Preparation and in vitro and in vivo evaluation of etoposide submicro-emulsion for intravenous injection.
- Author:
Ling-Ling TIAN
1
;
Xing TANG
;
Hai-Bing HE
;
Jing WANG
Author Information
1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antineoplastic Agents, Phytogenic;
administration & dosage;
pharmacokinetics;
Area Under Curve;
Drug Carriers;
Drug Compounding;
Drug Stability;
Drug Storage;
Emulsions;
Etoposide;
administration & dosage;
pharmacokinetics;
Female;
Hydrogen-Ion Concentration;
Injections, Intravenous;
Lecithins;
chemistry;
Male;
Particle Size;
Random Allocation;
Rats;
Rats, Wistar;
Solubility;
Soybean Oil;
chemistry;
Technology, Pharmaceutical;
methods;
Triglycerides;
chemistry
- From:
Acta Pharmaceutica Sinica
2007;42(8):892-897
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this thesis is to prepare etoposide submicro-emulsion (ESE) for intravenous injection and investigate its characteristics in vitro and in vivo. High-pressure homogenization was used to prepare ESE, using 10% (w/w) soybean oil and 10% (w/w) medium-chain triglyceride as mixed oil phase, and 1.8% (w/w) fabaceous lecithin as emulsifier. The pH was adjusted to 5.5 with 0.1 mol x L(-1) NaOH to keep the most stability of ESE. The particle size distribution and zeta potential were measured using photon correlation spectroscopy. Ultrafiltration was used to estimate the relative percentages of etoposide in each phase. Long-term storage test and accelerated isothermal test-Weibull distribution method were used to estimate the physical and chemical stability of ESE. Plasma pharmacokinetics in rats was monitored by high performance liquid chromatography by comparison with etoposide nonaqueous solution at the same time. The mean particle size, zeta potential and entrapment efficiency of ESE were (189.9 +/- 54.6) nm, - 32.6 mV and 91.7%, respectively. The emulsion was stable during 9 month storage at 4 degrees C. The shelf life (T0.9) of etoposide in lipid emulsion was estimated to be about 665 days at 4 degrees C. The drug concentration-time curves of ESE and solution were similar and could be described by two compartment model. The area under the curve of concentration versus time from zero to the last time point and the mean residence time of ESE and solution were (18.30 +/- 8.74) and (19.32 +/- 6.45) microg x h x mL(-1), and (1.46 +/- 0.32) and (1.71 +/- 0.52) h, respectively. Etoposide was incorporated in submicro-emulsion to improve its physical and chemical stability without addition of organic solvents with insignificant different characteristics in vivo when compared with solution.
