Ma Jingjing, Yang Yinxian, Sun Yinghua, Sun Jin
Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Asian J Pharm Sci. 2017 Jul;12(4):344-352. doi: 10.1016/j.ajps.2016.09.008. Epub 2016 Nov 18.
Azilsartan (AZL), a poorly soluble drug, was considered to be fit for nanocrystals to improve its solubility. Our study intended to prepare AZL nanocrystals by means of bead milling method. Eight stabilizers or their binary combination and the milling time were set to be variable factors to optimize AZL nanosuspension formulation, and six types of freeze-drying supports were investigated to reduce the aggregation of particles during the solidification. AZL nanocrystals with or without sodium deoxycholate (NaDC) as combined stabilizer with Poloxamer 188 (F68) were prepared owning mean particle sizes of about 300 nm and 460 nm. During the screening processes, the formulation containing NaDC showed a smaller particle size and better stability during lyophilization. The irregular shape and crystal form changing in AZL nanocrystals were discovered by various characterizations. And with physical mixture as reference, nanocrystals showed its improvement about dissolution and bioavailability. In conclusion, the nanocrystals of AZL could be prepared well in our study. Additionally, our results suggested that NaDC was an appreciated excipient on the nanocrystals platform, which can exhibit the abilities of size-reduction and stability-maintaining on freeze-drying.
阿齐沙坦（AZL）是一种难溶性药物，被认为适合制成纳米晶体以提高其溶解度。我们的研究旨在通过珠磨法制备AZL纳米晶体。将八种稳定剂或其二元组合以及研磨时间设定为可变因素，以优化AZL纳米混悬液的配方，并研究六种冻干载体以减少固化过程中颗粒的聚集。制备了以脱氧胆酸钠（NaDC）与泊洛沙姆188（F68）作为联合稳定剂的含或不含NaDC的AZL纳米晶体，其平均粒径分别约为300nm和460nm。在筛选过程中，含NaDC的配方显示出较小的粒径和冻干过程中更好的稳定性。通过各种表征发现了AZL纳米晶体的不规则形状和晶型变化。并且以物理混合物作为对照，纳米晶体显示出其在溶出度和生物利用度方面的改善。总之，在我们的研究中可以很好地制备AZL纳米晶体。此外，我们的结果表明，NaDC是纳米晶体平台上一种理想的辅料，其在冻干过程中可以表现出减小粒径和维持稳定性的能力。
