Pharmaceutics Department, Faculty of Pharmacy, Minia University, Minia, Egypt.
Pharm Res. 2018 Jun 18;35(8):160. doi: 10.1007/s11095-018-2443-0.
The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need.
In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed.
Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays.
Drugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, P for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. P for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at 'the door step' of absorption sites.
寻找一种简单且可扩展的方法来提高 BCS 类 II 和 BCS 类 IV 的两个关键生物制药过程（溶解度和渗透性）仍然是未满足的需求。
在这项研究中，L-赖氨酸被研究为一种潜在的赋形剂，以解决溶解度和渗透性问题。本研究选用苯扎氯铵（BCS 类 II）；槲皮素和芦丁（BCS 类 IV）作为模型药物。
通过共沉淀和共研磨制备药物-赖氨酸摩尔比为 1:1 的复合物；对溶解度、分配系数、DSC、FTIR、SEM、溶出速率和渗透性进行了表征。通过使用 Trolox 和 CUPRAC 测定法评估抗氧化能力来研究槲皮素-赖氨酸和芦丁-赖氨酸的化学稳定性。
证实了药物-赖氨酸盐/复合物的形成。与单独的药物相比，溶解度提高因子范围为 68 至 433 倍，溶解速率也显著提高了 6 倍。除了芦丁-赖氨酸，苯扎氯铵-赖氨酸和槲皮素-赖氨酸的 P 值分别提高了 2.3 至 4 倍。与赖氨酸形成复合物后，槲皮素（BCS 类 IV）的渗透性比苯扎氯铵（BCS 类 II）更受益。这项研究证明了 L-赖氨酸作为提高 BCS 类 II 和 BCS 类 IV 溶解度和渗透性的有前途的赋形剂的使用，前提是药物的溶解度在吸收部位的“门口”得到保证。
