Study On Liposomes And Submicroemulsion Loaded Azidothymidine Palmitate

Azidothymidine palmitate(AZTP) was synthesized from azidothymidine(AZT). The esterification of AZT was carried out in dry dichloromethane with palmityl chloride at room temperature. The product were chromatographed over silica gel columns and purified by means of recrystallization. The purity of product exceeded 99%. The final product was identified as AZTP using UV, IR, MS and NMR.The validated HPLC analytical method for AZTP was developed. Melting point was determined on a DSC apparatus. The solubilities of AZTP in different solvents and apparent partition coefficients in n-octyl alcohol :buffer systems were determined at ambient temperature by HPLC.The submicroemulsion were prepared with a ultrasonic homogenator. In a series of initial experiments, the optimal sonication conditions were evaluated with respect to energy-output and time. The effects of oil phase categories, the sequence of adding the emulsifier on submicroemulsion loaded AZTP were investigated. And the best formulation and technique were optimized by orthogonal design experiments. The HPLC method for the content of AZTP in submicroemulsion was established.AZTP liposomes formulations were prepared by ethanol injection-ultrasonic dispersion method using different cholesterol ratios in phospholipid mixtures. The lecithin categories and AZTP/lipid weight ratio used to evaluate in vitro stability and particle size distribution were optimized to obtain maximal stability and appropriate mean diameter. The HPLC method for the content of AZTP in liposomes was established. The entrapment efficiency of AZTP liposomes was determinated by ultracentrifugation-HPLC method.The regeneration of AZT from the AZTP solution and perparations by enzymatic hydrolysis was measured in vitro. The results showed degradations displayed apparent first-order kinetics in mice and rats blood plasma. Compared with AZTP solution, the degradation half-time of preparations prolonged from several times to over a hundred times.The HPLC method of parent compound AZT in blood plasma was established. Pharmacokinetics studies were conducted on the liposomes and submicroemulsion loaded AZTP using rats. The pharmacokinetics parameters were fitted and calculated by Topfit program with the obtained drug concentration data by HPLC.