| 摘要: | 本研究主要為探討norepinephrine親水凝膠奈米微粒製劑之製備及其特性。含藥奈米微粒
之製備是以親水凝膠包覆藥物，再使用均質研磨器製成奈米微粒；其物化性質是藉由粒徑
分析、流變學和熱卡式分析來評估。於體外實驗中，則分別研究藥物之包埋率、藥物由奈
米微粒之釋離、透皮試驗、皮膚內藥物殘存量以及長期安定性等，並以高效能液相層析儀
進行分析與評估。結果顯示奈米微粒之粒徑大小分佈、包埋率、體外釋離以及體外透皮均
受製備過程、藥物濃度、親水凝膠種類和使用之界面活性劑等因素的影響。其中，微粒粒
徑大小分佈範圍是介於40nm到500nm之間；微粒懸液之流變學特性為擴張性(搖變稠)流體；
為維持長期保存之安定性，微粒製劑需經冷凍乾燥後於低溫下保存，並可加水回復；其包
埋率仍可高達81.32%。熱分析結果顯示，藥物與親水凝膠及賦型劑之間並無物理化學反應
產生。體外釋離試驗中，微粒型藥物則呈現30-40% 之初期釋離，其持續釋離時間可長達24
小時以上。體外透皮試驗其結果顯示，微粒型藥物經皮輸移系統需添加界面活性劑來增加
透皮速率及通透量，並減少透皮時間。而界面活性劑benzalkonium chloride及sodium
lauryl sulfate之促進穿皮作用均較tween 80佳，其使用濃度以不高於1%為宜。
This study described the preparation and characterization of hydrogel
nanoparticles containing the neurochemical messenger norepinephrine (NE). NE
as a model drug was encapsulated in hydrogel nanospheres using homogenizer.
The size of the NE-hydrogel nanoparticles was evaluated by using Zetasizer
3000HS particle size analyzer. The rheological properties of ointments
including NE-hydrogel nanoparticles were characterized by Cone and Plate
Viscometer. All drug-polymer interactions and the skins were assessed by
Differential Scanning Calorimetry (DSC). For these nanoparticles, drug
loading, in vitro release of drug from the nanoparticles, drug concentration
after transdermal absorption , cumulative amount of drug in skin and long-term
stability determination were quantified by high performance liquid
chromatography (HPLC). The results revealed that particle size, encapsulation
efficiency, in vitro release and transdermal absorption properties of the
nanoparticles were affected by various hydrogels, preparative processes,
surfactants and drug concentrations. The measured particle size distribution
was ranged from 40nm to 500nm. The time-depentent behavior of ointments
including NE-hydrogel nanoparticles was mentioned to as 〝Dilatant〞 flow and
showed a shear-thickening liquid. In regard to the long-term stability, the
results suggested that the product containing NE nanoparticles ought to be
stored in the condition of lyophilized powder at lower temperature and
recovered by adding double deionized water before used. The DSC determinations
indicated that the physical and chemical interaction did not occur among the
components during manufacturing process and reconstituted lyophilized powders.
The encapsulation efficiency of NE in hydrogel nanoparticles was reached to 81.
32%. On the basis of in vitro release study, it revealed that NE was
encapsulated in the hydrogel matrix, following the initial burst release of
30% to 40%, the release was sustained over the 24-hours study period. For in
vitro transdermal absorption study, the skins were treated as well as the
ointments were added with and without different concentrations (0.5% and 1%)
of various surfactants (benzalkonium chloride, sodium lauryl sulfate and tween
80), the experimental results revealed that the rapid permeability was
correlated with surfactants and drug concentration, the skin barrier property
was significantly compromised with benzalkonium chloride and sodium lauryl
sulfate treatment, tween 80 had a lesser effect on skin barrier property
compared to benzalkonium chloride and sodium lauryl sulfate ( 1% > 0.5%,
benzalkonium chloride > sodium lauryl sulfate > tween 80). |
