ABSTRACT
The study evaluates the lipolysis rate and extent of type Ⅲ lipid formulations using testosterone undecanoate as a model drug after digestion with in vitro lipolysis model, and studies the digestive regularity with optical microscope and electrical conductivity. The results showed that for testosterone undecanoate type Ⅲ lipid formulations with castor oil as oil phase and Transcutol HP as latent solvent, the lipolysis rate and extent were increased with the increase of oil phase proportion and were decreased with excessive proportion of surfactant, in which can see liquid crystal phase during lipolysis process. The lipolysis rate of type ⅢB lipid preparations with different surfactant were ordered as Labrasol > Tween 80 > Cremophor EL, but the rate of type ⅢA is different in quick digestion phase and slow digestion phase. The lipolysis extent of type Ⅲ lipid formulations with different surfactant were ordered as Cremophor EL > Tween 80 > Labrasol. These may be related to the digestive effect of pancreatic lipase on different surfactants. This study implied that the lipolysis rate and extent of type Ⅲ lipid formulations are greatly influenced by the proportion of oil phase and surfactant, and the surfactant structure. These factors will affect the in vivo digestion and should be taken into account when screening type Ⅲ lipid formulations.
ABSTRACT
In vitro lipolysis model has become a new and promising technique to screen and evaluate oral lipid formula-tions .This model mimics the gastrointestinal tract environment and well reflects the fate of lipid formulations in GI tract after oral administration .This review summarizes the characteristics of lipid formulations ,process of gastrointestinal digestion ,ap-plications of in vitro lipolysis model and methods for the characterization of the lipolysis process ,which provides the basis for the research of oral absorption mechanism and in vivo-in vitro correlations of lipid formulations with lipolysis model .
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.