Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, University of Innsbruck, Institute of Pharmacy, 6020 Innsbruck, Austria.
IBMM, University of Montpellier, CNRS, ENSCM, 34095 Montpellier, France.
Mol Pharm. 2020 Sep 8;17(9):3236-3245. doi: 10.1021/acs.molpharmaceut.0c00343. Epub 2020 Jul 28.
The aim of this study was to investigate the fate and the impact of cosolvents in self-emulsifying drug delivery systems (SEDDS). Three different SEDDS comprising the cosolvents DMSO (F), ethanol (F), and benzyl alcohol (F) as well as the corresponding formulations without these cosolvents (F, F, and F) were developed. Mean droplet size, polydispersity index (PDI), ζ potential, stability, and emulsification time were determined. Cosolvent release studies were performed via the dialysis membrane method and Taylor dispersion analysis (TDA). Furthermore, the impact of cosolvent utilization on payloads in SEDDS was examined using quinine as a model drug. SEDDS with and without a cosolvent showed no significant differences in droplet size, PDI, and ζ potential. The emulsification time was 3-fold (F), 80-fold (F), and 7-fold (F) longer due to the absence of the cosolvents. Release studies in demineralized water provided evidence for an immediate and complete release of DMSO, ethanol, and benzyl alcohol. TDA confirmed this result. Moreover, a 1.4-fold (F), 2.91-fold (F), and 2.17-fold (F) improved payload of the model drug quinine in the selected SEDDS preconcentrates was observed that dropped after emulsification within 1-5 h due to drug precipitation. In parallel, the quinine concentrations decreased until reaching the same levels of the corresponding SEDDS without cosolvents. Due to the addition of hydrophilic cosolvents, the emulsifying properties of SEDDS are strongly improved. As hydrophilic cosolvents are immediately released from SEDDS during the emulsification process, however, their drug solubilizing properties in the resulting oily droplets are very limited.
本研究旨在探讨助溶剂在自乳化药物传递系统（SEDDS）中的命运和影响。开发了三种不同的 SEDDS，包含助溶剂二甲基亚砜（F）、乙醇（F）和苯甲醇（F）以及不含这些助溶剂的相应制剂（F、F 和 F）。测定了平均液滴大小、多分散指数（PDI）、ζ电位、稳定性和乳化时间。通过透析膜法和泰勒分散分析（TDA）进行了助溶剂释放研究。此外，还使用奎宁作为模型药物研究了助溶剂利用对 SEDDS 中载药量的影响。含有和不含有助溶剂的 SEDDS 在液滴大小、PDI 和 ζ 电位方面没有显著差异。由于缺乏助溶剂，乳化时间延长了 3 倍（F）、80 倍（F）和 7 倍（F）。去矿物质水中的释放研究表明，二甲基亚砜、乙醇和苯甲醇立即完全释放。TDA 证实了这一结果。此外，在选定的 SEDDS 预浓缩物中，模型药物奎宁的载药量提高了 1.4 倍（F）、2.91 倍（F）和 2.17 倍（F），但由于药物沉淀，在乳化后 1-5 小时内下降。同时，奎宁浓度下降，直到达到不含助溶剂的相应 SEDDS 的相同水平。由于添加了亲水性助溶剂，SEDDS 的乳化性能得到了极大改善。然而，由于亲水助溶剂在乳化过程中立即从 SEDDS 中释放出来，因此它们在形成的油性液滴中对药物的增溶能力非常有限。
