Effect of counterions on the physical properties of L-arginine in frozen solutions and freeze-dried solids
Effect of counterions on the physical properties of L-arginine in frozen solutions and freeze-dried solids
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DOI：
10.1016/j.ijpharm.2005.05.019
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发表时间：
2005-09-14
影响因子：
5.8
通讯作者：
Aoyagi, N
中科院分区：
文献类型：
--
作者：
Izutsu, KI;Fujimaki, Y;Aoyagi, N
本研究的目的是阐明L-精氨酸和各种反离子组合在冷冻水溶液和冻干固体中的物理性质。在-41.4℃的冷冻溶液中，L-精氨酸在高浓度非冰相中保持无定形状态，T-g‘(最大冷冻浓缩溶质的玻璃化转变温度)为-41.4℃。一些酸和盐(如H3PO_4、H_2SO_4、HNO_3和NaH_2PO_4)提高了T-g’，而其它酸和盐(如HCl、CH_3COOH、HCOOH、Na_2HPO_4和氯化钠)对L-精氨酸的T-g‘影响不大或降低。磷酸共冷冻干燥也提高了L精氨酸无定形冷冻干燥固体的玻璃化转变温度。精氨酸-H3PO4组合表现出的性质导致模型蛋白质(乳酸脱氢酶：LDH)在冷冻干燥过程中稳定或不稳定，这取决于它们的浓度比。傅立叶变换红外光谱(FT-IR)和扩散反射近红外光谱(NIR)表明，在无定形冻干蛋糕中，L精氨酸和磷酸盐离子的氨基和/或胍基之间存在相互作用。推测L-精氨酸与多价反离子的相互作用以及氢键网络的增加降低了冷冻溶液和冻干固体中分子的迁移率。(C)2005 Elsevier B.V.保留所有权利。
The objective of this study was to elucidate the physical properties Of L-arginine and various counterion combinations in frozen aqueous solutions and in freeze-dried solids. L-Arginine remains amorphous in the highly concentrated non-ice phase in frozen solutions with a T-g' (glass transition temperature of maximally freeze-concentrated solutes) of -41.4 degrees C. Some acids and salts (e.g., H3PO4, H2SO4, HNO3, and NaH2PO4) raised the T-g', whereas others (e.g., HCl, CH3COOH, HCOOH, Na2HPO4, and NaCl) had little effect or lowered the L-arginine T-g'. Co-lyophilization with phosphoric acid also raised the glass transition temperature (T-g) of amorphous freeze-dried L-arginine solids. Arginine-H3PO4 combinations exhibited properties that led to either the stabilization or destabilization of a model protein (lactate dehydrogenase: LDH) during freeze-drying, depending on their concentration ratios. Fourier-transform infrared (FT-IR) and diffusion reflectance near-infrared (NIR) spectra indicated the presence of interactions between the amino and/or guanidyl groups Of L-arginine and phosphate ions in the amorphous freeze-dried cakes. It was postulated that the interaction between L-arginine and the multivalent counterions, as well as an increase in hydrogen bonding network, reduced the mobility of molecules in the frozen solutions and freeze-dried solids. (C) 2005 Elsevier B.V. All rights reserved.