Mechanistic insight into gel-induced aggregation of amorphous curcumin during dissolution process
Amorphous curcumin (CUR) exhibited a decreased dissolution rate in comparison with the crystalline counterpart due to its gel formation during dissolution. The main purpose of the present study is to explore the mechanism of such gelation phenomenon. It was found that the dissolution of amorphous CUR and gel properties were influenced by the temperature and pH of the media. The formed gels were characterized by TPA, SEM, DSC, XRPD, FTIR and PLM. The results indicated that the gelation process led to the formation of a porous structure in which water molecules infiltrate, and entered into its supercooled liquid state with high viscosity when contacting aqueous media, accompanied by decreased Tg and crystalline transformation.
In addition, mixing with hydrophilic excipients (such as hydrophilic silica) accelerated the gel formation of amorphous CUR, while the addition of hydrophobic excipients (such as hydrophobic silica and magnesium stearate) could effectively weaken and even eliminate the gelation, hence significantly improving its dissolution. Furthermore, according to contact angle measurement and fluorescence microscope observation, hydrophilic excipients were found to be able to accelerate water entering into the interior of amorphous CUR, hence facilitating the gelation, while hydrophobic excipients would hinder water infiltration into the powder and thus achieve degelation. In conclusion, it is important to recognize that the gelation potential of some amorphous materials should be considered in developing robust amorphous drug product of high quality and performance.
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Jiawei Han, Luyuan Li, Zunting Pang, Meiling Su, Xiaoshuang He, Shuai Qian, Jianjun Zhang, Yuan Gao, Yuanfeng Wei,
Mechanistic insight into gel-induced aggregation of amorphous curcumin during dissolution process,
European Journal of Pharmaceutical Sciences, Volume 170, 2022, 106083, ISSN 0928-0987,
https://doi.org/10.1016/j.ejps.2021.106083.
Materials
Crystalline CUR (> 98%) (Fig. S2a) was acquired from Aladdin Biochemical Technology Co., Ltd. (Shanghai, China). Methanol, Tween-80 and phosphoric acid were supplied from Nanjing Chemical Reagent Co., Ltd. (Nanjing, China). Acetonitrile of chromatographic grade were purchased by Anpel Scientific Instrument Co., Ltd. (Shanghai, China). Hydrophilic silica (Fig. S2b) and hydrophobic silica (Fig. S2c) were obtained from Evonik Degussa Co., Ltd. (Parsippany, USA). Magnesium stearate (Fig. S2d) was provided from Sunhere Pharmaceutical Excipients Co., Ltd. (Anhui, China). Deionized water was prepared by ultrapure water purification system (OLABO, Boke Instruments, Shandong, China).