Gupta P K, Hung C T, Lam F C
Department of Pharmacy, University of Otago, Dunedin, New Zealand.
J Microencapsul. 1989 Apr-Jun;6(2):147-60. doi: 10.3109/02652048909098015.
The use of factorial design in the formulation of adriamycin-associated albumin microspheres, using the heat-stabilization technique, is illustrated. The effect of stabilization temperature, protein concentration and stabilization time on the entrapment and recovery of adriamycin in microspheres have been investigated using a 2 x 4 x 4 factorial design. The associated drug content in unwashed and four times washed microspheres was determined using HPLC. Maximum drug association and drug recovery were obtained from microspheres synthesised using 25 per cent w/v albumin solution and stabilized at 120 degrees C for 2.5 min. Under these conditions, the entrapped and total associated drug content of the microspheres was about 4 per cent and 12 per cent w/w respectively, and the drug recovery was about 75 per cent. The in vitro dissolution study carried out using dynamic dialysis revealed that the release of adriamycin from these particles follows a bi-phasic pattern. The results demonstrate that use of short stabilization time, low protein concentration and low stabilization temperature are required for the formulation of microspheres with high adriamycin content.
本文阐述了在制备阿霉素结合白蛋白微球时采用析因设计并结合热稳定技术的情况。采用2×4×4析因设计研究了稳定温度、蛋白质浓度和稳定时间对微球中阿霉素包封率和回收率的影响。使用高效液相色谱法测定未洗涤和洗涤四次的微球中的相关药物含量。使用25%（w/v）白蛋白溶液合成并在120℃稳定2.5分钟的微球获得了最大的药物结合量和药物回收率。在这些条件下，微球的包封药物含量和总结合药物含量分别约为4%（w/w）和12%（w/w），药物回收率约为75%。使用动态透析进行的体外溶出研究表明，阿霉素从这些颗粒中的释放遵循双相模式。结果表明，制备高阿霉素含量的微球需要较短的稳定时间、较低的蛋白质浓度和较低的稳定温度。
