注射用克拉霉素乳剂稳定性及影响因素考察

目的 考察克拉霉素乳剂稳定性及其影响因素。方法 以乳剂粒径,pH值变化和药物含量作为指标,考察了不同温度对克拉霉素乳剂稳定性的影响。结果 乳剂在低温保存时稳定性良好,温度升高会显著影响乳剂稳定性,导致粒径增大和pH降低。根据Arrhenius公式求得储存温度为5 ℃时,T_0.9=9.06年,长期稳定性试验结果表明,载药乳剂在12个月理化性质稳定。结论 低温保存有利于提高该乳剂的稳定性。     

注射用克拉霉素乳剂的制备及其体内外评价

目的制备克拉霉素乳剂并考察其刺激性和体内药物动力学行为。方法通过高压均质方法制备克拉霉素乳剂，并对其性质进行研究。以克拉霉素溶液剂为对照，观察了乳剂的刺激性和在大鼠体内的药物动力学行为。结果高压均质法制备克拉霉素乳剂，平均粒径为156 nm，zeta 电位为-31.8 mV。于4 ℃留样观察6个月内样品稳定。与克拉霉素溶液剂相比，乳剂可以明显降低刺激性。两种制剂在大鼠体内的药物动力学曲线相似，符合双隔室模型。克拉霉素乳剂和溶液剂AUC0-t分别为(66.76±16.34)和(59.00±11.20) μg·h·mL^-1。结论高压均质法可以制备出性质稳定的载药乳剂，克拉霉素乳剂可以明显降低静脉注射时引起的刺激性。     

顺铂静脉注射乳剂的制备及其性质考察

目的:制备顺铂静脉注射乳剂并对其性质进行考察。方法:通过正交设计优选了顺铂乳剂的最佳处方及其制备工艺,并通过粒径、ζ电位、pH值的测定和稳定性的考察初步研究了顺铂乳剂的一些基本性质。结果:顺铂乳剂的最佳处方为磷脂0.9%,泊洛沙姆-1882%和油酸0.2%,制备温度为70℃。所制备的乳剂平均粒径为144nm,ζ电位为-29.8mV。稳定性实验表明乳剂在高温灭菌、长期稳定性试验中粒径、pH值和含量无明显的变化。结论:本实验制备的顺铂乳剂粒径分布较窄,稳定性较好。     

葫芦素脂肪乳剂成型性影响因素考察

目的了解影响葫芦素脂肪乳剂成型性的因素.方法以葫芦素脂肪乳的外观、粒径、药物含量及稳定性为指标,分别考察渗透压、高压乳匀、pH、空气置换剂及灭菌等因素对乳剂成型性的影响.结果等渗调节剂甘油对乳剂粒径没有影响;高压乳匀可降低乳剂粒径,适当压力下多次乳匀可获得粒径小、均匀性好的乳剂;pH可影响乳剂中药物含量;使用空气置换剂的乳剂在37℃放置3个月后稳定性良好,而充空气的乳剂发生破裂;高压灭菌时,升温速度对乳剂的稳定性亦有影响.结论控制和掌握好高压乳匀、pH、空气置换剂及灭菌等因素,就可获得粒径大小适宜、粒度均匀、性质稳定、供静脉注射的葫芦素脂肪乳剂.     

克拉霉素黏附微球在低pH值溶液中的稳定性

目的 考察克拉霉素在不同pH值条件下的稳定性及微球对药物的稳定作用. 方法 使用乳化 溶剂挥发法制备克拉霉素生物黏附微球（Cla-Ec-Cb）. 以高效液相色谱法测定Cla-Ec-Cb中克拉霉素及克拉霉素原料药在不同低pH值条件下稳定性. 结果 克拉霉素原料药在pH值为1,2,3的盐酸溶液中的半衰期分别为（5.93±0.16）,（74.52±3.23）,（869.58±5.82） min; Cla-Ec-Cb微球中克拉霉素能保持相对稳定. 结论 克拉霉素在低pH值溶液中不稳定,将其制备成黏附微球对克拉霉素具有一定的保护作用.     

