Plasma deposited stability enhancement coating for amorphous ketoprofen

A hydrophobic fluorocarbon coating deposited onto amorphous ketoprofen via pulsed plasma-enhanced chemical vapor deposition (PPECVD) significantly prolonged the onset of recrystallization compared to uncoated drug. Rapid freezing (RF) employed to produce amorphous ketoprofen was followed by PPECVD of perfluorohexane. The effect of coating thickness on the recrystallization and dissolution behavior of ketoprofen was investigated. Samples were stored in open containers at 40 °C and 75% relative humidity, and the onset of recrystallization was monitored by DSC. An increase in coating thickness provided enhanced stability against recrystallization for up to 6 months at accelerated storage conditions (longest time of observation) when compared to three days for uncoated ketoprofen. Results from XPS analysis demonstrated that an increase in coating thickness was associated with improved surface coverage thus enabling superior protection. Dissolution testing showed that at least 80% of ketoprofen was released in buffer pH 6.8 from all coated samples. Overall, an increase in coating thickness resulted in a more complete drug release due to decreased adhesion of the coating to the substrate.     

Comparative study on schizontocidal activity of recrystallized or crude daphnetin against malaria parasites

Objective To compare the schizontocidal activity of recrystallized or crude daphnetin against malaria parasites in vivo. Methods Schizontocidal activity of recrystallized or crude daphnetin at various dosages was assessed in mice infected with Plasmodium berghei ANKA using a “4-day suppress assay”. Results The comparison of the reduction rate of parasitemia caused by either recrystallized or crude dephnetin showed that ED50 of crude daphnetin was 18.36 mg/kg, with 95% confidence limit of 5.96-56.54 mg/kg while ED50 of recrystallized daphnetin was 11.46 mg/kg, with 95% confidence limit of 8.63-15.22 mg/kg. Conclution The results indicate that the efficacy of recrystallized daphnetin is 37.6% higher than that of crude daphnetin.     

Understanding the solid-state forms of fenofibrate - A spectroscopic and computational study

The aim of this study was to investigate the structure of different solid-state forms of fenofibrate, a drug that lacks strong intermolecular interactions such as hydrogen bonding. In addition to a structural analysis of crystalline and amorphous fenofibrate using infrared and Raman spectroscopy combined with density functional theory calculations [B3LYP 6-31G(d)], solid-state changes that occur upon recrystallization of amorphous fenofibrate were monitored and described using in situ Raman spectroscopy. A comparison of the calculated vibrational spectra of a fenofibrate monomer and two dimer structures with the experimental vibrational spectra of crystalline and amorphous fenofibrate revealed conformational differences in the orientation of the two benzyl rings in the fenofibrate molecule and structural differences between the different solid-state forms in aliphatic parts of the drug molecule. The spectroscopic analysis suggests that non-hydrogen-bonded drug molecules are likely to exhibit more random molecular orientations and conformations in the amorphous phase since the weak intermolecular interactions that occur between such molecules can easily be disrupted. In situ Raman spectroscopy and multivariate analysis revealed multiple solid-state forms of fenofibrate, including the metastable crystalline form II, which were structurally analyzed with reference to the quantum chemical calculations. Overall, the study showed that vibrational spectroscopy, multivariate analysis, and quantum chemical modeling are well suited to investigate and characterize the structure of drug substances that exhibit only small structural differences between different solid-state forms.     

使用微粉化技术改善头孢呋新酯片的溶出

为改善头孢呋新酯的溶出,采用气流粉碎球磨、重结晶、固态分散技术等多种微粉化技术,通过差热分析和Ｘ衍射研究微粉化后头孢呋新酯的晶型特征。结果表明,固态分散技术可使该药由晶型转变为无定型,从而大大增加其生剂的溶出。溶解热的计算进一步证明了这一结果。     

紫杉烷二萜类化合物10-DABⅢ的分离纯化

目的:建立分离纯化紫杉烷二萜类化合物10-脱乙酰基巴卡亭Ⅲ(10-DABⅢ)的方法。方法:采用柱层析和重结晶的方法精制10-DABⅢ。以杂质含量为指标确定层析液比例;以纯度和收率为指标筛选第1次重结晶时三氯甲烷的用量,第2次重结晶时丙酮、正己烷的用量以及2次重结晶的温度和时间。结果:层析液丙酮与三氯甲烷体积比为2.25:7.75,此时杂质含量最小,为3.7%。用15倍体积(W/V)的三氯甲烷、-25℃冷冻24h第1次重结晶以及35倍体积的丙酮(W/V)和30倍体积的正己烷(W/V)、-25℃冷冻12h第2次重结晶,纯化后的样品纯度为99.34%,收率为83.50%。结论:该方法对10-DABⅢ分离纯化效果好。     

高纯度1，6一二磷酸果糖分离精制新工艺

本文报道了１，６一二磷酸果糖（ＦＤＰ）发酵液通过沉淀一吸附一重结晶法，代替国外反渗析法或联合柱色谱分离一分子膜过滤一冷冻干燥法分离精制ＦＤＰ的新工艺。本工艺简便地解决了反渗析法纯化过程中高达５０％ＦＤＰ严重损失问题，避免了过程冗长的柱色谱分离过程易引起的细菌性污染所导致的ＦＤＰ破坏和复杂价昂的分子膜过滤器及冷冻干燥，突破了ＦＤＰ难以结晶的关键技术。所用设备简单，便于工业生产。经４升规模试验研究表明，ＦＬＰ总收率达８０％，纯度达９９％，高于国外文献报道及意大利进口冻干粉指标。     

兰索拉唑生产工艺改进及产品质量的研究

对新型质子泵抑制剂兰素拉唑合成的最后一步氧化工艺和后处理进行改进,以提高产品的质量和稳定性。优化后的最佳条件是：二氯甲烷为溶剂;原料与氧化剂的用量比是（1∶0.98,mol）;-20℃反应115 min;用80%乙醇重结晶,纯度可达99.86%。     

A rapid-room temperature synthesis of α-cyanoacrylates, α-cyanoacrylonitriles and 4H-pyrans using water extract of pomegranate ash as catalytic media

In this article we report a sustainable and rapid-room temperature synthesis of α-cyanoacrylonitriles, α-cyanoacrylates, and 4H-pyrans via the condensation of active methylene compounds with aldehydes, and a three-component reaction of 1,3-dicarbonyl compounds/4-hydroxycoumarins, active methylene compounds and acetylene dicarboxylates in water extract of pomegranate ash (WEPA). The agro-waste-derived WEPA acts both as catalyst and aqueous reaction medium. The products of this process were separated by simple filtration and purified by recrystallization. This protocol did not require organic solvent-based work-up and column chromatography-assisted purifications. The use of renewable catalytic media, good reusability of catalyst, ease of handling, ambient and depleting resources-based catalyst free conditions, avoid of volatile organic solvents throughout the process, excellent product yields, and actual usage of waste are the highlights of this process.     

Mechanism of drug release from polymethacrylate-based extrudates and milled strands prepared by hot-melt extrusion

The aim of the study was the formulation of solid dispersions of the poorly water-soluble drug celecoxib and a polymethacrylate carrier by hot-melt extrusion. The objectives were to elucidate the mechanism of drug release from obtained extrudates and milled strands addicted to the solid-state properties of the solid dispersions and to examine and eliminate stability problems occurring under storage, exposure of mechanical stress, and in vitro dissolution.Transparent extrudates containing up to 60% drug could be prepared with a temperature setting below the melting point of celecoxib. XRPD and DSC measurements indicated the formation of a glassy solid solution, where the drug is molecularly dispersed in the carrier. The amorphous state of the glassy solid solution could be maintained during the exposure of mechanical stress in a milling process, and was stable under storage for at least 6 months. Solid-state properties and SEM images of extrudates after dissolution indicated a carrier-controlled dissolution, whereby the drug is molecularly dispersed within the concentrated carrier layer. The glassy solid solution showed a 58-fold supersaturation in 0.1 N HCl within the first 10 min, which was followed by a recrystallization process. Recrystallization could be inhibited by an external addition of HPMC.     

PAS-Na溶媒法工艺研究

本文以口服PAS-Na为原料,研究用重结晶法生产PAS-Na粉针剂原粉的新工艺,进而提高该品种质量降低生产成本.本文研究成果在生产中已得到应用和推广.