## 1 Introduction
To achieve the most effective potential prevention of drug crystallization in supersaturated solutions, it is necessary to have a thorough understanding of the nucleation kinetics and mechanisms that occur when polymers inhibit drug crystallization [14]. Molecular dynamics (MD) simulations have become essential for examining molecular structures, particularly in understanding how non-covalent adaptable networks (NANs) reorganize within amorphous formulations [15]. In MD simulations, nanoseconds (ns) are used to capture molecular interactions over very short timescales, allowing researchers to explore early-stage interactions such as the formation and dissociation of non-covalent and hydrogen bonds, as well as hydrophobic interactions between drug molecules and polymers. Although MD simulations cannot directly predict long-term behaviors, they provide valuable insights into initial stabilization mechanisms in amorphous drug formulations [16]. For instance, analyzing interaction energies and hydrogen bonds reveals the strength and type of molecular engagement, which is essential for assessing each polymer's potential to maintain the drug in a supersaturated state [17; 18]. This early understanding serves as a crucial foundation for guiding experimental validation (Figure 1). However, to fully capture long-term phenomena like crystallization, these short-term simulations need to be complemented by in-depth experimental characterization [21; 22]. Experimental approaches offer a more realistic perspective, helping to validate MD simulation results. By integrating insights from MD simulations with experimental data, researchers gain a comprehensive view of both the initial molecular interactions and the long-term stability of amorphous systems [23]. This combination of simulation and experimental data allows for a more accurate assessment of how NANs contribute to stabilizing amorphous formulations over time. This integrated approach, as highlighted by [PERSON] and [PERSON] (2023), not only deepens our understanding of NANs but also aids in selecting the optimal polymers to maintain drug solubility and stability, resulting in more effective and reliable pharmaceutical formulations [24]. In this study, we applied MD simulations to investigate the interaction between a drug and a polymer in supersaturated drug solutions, which affects crystallization inhibition. RTV was chosen as a model drug due to its low solubility and poor oral absorption, while PVP K30 and Eudragit L100 were selected for their ability to prevent crystallization in such solutions [25]. The statement that \"It is difficult to examine these interactions using experimental methods\" refers to challenges such as the rapid crystallization process and the dynamic nature of drug-polymer interactions, which are difficult to capture with traditional experimental techniques [26]. Additionally, experimental methods like HPLC and X-ray diffraction cannot fully observe these complex molecular-level interactions, whereas MD simulations provide valuable insights but are limited by assumptions and idealized conditions. These limitations of both experimental and computational approaches should be considered when interpreting the findings. Figure 1: Integrating experimental and molecular dynamics approaches for characterizing ASD formulations [19; 20].