Abstract：
Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (Tg) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 ℃ below Tg of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with Tg of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF.
摘要：
据广泛报道，无定形药物固体的结晶受聚合物添加的影响，而其潜在机制需要深入研究。在这里，系统研究了各种1％w/w聚合物掺杂的玻璃状灰黄霉素（GSF）的晶体生长行为。从分子结构来看,GSF不能与选定的聚合物聚（乙酸乙烯酯）形成氢键相互作用，聚乙烯吡咯烷酮(PVP),60:40乙烯基吡咯烷酮-乙酸乙烯酯共聚物(PVP/VA64)，和聚(环氧乙烷)(PEO)。1%w/w聚合物对GSF的玻璃化转变温度(Tg)表现出弱的或没有可检测的影响。然而,在低于GSFTg8℃时，GSF的晶体生长速率从4.27倍增加到2.57倍减少。有趣的是,加速和抑制GSF晶体生长速率的能力与聚合物的Tg密切相关，表明聚合物链段迁移的控制作用。此外，在聚合物掺杂体系中观察到GSF的环带生长。GSF的正常致密块状和环状带状晶体均被表征为热力学稳定的形式I。更重要的是，GSF环带晶体的形成可以显著削弱聚合物对玻璃态GSF结晶的抑制作用。
