Design, molecular docking, in vitro and in vivo evaluation of dimenhydrinate-cyclodextrin complex for fast-disintegrating tablet

Introduction: This study aimed to formulate and evaluate dimenhydrinate (DMH) as fastdisintegrating tablets (FDTs) complexed with β-cyclodextrin (β-CD) to enhance its solubility, dissolution profile, and pharmacological performance.
Methods: A DMH:β-CD inclusion complex was prepared at a 1:1 molar ratio using the kneading method. Characterization was performed through phase solubility studies, FTIR analysis, molecular docking, and in vitro dissolution testing. FDTs were developed using various superdisintegrants and assessed for quality attributes of a tablet, including hardness, friability, wetting time, water absorption ratio, and drug content.
Results: Phase solubility and FTIR analyses confirmed the formation of a stable DMH:β-CD complex. Molecular docking indicated a binding affinity of -4.2 kcal/mol between β-CD and diphenhydramine. Among the FDT formulations, CP3 containing 9% crospovidone showed the best performance, with a disintegration time of 4.3 seconds and the highest drug release rate. In vivo pharmacological tests demonstrated enhanced sedative and antiemetic activities of the optimized FDTs compared to conventional DMH formulations.
Discussion: The findings suggest that cyclodextrin-based complexation combined with orodispersible tablet technology can significantly enhance DMH's pharmacological efficacy and patient compliance. However, additional investigations on long-term stability, pharmacokinetics, and clinical scalability are warranted.
Conclusion: The DMH:β-CD FDTs developed in this study offer promising improvements in solubility, dissolution, and therapeutic performance, indicating their potential for better clinical outcomes and patient acceptability.