摘要
通过绘制伪三元相图优选处方,应用相转变法制备乙酰甲喹微乳,在透射电子显微镜(transmission electron microscope,TEM)下考察其形态,用Zetasizer Nano ZS分析仪以光子关联能谱法(photon correlation spectroscopy,PCS)测定其粒径和多分散系数(polydispersity index,PDI),并用上述仪器测定其zeta电位,通过恒温加速试验评价其稳定性,并研究其在小鼠皮肤上的体外经皮释药效果。结果显示:在所考察的油相中,肉桂醛对乙酰甲喹的溶解度最大,聚氧乙烯氢化蓖麻油(RH40)为最佳表面活性剂,用二者制备的乙酰甲喹微乳为黄色的澄清透明液体,流动性好;电镜观察微乳滴呈球形,纳米粒度仪测定其平均粒径为(13.9±0.3)nm,PDI为0.060±0.005;在25℃时,稀释5倍后的乙酰甲喹微乳的平均pH值为5.1±0.2,对应的平均zeta电位为(9.4±0.4)mV;高速离心、常温及低温下稳定,高温下颜色由黄色变为红色,但无药物析出,说明乙酰甲喹微乳符合微乳制剂的要求且稳定性较好;乙酰甲喹微乳配方中无氮酮和氮酮含量为2%及5%的表观透皮系数(Kp×10-3)分别为(12.701±0.012),(12.207±0.021)及(10.796±0.065)cm.h-1,而乙酰甲喹水溶液的表观透皮系数(Kp×10-3)是(4.908±0.034)cm.h-1,说明乙酰甲喹微乳的透皮效果优于其水溶液,且差异显著(P<0.01),其配方中无需透皮促进剂氮酮。
Aiming to develop the transdermal formulation of mequindox microemulsion （M-ME） and evaluate its stability and the transdermal permeability in vitro skin, the best prescription was optimized through the pseudoternary phase diagrams, and the M-ME was prepared by phase transformation. The drop shape was reviewed by the transmission electron microscope （TEM）. The average droplet size and polydispersity index （PDI） of M-ME were measured by photon correlation spectroscopy （PCS） using a Zetasizer Nano ZS instrument. Zeta potential measurements were carried out using the same equipment. The stability was also evaluated through the constant temperature acceleration test, and the transdermal effect was studied on epidermis of mice in vitro. The result showed that the mequindox had the maximum solubility in cinnamaldehyde among all the tested oils, and cremophor RH40 was the optimal surfactant. The M-ME containing cinnamaldehyde and RH40 was clear and transparent yellow fluid with excellent liquidity. The TEM presented it as spherical drops, and their average diameter was （13.9 ± 0.3） nm with PDI at 0. 060 ± 0. 005. At 25 ℃ ,the zeta potential of the M-ME diluted 5 times was （9.4 ±0.4） mV with pH of 5. 1 ± 0.2. High speed centrifugalization and low or normal temperature did not affect the M-ME, while its color changed from yellow to red at 60 ℃ without medicine separating out, indicating that M-ME satisfied the criteria of microemulsion formulation with fine stability. The permeability coefficients （Kp × 10^- 3） of M-ME with no azone, M ME with 2% azone and M-ME with 5% azone were （12. 701±0. 012）, （12. 207 ±0. 021） and （10. 796 ± 0. 065） cm.h^-1 respectively, while the Kp ×10^-3 of mequindox aqueous solution was （4. 908 ± 0. 034） cm. h ^-1, indicating that the transdermal permeability of M-ME exceeded its aqueous solution with significant difference （P 〈 0.01）, and there was no need to add azone to M-ME as transdermal enhancer.
出处
《浙江大学学报（农业与生命科学版）》
CAS
CSCD
北大核心
2012年第2期147-152,共6页
Journal of Zhejiang University:Agriculture and Life Sciences
基金
陕西省重大科技创新专项基金资助项目(K332020916)
关键词
乙酰甲喹
微乳
稳定性
透皮效果
氮酮
mequindox
microemulsion
stability
transdermal effect
azone
