From Crystalline to Amorphous Structure of Carbamazepine Regulated by Dipeptide-Based Supramolecular Gel

Many solid drugs exist in polycrystalline state, which markedly hinder their pharmacological effectiveness. Given the designability and biocompatibility, the development of peptide-based supramolecular gel that can regulate crystal growth of drug has a strong potential. In this research, the polycrystalline drug carbamazepine (CBZ) was successfully transformed from orthorhombic dihydrate into amorphous form through the introduction of 9-fluorenylmethoxycarbonyl diphenylalanine (FmocFF) gel and co-assembled supramolecular gel was obtained. The intermolecular mechanism of structural transformation was elucidated in detail by various spectral techniques. The dihydrate of CBZ was restrained through the inhibition of hydration of the NH2 groups and the it-it stacking interaction among the aromatic rings of FmocFF and CBZ. Especially, principal component analysis (PCA), and two-dimensional correlation spectroscopy (2DCOS) techniques were conducted to analyze the time-dependent IR spectra, which indicated that the it-it stacking interaction mainly affected the FmocFF gel fiber elongation after co-assembly with CBZ. In addition, the FmocFF gel matrix significantly influenced the release behavior of CBZ in vitro, which providing theoretical guidance for the development of short-peptide assembly strategies in drug delivery materials.