Volkova Tatyana, Simonova Olga, Perlovich German
G.A. Krestov Institute of Solution Chemistry RAS, 1 Akademicheskaya str., 153045 Ivanovo, Russia.
Pharmaceutics. 2023 Jan 27;15(2):422. doi: 10.3390/pharmaceutics15020422.
This study describes the influence of pluronic F-127 (F-127) and ethanol (EtOH) on the solubility of umifenovir (UMF) in buffer solutions of pH 2.0 and pH 7.4, and its permeability through cellulose membranes. A 44.4-fold greater UMF solubility in acidic medium as compared to an alkaline one was estimated at 310.15 K. The concentration of UMF in the saturated solution was enhanced by the interaction with F-127 micelles. The combined positive effect of EtOH and F-127 on the solubility was estimated. The aggregation number of F-127 micelles in the presence of 10% and 20% ethanol appeared to be reduced by 2.1-fold and 4.1-fold, respectively, as compared to buffer pH 7.4. The presence of ethanol in buffer pH 7.4 solution provided better solvent conditions but inhibited the formation of F-127 micelles. The impact of UMF on the aggregation number of F-127 was not pronounced and was expressed only by a slight increase of 1 and 3 units in 10% and 20% EtOH, respectively. According to the values of zeta potential, addition of EtOH reduced the stability of the system. The permeation of UMF in buffer pH 7.4 measured through the cellulose membrane MWCO 12-14 kDa was increased 1.4-fold by 10% EtOH. An increase in EtOH content to 20% reduced this effect to 1.2-fold. Decreasing effect of 1.5% F-127 on the permeability was inhibited by using 10% EtOH. The solution containing 1.5% F-127 and 10% EtOH was shown to be an advantageous system for UMF in view of the solubility-permeability balance. The authors suppose the findings of the study to be useful for the design of pharmaceutical formulations based on UMF antiviral drugs.
本研究描述了泊洛尼克F - 127（F - 127）和乙醇（EtOH）对乌米芬诺尔（UMF）在pH 2.0和pH 7.4缓冲溶液中的溶解度及其透过纤维素膜的渗透性的影响。在310.15 K时，估计UMF在酸性介质中的溶解度比在碱性介质中高44.4倍。与F - 127胶束的相互作用提高了饱和溶液中UMF的浓度。评估了EtOH和F - 127对溶解度的联合积极作用。与pH 7.4缓冲溶液相比，在10%和20%乙醇存在下，F - 127胶束的聚集数分别减少了2.1倍和4.1倍。pH 7.4缓冲溶液中乙醇的存在提供了更好的溶剂条件，但抑制了F - 127胶束的形成。UMF对F - 127聚集数的影响不明显，仅在10%和20% EtOH中分别略有增加1和3个单位。根据zeta电位值，添加EtOH降低了体系的稳定性。通过MWCO 12 - 14 kDa纤维素膜测得的pH 7.4缓冲溶液中UMF的渗透率因10% EtOH而提高了1.4倍。EtOH含量增加到20%时，这种效果降低到1.2倍。10% EtOH抑制了1.5% F - 127对渗透率的降低作用。鉴于溶解度 - 渗透率平衡，含有1.5% F - 127和10% EtOH的溶液被证明是UMF的有利体系。作者认为该研究结果对基于UMF抗病毒药物的药物制剂设计有用。
