Enhancing capsaicin solubility in lidocaine-based therapeutic deep eutectic solvents (THEDES): a COSMO-RS predictive study: .

Nur Asma; Ratna Surya Alwi; Delly Ramadon; Abdul Mun'im

doi:10.35814/jifi.v23i2.1665

Authors

Nur Asma Department of Pharmacy, Faculty of Medicine and Health Science, Alauddin State Islamic University, Samata Gowa 92113, South Sulawesi, Indonesia ,
Ratna Surya Alwi Research Centre for Computing, National Research and Innovation Agency (BRIN), Cibinong, Indonesia ,
Delly Ramadon National Metabolomics Collaborative Research Center, Faculty of Pharmacy, Universitas Indonesia, Kampus UI, Depok, West Java 16424, Indonesia ,
Abdul Mun'im Faculty of Pharmacy, Universitas Indonesia, Kampus UI, Depok, West Java 16424, Indonesia

DOI:

https://doi.org/10.35814/jifi.v23i2.1665

Keywords:

Capsaicin, Lidocaine, Therapeutic Deep Eutectic Solvents (THEDES), COSMO-RS, Solubility, Betaine, in silico screening

Abstract

Capsaicin, a potent analgesic, suffers from poor aqueous solubility and low bioavailability. Therapeutic deep eutectic solvents (THEDES) have emerged as a promising platform to enhance the solubility of poorly soluble drugs. This study employed the conductor-like screening model for real solvents (COSMO-RS) for the in-silico screening of capsaicin solubility in 34 lidocaine-based THEDES, comprising 10 hydrogen bond acceptors (HBAs) and 26 hydrogen bond donors (HBDs) at 1:1 and 1:2 molar ratios. The σ-profiles and σ-potentials of the components were analysed to understand the intermolecular interactions governing solubility. Our predictions revealed a remarkable solubility range from below 1 g/L to over 437 g/L. The betaine-lidocaine (1:1) system was identified as the optimal solvent, achieving a capsaicin solubility of 437.47 g/L at 333.15 K, attributed to betaine's zwitterionic nature facilitating multifaceted hydrogen-bonding. Small polyols like ethylene glycol also performed excellently. A consistent enhancement in solubility was observed in HBD-rich (1:2) compositions and with increasing temperature. Molecular interaction analysis confirmed a robust network of conventional and non-conventional hydrogen bonds within the optimal betaine-lidocaine-capsaicin system. This work demonstrates the power of COSMO-RS as a rational design tool for formulating high-loading THEDES-based drug delivery systems, with betaine-lidocaine emerging as a top candidate for advanced capsaicin topical formulations.

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