Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, USF Health College of Medicine, University of South Florida, Tampa, Florida, USA.
Mol Pharm. 2011 Oct 3;8(5):1867-76. doi: 10.1021/mp200209j. Epub 2011 Aug 25.
Flavonoids have been studied extensively due to the observation that diets rich in these compounds are associated with lower incidences of many diseases. One of the most studied flavonoids, quercetin, is also the most abundant of these compounds in the plant kingdom. Numerous therapeutic bioactivities have been identified in vitro. However, its in vivo efficacy in pure form is limited by poor bioavailability, primarily due to its low solubility and consequent low absorption in the gut. Cocrystallization has gained attention recently as a means for improving the physicochemical characteristics of a compound. Here, we synthesized and evaluated four new cocrystals of quercetin (QUE): quercetin:caffeine (QUECAF), quercetin:caffeine:methanol (QUECAF·MeOH), quercetin:isonicotinamide (QUEINM), and quercetin:theobromine dihydrate (QUETBR · 2H(2)O). Each of these cocrystals exhibited pharmacokinetic properties that are vastly superior to those of quercetin alone. Cocrystallization was able to overcome the water insolubility of quercetin, with all four cocrystals exhibiting some degree of solubility. The QUECAF and QUECAF·MeOH cocrystals increased the solubility of QUE by 14- and 8-fold when compared to QUE dihydrate. We hypothesized that this improved solubility would translate into enhanced systemic absorption of QUE. This hypothesis was supported in our pharmacokinetic study. The cocrystals outperformed QUE dihydrate with increases in bioavailability up to nearly 10-fold.
类黄酮由于其饮食中富含此类化合物与许多疾病的低发病率有关而受到广泛研究。其中研究最多的黄酮类化合物槲皮素也是植物界中此类化合物中含量最丰富的。体外已鉴定出许多治疗生物活性。然而，其在纯形式下的体内功效受到生物利用度差的限制，主要是由于其低溶解度和随后在肠道中的低吸收。最近，共晶化作为一种改善化合物物理化学特性的方法引起了人们的关注。在这里，我们合成并评估了槲皮素（QUE）的四个新共晶：槲皮素：咖啡因（QUECAF）、槲皮素：咖啡因：甲醇（QUECAF·MeOH）、槲皮素：异烟酰胺（QUEINM）和槲皮素：可可碱二水合物（QUETBR·2H（2）O）。这些共晶中的每一个都表现出远优于单独使用 QUE 的药代动力学特性。共晶化能够克服 QUE 的水不溶性，所有四个共晶都表现出一定程度的溶解度。与 QUE 二水合物相比，QUECAF 和 QUECAF·MeOH 共晶将 QUE 的溶解度提高了 14 倍和 8 倍。我们假设这种提高的溶解度将转化为 QUE 的系统吸收增强。我们的药代动力学研究支持了这一假设。与 QUE 二水合物相比，共晶使生物利用度提高了近 10 倍。
