Imperiale Julieta C, Bevilacqua Gabriela, Rosa Paulo de Tarso Vieira E, Sosnik Alejandro
The Group of Biomaterials and Nanotechnology for Improved Medicines (BIONIMED), Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires , Buenos Aires , Argentina .
Drug Dev Ind Pharm. 2014 Dec;40(12):1607-15. doi: 10.3109/03639045.2013.838581. Epub 2013 Sep 19.
This work investigated the production of pure indinavir free base nanoparticles by a supercritical anti-solvent method to improve the drug dissolution in intestine-like medium.
To increase the dissolution of the drug by means of a supercritical fluid processing method.
Acetone was used as solvent and supercritical CO2 as antisolvent. Products were characterized by dynamic light scattering (size, size distribution), scanning electron microscopy (morphology), differential scanning calorimetry (thermal behaviour) and X-rays diffraction (crystallinity).
Processed indinavir resulted in particles of significantly smaller size than the original drug. Particles showed at least one dimension at the nanometer scale with needle or rod-like morphology. Results of X-rays powder diffraction suggested the formation of a mixture of polymorphs. Differential scanning calorimetry analysis showed a main melting endotherm at 152 °C. Less prominent transitions due to the presence of small amounts of bound water (in the raw drug) or an unstable polymorph (in processed IDV) were also visible. Finally, drug particle size reduction significantly increased the dissolution rate with respect to the raw drug. Conversely, the slight increase of the intrinsic solubility of the nanoparticles was not significant.
A supercritical anti-solvent method enabled the nanonization of indinavir free base in one single step with high yield. The processing led to faster dissolution that would improve the oral bioavailability of the drug.
本研究采用超临界抗溶剂法制备纯茚地那韦游离碱纳米颗粒，以提高药物在肠样介质中的溶解度。
通过超临界流体处理方法提高药物的溶解度。
以丙酮为溶剂，超临界二氧化碳为抗溶剂。通过动态光散射（粒径、粒径分布）、扫描电子显微镜（形态）、差示扫描量热法（热行为）和X射线衍射（结晶度）对产物进行表征。
处理后的茚地那韦颗粒尺寸明显小于原药物。颗粒在纳米尺度上至少有一个维度，呈针状或棒状形态。X射线粉末衍射结果表明形成了多晶型混合物。差示扫描量热分析显示在152°C有一个主要的熔融吸热峰。由于存在少量结合水（原料药中）或不稳定的多晶型物（处理后的茚地那韦中）导致的不太明显的转变也可见。最后，药物粒径减小显著提高了相对于原料药的溶解速率。相反，纳米颗粒固有溶解度的轻微增加并不显著。
超临界抗溶剂法能够一步高产率地实现茚地那韦游离碱的纳米化。该处理方法导致更快的溶解，这将提高药物的口服生物利用度。
