.014μm,复合微球的FT-IR谱图中既有EC的特征峰,又有萘普生的特征峰,但没有新基团产生,表明EC包覆萘普生过程中未产生新化合物。体外释放实验表明复合微球的累积释药率随溶出介质pH值的增大而增大,在溶出介质pH值为9时,复合微球的累积释药率最大,达到82.5%,缓释性能较好。     

疏水缔合水溶性聚合物P(NVP-DMDAAC-BA)的制备及释药特性

以水为介质,采用自由基胶束聚合制备了二甲基二烯丙基氯化铵(DM DAAC)、N-乙烯基吡咯烷酮(NVP)和丙烯酸丁酯(BA)三元共聚的疏水缔合水溶性聚合物P(NVP-DM DAAC-BA),产物结构经1H-NM R和IR确证。研究了疏水单元含量对聚合物溶液表观黏度的影响及共聚物对药物萘普生的缓释性能。     

多形貌萘普生药物晶体生长的可视化研究

采用毛细显微摄像技术对反应结晶法制备多形貌萘普生药物的晶体生长进行了直观、实时的观察和研究. 实验考察了表面活性剂种类和浓度、药物浓度及反应温度对生成的萘普生结晶颗粒形貌和尺寸的影响,并对颗粒的生长机理进行了讨论. 结果表明,在表面活性剂Tween-80, PVP, Karomic-90或CMC的作用下,可分别得到针状、球状、蝴蝶状及棒状萘普生晶体,药物浓度、表面活性剂浓度及反应温度对萘普生晶体的尺寸均有显著的影响.