Molecular Modeling of Isoniazid Encapsulation by β-Cyclodextrin for Drug Delivery: Molecular Dynamics, Interaction Energies, and DFT Insights

β-cyclodextrin (β-CD) plays a crucial role in advanced drug delivery processes, with potential applications in drug protection and release modulation. Therefore, the encapsulation potential of β-CD towards isoniazid (ISO) was herein comprehensively examined by performing molecular dynamics (MD) simulation with density functional theory (DFT) calculations. From an energetic perspective, the encapsulation process within the ISO⋯β-CD complex was energetically preferable, as evidenced by the negative interaction energy (Eint) values of configurations A–E. Compared to the other configurations, configuration A exhibited the most favorable Eint, reaching −41.66 kcal/mol. From FMO and TDOS analyses, a reduction in energy gap values was observed following the encapsulation process, indicating a change in the electronic structure of the ISO⋯β-CD complex. The effect of water on the encapsulation process within the ISO⋯β-CD complex was investigated. Furthermore, the potential release of ISO from β-CD was qualitatively assessed using simplified recovery-time estimates. Moreover, ISO adsorption over the β-CD surface was examined using the same approaches as the encapsulation model; however, it was energetically less favorable, with Eint values reaching only −18.42 kcal/mol. Overall, the MD-enhanced DFT results underscored the potential of β-CD as a candidate platform for ISO drug encapsulation; however, experimental validation is required to establish loading efficiency, release behavior, bioavailability, and toxicity.