Understanding Polymer Properties Important for Crystal Growth Inhibition-Impact of Chemically Diverse Polymers on Solution Crystal Growth of Ritonavir
Understanding Polymer Properties Important for Crystal Growth Inhibition-Impact of Chemically Diverse Polymers on Solution Crystal Growth of Ritonavir
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DOI：
10.1021/cg300325p
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发表时间：
2012-06-01
影响因子：
3.8
通讯作者：
Taylor, Lynne S.
中科院分区：
文献类型：
--
作者：
Ilevbare, Grace A.;Liu, Haoyu;Taylor, Lynne S.
使用过饱和剂型，例如无定形分散体，是用于改善水溶性差的药物的递送的越来越常见的方法。必须防止结晶以维持过饱和，因此，溶液中有效晶体生长抑制剂的存在对于延长过饱和是理想的。在这项研究中，一组化学上不同的聚合物，包括一些新的纤维素衍生物，在抑制利托那韦从溶液中的晶体生长的有效性进行了量化，使利托那韦的晶体生长抑制的重要的关键聚合物的性能得到阐明。在一般情况下，相对于合成聚合物的纤维素衍生物的更大的有效性归因于一个中等水平的疏水性，纤维素聚合物的半刚性结构，和它们的两亲性。有趣的是，发现一些新型纤维素聚合物是比市售纤维素衍生物更有效的晶体生长抑制剂。正交偏最小二乘分析进一步指出了聚合物疏水性的重要性。基于纤维素的聚合物的这些性质可能促进吸附到结晶药物表面上。考虑到聚合物对晶体生长抑制的影响的多样性，在选择用于过饱和剂型的聚合物时考虑该因素显然是重要的。
The use of supersaturating dosage forms, such amorphous dispersions, is an increasingly common approach for improving delivery of poorly water-soluble drugs. Crystallization must be prevented to maintain supersaturation, and so, the presence of an effective crystal growth inhibitor in solution is desirable to prolong supersaturation. In this study, the effectiveness of a group of chemically diverse polymers, including a number of novel cellulose derivatives, at inhibiting the crystal growth of ritonavir from solution was quantified, enabling key polymer properties important for crystal growth inhibition of ritonavir to be elucidated. In general, the greater effectiveness of the cellulose derivatives relative to the synthetic polymers was ascribed to a moderate level of hydrophobicity, the semirigid structure of the cellulose polymers, and their amphiphilicity. Interestingly, some of the novel cellulose polymers were found to be more effective crystal growth inhibitors than commercially available cellulose derivatives. Orthogonal partial least-squares analysis further pointed to the importance of polymer hydrophobicity. These properties of the cellulose-based polymers are likely to promote adsorption onto the crystallizing drug surface. Given the diversity of impact of polymers on crystal growth inhibition, it is clearly important to consider this factor when choosing a polymer for a supersaturating dosage form.