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。     

HPLC法测定红花微乳中羟基红花黄色素A的含量

目的:建立HPLC法测定红花微乳中羟基红花黄色素A的含量。方法:采用色谱柱:Diamonsil C18(2)5μm,250mm×4.6mm;流动相:甲醇-0.4%的磷酸水溶液(三乙胺调至pH=3.3)为30∶70;检测波长:402nm;柱温:室温。结果:羟基红花黄色素A在0.3128～3.128μg的范围内呈良好的线性关系(r=0.9990)。结论:本测定方法快捷,简便,准确,重现性好。     

醒脑静微乳的体外释放研究

目的:研究醒脑静微乳体外释放的特性,探讨其释药机制.方法:采用HPLC测定栀子苷含量,GC测定龙脑含量,以透析法研究醒脑静微乳的体外释放并利用药物释放模型方程拟合释放曲线.结果:微乳中水溶性成分栀子苷2h内基本释放完全,释放符合Weibell方程,脂溶性成分龙脑释放符合一级方程.结论:微乳中不同性质的药物成分释放行为存在较大差异,各成分分布于微乳的不同相中.     

蛇床子素微乳止痒及抗Ⅳ型变态反应的实验研究

目的：观察蛇床子素微乳止痒及抗Ⅳ型变态反应的作用。方法：采用磷酸组织胺诱发豚鼠局部瘙痒、4-氨基吡啶（4-AP）诱发小鼠皮肤瘙痒及对二硝基氯苯丙（DNCB）酮溶液诱发小鼠迟发超敏反应的实验动物模型,以不同浓度的蛇床子素微乳局部外用,观察其对磷酸组织胺、4-AP致痒反应的影响和对DNCB丙酮溶液诱发迟发超敏反应的影响。结果：蛇床子素微乳局部外用可显著提高磷酸组织胺对豚鼠的致痒阈;显著抑制由4-AP所引起的小鼠皮肤瘙痒反应;显著抑制DNCB诱发的小鼠迟发超敏反应。结论：蛇床子素微乳局部外用具有良好的止痒作用和抗Ⅳ型变态反应的作用。     

刺五加的微乳液毛细管电动色谱指纹图谱研究

目的:在比较毛细管胶束电动色谱(MEKC)和毛细管区带电泳后(CZE)采用微乳液毛细管电动色谱法对刺五加进行指纹图谱的研究。方法:以1.0%(w/w)SDS,6.6%(w/w)正丁醇,0.7%(w/w)正庚烷,25 mmol/L硼砂溶液(91.6%,w/w,pH 9.5)的微乳液为运行介质,波长为222 nm。结果:与毛细管区带电泳、毛细管胶束电动色谱相比,微乳液毛细管电动色谱对刺五加提取物中的复杂组分具有很好的分离能力;指纹图谱中标定了12个指纹峰,重现性、稳定性和方法的精密度较好。结论:微乳液毛细管电动色谱指纹图谱对刺五加的质量控制优于MEKC和CZE法。     

环孢素A双连续型微乳在大鼠皮肤中的药物滞留量考察

目的考察环孢素A双连续型微乳经大鼠皮肤给药的可行性及对药物体内分布的影响,并与大鼠灌胃给予新山地明比较。方法将环孢素A双连续型微乳非封闭的应用于大鼠皮肤,给药皮肤用胶带剥离法分离角质层,得到的全血、肾脏、肝脏、皮肤(除去角质层)经提取后用RP-HPLC法测定药物的含量,观察药物在血液中质量浓度的经时变化以及在肾脏、肝脏和皮肤的分布状况。结果与灌胃给予同剂量新山地明的体内行为相比,微乳经皮给药后皮肤中药物的含量显著高于口服组(P<0.01),而血液及肝脏、肾脏中药物的含量明显低于口服组。结论双连续型微乳能够有效的提高环孢素A在大鼠皮肤中的滞留量,同时可以降低药物在肝肾的蓄积。