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The nanoparticles were fabricated using different concentrations of STC (10–35 mM) as a stabilizer. The characterization results of the prepared batches are presented in Table 2. It was observed that the DLE was maximum (98.2%) at 10 mM STC concentration (Batch I), and it decreased drastically with increase in STC concentration. The high DLE achieved was in agreement with the ability of STC to significantly retard solubility of the drug particularly at 10 mM concentration in pH 7.2 (with respect to other surfactant concentrations and the buffer alone), as observed in our earlier study[18]. However, none of the batches with only STC (Batches I–V) as stabilizer were found to be stable as phase separation occurred within 15 days of storage at room temperature (Fig. 1A). In order to achieve a homogenous dispersion, PVA,a polymeric excipient was added to the nanoemulsion. Addition of 1% (w/v) PVA (Batch VI) significantly improved the stability of the nanodispersion, as shown in Fig. 1B. The increased viscosity (from 1.08 cps (Batch I) to 4.3 cps (Batch VI)), by almost four folds, of the nanoemulsion upon addition of PVA may be the factor responsible to prevent the agglomeration by reducing the mobility of the nanoparticles in the dispersion medium. Moreover, PVA being a hydrophilic polymer acts as a coat to shield the particle surface charge responsible to cause their agglomeration [21]. It is probably due to this reason that the nanoparticles were found to be stable despite its low zeta potential. Preparation of a stable nanodispersion in presence of PVA alone (Batch VII) indicates its ability to immobilize nanoparticles by the viscosity imparted by the polymeric solution. However, the DLE of the batch was significantly the lattice arrangement or less ordered crystal lattice of the lipid of Batch V which shows incomplete lipid solidification or the coexistence of its amorphous state. The thermogram of lipid particles of Batches V and VI showed shifted peaks with relatively low heat of enthalpy than that of the pure lipid. This may be due to the presence of drug as a foreign body in the pure lipid and drastic reduction in particle size of lipid which together result in imperfections in the crystal lattice and, therefore, decrease in melting enthalpy. As the quantity of heat required to melt the impure lipid is reduced, a shift in the melting point of the lipid in the nanoparticles is observed. The X-ray diffraction patterns of Batches V and VI along with the pure lipid and drug are presented in Fig. 4(A–D). The XRD results obtained are in good agreement with the results established by DSC measurements. Although, crystalline reflections are visible for SLN of Batch V, the figures demonstrate that the scattering profile exhibited by nanoparticles of Batch VI were of much higher intensity which is again an indication of the existence of lower ordered crystalline state and/or amorphous state of the latter. It can be also observed that after the addition of drug, scattering profile of the lipid remains unchanged, indicating that the lattice order inside the hydrocarbon chains is still conserved. The disappearance of the drug peaks in the formulation shows that the lipid has arrested the re-crystallization of the drug particles from the solvent system upon its evaporation. The investigations related to morphology and solid state characteristics confirm that the crystal structure of the lipid in Batch V has several imperfections and, therefore, exists in a solid liquid transition state or a semisolid state. The inability of the lipid emulsion to recrystallize in presence of Buffer-I may be attributed to partial neutralization of stearic acid in the presence of metallic hydroxide due to which the lipid forms a creamy base and, therefore, fails to regain its solid state in the aqueous medium [22].However, the drug retention ability of the Batches V and VI was independent of the crystal arrangement as no significant difference in their DLE was observed which indicates that the lipid crystals have sufficient space to accommodate the added quantity of drug. The PDI values of Batches VI and VII reveal sufficiently uniform particle size distribution. The comparatively larger PDI of Batch V may be attributed to its physical state, as discussed above, due to which the particles have a tendency of agglomeration and is even to prepare ALN. Approximately, 7–8 ml of the nanodispersion was found to saturate 50 mg of the adsorbent used in each process of each batch. The physiochemical properties of the ALN were evaluated and are presented in Table 3. The drug loading efficiency of the adsorbent was estimated to be 79.8 ± 2.3%. Apart from free drug, the loss during the separation process can also be related to particle size and PDI of the nanoparticles. The improvement in the PDI and relative increase in the average particle size of the re-dispersed nanoparticles relative to that of the nanodispersion indicates that a part of nanoparticles of lower size range were screened and not adsorbed on the adsorbents. This may be due to the fact that the pores of the adsorbents were filled with the nanodispersion and after saturation of these pores; the adsorbent was able to retain nanoparticles of only higher size range trapped in the inter-particulate void space. The above fact was determined by the analysis of the pooled eluent which revealed nano dispersion with 84.5 ± 9.3 nm particle size (PDI = 0.09 ± 0.01). Further drug content analysis on re-dispersion of nanoparticles in aqueous solution containing 1.0% PVA indicated that the re-dispersed amount corresponds to the amount of nanoparticles adsorbed. The photo micrograph of the ALN (Fig. 5) reveals Neusilin particles randomly

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The nanoparticles were fabricated using different concentrations of STC (10–35 mM) as a stabilizer. The characterization results of the prepared batches are presented in Table 2. It was observed that the DLE was maximum (98.2%) at 10 mM STC concentration (Batch I), and it decreased drastically with increase in STC concentration.