克拉霉素脂肪乳剂在大鼠体内药动学和组织分布研究

目的研究克拉霉素脂肪乳剂在大鼠体内药动学和组织中的分布情况,并与克拉霉素注射液相比。方法通过高压均质方法制备克拉霉素脂肪乳剂,通过微生物管碟法测定克拉霉素在大鼠体内血药浓度和组织中药物浓度。结果克拉霉素脂肪乳剂和克拉霉素注射液药-时曲线相似并均符合二室模型,两种剂型的AUC0-t分别为(66.76±16.34)和(59.00±11.20)μg·h/ml。大鼠单剂量静脉注射37.5mg/kg克拉霉素脂肪乳剂和溶液剂后,测定各时间点各组织中药物浓度,以肺为最高。与溶液剂相比,脂肪乳剂提高了脾、肺、肝、肾和脑的药物分布。结论克拉霉素脂肪乳剂与克拉霉素溶液剂血药浓度相似,但脂肪乳剂明显改变了克拉霉素体内组织分布,说明更有助于治疗局部脏器感染。     

乳化-溶剂扩散法制备克拉霉素缓释微球

目的探讨克拉霉素缓释微球的制备工艺。方法以Eudragit RS／RL为囊材,采用乳化一溶剂扩散法制备克拉霉素缓释微球,考察对微球质量、收率、载药量和包封率有影响的处方因素。结果EudragitRS／RL与药物按4：1混合时可得到成形性较好、表面光滑、均匀圆整、分散性好的克拉霉素微球。克拉霉素微球的粒径范围为88～180μm,微球的收率为76．0％,载药量为17．8％,包封收率为67．0％。在pH=5．0的磷酸缓冲液中微球中的克拉霉素缓慢释放。结论乳化-溶剂扩散法适合于克拉霉素缓释微球制备。     

盐藻β-胡萝卜素微乳的制备及其稳定性

目的制备盐藻β-胡萝卜素微乳并进行初步稳定性考察。方法以盐藻β-胡萝卜素微乳的外观、颜色、粒径、Zeta电位、稳定性参数(Ke)、β-胡萝卜素含量作为指标,考察了高温、强光照射对乳剂稳定性的影响,并通过加速实验和常温留样观察考察了盐藻β-胡萝卜素微乳初步稳定性。结果高温、强光照射对乳剂的物理性质无明显影响,但降低了β-胡萝卜素含量;在加速实验和常温留样实验中,乳剂性质稳定,β-胡萝卜素含量无明显变化。结论盐藻β-胡萝卜素微乳为均一稳定的制剂,但需避光低温保存。     

对乙酰氨基酚鼻用乳剂的制备

摘要目的制备对乙酰氨基酚鼻用乳剂。方法以对乙酰氨基酚乳剂的稳定常数Ke、粒径、含量为综合评价指标;设计L16（45）正交实验考察油相、稳定剂的用量、乳化时间及温度对乳剂稳定性的影响。结果油相为40%,稳定剂为0.5%,乳化时间12 min,乳化温度35 ℃;含量、pH、外观等符合鼻用制剂的要求。结论研制的对乙酰氨基酚鼻用乳剂性质稳定。     

挤出法制备乳剂的工艺优化

目的确定挤出法制备乳剂的最优工艺。方法经挤出仪制备乳剂,采用正交设计法,以乳剂的平均粒径、变异系数为评价指标,考察了乳剂挤出工艺中滤膜孔径、挤出次数、温度及压力对制剂的影响,及最优工艺制得乳剂的离心稳定性、灭菌稳定性和冻融稳定性。结果采用优化挤出工艺制得乳剂的平均粒径为(116.7±2.2)nm,变异系数为(0.453±3.400),且离心稳定性、灭菌稳定性和冻融稳定性良好。结论挤出法可以制备粒径小、粒度分布均匀、稳定性良好的乳剂,该方法在热不稳定性药物乳剂的制备中具有很大的应用前景。     

Optimization of tocol emulsions for the intravenous delivery of clarithromycin

In the present study, novel less-painful tocol emulsions for the intravenous delivery of clarithromycin were prepared and optimized. The therapeutically effective concentration of clarithromycin, 5mg/ml, was achieved using tocopherol succinate (TS) combined with oleic acid as lipophilic counterions. The possibility of employing the microdialysis technique to investigate the distribution of the drug in emulsions was explored. A three-level three-factorial Box-Behnken experimental design was utilized to conduct the experiments. The effects of selected variables, tocopherol succinate/oleic acid relation, poloxamer 188 content and 0.1M NaOH amount, on three considered responses were investigated. The particle size, zeta potential and the oil phase distribution of clarithromycin for the optimized formulation were observed to be 138.5 nm, -32.16 mV and 97.28%, respectively. The emulsions prepared with the optimized formula demonstrated good physical stability during storage at 4 degrees C and room temperature. The histopathological examination for rabbit ear vein irritation test indicated that the irritation of clarithromycin could be eliminated by formulating the drug in a tocol emulsion.     

