Toward “Crystal De-Engineering”: Stable, Homogeneous Coamorphous Drug-Tannic Acid Systems Exhibiting Modified Dissolution Rates

Modifying the solid-state forms of drugs is an effective way to enhance their physicochemical properties, such as solubility and stability. While the conventional cocrystal approach in crystal engineering seeks to alter the crystal packing of drugs, coamorphous solid formulation aims to inhibit crystal formation altogether. Here, we report the coamorphous formulations of two poorly aqueous soluble drugs, clonixin (CLX) and niflumic acid (NIF), and a moderately soluble drug, ciprofloxacin (CIP), with a biocompatible coformer, tannic acid (TA), which is a plant-based tannin derivative. The drug-co-former systems prepared by slow solvent evaporation were characterized to be single-phase coamorphous systems (CAMS) by powder X-ray diffraction (PXRD) and differential scanning calorimetric (DSC) analysis. These coamorphous systems remained stable for over ∼6 or 12 months, as investigated periodically by PXRD. Further, the domain-level homogeneity of the coamorphous glassy solids was characterized by energy dispersive X-ray (EDX) mapping. Computational studies reveal that the drug-TA complexes are stabilized by hydrogen bonding and π–π interactions, leading to host–guest binding energies of −38.65, −10.51, and −10.12 kcal/mol for the most stable conformations of the CIP-TA, CLX-TA, and NIF-TA complexes. Dissolution rate studies show enhanced drug release in CAMS of CLX-TA and NIF-TA and suppressed but consistent release in CIP-TA CAMS. Thus, we propose tannic acid as a promising coformer for “crystal de-engineering” of drugs.