Co-amorphization of felodipine with puerarin: Enhanced dissolution, photostability and oral bioavailability

The antihypertensive drug felodipine (FEL) suffers from poor solubility, leading to low bioavailability, and is also known to undergo photodegradation. Co-amorphous formulations represent a promising strategy for simultaneously enhancing the physicochemical properties and stability of drugs. This study aimed to develop and characterize a novel co-amorphous system composed of FEL and puerarin (PUE) to address these challenges. The screened co-amorphous with an FEL:PUE ratio of 1:2 was obtained by solvent rotary evaporation and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR), and Raman spectroscopy. The formation of co-amorphous is supported by the typical halo pattern in the PXRD, as well as a single T_g of 51.9 °C. FT-IR and Raman spectroscopy revealed that this co-amorphous supramolecular system was connected by CO···H-O and N-H···OC interactions. The results of the dissolution experiment showed that the dissolution rate of FEL was significantly accelerated after co-amorphization. By measuring the oil-water partition coefficient, increased hydrophilicity of FEL and lipophilicity of PUE in the co-amorphous form were observed. Multiple tests suggested that the co-amorphous material had superior physical stability under accelerated or illumination conditions. Encouragingly, the enhanced in vitro physicochemical properties were effectively converted into the in vivo pharmacokinetic performance with the expedited C_max, enhanced AUC_0-t and AUC_0-∞ for both FEL and PUE in co-amorphous. The current contribution not only proves that co-amorphization can improve drug bioavailability but also provides a new idea for combined treatment using traditional Chinese and chemical medicines.