Preparation Of Etoposide Microemulsion

Etoposide is an antitumor drug with broad spectra, and widely used in the clinic. But it was hydrophobic and the pharmacokinetics between patients was very diverse. To solve the problems, etoposide microemulsion was prepared.After the pharmaceutical preformulation investigation and pseudo-ternary phase diagram research, etoposide microemulsion formulation was developed. It was composed of 18.8% of Cremophor RH40, 18.8% of ethanol, 18.8% of PEG 400, 4.9% of isopropyl miristate, 37.7% of water and 1.0% of etoposide. An HPLC method was established to determine the etoposide content in the microemulsion. Etoposide was eluted with the mobile phase of methanol-water(70:30) at the flow rate of 0.7mL?min^-1 on a C18 column at 30 oC. Etoposide was detected at 285nm and the retention time was about 5.2min. The linear range was 20¹00μg?mL^-1 with the relative coefficient of 0.9998.The physicochemical properties of blank microemulsion and etoposide microemulsion were studied. Both were nearly Newton fluid. Their viscosities were 5.10×10-3 Pa·s and 5.02×10-3 Pa·s, and the interfacial tensions were 44.04 mN·m^-1 and 42.61 mN·m^-1 respectively. The microemulsion style was qualified as oil-in-water microemulsion. Etoposide release pattern was studied using the bulk-equilibrium dialysis bag technique at 37 oC with 500mL water being the release media, and the paddle was used at the rotation speed of 100r?min^-1. Etoposide released about 85% in 3h. The release profile closely confirmed to Weibull distribution model. From the stability experiments results, it could be concluded that the blank microemulsion was stable while the etoposide content would decrease slightly. After 10 days under 4500 lx and 60 oC, the content decreased 3.5% and 3.9% respectively. With three months'accelerated experiments under 40 oC, the content declined 1.3%. The content decreased averagely 1.6% and 1.9% after six months at 4 oC and 25 oC respectively. The other properties were stable.The oral etoposide microemulsion was firstly prepared in the paper. Etoposide and its preparation were stable in 6 months at 4 oC.