Effect of drug-coformer interactions on drug dissolution from a coamorphous in mesoporous silica

Abstract

In this study, the molecular state of ritonavir (RTN)-saccharin (SAC) coamorphous incorporated into mesoporous silica by solvent evaporation and the effect of SAC on the RTN dissolution from mesopores were investigated. The amorphization of RTN-SAC was confirmed as a halo pattern in powder X-ray diffraction measurements and a single glass transition event in the modulated differential scanning calorimetry (MDSC) curve. ¹³C solid-state NMR spectroscopy revealed a hydrogen bond between the thiazole nitrogen of RTN and the amine proton of SAC. The glass transition of the RTN-SAC coamorphous in mesoporous silica was not found in the MDSC curve, indicating that RTN and SAC were monomolecularly incorporated into the mesopores. Solid-state NMR measurements suggested that the co-incorporation of SAC into the mesopores decreased the local mobility of the thiazole group of RTN via hydrogen bond formation. The RTN-SAC 1:1 coamorphous in mesoporous silica retained the X-ray halo-patterns after 30 d of storage, even under high temperature and humidity conditions. In the dissolution test, the RTN-SAC 1:1 coamorphous in mesoporous silica maintained RTN supersaturation for a longer time than the RTN amorphous in mesoporous silica. This study demonstrated that the drug-coformer interaction within mesoporous silica can significantly improve drug dissolution.

Keywords: Coamorphous; Dissolution; Hydrogen bond; Mesoporous silica; Mobility; Supersaturation.