Enhanced Apigenin Dissolution and Effectiveness Using Glycyrrhizin Spray-Dried Solid Dispersions Filled in 3D-Printed Tablets

Abstract

This study aimed to prepare glycyrrhizin–apigenin spray-dried solid dispersions and develop PVA filament-based 3D printlets to enhance the dissolution and therapeutic effects of apigenin (APN); three formulations (APN1–APN3) were proportioned from 1:1 to 1:3. A physicochemical analysis was conducted, which revealed process yields of 80.5–91% and APN content within 98.0–102.0%. FTIR spectroscopy confirmed the structural preservation of APN, while Powder-XRD analysis and Differential Scanning Calorimetry indicated its transformation from a crystalline to an amorphous form. APN2 exhibited improved flow properties, a lower Angle of Repose, and Carr’s Index, enhancing compressibility, with the Hausner Ratio confirming favorable flow properties for pharmaceutical applications. In vitro dissolution studies demonstrated superior performance with APN2, releasing up to 94.65% of the drug and revealing controlled release mechanisms with a lower mean dissolution time of 71.80 min and a higher dissolution efficiency of 19.2% compared to the marketed APN formulation. This signified enhanced dissolution and improved therapeutic onset. APN2 exhibited enhanced antioxidant activity; superior cytotoxicity against colon cancer cells (HCT-116), with a lower IC50 than APN pure; and increased antimicrobial activity. A stability study confirmed the consistency of APN2 after 90 days, as per ICH, with an f2 value of 70.59 for both test and reference formulations, ensuring reliable pharmaceutical development. This research underscores the potential of glycyrrhizin–apigenin solid dispersions for pharmaceutical and therapeutic applications, particularly highlighting the superior physicochemical properties, dissolution behavior, biological activities, and stability of APN2, while the development of a 3D printlet shell offers promise for enhanced drug delivery and therapeutic outcomes in colon cancer treatment, displaying advanced formulation and processing techniques.