Exploring Key Factors Affecting the Encapsulation Efficiency of Ligusticum Chuanxiong–Vinegar Cyperus Rotundus Essential Oil Based on QbD Principles

<b>Objective</b>: The objective is to investigate and optimize the β-cyclodextrin inclusion process for volatile oils in Ligusticum Chuanxiong-Vinegar cyperus rotundus based on Quality by Design (QbD) principles. <b>Methods</b>: First, ligustilide and α-cyperone were selected as inclusion process indicator components using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Single-factor experiments were conducted to preselect the inclusion speed based on ligustilide and α-cyperone content as evaluation criteria. Subsequently, using the inclusion rates of ligustilide and α-cyperone as evaluation criteria, a factorial design was employed to investigate the inclusion temperature, inclusion time, and the volume ratio of β-cyclodextrin solution to essential oil, thereby optimizing the inclusion process parameters. Finally, the inclusion process parameters were validated, and the inclusion rates were determined. The obtained inclusion complexes were characterized by microscopic analysis, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC). Furthermore, phase dissolution studies and molecular docking were employed for confirmation. <b>Results</b>: The optimal process parameters were determined as follows: encapsulation speed of 300 rpm, β-cyclodextrin solution excess of 6, encapsulation time of 2.5~3 h, and encapsulation temperature of 30~35 °C. The encapsulation rates for ligustilide and α-cyperone in the resulting inclusion complex were 63.15~64.74% and 71.33~76.89%, respectively. Structural characterization confirmed the formation of the inclusion complex. <b>Conclusions</b>: This inclusion process is reliable and provides a reference for preparing β-cyclodextrin inclusion complexes of volatile oils in formulations containing the Chuanxiong-Vinegar cyperus rotundus drug pair.