Clarification of the Dissolution Mechanism of an Indomethacin/Saccharin/Polyvinylpyrrolidone Ternary Solid Dispersion by NMR Spectroscopy
Clarification of the Dissolution Mechanism of an Indomethacin/Saccharin/Polyvinylpyrrolidone Ternary Solid Dispersion by NMR Spectroscopy
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DOI：
10.1016/j.xphs.2020.09.009
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发表时间：
2020-12-01
影响因子：
3.8
通讯作者：
Moribe, Kunikazu
中科院分区：
文献类型：
--
作者：
Kosaka, Mami;Higashi, Kenjirou;Moribe, Kunikazu
本文采用喷雾干燥法制备吲哚美辛（IMC）/糖精（SAC）/聚乙烯吡咯烷酮（PVP）三元固体分散体（SD），并对其溶出机理进行了研究。固态核磁共振谱表明，IMC和SAC在三元SD通过氢键以类似的方式在IMC/SAC共晶相互作用。从三元SD的初始IMC溶解是慢于从二元SD，虽然IMC过饱和保持了相对较长的时间在三元SD。溶解试验中分散颗粒的固态和溶液态NMR测量显示，IMC/PVP二元SD的颗粒由分散在PVP基质中的无定形IMC和α-形式IMC组成。相比之下，三元SPD的颗粒由分散在PVP基质中的无定形IMC和IMC/SAC共晶组成。扫描电子显微镜表明，在二元SD中，在溶解测试后，在颗粒表面上生成无定形IMC微纤维-凝胶，防止无定形IMC与水接触。相比之下，在三元SD中，IMC/SAC共晶在颗粒表面上生成，并且在表面上形成中间空间，这允许水侵入颗粒中并且IMC持续溶解。(C)2020年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
Here, an indomethacin (IMC)/saccharin (SAC)/polyvinylpyrrolidone (PVP) ternary solid dispersion (SD) prepared by spray-drying was characterized to clarify its dissolution mechanism. Solid-state NMR spectroscopy revealed that IMC and SAC in the ternary SD interacted via hydrogen bonding in a similar manner as that in the IMC/SAC co-crystal. Initial IMC dissolution from the ternary SD was slower than that from the binary SD, although IMC supersaturation was maintained for a relatively longer time in the ternary SD. Solid- and solution-state NMR measurements for dispersed particles in the dissolution test revealed that the particle for IMC/PVP binary SD was composed of amorphous IMC dispersed in PVP matrix and alpha-form IMC. In contrast, the particles for the ternary SPD was composed of amorphous IMC dispersed in PVP matrix and IMC/SAC co-crystals. Scanning electron microscopy indicated that in the binary SD, amorphous IMC microfiber-gel was generated on the surface of particles after the dissolution test, preventing amorphous IMC from contacting with water. In contrast, in the ternary SD, IMC/SAC co-crystals were generated on the surface of particles, and intermediate spaces were formed on the surface, which allowed water intrusion into the particles and continuous dissolution of IMC. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.