Studies On Gemcitabine Hydrochloride Liposome

Gemcitabine,2’,2’-difluoro-2’-deoxycytidine (dFdC), is an anti-tumor agent effective in the treatment of several solid tumors including non-small cell lung cancer, pancreatic cancer and breast cancer.The purpose of the present study was to prolong its duration in the circulation after iv administration. Therefore, the freeze-dried dFdC liposome (dFdC-FL) was researched to fulfill this purpose.The HPLC analytical method for dFdC in vitro was developed. And the apparent solubilities of dFdC in water and B-R buffers with different pH and the apparent partition coefficient in n-octyl alcohol/water were determined. Then the stability of dFdC in aqueous media was investigated. The entrapment efficiency of dFdC-L was determined by ultrafiltration-UV method. Besides, the ammonium sulfate gradient of blank liposome was determined by the conductivity method, providing scientific basic for the dialyzing procedure.The dFdC-L was prepared by thin film evaporation in combination with the ammonium sulfate gradient method. Single factor test had been done and the orthogonal design was adopted to obtain the optimized prescription, the entrapment efficiency of dFdC-L was 78.62±2.63%.To resolve the instability problem of liposome dispersion, the freeze-drying technique was utilized to prepare dFdC-FL. The technology of freeze-drying especially on the kinds and ratio of cryoprotectants had been researched.The physicochemical properties of dFdC-FL were studied. The liposome was spherical and uniform, the volume diameters of dFdC-L and dFdC-FL were 169±24 nm and 186±50 nm respectively, the entrapment efficiency of these were 79.48±1.23% and 68.46±3.12% differently. The in vitro release study showed that the drug release from dFdC-L was slower than that from dFdC solution with Higuchi’s equation for the best fitting model. The results of stability tests indicated that dFdC-FL was stable under the condition of room temperature and 4℃,the entrapment efficiency and drug content were stable without any significant change. The security investigation indicated that the dFdC-L injection was non-irritant and non-hematolytic, meeting the regulations of the iv administration.