A pharmacokinetic comparison of the corn oil versus microemulsion gelcap formulation of cyclosporin used de novo after renal transplantation

The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (C_av) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC. Received: 13 September 1996 Accepted: 7 January 1997     

Arsenic trioxide–loaded, microemulsion-enhanced cytotoxicity on MDAH 2774 ovarian carcinoma cell line

The antiproliferative effect of As(2)O(3)-loaded microemulsion (As(2)O(3)-M) on human MDAH 2774 ovarian cancer cells was compared with a regular solution of the As(2)O(3). We used MDAH 2774 as model cell lines for ovarian cancer. The (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) (XTT) and trypane blue dye exclusion tests were used to evaluate cytotoxicity. Apoptotic effect of solutions was evaluated using cell death detection kit. Standard microemulsion formulation used in this experiment contains 5 x 10(-6) M As(2)O(3). It was clearly demonstrated that As(2)O(3)-M had a significant cytotoxic effect on MDAH 2774 cell line, and the cytotoxic effect of As(2)O(3)-M was significantly higher than that of regular As(2)O(3) solutions. Even approximately 6000 times diluted microemulsion formulation loaded with 5 x 10(-6) M As(2)O(3) showed a cytotoxic effect. As a result, this diluted concentration (approximately 8 x 10(-10) M) was found to be approximately 6000 times more effective than regular As(2)O(3) solutions (5 x 10(-6) M). Moreover, this diluted concentration resulted in 1.5-fold enhancement of apoptosis. According to the in vitro cytotoxicity studies, we concluded that by incorporating As(2)O(3) into the microemulsion (As(2)O(3)-M), which is a new drug carrier system, it is possible to increase antiproliferative effect of regular As(2)O(3) on MDAH 2774 cells. Translating these results to in vivo conditions would open new windows in the treatment of ovarian cancer.     

微乳液反应法制备磺胺嘧啶银均匀微晶及其最佳处方评价

目的：应用微乳液反应法制备磺胺嘧啶银均匀微晶,均匀制得的微晶的粒径大小约为2～4um,均匀微晶的结晶性好,纯度高。用均匀设计方法优化条件,制备的均匀的微晶平均粒径大小为2.09um,实验结果达到预测结果要求。结论：用微乳液反应法能获得磺胺嘧啶银均匀微晶。     

Characterization of Oil-in-Water Emulsions Prepared from Solid-State Emulsions: Effect of Matrix and Oil Phase

Emulsions (o/w) were prepared from solid-state emulsions comprised of various matrix materials and oils and the resultant particle size properties determined. Results suggest that for those matrices that can form solid-state emulsions, the droplet size decreased as a function of time, as previously observed. The final droplet size was dependent on the oil utilized but was independent of the matrix material. The use of mineral oil resulted in the smallest droplet diameter (1.5 µm) while isopropyl myristate resulted in the largest droplet diameter (3 µm). With the exception of mineral oil, the oil/water interfacial tension was found to be directly proportional to the droplet diameter. The rate of emulsification appeared to be bi-phasic. The initial emulsification phase appeared to be independent of the matrix material while the terminal phase was a function of the matrix material. Most importantly, it was found that solid state emulsions could be prepared from a diverse, yet specific, list of matrices.     

微乳液反应法制备磺胺嘧啶银均匀微晶及其质量评价

目的：应用微乳液反应法制备磺胺嘧啶银均匀微晶,并评价其质量。方法：利用磺胺嘧啶钠微乳和硝酸银微乳混合后反应的方法,制备磺胺嘧啶银均匀微晶,用透射电镜观察其形态和大小,以Ｘ－射线衍射分析、红外光谱、核磁共振、差热分析等手段检测磺胺嘧啶银均匀微晶各种理化特性。结果：磺胺嘧啶银均匀微晶的粒径大小约为２～４μｍ,均匀微晶的结晶性好,纯度高。体外抑菌实验表明该品比市售磺胺嘧啶银具有更好的抑菌效果。结论：用微乳液反应法能获得磺胺嘧啶银均匀微晶。     

环孢素微乳剂在中国健康志愿者中的人体生物利用度

目的　研究环孢素(CyA)微乳剂的药动学和相对生物利用度。方法　2 0名健康志愿者单剂量口服CyA微乳剂和普通乳剂,用HPLC法测定血药浓度。结果　微乳剂的相对生物利用度为(2 2 9.2 8±95 .0 0 ) % ,微乳剂和普通乳剂的药动学参数分别为AUC0→2 4:(10 76 4 .32±2 6 6 9.4 4 )、(5 187.35±1913.80 ) μg·h·L-1,cmax:(194 8.0 1±35 0 .0 7)、(890 .0 1±2 73.6 4 ) μg·L-1;tmax:(1.6 8±0 .5 9)、(2 .98±0 .77)h。2种制剂的主要药动学参数AUC0→2 4、cmax和tmax经方差分析显示差异均具显著性意义(P <0 .0 5 )。双单侧t检验结果显示2种制剂不具生物等效性。结论　CyA微乳剂生物利用度优于普通乳剂     

高浓度澄明氯霉素泼尼松龙微乳滴眼液的药剂学实验研究

OBJECTIVETo solve the problem that effective density in chloramphenicol among chloramphenicol prednisolone is lower and, the mixture and float in corpuscle easily sinks. METHODSPreparation for clarifying high density chloramphenicol prednisolone microemul     

阿托伐他汀自微乳释药系统的制备和评价

目的制备阿托伐他汀自微乳，为自微乳释药系统的处方设计和体内外评价提供参考。方法采用伪三元相图法研究不同乳化剂、助乳化剂和油相形成微乳的能力和区域，绘制不同处方组成的相图，在此基础上制备阿托伐他汀自微乳，比较温度、介质、稀释等因素对自微乳效率的影响，进行自微乳时间、所成微乳的形态、粒径分布、zeta电位、含量和稳定性等体外评价Beagle犬体内药代动力学研究。结果理想的处方经分散后可得到平均粒径在100 nm以下、呈高斯分布的微乳，稳定性好，自微乳效率高，在Beagle犬体内的吸收明显高于市售片剂。结论本文首次研制阿托伐他汀自微乳，稳定性好，在Beagle犬体内的生物利用度高。     

星点设计-效应面法优化鹿角灵芝微乳超声提取工艺

目的 探讨以微乳超声法同时提取鹿角灵芝中灵芝酸和灵芝多糖的最佳条件。方法 采用星点设计-效应面法,以物料溶剂比(X₁)、超声提取时间(X₂)和超声功率(X₃)作为考察因素,以灵芝酸A、灵芝酸C₂、灵芝多糖含量和提取物得率为考察指标,并对考察因素和考察指标总评归一值进行多元线性回归和二项式拟合,以效应面优选最佳的微乳超声提取工艺,并做验证试验。结果 微乳超声提取鹿角灵芝的最佳条件为物料溶剂比1∶18、超声提取时间59 min、超声功率513 W,此条件下灵芝酸A、灵芝酸C₂、灵芝多糖含量和提取物得率分别为0.647 8,0.108 5,11.20 mg·g^-1和34.28%。结论 微乳超声可同时提取鹿角灵芝中脂溶性和水溶性成分,并且节能、省时、操作简便,为工业化提取鹿角灵芝提供了新途径。     

Acute and sub-chronic toxicity studies of honokiol microemulsion

The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD₅₀) was 50.5 mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication.