Study on the crystallinity of PEG on the crystalline size of flavonoids in a crystalline dispersion system

Abstract

Poor water solubility and low bioavailability of flavonoids present significant barriers to their development and application. To address these challenges, this study explores the use of crystalline solid dispersions (CSDs) to reduce drug crystalline size and enhance in vivo bioavailability. The CSDs were prepared using a spray-drying technique with chrysin (CHY) and quercetin (QUR) as model drugs and various molecular weights of polyethylene glycol (PEG) as carriers. The authors systematically investigated the factors influencing the interaction between flavonoids and PEG in CSDs. These factors included the relationships between intermolecular interactions and PEG molecular weight, crystallinity, microstructures such as crystalline domain size and crystal morphology of the flavonoids and PEG in CSDs, crystalline size of the drug in CSDs, and in vitro dissolution rate and in vivo pharmacokinetics. Our results indicated that the interaction between flavonoids and PEG in CSDs was influenced more by PEG crystallinity than by its molecular weight. Lower crystallinity of PEG, achieved through recrystallization, led to stronger intermolecular interactions with the drugs. Specifically, PEG8000 exhibited the lowest crystallinity, indicating a higher content of PEG in the amorphous state, which interacted more effectively with the amorphous drug in CSDs. This interaction significantly inhibited drug crystallization growth, resulting in a marked decrease in drug crystalline domain size and crystalline size. Consequently, PEG8000 was identified as the optimal carrier for preparing CSDs, achieving the best cumulative dissolution percentage. The QUR/PEG8000-CSD formulation increased the cumulative dissolution percentage and oral bioavailability of QUR by 18.76 and 20.66 times, respectively, compared to QUR alone. This study demonstrates that PEG crystallinity, following recrystallization, directly affects its intermolecular interactions with the drug, thereby impacting drug crystalline size and dissolution rate.