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Influence of degree of substitution on the hydroxypropyl-β-cyclodextrin complexation with rifampicin in water solution: a molecular simulation

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Abstract

Context

Hydroxypropyl-β-cyclodextrin (HPβCD) is one of the derivatized cyclodextrins most widely used as an excipient in the pharmaceutical industry, for its capacity to improve certain drugs properties. Different configurations of HPβCD are possible depending on the number and location of the 2-hydroxypropyl groups substituted on the glucose rings. Rifampicin has become the most commonly clinically used antibiotic against tuberculosis in recent years, despite its low solubility and variable bioavailability. Different techniques and materials have been proposed to enhance the properties of rifampicin: cyclodextrin complexation is one of them. The van der Waals term was the main contribution to the interaction energy, which then decisively conditioned the complex configurations. The size of rifampicin did not allow the whole molecule to fit into the host. Moreover, interaction energy was much greater when the guest was located near each rim of HPβCD, where rifampicin was partially included in the cavity and formed inclusion complexes. The piperazine tail of rifampicin was included inside the host in minimum energy structures and the guest was situated near the primary rim of HPβCD in most cases, although the complex configurations depended on the degree of substitution.

Methods

A molecular mechanics simulation based on the GROMOS 53A6 force field was applied in this work to study the inclusion complexes formed by twelve configurations of HPβCD, with different degrees of substitution and rifampicin in water solution. We determined the penetration potential, the complex structures with minimum energies, the possibility of forming inclusion complexes other than those of minimum energies and potential energy surfaces.

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Funding

This research was funded by the Ministerio de Ciencia e Innovación, under Grant number PID2019-105225 GB-I00.

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  1. Department of Physics, University of La Laguna, La Laguna, Spain

    Elena Alvira

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  1. Elena Alvira
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E. Alvira, The author confirms sole responsibility for the following: study conception and design, data collection, analysis and interpretation of results, manuscript writing and preparation of figures.

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Correspondence to Elena Alvira.

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Alvira, E. Influence of degree of substitution on the hydroxypropyl-β-cyclodextrin complexation with rifampicin in water solution: a molecular simulation. J Mol Model 30, 113 (2024). https://doi.org/10.1007/s00894-024-05916-1

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