Breaking barriers: enhancing solubility and dissolution of efonidipine using co-amorphous formulations

The study aims to enhance the solubility and dissolution characteristics of efonidipine hydrochloride ethanolate (EFD), an antihypertensive drug, through the co-amorphous approach. Hypertension is a prevalent chronic condition characterized by consistently elevated blood pressure. Efonidipine, a BCS class II drug, has high permeability but low solubility, limiting its therapeutic effectiveness. Amorphization, which disrupts the crystal lattice of crystalline medications, can significantly enhance drug solubility and dissolution rates. Co-amorphous systems of EFD were prepared using solvent evaporation, ball milling, and liquid-assisted grinding methods. The drug and co-former were used in a different ratio, a stoichiometric proportion known for forming stable amorphous phases. The in vitro dissolution of the co-amorphous form was evaluated and compared with the pure crystalline form of EFD. The co-amorphous system of EFD with benzoic acid demonstrated significantly higher dissolution rates in vitro compared to the pure drug. PXRD analysis confirmed the transformation from a crystalline to an amorphous state, indicated by the disappearance of sharp peaks characteristic of the crystalline form. The resultant co-amorphous system exhibited dissolution properties. The co-amorphous approach effectively improved the solubility and dissolution of efonidipine hydrochloride ethanolate. Benzoic acid, as a co-former, facilitated the formation of a stable amorphous phase, thereby enhancing the drug’s dissolution rate. The developed a co-amorphous system of EFD with benzoic acid, significantly enhancing its dissolution characteristics. PXRD analysis confirmed the amorphous nature and improved stability of the co-amorphous form, indicating its potential for better therapeutic efficacy in hypertension management.