Coprecipitation of Cefuroxime Axetil-PVP composite microparticles by batch supercritical antisolvent process

Batch supercritical antisolvent precipitation (SAS) process was used to coprecipitate Cefuroxime Axetil amorphous (CFA, antibiotic) and Polyvinylpyrrolidone (PVP-K30) for preparing drug-polymer composite particles. Solutions of CFA and PVP-K30 in methanol with overall concentrations of 50-150 mg/ml and polymer/drug ratios of 1/1-4/1 were sprayed into the CO₂ at 70-200 bar and 35-50 °C with drug + polymer solution injection rates of 0.85 and 2.5 ml/min. Spherical particles having mean diameters of 1.88-3.97 μm, distribution ranges of 0.82-9.7 μm (the narrowest distribution) and 0.91-46.64 μm (the broadest distribution) were obtained. Mean particle size was not affected significantly with the change of process parameters. It was only affected by pressure change. On the other hand particle size distribution was affected by pressure, temperature, drug + polymer solution injection rate and concentration. It was observed that temperature and polymer/drug ratio affected the particle morphology most. The drug release rate of SAS-coprecipitated CFA-PVP (1/1) particles was almost 10 times slower than the drug alone. As the ratio of the polymer increased drug release rate also increased due to the wetting effect of PVP.     

Preparation of cefuroxime axetil nanoparticles by rapid expansion of supercritical fluid technology

As a poorly water-soluble drug, cefuroxime axetil (CFA) features a low solubility and dissolution rate in the gastrointestinal tract, which limits its effective absorption and bioavailability. The objective of this study was production of amorphous CFA nanoparticles directly without any additive by rapid expansion of supercritical solution technology. The effects of process parameters, such as the temperature of nozzle (50-70 °C) and extraction port (60-90 °C) were investigated each in three levels, on the properties of the formed particles by a full factorial design. The particles were then analyzed for differential scanning calorimetry (DSC), X-ray diffraction (XRD), particle size, zeta potential and dissolution properties. Z-average particle size of different nanoparticles was between 158 and 513 nm and zeta potential also changed from − 4.29 to − 42.8 mV. The lowest particle size was seen in sample with nozzle temperature at 60 °C and the extraction temperature at 90 °C. However, when temperatures of nozzle and extraction column were decreased to 50 °C and 75 °C respectively, the particle size was increased to 465 nm. More than 90% of the some nano-sized CFA formulations were dissolved in 3 min and complete dissolution occurred within 20 min, while the commercial CFA did not achieve complete dissolution (only about 50%) during 60 min of the testing period.     

头孢呋辛酯掩味颗粒剂的制备

采用明胶作为主要掩昧材料,利用固体分散技术制备头孢呋辛酯颗粒剂,并进行掩味效果及稳定性考察。结果表明,该制剂口感、长期稳定性良好,是理想的临床用药。     

头孢呋新酯的合成改进

将头孢呋新钠溶于偶极非质子性溶剂 N,N-二甲基乙酰胺 ( DMAC)溶液中 ,加入三乙胺( Et3N) ,在室温下 ,滴加 1 -乙酰氧 - 1 -溴乙烷 ,高产率合成头孢呋新酯。产品结构用 IR,1H NMR与HPLC验证     

Modelling the performance of membrane nanofiltration—recovery of a high-value product from a process waste stream

For traditional separation processes there are widely available process design methodologies for scale-up and optimization. However, there is an increasing need for such a rational approach to membrane separation processes, identifying at an early stage operating limits and process options. Such predictive models will reduce development risk and time, thus promoting the wider use of membrane technology in process industries such as pharmaceutical manufacture. Design methods exist that have been verified experimentally at the laboratory scale for simple aqueous solutions. There is now a need for the application of the existing theoretical and experimental methods to separations of real industrial interest.In this paper, we demonstrate this philosophy by describing the rationale for modelling the performance of membrane nanofiltration (NF) used in the recovery of sodium cefuroxime, an industrially important cephalosporin antibiotic having activity against most gram-positive cocci. Sodium cefuroxime is produced in a multi-stage biotransformation process with final purification achieved by low-temperature crystallization with excess quantities of sodium lactate. The efficiency of the crystallization process is not 100% and cefuroxime is lost in the waste stream from the crystallization units. Traditionally, this waste stream has been sent for industrial disposal as the concentrations of sodium cefuroxime are too low for normal separation processes to recover.A systematic study of three commercially available membranes indicated that the Desal-5-DK membrane was most suitable for the recovery process. Excellent agreement between the experimental findings and model predictions was observed for batch NF and a membrane charge isotherm was developed for use in process modelling. The full-scale recovery process was modelled theoretically and NF proved more than adequate for the separation required. An estimate of the industrial scale process operating constraints was made and the NF process was considered as a favourable modification to existing plants.