Abstract
The current investigation aimed to prepare and characterize the inclusion complex of thymol with hydroxypropyl-β-cyclodextrin (HP-β-CD) to uniformly incorporate in hydrogel system for its topical application. An inclusion complex of thymol with HP-β-CD was formulated through different methods viz. physical mixture, kneading, and co-precipitation. Phase solubility study was carried out to find the stability constant of complex. Further, the inclusion complex of thymol with HP-β-CD was characterized by DSC, FT-IR, and 1H NMR spectroscopy. The molecular docking studies were also performed to understand the molecular interactions of stable supra-molecular host-guest inclusion complex of thymol with HP-β-CD. After that inclusion complex was incorporated in carbopol 940 hydrogel and evaluated for its drug content, pH, homogeneity, rheological behavior, and in-vitro release. The phase solubility graph demonstrated AL type correlation with apparent stability constant (K1:1) of 370 M−1. The inclusion complex formulated by the co-precipitation technique exhibited the highest dissolution rate (98.73%) of thymol as compared to kneading and physical methods. The DSC, FT-IR and 1H NMR spectroscopic analysis confirmed the formation of inclusion complex between thymol and HP-β-CD. The molecular docking study has confirmed that the binding affinity of thymol with the HP-β-CD was −9.6 kcal/mol, indicating desirable stability of the prepared inclusion complex. The diffusion flux of thymol in a form of inclusion complex was found to be approximately 4.4 folds higher as compared to that of thymol in the hydrogel system for topical administration. The in vitro release of thymol from carbopol 940 hydrogel system exhibited a sustained release profile with thixotropic behaviour. The thymol in a form of inclusion complex was found to be stable in the developed hydrogel system according to ICH guidelines. Therefore, incorporation of thymol in form of inclusion complex in hydrogel system is an effective approach to improve its biopharmaceutical performance for topical administration.
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