Freie Universität Berlin, Institute of Pharmacy, Kelchstraße 31, 12169 Berlin, Germany.
Karlsruher Institute of Technology, Institute of Functional Interfaces, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
Int J Pharm. 2019 Apr 20;561:228-235. doi: 10.1016/j.ijpharm.2019.02.028. Epub 2019 Mar 2.
Glabridin, a compound in the root extract of Glycyrrhiza glabra, has been identified as an effective tyrosinase inhibitor. Applied on skin, melanin synthesis is inhibited, making glabridin an interesting candidate for skin whitening or for the treatment of age spots. However, main obstaclefor its practical use is its low dermal bioavailability, caused by its poor water solubility. In this work smartPearls technology was used to increase the glabridins water solubility. smartPearls consist of silica particles with mesopores in which actives can be loaded. By this, actives are stabilized in amorphous state and simultaneously finely distributed in nm-range. Both amorphization and nanoization are well known approaches to increase saturation solubilities. In smartPearls these approaches are combined. In the first step, glabridin smartPearls formulation was developed, screening systematically the suitability of 4 different silicas varying in their pore sizes (3, 6, 10, 17 nm). Also, most suited filling level of glabridin was determined (25, 50, 80% referred to total pore volume of respective silica). Silica loading was performed by the immersion-evaporation method, resulting in pores filled with glabridin from bottom to top. By light microscopy, dynamic scanning calorimetry and X-ray diffraction the sample with 6 nm pore size and filling levels of 25% and 50% have been verified to be completely amorphous. Highest physical storage stability of 7 months up to now was obtained for the 25% filled sample. In the next step, concept of increased saturation solubility for smartPearls was proven. Dissolution profiles were recorded in situ for glabridin smartPearls and compared to glabridin raw drug powder. Both saturation solubility and dissolution velocity were remarkably improved. The water solubility for example increased by a factor of more than 4. This makes glabridin smartPearls promising for creating skin products with improved dermal bioavailability.
甘草查尔酮 A 是甘草根提取物中的一种化合物，已被确定为一种有效的酪氨酸酶抑制剂。将其涂抹于皮肤，可抑制黑色素合成，因此甘草查尔酮 A 是一种很有前途的皮肤美白或治疗老年斑的候选药物。然而，其实际应用的主要障碍是其低皮肤生物利用度，这是由于其较差的水溶性所致。在这项工作中，使用了 smartPearls 技术来提高甘草查尔酮 A 的水溶性。smartPearls 由具有介孔的二氧化硅颗粒组成，其中可以装载活性成分。通过这种方式，活性成分以无定形态稳定，并同时在纳米范围内精细分布。无定形化和纳米化都是提高饱和溶解度的众所周知的方法。在 smartPearls 中，这两种方法结合在一起。在第一步中，开发了甘草查尔酮 A smartPearls 制剂，系统筛选了 4 种不同孔径（3、6、10、17nm）的二氧化硅的适用性。同时，还确定了最适合的甘草查尔酮 A 填充水平（25%、50%、80%，分别为相应二氧化硅总孔体积的填充水平）。通过浸渍-蒸发法进行硅石负载，结果是从底部到顶部填充了甘草查尔酮 A 的孔。通过光显微镜、动态扫描量热法和 X 射线衍射法，验证了孔径为 6nm、填充水平为 25%和 50%的样品完全呈无定形态。迄今为止，填充水平为 25%的样品获得了最长的 7 个月物理储存稳定性。在下一步中，证明了 smartPearls 提高饱和溶解度的概念。原位记录了甘草查尔酮 A smartPearls 的溶解曲线，并与甘草查尔酮 A 原料药粉末进行了比较。结果，溶解度和溶解速度都有显著提高。例如，水溶解度提高了 4 倍以上。这使得甘草查尔酮 A smartPearls 有望用于开发具有改善皮肤生物利用度的皮肤产品。
