The formation of small hybrid aggregates between excipient and drug molecules is one of the mechanisms that contributes to the solubilization of active principles in pharmaceutical formulations. The characterization of the formation, governing interactions and structure of such entities is not trivial since they are highly flexible and dynamic, quickly exchanging molecules from one to another. In the case of cyclodextrins, this mechanism and the formation of inclusion complexes synergistically cooperate to favour the bioavailability of drugs. In a previous study we reported a detailed characterization of the possible formation of inclusion complexes with 1:1 stoichiometry between remdesivir, the only antiviral medication currently approved by the United States Food and Drug Administration for treating COVID-19, and sulphobutylether-β-cyclodextrins. Here we extend our study to assess the role of the spontaneous aggregation in the solubilization of the same drug, by molecular dynamics simulations at different relative concentrations of both compounds. The number of sulphobutylether substitutions in the cyclodextrin structure and two different protonation states of the remdesivir molecule are considered. We aim to shed light in the solubilization mechanism of sulphobutylether-β-cyclodextrins, broadly used as an excipient in many pharmaceutical formulations, in particular in the case of remdesivir as an active compound.

赋形剂和药物分子之间形成小的混合聚集体是有助于药物制剂中活性成分溶解的机制之一。这些实体的形成、控制相互作用和结构的表征并不是微不足道的，因为它们具有高度的灵活性和动态性，可以快速地将分子从一个分子交换到另一个分子。就环糊精而言，这种机制和包合物的形成协同作用，有利于药物的生物利用度。在之前的一项研究中，我们报告了瑞德西韦（美国食品和药物管理局目前唯一批准用于治疗 COVID-19 的唯一抗病毒药物）与磺基丁基醚-β-环糊精之间可能形成 1:1 化学计量的包合物的详细特征。在这里，我们扩展了我们的研究，通过两种化合物不同相对浓度下的分子动力学模拟来评估自发聚集在同一药物溶解中的作用。考虑了环糊精结构中磺基丁基醚取代的数量以及瑞德西韦分子的两种不同质子化状态。我们的目标是阐明磺基丁基醚-β-环糊精的增溶机制，磺基丁基醚-β-环糊精广泛用作许多药物制剂中的赋形剂，特别是在瑞德西韦作为活性化合物的情况下。