硫酸沙丁胺醇肺吸缓释微球的制备与评价

Preparation and evaluation of sustained release salbutamol sulfate microspheres for pulmonary drug delivery

目的制备可通过肺部吸入方式给药的硫酸沙丁胺醇缓释微球。方法以透明质酸为载体材料,采用乳化溶剂挥发法制备硫酸沙丁胺醇的透明质酸微球,以微球的体积平均直径为指标考察不同工艺和处方因素的影响,并对优化处方的微球进行体外释放评价。结果经优化,得到的最佳制备工艺和处方为:透明质酸质量浓度为6 g·L^(-1),油相为含质量分数1.0%Span80的蓖麻油,药物与载体的质量比为1∶1,内外相的质量比为1∶10,匀质转速为1.2×104 r·min^(-1),超声功率为500 W。制备得到的最优硫酸沙丁胺醇微球,粒径较小,平均粒径为(4.75±2.56)μm;粒径分布较窄,跨距为1.55±0.09;表面粗糙;其体外释放行为表现出一定的缓释效果。结论透明质酸的质量浓度、乳化方式、超声功率是影响微球粒径的重要因素,透明质酸的性质对微球的体外释放行为有显著影响。

Objective To prepare sustained release microspheres suitable for pulmonary drug delivery.Methods Hyaluronic acid was used as carrier material and salbutamol sulfate was applied as model drug to prepare salbutamol sulfate loaded hyaluronic acid microspheres by emulsion solvent evaporation method. Effects of various parameters of formulation and process on volume mean diameter of microspheres were studied, and the in vitro release study of optimal microspheres was conducted as well. Results Optimal formulation was set as follows: 6 g·L^(-1) HA as dispersed phase, castor oil contained 1.0% Span80 as continuous phase, ratio of drug polymer ratio as 1∶1, ratio of dispersed phase to continuous phase as 1∶10, homogenization speed(1.2×104 r·min^(-1), 10 min) and ultrasonic power(500 W, 5 min). The drug-loaded HA microspheres prepared from optimal formulation were spherical with rough surfaces and possessed a average diameter of(4.75±2.56) μm, and also possessed small particle size distribution of 1.55±0.09. The in vitro release study suggests microspheres formed had a sustained release effect. Conclusions Polymer concentration, emulsification techniques and surfactant concentration show significant influence on the particle sizes of microspheres. The characteristics of hyaluronic acid significantly affect the in vitro release behavior of prepared microspheres.