A rapid and sensitive method for quantitative determination of paclitaxel in rat plasmawas developed and validated by using ultra-performance liquid chromatography-tandemmass spectrometry (UPLC-MS/MS). Docetaxel was used as an internal standard anddiethyl ether was the liquideliquid extraction agent. Multiple reaction monitoring (MRM)mode via positive electrospray ionization (ESI) was applied to detect paclitaxel and IS at thetransitions m/z 854 / 286 and m/z 808.48 / 527.3, respectively. This method covered alinearity range from 5 to 5000 ng/ml, with the total run time of 3.0 min. In summary, a highthroughout UPLC-MS/MS method was successfully developed to measure paclitaxel in ratplasma and was applied to pharmacokinetic study after intravenous administration ofpaclitaxel.
The aim of this study was to enhance oral bioavailability of itraconazole(ITZ) by developing Liposome containing sodium deoxycholate(ITZ-Lip-NaDC). The liposome, consisting of egg yolk lecithin and sodium deoxycholate, was prepared by thin-film dispersion method.Differential Scanning Calorimetry(DSC) results indicated an amorphous state in the liposome. The physicochemical characteristics including particle size, morphology, entrapment efficiency, dissolution properties were also investigated. The performance of single-pass intestinal infusion exhibited that the transport order of intestinal segment was jejunum,duodenum, colon and ileum, and that all the segments participated in the absorption of ITZ in intestinal tract. The bioavailability study in rats showed that the AUC0-72 of the liposome was nearly 1.67-fold higher than that of commercial capsules(SPORANOX) in terms of oral administration, and the RSD of AUC0-72 of ITZ-Lip-NaD C was also decreased. Our results indicated that ITZ-Lip-NaDC liposome was facilitated to improve dissolution efficiency,augment transmembrane absorption, and then enhance the oral bioavailability of ITZ,successfully.
Cefuroxime axetil(CA)is an ester prodrug of cefuroxime with an unpleasant taste when administrated orally.This work was to mask the bitter taste of CA and enhance its oral bioavailability.Dry suspensions were prepared by means of wet granulation method and solid dispersion method.Binders,suspending agents and other compositions involved in the formulation were optimized.The differential scanning calorimetry(DSC)analysis indicated that CA was amorphous in the solid dispersion with stearic acid as the carrier,which contributed to an improvement of the dissolution rate.Taste evaluation was performed by three volunteers and taste masking was successfully achieved by the methods mentioned above.A pH 7.0 phosphate buffer was adopted to study the in vitro dissolution performance of the three formulations,i.e.,two self-made dry suspensions and the commercial one.With a better release characteristic and a satisfying taste masking ability,the solid dispersion suspension was selected as the optimal formulation for the further pharmacokinetic study in beagle dogs.The values of Cmax and AUC0e12 for the solid dispersion suspension were about 1.78-fold and 2.17-fold higher than these of reference suspension,respectively.The obtained results demonstrated that the solid dispersion can efficiently mask the bitter taste of CA and significantly enhance its oral bioavailability.
Yuqian DuYinglei ZhaiJuhong ZhangChunnuan WuCong LuoJin SunZhonggui He