Stability of a less-painful intravenous emulsion of clarithromycin

The chemical stability of a less-painful ready-to-use o/w emulsion for intravenous (i.v.) delivery of clarithromycin was investigated. The formulation contained 0.5% w/v drug, 2% w/v soybean oil, 5% w/v egg phosphatide, 0.6% w/v oleic acid, 0.3% hexanoic acid and 2.5% w/v glycerin in water. The change in the initial pH of emulsion (range: 6.5–8.0) did not significantly influence drug stability over a period of 30 days at 5 and 30°C. The increase in the initial pH of emulsion as well as its storage temperature gradually decreased the final pH over time. The emulsion prepared at pH 7.5 demonstrated a constant drop in pH over 9 months at 30°C at the rate of about 0.002 units drop in pH per day; however, it did not demonstrate significant loss of drug. Actual as well as projections using accelerated stability studies indicated the shelf-life (i.e., time to retain 90% of the label claim, t_90%) of the emulsion formulation, at 25°C, to be ≥ 21 months. Overall, the results suggest that the development of a less-painful ready-to-use o/w emulsion of clarithromycin is feasible.     

处方因素对亚微乳物理稳定性的影响

目的 初步探讨亚微乳处方中乳化剂及油相因素对其物理稳定性的影响.方法 采用高速剪切分散和高压均质乳化工艺制备亚微乳,单因素试验法考察处方中乳化剂与油相对亚微乳物理稳定性的影响;以平均粒径、D50值、D99值及ζ电位为指标,考察不同处方中亚微乳灭菌前后的物理稳定性,并留样观察其长期稳定性.结果 泊洛沙姆188与中链油相互配伍不能得到性质稳定的亚微乳,且单独以泊洛沙姆188为乳化剂的各处方制剂长期放置后平均粒径明显增大;聚乙二醇硬脂酸酯( HS15)与各油相结合制得的亚微乳均较稳定,长期放置后各项指标基本不变;聚山梨酯80与大豆油-中链油(1∶1)混合油或大豆油配伍制成的亚微乳在灭菌后产生较大粒径的乳滴,而与中链油相配伍可制得粒径较小且均匀分散的体系;蛋磷脂E80单独作为亚微乳乳化剂,乳化效果欠佳.结论 大豆油、中链油及混合油与不同性质的乳化剂相互作用可共同影响亚微乳的粒径,但不同制剂的处方对亚微乳ζ电位无显著影响.     

Studies on the effect of pilocarpine incorporation into a submicron emulsion on the stability of the drug and the vehicle.

In order to obtain a novel ocular formulation with a potential for prolonging pilocarpine activity, the drug (2.0%) was incorporated into a submicron emulsion containing soya-bean oil and lecithin as emulgator. The effect of drug incorporation into the emulsion on its physical stability and on the other hand, the potential of the vehicle to reduce drug degradation at pH higher than 5.0 was studied. The pH was adjusted to 6.5 or 5.0 and the physicochemical stability of the formulations was observed. The mean diameter of oily particles in the resulting emulsions measured by a laser diffractometer was 0.6-0.7 micron and this was larger than in a drug-free emulsion where a 0.33 micron value was measured. The formulations were physically stable for 6 months at 4 degrees C, but progressing chemical degradation of pilocarpine was noted at pH 6.5. At that pH nearly 8% of pilocarpine was degraded to isopilocarpine and pilocarpic acid, both in the emulsion and in the solution. Thus, it may be concluded that pilocarpine in submicron emulsion is not protected against degradation. The presence of pilocarpine changes the physical stability of the vehicle since the formulation was easily destabilized during autoclaving or at room temperature. In the presence of higher concentration of lecithin (2.4%) or co-emulgators (poloxamer 2.0% or Tween 80 0.5%) the mean droplet size in the emulsions was the same as in a drug-free system. However the emulsions containing poloxamer were not stable during storage. Viscosity of pilocarpine emulsions can be increased by addition of methylcellulose or sodium carmellose (1.0%), but an intensive creaming occurs in these systems. Pilocarpine base is less suitable for emulsion preparation than hydrochloride salt, and emulsions prepared at pH 5.0 show the most satisfying stability.     

