Hasegawa Yuki, Higashi Kenjirou, Yamamoto Keiji, Moribe Kunikazu
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Mol Pharm. 2015 May 4;12(5):1564-72. doi: 10.1021/mp500872g. Epub 2015 Apr 17.
A nanosuspension of piroxicam (PXC) and poloxamer 407 (poloxamer) prepared by the wet milling method was directly evaluated at the molecular level from the viewpoint of both solution and solid phases. (13)C solution-state NMR measurements revealed a reduction in the concentration of dissolved poloxamer in the nanosuspension. Furthermore, the fraction of dissolved poly(ethylene oxide) (PEO) chain, which is the hydrophilic part of poloxamer, was higher than that of dissolved poly(propylene oxide) (PPO) chain, the hydrophobic part. (13)C suspended-state NMR and Raman spectroscopies detected both solid-state PXC and poloxamer involved in the nanoparticles. Interestingly, the coexistence of crystalline and amorphous PXC in the nanoparticle was demonstrated. The yellow color of the nanosuspension strongly supported the existence of amorphous PXC. Changes in the peak intensity depending on the contact time in the suspended-state NMR spectrum revealed that the PEO chain of poloxamer in the nanoparticle had higher mobility compared with the PPO chain. The PEO chain should project into the water phase and form the outer layer of the nanoparticles, whereas the PPO chain should face the inner side of the nanoparticles. Amorphous PXC could be stabilized by intermolecular interaction with the PPO chain near the surface of the nanoparticles, whereas crystalline PXC could form the inner core.
通过湿磨法制备的吡罗昔康（PXC）与泊洛沙姆407（泊洛沙姆）的纳米混悬液，从溶液和固相两个角度在分子水平上进行了直接评估。（13）C溶液态核磁共振测量结果显示，纳米混悬液中溶解的泊洛沙姆浓度降低。此外，泊洛沙姆亲水性部分聚环氧乙烷（PEO）链的溶解分数高于疏水性部分聚环氧丙烷（PPO）链。（13）C悬浮态核磁共振和拉曼光谱检测到纳米颗粒中同时存在固态PXC和泊洛沙姆。有趣的是，证明了纳米颗粒中存在结晶态和非晶态的PXC。纳米混悬液的黄色强烈支持了非晶态PXC的存在。悬浮态核磁共振谱中峰强度随接触时间的变化表明，纳米颗粒中泊洛沙姆的PEO链比PPO链具有更高的流动性。PEO链应伸向水相并形成纳米颗粒的外层，而PPO链应面向纳米颗粒的内侧。非晶态PXC可通过与纳米颗粒表面附近的PPO链发生分子间相互作用而稳定，而结晶态PXC可形成内核。
