The comparison of anticrystallization effects of cellulose derivatives with polyvinylpyrrolidone and poloxamer on andrographolide: In vitro and in vivo characterization

Abstract

Cellulose derivatives play important roles in the development of pharmaceutical oral solid formulations. Owing to their high molecular weight and functional groups, these polymers can interact with water-insoluble drug crystals, influencing not only the drug's physicochemical properties but also its absorption efficiency. In this study, an anticrystallization experiment was designed to compare the inhibitory effects of cellulose derivatives (methylcellulose (MC), hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC)) with those of polyvinylpyrrolidone (PVP) and poloxamer (F68) on the crystallization of model drugs (andrographolide, AG). Both in vitro characterization experiments and in vivo pharmacokinetic studies were conducted to evaluate the interaction patterns between andrographolide crystals and polymers. The results indicated that cellulose derivatives exhibited stronger anticrystallization effects, with HPMC showing the most pronounced interaction with drug crystals among all the tested polymers. HPMC significantly prolonged the crystallization time and increased the degree of supersaturation. By adsorbing onto specific crystal surfaces, HPMC was able to modulate the crystal growth orientation, reduce the contact angle, and improve the wettability of drug crystals. Furthermore, andrographolide crystals adsorbed by HPMC exhibited rapid in vitro drug release behavior and upgraded in vivo absorption efficiency, demonstrating its potential to improve the utilization of water-insoluble drugs.