Stability and degradation kinetics of etoposide-loaded parenteral lipid emulsion

Etoposide was incorporated in lipid emulsion to develop an i.v. formulation, and improve its physical and chemical stability without addition of organic solvents, for use as a commercial formulation. High-pressure homogenization was used to prepare the lipid nanospheres and localize the drug at the surfactant layer. The particle size distribution and zeta potential were measured using photon correlation spectroscopy (PCS). Ultrafiltration was used to estimate the relative percentage of etoposide in each phase. The stability profile of etoposide in the lipid emulsion at various temperatures, pH values, and concentrations of drug was monitored by high performance liquid chromatography (HPLC). The degradation pattern of etoposide in lipid emulsion followed pseudo-first-order kinetics. The shelf life (T(90%)) of etoposide in lipid emulsion was estimated to be 47 days at 25 degrees C and it would be stable when stored for 427 days at 4 degrees C, which is a significant improvement compared with a stability of 9.5 days in aqueous solution at 25 degrees C. Etoposide in lipid emulsion and aqueous solution were both most stable at pH 5.0 with a half-life of 54.7 h and 38.6 min at 80 degrees C, respectively. The hydrolysis kinetics of etoposide in lipid emulsion was also shown to be dependent on the drug concentration.     

3-正丁基苯酞静脉注射亚微乳的制备和稳定性考察

目的制备3-正丁基苯酞(NBP)静脉注射亚微乳并考察其稳定性。方法采用高速剪切法制备初乳,二次高压均质法制备终乳。以灭菌前后乳剂的外观性状、粒径变化和稳定性常数(Ke)等为评价指标,考察制剂工艺的影响因素,同时采用正交设计实验优化处方。所得制剂分别在4、25、40℃条件下放置3个月,观察其外观性状、粒径、Zeta电位、pH值、药物含量、游离脂肪酸值和过氧化值等的变化。结果在优化处方及工艺条件下,所制备的NBP亚微乳稳定性良好,平均粒径为(128.0±3.4)nm(n=3),Zeta电位为-(34.3±5.3)mV(n=3)。稳定性实验结果表明,样品放置3个月后pH值降低约0.3,40℃条件下样品略变黄,其余各项指标无明显变化。结论该处方和工艺可行,制备的NBP亚微乳性质稳定,可供静脉使用。     

Formulation of an intravenous emulsion loaded with a clarithromycin-phospholipid complex and its pharmacokinetics in rats

The purpose of this paper is to prepare a new formulation of clarithromycin emulsion (ClaE) with the clarithromycin-phospholipid complex which was analyzed by DSC. High-pressure homogenization, Nicomp 380 Particle Sizing system, and HPLC were used to prepare and investigate ClaE, while UPLC/MS/MS for pharmacokinetic study. Clarithromycin and soybean lecithin were reacted in dehydrated alcohol at a ratio of 1:10 for 3 h at 65 degrees C to prepare the complex. The ClaE formulation consisted of, according to quality percentage, the complex (clarithromycin 0.25% in ClaE), LCT 4%, MCT 16%, soybean lecithin 1.0%, F68 0.2%, Tween80 0.2%, glycerol 2.5%, sodium oleate 0.1% and L-cysteine 0.02%. ClaE was sterilized in a 100 degrees C revolving water bath for 30 min. The drug content, particle size distribution and entrapment efficiency of ClaE before and after sterilization and over 6 months storage at 10 degrees C were almost unchanged, while zeta-potential increased from -20.32 mV to -23.71 mV. These results show that ClaE has enough physicochemical stability to undergo sterilization and storage. The pharmacokinetic study showed that both ClaE and ClaS fitted a three-compartment model, their pharmacokinetic curves were similar and the main parameters showed no significant difference except Vss. ClaE has a great potential for clinical applications and industrial-scale production.     

英脱利匹特注射剂的稳定性研究

在8℃、15℃、30℃、40℃下不同贮藏时间(最长达26个月),对英脱利匹特进行“静置分层”观察,测定其pH、游离脂肪酸及乳粒大小等项目,观察及测定结果表明:本品贮藏期内会产生分层现象,但乳化体系稳定,不影响使用。贮藏期间,药液pH下降,游离脂肪酸含量增加。贮藏温度升高会加速产品水解。     

神经酸口服乳剂的处方及制备工艺优化

目的 制备神经酸口服乳剂,对其处方及制备工艺进行优化,并考察其稳定性.方法 通过机械法制备神经酸口服乳剂.在单因素实验的基础上,以乳剂外观、离心稳定性、离心稳定常数(Ke)、粒径为指标,采用正交实验设计,以油酸用量、辛基苯酚聚氧乙烯醚-10用量、丙二醇用量为因素,对其处方进行优化;以乳化温度、剪切时间、高压均质压力、高...