Formulation, Stabilization, and Antimicrobial Activity of Carvacrol–β-Cyclodextrin Complexes in Hydrophilic Polymer Hydrogels

Abstract

ABSTRACT: This research aimed to develop hydrogel formulations incorporating carvacrol-β-cyclodextrin inclusion complexes to overcome carvacrol's inherent challenges: high volatility, chemical instability, and poor water solubility, while retaining antimicrobial properties. The study focused on characterizing formulations using different hydrophilic polymer matrices—carbomer and hydroxyethyl cellulose (HEC) while maintaining fixed carvacrol concentrations. Carvacrol-β-cyclodextrin complexes were synthesized using co-precipitation methodology at 20:80 ratio, achieving enhanced solubility (0.005 g/ml) compared to free carvacrol. Four hydrogel variants were formulated: two carbomer-based (0.2%) and two HEC-based (3%), with select formulations containing or not chamomile essential oil as an additional active component that potentially contributes with anti-inflammatory benefits. Rheological evaluation demonstrated distinct viscosity profiles between polymer systems. Carbomer formulations showed significantly higher viscosity, indicating superior mechanical stability and extended residence time at application sites. Conversely, HEC formulations exhibited mucoadhesive properties, facilitating application and uniform distribution. These characteristics suggest carbomer systems favor applications requiring structural durability and controlled release, while HEC systems excel in mucoadhesive topical applications. All formulations maintained excellent homogeneity with physiological pH ranges (6.74-7.00), and were evaluated for antibacterial activity before and after incorporation into carbomer and hydroxyethyl cellulose (HEC) hydrogels. They exhibited strong, concentration-dependent antimicrobial activity against the target bacterial strains. A slight reduction in activity (2–3%) was observed post-formulation, confirming the successful release of essential oils from the hydrogel matrices. The integration of carvacrol-β-cyclodextrin complexes into hydrophilic polymer matrices successfully addressed solubility limitations while maintaining stability. Both polymers proved suitable as hydrogel bases with distinct rheological profiles offering flexibility for different applications, opening new therapeutic possibilities for carvacrol in clinically relevant formulations

Keywords

• Carvacrol–β-Cyclodextrin Complexes
• hydrophilic polymer,
• antimicrobial activity

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