Drug distribution during in vitro lipolysis of SNEDDSs containing griseofulvin / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish and optimize in vitro lipolysis model, and then to study griseofuvin(GRI) distribution during in vitro lipolysis of self-nanoemulsifying drug delivery systems(SNEDDSs). METHODS: The lipolysis rate and extent of triglyceride (TG)were two index for in vitro lipolysis model optimization. The partitioning of GRI into lipolysis phases (aqueous phase, pellet phase, lipid phase) was exploited to investigate the impact of structure and lipid loaded of TG on GRI distribution of SNEDDSs in vitro lipolysis. RESULTS: The optimal lipolysis model at the start of the experiment was as follows 800 U · mL-1 Pancreatin extract, 5/1.25 mmol · L-1 NaTDC/PC micelle and 50 mmol · L-1 Trizma maleate. The addition way of Ca2+ for medium chain triglyceride (MCT) and long chain triglyceride (LCT) were fixed addition 5 mmol · L-1 and continuous addition 0.008 mmol · min-1, respectively. With the same amount of TG in SNEDDSs, percent content of GRI in aqueous phase of LCT-SNEDDS was higher than MCT-SNEDDS. When TG loaded doubled, GRI in aqueous phase of LCT-SNEDDS significantly increased by 32.4%, and which of MCT-SNEDDS raised only 5.7%, respectively. CONCLUSION: The lipolysis rate and extent of TG were correlated with its structure and composition of TG and in vitro lipolysis model. Compared to GRI-SNEDDS without lipolysis, during in vitro lipolysis GRI had transferred to aqueous phase, pellet phase and lipid phase from which was only dispersed in emulsion droplet. And the distribution of GRI during in, vitro lipolysis depended on the composition and loading rate of TG in SNEDDS. These results may provide useful references to study the absorption mechanism of SNEDDS.