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Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir.

ABSTRACT: 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.

SUBMITTER: Pineiro A

PROVIDER: S-EPMC8447550 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Inclusion Complexes of Non-Steroidal Anti-Inflammatory Drugs with Cyclodextrins: A Systematic Review.

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| S-EPMC7996898 | biostudies-literature

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| S-EPMC10143540 | biostudies-literature

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Study to Probe Subsistence of Host-Guest Inclusion Complexes of ? and ?-Cyclodextrins with Biologically Potent Drugs for Safety Regulatory Dischargement.

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Evaluation of the molecular inclusion process of β-hexachlorocyclohexane in cyclodextrins.

Project description:The present work aimed to study the guest-host complexes of β-hexachlorocyclohexane (β-HCH), a pesticide with high environmental stability that can cause severe health problems, with the most common cyclodextrins (α-, β-, and γ-CDs). The formation reactions of these molecular inclusion complexes were addressed in this research. The multiple minima hypersurface methodology, quantum calculations based on density functional theory and a topological exploration of the electron density based on the quantum theory of atoms in molecules approach were used to characterize the interaction spaces of the pollutant with the three CDs. Additionally, charge distribution, charge transfer and dual descriptor analyses were employed to elucidate the driving forces involved in the formation of these molecular inclusion complexes. Three types of fundamental interactions were observed: total occlusion, partial occlusion and external interaction (non-occlusion). Finally, experiments were performed to confirm the formation of the studied complexes. The most stable complexes were obtained when γ-CD was the host molecule. The interactions between the pesticide and CDs have fundamentally dispersive natures, as was confirmed experimentally by spectroscopic results. All the obtained results suggest the possibility of using CDs for the purification and treatment of water polluted with β-HCH.

| S-EPMC9070783 | biostudies-literature

Modified cyclodextrins solubilize elemental sulfur in water and enable biological sulfane sulfur delivery.

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| S-EPMC8162768 | biostudies-literature

Evaluation on the inclusion behavior of β-cyclodextrins with lycorine and its hydrochloride.

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| S-EPMC10023205 | biostudies-literature

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