甜味剂对用于热熔挤压固定剂量无定形姜黄素-橙皮素固体分散体的 PVP K30-A 溶液具有增塑作用

K. Wdowiak, L. Tajber, A. Miklaszewski, J. Cielecka‐Piontek
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引用次数: 0

摘要

同时服用姜黄素和橙皮素可能有利于神经保护活性;因此,在本研究中,我们尝试开发一种固定剂量制剂,其中包含无定形状态的这两种化合物。获得无定形状态的目的是克服活性化合物溶解度低的限制。首先,我们评估了使用常用甜味剂(赤藓糖醇、木糖醇和山梨醇)作为增塑剂的可能性,以降低 PVP K30 的玻璃化转变温度,从而制备聚合物-赋形剂混合物,这样就可以在低于 PVP K30 原始玻璃化转变温度的条件下通过热熔挤出法制备无定形固体分散体。事实证明,赤藓糖醇是一种优良的增塑剂。然后,我们重点开发了姜黄素和橙皮素的固定剂量无定形固体分散体。粉末 X 射线衍射和热分析证实了分散体的无定形特性,而红外光谱则有助于评估分子间相互作用的存在。稳定性研究表明,所生产的分散体的无定形状态可保持 6 个月。对溶解速率、溶解度和体外人工膜渗透性等药物参数进行了评估。结果表明,以赤藓糖醇为增塑剂、活性化合物含量占总含量 15%的分散体对这些参数的改善效果最佳。
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Sweeteners Show a Plasticizing Effect on PVP K30—A Solution for the Hot-Melt Extrusion of Fixed-Dose Amorphous Curcumin-Hesperetin Solid Dispersions
The co-administration of curcumin and hesperetin might be beneficial in terms of neuroprotective activity; therefore, in this study, we attempted to develop a fixed-dose formulation comprising these two compounds in an amorphous state. The aim of obtaining an amorphous state was to overcome the limitations of the low solubility of the active compounds. First, we assessed the possibility of using popular sweeteners (erythritol, xylitol, and sorbitol) as plasticizers to reduce the glass transition temperature of PVP K30 to prepare the polymer–excipient blends, which allowed the preparation of amorphous solid dispersions via hot-melt extrusion at a temperature below the original glass transition of PVP K30. Erythritol proved to be the superior plasticizer. Then, we focused on the development of fixed-dose amorphous solid dispersions of curcumin and hesperetin. Powder X-ray diffraction and thermal analysis confirmed the amorphous character of dispersions, whereas infrared spectroscopy helped to assess the presence of intermolecular interactions. The amorphous state of the produced dispersions was maintained for 6 months, as shown in a stability study. Pharmaceutical parameters such as dissolution rate, solubility, and in vitro permeability through artificial membranes were evaluated. The best improvement in these features was noted for the dispersion, which contained 15% of the total content of the active compounds with erythritol used as the plasticizer.
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