Exploration of enalapril-lacidipine co-amorphous system with superior dissolution, in vivo absorption and physical stability via incorporated into mesoporous silica

Abstract

In the present study, enalapril (ENP) was taking as a potential co-former to fabricate co-amorphous system with lacidipine (LCDP). The ENP/LCDP co-amorphous system was firstly prepared with or without mesoporous SiO₂ and characterized by DSC, XRD and SEM technologies. The potential molecular interactions were evaluated by FTIR spectrums. Furthermore, the dissolution and pharmacokinetics behavior of various formulations were also carried out. It was demonstrated that the completely co-amorphization was obtained at ENP/LCDP 2:1 molar ratio by the intermolecular interactions between ENP and LCDP. The ENP/LCDP co-amorphous system significantly improve the dissolution rate of LCDP and ENP respectively. Compared to the naked ENP/LCDP co-amorphous system, remarkable enhancement of dissolution rate and bioavailability of model drugs was observed by incorporated the co-amorphous system into mesoporous SiO₂, and a superior physical stability was also observed after accelerated study. Raman mapping revealed that the less microstructure phase separation could be the main reason for the better stability in presence of mesoporous SiO₂. In conclusion, ENP could be successfully used as a potential co-former to fabricate co-amorphous system with poorly water-soluble drugs and collaborates the co-amorphous with mesoporous SiO₂ become a promising strategy to achieve stable amorphous formulation for further enhancement of dissolution rate and bioavailability.