Cocrystals to facilitate delivery of poorly soluble compounds beyond-rule-of-5.
Cocrystals to facilitate delivery of poorly soluble compounds beyond-rule-of-5.
复制标题
共晶以促进5杆超过5的可溶性化合物的递送。
DOI：
10.1016/j.addr.2016.04.022
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发表时间：
2016-06-01
影响因子：
16.1
通讯作者：
Rodríguez-Hornedo N
中科院分区：
文献类型：
--
作者：
Kuminek G;Cao F;Bahia de Oliveira da Rocha A;Gonçalves Cardoso S;Rodríguez-Hornedo N
Besides enhancing aqueous solubilities, cocrystals have the ability to fine-tune solubility advantage over drug, supersaturation index, and bioavailability. This review presents important facts about cocrystals that sets them apart from other solid-state forms of drugs, and a quantitative set of rules for the selection of additives and solution/formulation conditions that predict cocrystal solubility, supersaturation index, and transition points. Cocrystal eutectic constants are shown to be the most important cocrystal property that can be measured once a cocrystal is discovered, and simple relationships are presented that allow for prediction of cocrystal behavior as a function of pH and drug solubilizing agents. Cocrystal eutectic constant is a stability or supersatuation index that: (a) reflects how close or far from equilibrium a cocrystal is, (b) establishes transition points, and (c) provides a quantitative scale of cocrystal true solubility changes over drug. The benefit of this strategy is that a single measurement, that requires little material and time, provides a principled basis to tailor cocrystal supersaturation index by the rational selection of cocrystal formulation, dissolution, and processing conditions.
