Borghetti Greice S, Lula Ivana S, Sinisterra Ruben D, Bassani Valquiria L
Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
AAPS PharmSciTech. 2009;10(1):235-42. doi: 10.1208/s12249-009-9196-3. Epub 2009 Mar 12.
The present study was designed to investigate the influence of operating conditions (temperature, stirring time, and excess amount of quercetin) on the complexation of quercetin with beta-cyclodextrin using a 2(3) factorial design. The highest aqueous solubility of quercetin was reached under the conditions 37 degrees C/24 h/6 mM of quercetin. The stoichiometric ratio (1:1) and the apparent stability constant (Ks = 230 M(-1)) of the quercetin/beta-cyclodextrin complex were determined using phase-solubility diagrams. The semi-industrial production of a 1:1 quercetin/beta-cyclodextrin solid complex was carried out in aqueous solution followed by spray-drying. Although the yield of the spray-drying process was adequate (77%), the solid complex presented low concentration of quercetin (0.14%, w/w) and, thus, low complexation efficiency. The enhancement of aqueous solubility of quercetin using this method was limited to 4.6-fold in the presence of 15 mM of beta-cyclodextrin. Subsequently, an inclusion complex was prepared via physical mixture of quercetin with beta-cyclodextrin (molar ratio of 1:1 and quercetin concentration of 23% (w/w)) and characterized using infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, and scanning electron microscopy analyses. The enhancement of aqueous solubility of quercetin using this method was 2.2-fold, similar to that found in the complex prepared in aqueous solution before the spray-drying process (2.5-fold at a molar ratio of 1:1, i.e., 6 mM of quercetin and 6 mM of beta-cyclodextrin).
本研究旨在采用二水平三因素析因设计，研究操作条件（温度、搅拌时间和槲皮素过量量）对槲皮素与β-环糊精络合的影响。在37℃/24小时/6 mM槲皮素的条件下，槲皮素的水溶性达到最高。使用相溶解度图确定了槲皮素/β-环糊精络合物的化学计量比（1:1）和表观稳定常数（Ks = 230 M⁻¹）。在水溶液中进行1:1槲皮素/β-环糊精固体络合物的半工业生产，随后进行喷雾干燥。尽管喷雾干燥过程的产率足够（77%），但固体络合物中槲皮素的浓度较低（0.14%，w/w），因此络合效率较低。在15 mM β-环糊精存在下，使用该方法提高槲皮素的水溶性仅限于4.6倍。随后，通过槲皮素与β-环糊精的物理混合物（摩尔比为1:1，槲皮素浓度为23%（w/w））制备包合物，并使用红外光谱、差示扫描量热法、核磁共振光谱和扫描电子显微镜分析进行表征。使用该方法提高槲皮素的水溶性为2.2倍，与喷雾干燥前在水溶液中制备的络合物中发现的结果相似（摩尔比为1:1时为2.5倍，即6 mM槲皮素和6 mM β-环糊精）。
