[show abstract][hide abstract] ABSTRACT: The aim of this study was to develop a new phospholipid complex self-emulsifying drug delivery system (PC-SEDDS) to enhance bioavailability of oral etoposide, a drug with poor water solubility.
Etoposide-phospholipid complex (EPC) was prepared by reacting etoposide and phospholipid in tetrahydrofuran and confirmed as a phospholipid compound by differential scanning calorimetry (DSC). Solubility of EPC and etoposide was determined in various vehicles. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsification region of EPC-SEDDS, and the effects of oil concentration, drug loading, and aqueous media on droplet size were investigated.
The optimal formulation of EPC-SEDDS was EPC:octyl and decyl monoglyceride (ODO):Cremopher EL:PEG-400 (1:20:48:32) (w/w/w/w). Compared with etoposide-phospholipid complex suspension (EPCS) and etoposide suspension (ES), cumulative release of etoposide from EPC-SEDDS increased by 1.31 and 2.65 fold at 24 hours, respectively. Compared with ES, relative bioavailability of EPC-SEDDS, E-SEDDS, and EPCS after oral administration in rats was enhanced by 60.21-, 44.9-, and 8.44- fold, respectively.
The synergistic effect between PC and SEDDS contributed to the enhanced bioavailability of etoposide. It was concluded that PC-SEDDS proved to be a potential system for delivering orally administered hydrophobic compounds including etoposide.
Drug Development and Industrial Pharmacy 08/2010; 37(1):103-12. · 1.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: A LC/MS/MS method was developed and validated for determination of nobiliside A in rat plasma. Analyses were separated by an Agella Venusil ASB-C18 column and isocratic elution with methanol:water (80:20, v/v) as a mobile phase. A tandem mass spectrometer was used as a detector for quantitative analysis. Calibration curves (R(2)>0.999) in spiked plasma were linear over the concentration range of 50-5000 ng/mL. The overall accuracy of this method was 93-104% for nobiliside A. Within-day and between-day variability was both less than 9% in plasma. The data indicate that the LC/MS/MS method is an effective method for the pharmacokinetics study of nobiliside A in rat plasma.
Journal of Chromatography B 01/2009; 877(3):323-7. · 2.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: To reduce the hemolysis and toxicity of nobiliside A (Nob), liposomes were used as a carrier in this study. Response surface methodology (RSM) based on central composite rotatable design (CCRD) was applied for formulation optimization. Phosphatidyl choline (PC) proportion, cholesterol (CH) proportion, and lipids/drug ratio were selected as the independent variables while the encapsulation efficiency (EE) and hemolytic rate (HR) of the liposomes as the dependent variables. The results indicated CH proportion and lipids/drug ratio were the major contributing variables for EE and PC/CH ratio was the major contributing variables for HR. The optimum formulation of Nob liposomes, in which PC proportion of 2% (w/v), CH proportion of 0.9% (w/v), and lipids/drug ratio (w/w) of 40, had higher EE (>95%) and lower HR (<1% at the concentration of 80 microg mL(-1)) with spherical shape and uniform sizes. The intravenous LD50 increased to 9.5 mg kg(-1) compared to 4.1 mg kg(-1) of Nob solution. In conclusion, the liposome was a safety and effective carrier for intravenous Nob.
International journal of pharmaceutics 12/2008; 371(1-2):197-203. · 2.96 Impact Factor