Ibuprofen and Palmitic Acid-Based Solvent Exchange-Induced In Situ Forming Matrices With Gentian Violet for...

Gentian violet (GV) is a broad-spectrum antimicrobial agent with documented efficacy against oropharyngeal candidiasis and periodontal pathogens, but its clinical use is limited by poor local retention. In situ forming matrices (ISMs) offer a promising strategy for sustained, localized drug delivery.

This study aimed to develop and evaluate GV-loaded ISMs using ibuprofen (IBU) and palmitic acid (PA) as dual-function matrix-forming agents in DMSO and NMP solvents for the localized treatment of oropharyngeal candidiasis and periodontitis.

ISM formulations were prepared by simple mixing and characterized for viscosity, rheological behavior, injectability, mechanical properties, and in situ matrix formation. In vitro drug release of GV and IBU was quantified by a validated simultaneous HPLC method using an ACE C18 column with UV detection at 590 and 222 nm, respectively. Drug-release kinetics were modeled using zero-order, first-order, Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin models. Antimicrobial activity against Staphylococcus aureus, Candida albicans, C. tropicalis, and Porphyromonas gingivalis was assessed by agar diffusion over 15 days. Molecular interactions were investigated using density functional theory (DFT) calculations at the B3LYP-D3BJ/6-31G(d,p) level.

All formulations showed Newtonian-flow behavior and acceptable injectability (0.78-1.50 N). GV and IBU release followed the Peppas-Sahlin model, with NMP-based systems releasing GV and IBU faster due to more porous matrix architecture, while DMSO-based systems formed denser matrices with slower release. All GV-containing formulations maintained antimicrobial inhibition zones for up to 15 days. DFT calculations revealed strong GV-IBU (-1.63 eV) and GV-PA (-1.53 eV) binding energies, supporting sustained drug entrapment.

GV-loaded IBU/PA-based ISMs demonstrate sustained antimicrobial efficacy for up to 15 days with solvent-dependent release behavior. These systems show potential as localized, single-injection therapies for oral infections. Stability evaluation and in vivo biocompatibility studies are identified as necessary future steps.