Department of Pharmacognosy, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland.
Institute of Materials Science and Engineering, Poznan University of Technology, Jana Pawla II 24, 61-138 Poznan, Poland.
Int J Mol Sci. 2023 Mar 2;24(5):4859. doi: 10.3390/ijms24054859.
The low bioaccessibility of hesperetin and piperine hampers their application as therapeutic agents. Piperine has the ability to improve the bioavailability of many compounds when co-administered. The aim of this paper was to prepare and characterize the amorphous dispersions of hesperetin and piperine, which could help to improve solubility and boost the bioavailability of both plant-origin active compounds. The amorphous systems were successfully obtained by means of ball milling, as confirmed by XRPD and DSC studies. What's more, the FT-IR-ATR study was used to investigate the presence of intermolecular interactions between the systems' components. Amorphization enhanced the dissolution rate as a supersaturation state was reached, as well as improving the apparent solubility of both compounds by 245-fold and 183-fold, respectively, for hesperetin and piperine. In the in vitro permeability studies simulating gastrointestinal tract and blood-brain barrier permeabilities, these increased by 775-fold and 257-fold for hesperetin, whereas they were 68-fold and 66-fold for piperine in the GIT and BBB PAMPA models, respectively. Enhanced solubility had an advantageous impact on antioxidant as well as anti-butyrylcholinesterase activities-the best system inhibited 90.62 ± 0.58% of DPPH radicals and 87.57 ± 1.02% butyrylcholinesterase activity. To sum up, amorphization considerably improved the dissolution rate, apparent solubility, permeability, and biological activities of hesperetin and piperine.
橙皮素和胡椒碱的生物利用度低，限制了它们作为治疗剂的应用。胡椒碱与许多化合物联合使用时具有提高生物利用度的能力。本文的目的是制备和表征橙皮素和胡椒碱的无定形分散体，这有助于提高它们的溶解度并提高这两种植物源活性化合物的生物利用度。通过球磨成功获得了无定形系统，这一点通过 X 射线粉末衍射和差示扫描量热法研究得到了证实。此外，傅里叶变换衰减全反射红外光谱研究用于研究系统成分之间是否存在分子间相互作用。无定形化提高了溶解速率，达到过饱和状态，同时使橙皮素和胡椒碱的表观溶解度分别提高了 245 倍和 183 倍。在模拟胃肠道和血脑屏障通透性的体外渗透研究中，橙皮素在胃肠道和血脑屏障 PAMPA 模型中的渗透性分别提高了 775 倍和 257 倍，而胡椒碱的渗透性分别提高了 68 倍和 66 倍。增强的溶解度对抗氧化和抗丁酰胆碱酯酶活性产生了有利的影响-最佳系统抑制了 90.62±0.58%的 DPPH 自由基和 87.57±1.02%的丁酰胆碱酯酶活性。总之，无定形化大大提高了橙皮素和胡椒碱的溶解速率、表观溶解度、渗透性和生物活性。
