The influence of log P value of insoluble drugs on drug-loading properties of nano-lipid emulsion
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摘要: 目的 考察难溶性药物油/水分配系数(log P值)对纳米脂肪乳载药量、体外释药特性、相分布等载药特性的影响。 方法 选取6种难溶性药物:尼莫地平(NIM)、多西紫杉醇(DTX)、姜黄素(CUR)、紫杉醇(PTX)、替尼泊苷(TEN)、水飞蓟宾(SLB),分别考察其log P值与PEG400中溶解度、载药纳米脂肪乳的载药量、粒径、Zeta电位、体外释药特性以及相分布等的关系。 结果 随着log P值的增加,药物在PEG400中的溶解度呈先上升后下降的趋势,在纳米脂肪乳中的载药量增高,体外释放速率减慢,在油相中的分布增加,在乳化剂层的分布减小;药物log P值与载药纳米脂肪乳的粒径及Zeta电位无关。 结论 可综合考虑药物的log P值及PEG400中的溶解度,用以初步判断纳米脂肪乳的载药特性。Abstract: Objective To study the influence on common logarithm of partition-coefficient (log P) value of insoluble drugs on nano-lipid emulsion properties, including drug-loading amount, in vitro release, and phase distribution etc. Methods 6 insoluble drugs, nimodipine (NIM), docetaxel (DTX), curcumin (CUR), paclitaxel (PTX), teniposide (TEN), silybin (SLB), were selected as the model drugs, to investigate the relationship between log P value and nano-lipid emulsion of the dissolubility in PEG400, the amount of drug-loading, particle diameter, Zeta potential, in vitro release, and phase distribution respectively. Results With the increase of log P value, drug solubility in PEG400 first increased and then decreased, drug-loading in nano-lipid emulsion increased, release rate in vitro of drug slowed down, drug distribution in oil phase increased while in emulsion layer decreased. Log P value has no correlation with particle diameter and Zeta potential. Conclusion The properties of drug-loading nano-lipid emulsion can be preliminarily judged by log P values and the solubility in PEG400 of drugs.
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Key words:
- lipid emulsion /
- insoluble drug /
- log P value /
- drug-loading properties
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