Faculty of Pharmaceutical Sciences, University of Iceland, IS-107 Reykjavik, Iceland.
J Pharm Sci. 2012 Sep;101(9):3019-32. doi: 10.1002/jps.23077. Epub 2012 Feb 14.
Cyclodextrins have gained currency as useful solubilizing excipients with an ever increasing list of beneficial properties and functionalities. Although their use in liquid dosage forms including oral and parenteral solutions is straightforward, their application to solids can be confounded by the added bulk that is contributed to the formulation. This factor has limited the use of cyclodextrin in tablets and relates systems mainly to potent drug substances. Increasing the ability of cyclodextrins to complex with drug through a manipulation of their complexation efficiency (CE) may expand the use of these materials to the increasing list of drug candidates and marketed drugs who may benefit from this technology. This brief review assesses tools and materials that have been suggested for increasing the CE for pharmaceutically useful cyclodextrins and drugs. The relative importance of impacting the drug solubility (S(0) ) and phase-solubility isotherm slope is discussed in the context of drug ionization and salt use; the impact of polymers, charge interactions, and charge shielding; and the coincidental formation of other complex types in the media. The influence of drug form as well as supersaturation is also discussed in the context of the responsible mechanisms along with aggregation, inclusion, and noninclusion complex formation.
环糊精作为一种有用的增溶赋形剂，具有越来越多的有益性质和功能，已得到广泛应用。尽管它们在包括口服和肠胃外溶液在内的液体剂型中的应用很简单，但由于制剂中添加了大量的环糊精，其在固体中的应用可能会变得复杂。这个因素限制了环糊精在片剂和相关系统中的应用，主要是针对强效药物物质。通过操纵其包合效率（CE）来增加环糊精与药物的络合能力，可能会扩大这些材料的应用范围，涵盖越来越多的候选药物和已上市的药物，这些药物可能受益于这项技术。本文简要综述了提高药用环糊精和药物 CE 的工具和材料。讨论了在药物离解和盐类使用的情况下，影响药物溶解度（S（0））和相溶解度等温线斜率的相对重要性；聚合物、电荷相互作用和电荷屏蔽的影响；以及在介质中同时形成其他类型的复合物。还讨论了药物形式以及过饱和度的影响，以及聚集、包合和非包合复合物形成的影响。
