Study On The Preparation And Stability Of Paclitaxel-hyaluronan

Paclitaxel is a kind of cytotoxic drug. To alleviate the adverse effect and enhance the efficacy of anti-cancer growth, the HA-paclitaxel freeze-drying preparation was prepared. As a carrier, HA has the effect of targeting to cancer cell and sustained releasing. In this paper, the prescription and preparation of HA-paclitaxel were optimized by the investigation of its stability, dissolution, and other characters of the preparation.As a drug carrier, molecular weight and viscosity of hyaluronic acid may work on the effect of the preparation. So 6mg.ml-1 was identified as the proper concentration used.A method was established for preparation by HPLC. Chromatographic assay was performed on Unimicro NC-04C18 column (200mm×4.6mm, 5μm). The mobile phase consisted of methanol-water (75:25). Paclitaxel had a good linearity (R>0.9999) in the range of 1-100μg/ml. The average recovery was 98.57%, and RSD = 1.206%(n = 5). The result showed that this method was steady and dependable.The prescription of this formulation was optimized by orthogonal design. HA: mannitol was 1:20, molecular weight of HA was 31w, Cremophor EL was 2ml per dose. And different factors on the effect of preparation were inspected. Accelerated test was used to investigate the stability of the formulation. The morphology of preparation is characterized by TEM and ESEM, and X-ray is used to analysis the crystal changes. These results showed that high temperature can influence the stability.Rotating basket method was used to study the in vitro release kinetics of the drug. Paclitaxel released about 80% in 4 hours. The release profile confirmed closely to Weibull distribution model(R2=0.9976).