利用不同浓度的STC(10-35mM)作为稳定剂,我们成功地合成了纳米颗粒。研究结果表明DLE在STC浓度为10mM的时候为最大(98.2%),而继后随着STC的浓度上升而显著下降。
2楼2011-01-09 17:16:29
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kaichang(金币+30, 翻译EPI+1):谢谢。 2011-01-09 22:21:52
ringzhu(金币+10):辛苦~~欢迎常来翻译版~~O(∩_∩)O~ 2011-01-10 11:15:05
该纳米粒子用作为稳定剂的不同浓度的STC(10-35mM)制备。样品的表征结果见表2。可以看到在STC浓度为10mM(釜I)时DLE达到最大(98.2%)。随着STC浓度的继续加大,DLE急剧下降。高浓度DLE的制得与我们早期观察的STC显著阻碍该药物在pH7.2、10mM浓度时的溶解度相吻合(和其它表面活性剂相比)。但是,在室温储存15天的时间内,釜I~V没有发现一批STC出现稳定的相分离(图1A)。为了达到均质分散的效果,把PVA这样一种聚合赋形剂加入到纳米浮浊液中。釜I添加了1%的PVA可以显著提高其纳米分散液的稳定性,如图1B所示。粘度增加了将近四倍(从釜I的1.08cp增加到釜VI的4.3cp)通过向纳米乳浊液中添加PVC可以起到通过减少纳米颗粒在分散介质中的流动性从而阻止颗粒团聚的作用。而且PVA作为一种亲水聚合物在粒子表面涂膜阻止其团聚。可能由于此原因,尽管纳米颗粒的电位较低但相对而言还是比较稳定的。在只加PVA的纳米分散液(釜VI)表明通过聚合物溶胶的粘度能使纳米颗粒固定。该釜里DLE的晶格排列或釜VI的无序晶格排列说明脂类出现固化或同时存在无定形态。釜V和釜VI脂类粒子的热谱分析显示与纯脂类相比有低焓热同时显著减小脂类的粒径引起晶格的缺陷,因此,引起熔化焓的减小。当所需熔化不纯脂类的热值减小时,观察到了在纳米粒子中脂类熔点的变化。图4(A-D)为釜V(纯脂类)和釜VI(药类)的XRD图,XRD结果与DSC结果一致。尽管对釜V的SLN来说其晶型可见,说明了釜VI中纳米颗粒的有较高的散射强度再一次说明低有序晶格的存在或者晶格中存在无定形态。同时能发现当添加药物后,脂类的散射图仍然保持不变,说明C-H键仍然保持着。药物峰的消失说明脂类已经使药物粒子从溶液中由于蒸发作用发生重结晶。形貌表征和固体的性质证实了釜V中脂类晶体结构的几种缺陷,因此在固液相态转变的过程中存在着中间态。添加缓冲剂I的脂类乳浊液不能重结晶是由于脂类形成奶油状金属氢氧化物碱而使硬脂酸部分中和引起的,因此在水介质中不能得到其固态。但釜V和釜VI中药物的滞留能力与晶格排列的独立性有关,DLE没有显著变化说明脂类晶体具有足够大的空间来储存加入的药物。釜VI和VII的PDI值说明粒径均匀分布,相比较而言釜V的PDI值大一点可以归因于其物理状态。如上所讨论,由于在制备ALN时粒子有团聚的趋势,在每一个釜的每一步处理过程中,7-8mL纳米乳浊液在50mg的吸附剂中达到饱和,对ALN生物化学性质的评价见表3。吸附剂对药物的吸附效率大约为79.8±2.3%。除了游离药物,分离过程中的损失取决于纳米粒子的PDI值。平均粒子尺寸PDI的增大以来于纳米乳浊液的再分散,这表明低小尺寸分布的纳米粒子不会被吸附,这可能是由于在孔过饱和后吸附剂的孔和纳米乳浊液结合了;吸附剂只能在宽尺寸的范围内起作用。上述现象可通过洗脱分析证实,粒径在84.5±9.3nm之间(PDI = 0.09 ± 0.01).进一步对水中药物含量的分析可知PVA的含量为1.0%,这表明再分散的量与纳米粒子被吸附的量一致。ALN的显微镜图(图5)揭示了粒子是随机分布的。
3楼2011-01-09 18:45:05
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