Mutual solubilization of rosiglitazone and ibuprofen: Investigation and mechanistic insight

TL;DR

Rosiglitazone and ibuprofen increase each other's solubility in water through molecular interactions, offering a new way to improve drug dissolution.

Contribution

This study is the first to demonstrate mutual solubilization between rosiglitazone and ibuprofen and explain its molecular mechanism.

Findings

Rosiglitazone and ibuprofen mutually enhance their aqueous solubility by 6–27%.

Molecular interactions and enhanced solvent compatibility hinder nucleation and crystal growth.

No new chemical entity or crystal phase forms during mutual solubilization.

Abstract

We report for the first time that co-dissolved rosiglitazone and ibuprofen mutually enhance their aqueous solubility; the study was designed to quantify this phenomenon and clarify its origin.

Solubility was measured by HPLC. Fluorescence and FT-IR spectroscopy were used to probe molecular interactions, while classical molecular dynamics simulations provided atomistic insight.

The fluorescence intensity of the mixed solution was markedly lower than that of either drug alone, indicating ground-state complexation or close association. FT-IR spectra showed no new peaks, confirming the absence of a new chemical entity or distinct crystal phase. Simulations revealed that each drug increases the solvent–solute compatibility of the other; the resulting hetero-association hinders nucleation and crystal growth, raising apparent solubility. At 30–60 °C, rosiglitazone solubility rose from 60.4–79.9 to 69.2–92.4 μg/mL (+6–16%), while ibuprofen increased from 50.6–89.5 to 56.3–105.0 μg/mL (+11–27%), confirming mutual enhancement.

The observed mutual solubilization is attributed to specific intermolecular interactions and enhanced solvent compatibility. These findings offer a simple, formulation-free strategy for improving the dissolution of poorly water-soluble drugs.

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