Velaga Sitaram P, Berger Rolf, Carlfors Johan
Department of Pharmacy, Uppsala University, Sweden.
Pharm Res. 2002 Oct;19(10):1564-71. doi: 10.1023/a:1020477204512.
Budesonide and flunisolide anhydrate were crystallized using the solution enhanced dispersion by supercritical fluids (SEDS) technique. The aim was to investigate the possibility of preparing different pure polymorphs.
0.25% w/v solutions of each drug were prepared from acetone and methanol. Operating conditions were 40-80 degrees C and 80-200 bars. The flow rate of drug solution was 0.3 mL/min and that of CO2 was 9-25 mL/min. Sample characterizations included differential scanning calorimetry, X-ray powder diffraction, variable temperature X-ray diffraction, scanning electron microscopy, and solubility studies.
The particle morphology of budesonide was dependent on the nature of the solvent. SEDS processing of flunisolide with acetone at 100 bars resulted in the formation of polymorphic mixtures at 80 degrees C and a new polymorph III at 60 C and 40 degrees C. With methanol at 100 bars another new polymorph IV was formed with different particle morphology at 80 degrees C and a polymorphic mixture at 60 degrees C.
Using the SEDS, microparticles of crystalline budesonide were prepared and new polymorphs of flunisolide were produced. Particle characteristics were controlled by the temperature, pressure and relative flow rates of drug solution and CO2.
采用超临界流体增强溶液分散技术（SEDS）使布地奈德和氟尼缩松无水物结晶。目的是研究制备不同纯多晶型物的可能性。
由丙酮和甲醇制备每种药物的0.25%w/v溶液。操作条件为40 - 80℃和80 - 200巴。药物溶液流速为0.3 mL/min，二氧化碳流速为9 - 25 mL/min。样品表征包括差示扫描量热法、X射线粉末衍射、变温X射线衍射、扫描电子显微镜和溶解度研究。
布地奈德的颗粒形态取决于溶剂的性质。在100巴下用丙酮对氟尼缩松进行SEDS处理，在80℃时形成多晶型混合物，在60℃和40℃时形成新的多晶型III。在100巴下用甲醇处理，在80℃时形成另一种具有不同颗粒形态的新多晶型IV，在60℃时形成多晶型混合物。
使用SEDS制备了结晶布地奈德的微粒，并制备了氟尼缩松的新多晶型物。颗粒特性受药物溶液和二氧化碳的温度、压力及相对流速控制。
