正交实验法优化超细硫酸沙丁胺醇的制备工艺

Optimization of process conditions for preparation ofsalbutamol sulfate ultrafine particles by orthogonal test

以沙丁胺醇和硫酸为反应物 ,在异丙醇溶液中采用反应结晶法制备超细硫酸沙丁胺醇颗粒。通过正交实验 ,对制备过程中影响产物粒度和产率的因素 ,如 :硫酸浓度、反应温度、搅拌转速、反应时间等进行了系统研究并对优选条件进行了验证。实验结果表明 :当硫酸浓度为 1 0mol/L、反应温度为 5℃、搅拌转速为 90 0r/min、反应时间为 1 0min时 ,可以得到短轴为 5 0～ 6 0nm、长径比为 2 0～ 35且粒度分布较窄的针状硫酸沙丁胺醇颗粒。经IR、XRD分析表明 ,所得产品的纯度大于 98 0 % ,产率大于 95 0 % 。

It is well known that ultrafine salbutamol sulfate drug particles have higher bioavaibability than larger particles. A novel reactive precipitation process was used to prepare ultra fine salbutamol sulfate powders. In this work, salbutamol and sulphuric acids were used as reactants and isopropanol was used as a solvent. The effects of the concentration of sulphuric acid, reaction temperature, stirring speed and the reaction time on the particle size and the product yield of ultrafine salbutamol sulfate were investigated by orthogonal test. The ultrafine particles of salbutamol sulfate can be obtained and their particle sizes can be well controlled under following optimized conditions i.e. the sulphuric acid concentration of 1 0?mol/L, reaction temperature of 5?℃, stirring speed of 900?r/min and reaction time of 10?min. The particles are needle shaped, with mean short diameter of 50～60?nm, average aspect ratio of 20～35 and narrow particle size distribution. The product purity is more than 98% and its yield reaches 95 0%. All those characteristics were in accord with Chinese Pharmacopoeia (2002) and B. P. (1993). The operation of the experiment was very simple, and the particles were separated easily.