结构相关化合物的对脱和动力学上的作用 印米甲素的脱和动力学
Arushi Manchanda1, Mustafa Bookwala2, Peter L D Wildfong2
1Department of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT, 06269, USA.
结构相关化合物 (SRCs) 影响了玛-印米他素 (γ-IMC) 的结晶动力学. 跨-苏林达克 (t-SUL) 有效地抑制了γ-IMC结晶,不同于与印米他素相关的化合物-A (IMC-A),它被纳入了晶格.
科学领域:
- 制药科学 制药科学
- 物理化学 物理化学
- 结晶科学 结晶科学
背景情况:
- 由于高度的超和,可以停止平衡水平以上的溶解度.
- 了解影响这种现象的因素对于制药配方和制造至关重要.
研究的目的:
- 调查结构相关化合物 (SRCs) 对玛-米素 (γ-IMC) 脱和动力学的影响.
- 探索在晶体生长后观察到的高于平衡的γ-IMC溶解度的潜在解释.
主要方法:
- 在pH2.0下测量了γ-IMC的脱超和动力学,在存在三种SRC的情况下:cis-sulindac (c-SUL),trans-sulindac (t-SUL) 和因多甲相关化合物-A (IMC-A).
- 评估了每个SRC的结晶抑制潜力.
主要成果:
- cis-sulindac和trans-sulindac证明有效地抑制了γ-IMC的结晶.
- 与cis-sulindac相比,trans-sulindac表现出更强的抑制作用.
- 与印美甲相关的化合物-A不是一种强有力的抑制剂;它被纳入了γ-IMC晶格.
- 用SRC培养的γ-IMC晶体的表面溶解度与平衡溶解度相匹配,除非IMC-A存在.
结论:
- 由于IMC-A杂质, γ-IMC的高表面溶解度在结晶后不太可能.
- 苏林达克异构体 (t-SUL > c-SUL) 的差异抑制支持在γ-IMC晶体表面上提出的吸附机制.
- 这提供了关于在脱超和过程中对结晶抑制的机械洞察力.
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