Martin Todd M, Bandi Nagesh, Shulz Ryan, Roberts Christopher B, Kompella Uday B
Department of Chemical Engineering, Auburn University, AL 36849, USA.
AAPS PharmSciTech. 2002;3(3):E18. doi: 10.1208/pt030318.
The objective of this study was to prepare and characterize microparticles of budesonide alone and budesonide and polylactic acid (PLA) using supercritical fluid (SCF) technology. A precipitation with a compressed antisolvent (PCA) technique employing supercritical CO2 and a nozzle with 100- microm internal diameter was used to prepare microparticles of budesonide and budesonide-PLA. The effect of various operating variables (temperature and pressure of CO2 and flow rates of drug-polymer solution and/or CO2) and formulation variables (0.25%, 0.5%, and 1% budesonide in methylene chloride) on the morphology and size distribution of the microparticles was determined using scanning electron microscopy. In addition, budesonide-PLA particles were characterized for their surface charge and drug-polymer interactions using a zeta meter and differential scanning calorimetry (DSC), respectively. Furthermore, in vitro budesonide release from budesonide-PLA microparticles was determined at 37 degrees C. Using the PCA process, budesonide and budesonide-PLA microparticles with mean diameters of 1 to 2 microm were prepared. An increase in budesonide concentration (0.25%-1% wt/vol) resulted in budesonide microparticles that were fairly spherical and less agglomerated. In addition, the size of the microparticles increased with an increase in the drug-polymer solution flow rate (1.4-4.7 mL/min) or with a decrease in the CO2 flow rate (50-10 mL/min). Budesonide-PLA microparticles had a drug loading of 7.94%, equivalent to approximately 80% encapsulation efficiency. Budesonide-PLA microparticles had a zeta potential of -37 +/- 4 mV, and DSC studies indicated that SCF processing of budesonide-PLA microparticles resulted in the loss of budesonide crystallinity. Finally, in vitro drug release studies at 37 degrees C indicated 50% budesonide release from the budesonide-PLA microparticles at the end of 28 days. Thus, the PCA process was successful in producing budesonide and budesonide-PLA microparticles. In addition, budesonide-PLA microparticles sustained budesonide release for 4 weeks.
本研究的目的是使用超临界流体（SCF）技术制备并表征布地奈德单独制剂以及布地奈德与聚乳酸（PLA）的微粒。采用超临界CO₂和内径为100微米的喷嘴的压缩抗溶剂沉淀（PCA）技术来制备布地奈德和布地奈德 - PLA微粒。使用扫描电子显微镜确定各种操作变量（CO₂的温度和压力以及药物 - 聚合物溶液和/或CO₂的流速）和配方变量（二氯甲烷中0.25%、0.5%和1%的布地奈德）对微粒形态和尺寸分布的影响。此外，分别使用zeta电位仪和差示扫描量热法（DSC）对布地奈德 - PLA微粒的表面电荷和药物 - 聚合物相互作用进行表征。此外，在37℃下测定了布地奈德从布地奈德 - PLA微粒中的体外释放情况。使用PCA工艺制备了平均直径为1至2微米的布地奈德和布地奈德 - PLA微粒。布地奈德浓度的增加（0.25% - 1%重量/体积）导致布地奈德微粒相当呈球形且团聚较少。此外，微粒尺寸随着药物 - 聚合物溶液流速的增加（1.4 - 4.7毫升/分钟）或CO₂流速的降低（50 - 10毫升/分钟）而增大。布地奈德 - PLA微粒的载药量为7.94%，相当于约80%的包封效率。布地奈德 - PLA微粒的zeta电位为 - 37 ± 4 mV，DSC研究表明布地奈德 - PLA微粒的SCF处理导致布地奈德结晶度丧失。最后，在37℃下的体外药物释放研究表明，在28天结束时，布地奈德从布地奈德 - PLA微粒中的释放率为50%。因此，PCA工艺成功制备了布地奈德和布地奈德 - PLA微粒。此外，布地奈德 - PLA微粒可持续释放布地奈德4周。
