刘辉, 汤韧, 何晓霞, 张宜. 脂质体处方和制备方法对阿昔洛韦棕榈酸酯脂质体稳定性的影响J. 药学学报, 2002, 37(7): 563-566.
引用本文: 刘辉, 汤韧, 何晓霞, 张宜. 脂质体处方和制备方法对阿昔洛韦棕榈酸酯脂质体稳定性的影响J. 药学学报, 2002, 37(7): 563-566.
LIU Hui, TANG Ren, HE Xiao-xia, ZHANG Yi. EFFECTS OF LIPOSOMES FORMULATION AND PREPARATION METHODON THE STABILITY OF ACYCLOVIR PALMITATE LIPOSOMESJ. Acta Pharmaceutica Sinica, 2002, 37(7): 563-566.
Citation: LIU Hui, TANG Ren, HE Xiao-xia, ZHANG Yi. EFFECTS OF LIPOSOMES FORMULATION AND PREPARATION METHODON THE STABILITY OF ACYCLOVIR PALMITATE LIPOSOMESJ. Acta Pharmaceutica Sinica, 2002, 37(7): 563-566.

脂质体处方和制备方法对阿昔洛韦棕榈酸酯脂质体稳定性的影响

EFFECTS OF LIPOSOMES FORMULATION AND PREPARATION METHODON THE STABILITY OF ACYCLOVIR PALMITATE LIPOSOMES

  • 摘要: 目的研究不同处方组成和制备方法对阿昔洛韦棕榈酸酯脂质体在4℃和25℃分别贮存90 d和180 d后的稳定性的影响。方法用卵磷脂(PC)/胆固醇(CH)/磷脂酰丝氨酸(PS),卵磷脂(PC)/胆固醇(CH)/硬脂酰胺(SA),卵磷脂(PC)/胆固醇(CH)/胆固醇硫酸酯(CS),神经酰胺(CM)/胆固醇(CH)/棕榈酸(PA)/胆固醇硫酸酯(CS),以薄膜分散法、逆向蒸发法和去水化/水化法,分别制备多室脂质体(MLV)、大单室脂质体(LUV)、去水化/水化脂质体(DRV),以平均粒径、渗漏率、pH值和Zeta电位4个指标考察不同贮存条件下脂质体的稳定性。结果脂质体稳定性顺序依次为,对不同脂质体处方:PC/CH/CS>CM/CH/PA/CS>PC/CH/PS>PC/CH/SA;对不同制备方法:LUV优于MLV和DRV;4℃时脂质体的稳定性优于25℃时的脂质体。结论脂质体的稳定性与制剂处方和制备方法密切相关。

     

    Abstract: AIMTo study the effects of various liposomes formulations and preparation methods on the stability of acyclovir palmitate (ACV-C16) liposomes on storage at 4℃ and 25℃ over a 6 months period. METHODSThe mean particle size, Zeta potential, pH and leaking ratio of ACV-C16 liposomes were the parameters chosen to indicate the stability of liposomes. All of the parameters were compared among various lipid compositions [egg lecithin/cholesterol/hosphatidylserine (PC/CH/PS), egg lecithin/cholesterol/stearylamine (PC/CH/SA), egg lecithin/cholesterol/cholesteryl sulphate (PC/CH/CS), bovine brain ceramides/cholesterol/palmitic acid/cholesteryl sulphate (CM/CH/PA/CS)], different preparation methods (film dispersing, reverse phase evaporation, dehydration/rehydration), charges (positive, negative), as well as among multilamellar vesicles liposomes (MLV), large unilamellar vesicles liposomes (LUV) and dehydration/rehydration vesicles liposomes (DRV). RESULTSAn analysis of various parameters led to the conclusion that the stability of liposomes followed the order of PC/CH/CS>CM/CH/PA/CS>PC/CH/PS>PC/CH/SA at the same storage conditions; the positively charged system showed the most unstable delivery system of liposomes as compared to the other three systems. As far as stability was concerned, LUV liposomes proved to be superior to MLV liposomes and DRV liposomes, and the modified reverse phase evaporation method of Szoka provided the best preparation method. The stability in systems was enhanced when systems were stored at 4℃ as compared to storage at 25℃. CONCLUSION The stability of liposomes was significantly interrelated with lipid composition of various liposomes, preparation method and different storage conditions.

     

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