Choi I, Park S Y, Lee S-W, Kang Z, Jin Y S, Kim I W
Pharmazie. 2020 Jan 2;75(1):13-17. doi: 10.1691/ph.2020.9120.
Sorafenib (SOR) is an important multikinase inhibitor for the treatment of cancers. It is commercially available (Nexavar from Bayer) in the form of sorafenib tosylate (SORt) due to its very low solubility. Studies have been made to further improve the dissolution behavior of the tosylate form (SORt), which could ultimately moderate the currently high daily dose. In the present study, SORt nanoparticles (SORt-NP) were prepared through a process that combined two industrially well-accepted techniques of co-milling and supercritical extraction. SORt was co-milled with hydrophilic polymers and tetradecanol, and the tetradecanol was post-extracted using supercritical carbon dioxide. The process enabled the formation of SORt-NP without using any toxic organic solvents, and the drug/excipient ratio (1:0.38) was substantially higher than determined in other studies (1:5.4-10). The enhanced dissolution behavior of SORt-NP was possible with an optimized number of milling cycles. Combining co-milling and supercritical extraction was able to form overall porous network structures with reduced crystallite size, which accelerated the dissolution of SORt-NP. The current method could be easily extended to other poorly soluble drugs as a general approach to improve their dissolution behaviors.
索拉非尼（SOR）是一种用于治疗癌症的重要多激酶抑制剂。由于其溶解度极低，它以甲苯磺酸索拉非尼（SORt）的形式上市销售（拜耳公司的多吉美）。已经开展了相关研究以进一步改善甲苯磺酸盐形式（SORt）的溶解行为，这最终可能会降低目前较高的每日剂量。在本研究中，通过将两种工业上广泛认可的技术——共研磨和超临界萃取相结合的过程制备了SORt纳米颗粒（SORt-NP）。SORt与亲水性聚合物和十四烷醇进行共研磨，然后使用超临界二氧化碳对十四烷醇进行后萃取。该过程无需使用任何有毒有机溶剂即可形成SORt-NP，且药物/辅料比例（1:0.38）显著高于其他研究中所确定的比例（1:5.4 - 10）。通过优化研磨循环次数，SORt-NP的溶解行为得以增强。将共研磨和超临界萃取相结合能够形成具有减小的微晶尺寸的整体多孔网络结构，从而加速了SORt-NP的溶解。作为一种改善其他难溶性药物溶解行为的通用方法，当前方法可轻松扩展至其他难溶性药物。
