University of Applied Sciences and Arts Northwest. Switzerland, Institute of Pharma Technology Hofackerstr. 30, Muttenz CH-4132, Switzerland; Institute of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, Basel 4056, Switzerland.
Zentiva, k.s., U Kabelovny 130, 102 00 Praha 10, Czech Republic.
Eur J Pharm Sci. 2023 Jul 1;186:106463. doi: 10.1016/j.ejps.2023.106463. Epub 2023 May 9.
There is a growing interest in using deep eutectic solvents (DES) as a pharmaceutical delivery system for poorly water-soluble compounds. To reduce the risk of drug precipitation following oral administration, this study addresses the hypothesis that directly including a polymeric precipitation inhibitor (PI) in a DES mixture could obtain a polymer-embedded deep eutectic system (PEDES) as a novel bio-enabling formulation principle. Following broad formulation screening, a PEDES embedding 15% w/w of polyvinyl pyrrolidone K30 (PVP) in L-carnitine:ethylene glycol (1:4, molar ratio) DES was successfully formulated as a supersaturating formulation using indomethacin as model compound. The drug solubility of 175.6 mg/mL obtained in DES was remarkably high, and upon release (phosphate buffer, pH 6.5) a maximum supersaturation factor of 9.8 was recorded, whereby the release kinetics displayed a suitable "parachute effect". The formulation was further characterized to include a molecular dynamics simulation. It can be concluded that PEDES appears to be a viable novel formulation approach, setting solid grounds for further research to assess the full potential of this novel type of supersaturating drug delivery system.
人们越来越感兴趣地将深共晶溶剂 (DES) 用作难溶性化合物的药物传递系统。为了降低口服给药后药物沉淀的风险，本研究提出了一个假设，即直接将聚合物沉淀抑制剂 (PI) 包含在 DES 混合物中，可以获得一种聚合物嵌入的深共晶系统 (PEDES)，作为一种新的生物赋形剂原理。在广泛的配方筛选之后，成功地将 15% w/w 的聚乙烯吡咯烷酮 K30 (PVP) 嵌入到 L-肉碱：乙二醇 (1:4，摩尔比) DES 中，作为模型化合物的吲哚美辛制成超饱和配方。DES 中获得的 175.6 mg/mL 的药物溶解度非常高，并且在释放时（磷酸盐缓冲液，pH 6.5）记录到最大过饱和度因子为 9.8，其中释放动力学显示出合适的“降落伞效应”。该配方进一步进行了特征描述，包括分子动力学模拟。可以得出结论，PEDES 似乎是一种可行的新型配方方法，为进一步研究这种新型超饱和药物传递系统的全部潜力奠定了坚实的基础。
