Teeranachaideekul Veerawat, Müller Rainer Helmut, Junyaprasert Varaporn Buraphacheep
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayutthaya Road, Rajathavee, Bangkok 10400, Thailand.
Int J Pharm. 2007 Aug 1;340(1-2):198-206. doi: 10.1016/j.ijpharm.2007.03.022. Epub 2007 Mar 24.
Enhancement of the chemical stability of ascorbyl palmitate (AP) after incorporation into nanostructured lipid carriers (NLC) has been reported. However, the formulation parameters of AP-loaded NLC have not been completely investigated. Moreover, the long-term chemical stability of AP in any colloidal systems has not been yet achieved. Therefore, in this study the formulation parameters affecting the stability of AP after incorporation into NLC were evaluated including types of lipids, types of surfactants, storage conditions, i.e. temperature and nitrogen gas flushing, the effects of drug loading as well as types of antioxidants. After storage for 90 days, the mean particle size analyzed by photon correlation spectroscopy (PCS) was lower than 350 nm. The zeta potential measured by the Zetasizer IV was higher than -30 mV in all developed AP-loaded NLC formulations which varied according to the types of lipid and surfactant. Concerning the chemical stability of AP, it was found that AP-loaded NLC prepared and stored in non-degassing conditions, a higher percentage of AP loading in NLC, lower storage temperature (4 degrees C), addition of antioxidants as well as selection of suitable surfactants and solid lipids improved the chemical stability of AP. Moreover, an improvement of long-term chemical stability of AP was achieved by addition of antioxidants with nitrogen gas flushing as compared to those without antioxidant. The percentage of drug remaining at both 4 degrees C and room temperature (25 degrees C) was higher than 85% during 90 days of storage.
据报道,抗坏血酸棕榈酸酯(AP)在被载入纳米结构脂质载体(NLC)后,其化学稳定性得到了增强。然而,载AP的NLC的配方参数尚未得到全面研究。此外,AP在任何胶体系统中的长期化学稳定性尚未实现。因此,在本研究中,评估了影响AP载入NLC后稳定性的配方参数,包括脂质类型、表面活性剂类型、储存条件,即温度和氮气冲洗、药物负载的影响以及抗氧化剂类型。储存90天后,通过光子相关光谱法(PCS)分析的平均粒径低于350 nm。在所有开发的载AP的NLC配方中,通过Zetasizer IV测量的zeta电位高于 -30 mV,该电位根据脂质和表面活性剂的类型而变化。关于AP的化学稳定性,发现制备并储存在非脱气条件下的载AP的NLC、NLC中较高的AP负载百分比、较低的储存温度(4℃)、添加抗氧化剂以及选择合适的表面活性剂和固体脂质可提高AP的化学稳定性。此外,与未添加抗氧化剂的情况相比,添加抗氧化剂并进行氮气冲洗可提高AP的长期化学稳定性。在90天的储存期内,4℃和室温(25℃)下药物残留百分比均高于85%。