Simultaneous Improvements of Physicochemical Properties and Anti-Microbial Activity of Berberine via Forming Salt with Gallic Acid

Abstract

Implementing combination medication through crystal engineering technology receives increasing attention from researchers due to improvements in the clinical treatment effects as well as the physicochemical properties of the drug. Berberine (BER) is commonly used to treat gastroenteritis and bacterial diarrhea, with the problems of poor solubility and low oral bioavailability. Recently, it is found that gallic acid (GA) also has anti-inflammatory and anti-bacterial activities. Therefore, if the above-mentioned two ingredients can be combined, it is possible to enhance the therapeutic effects and physicochemical properties of BER. Inspired by this, 8-hydroxy-7,8-dihydroberberine (8H-HBER) in this study is employed to react with gallic acid to yield BER gallate dihydrate (2BER-2GA-2 W). Furthermore, dissolution experiments demonstrate that the maximum apparent solubility (MAS) of 2BER-2GA-2 W in dilute hydrochloric acid solution medium (pH 1.2) has increased by 7 times compared to the commercial form of BER, because of avoiding the common-ion effect. Moreover, 2BER-2GA-2 W has also obviously enhanced stability relative to the commercial form of BER. In addition, 2BER-2GA-2 W has a better inhibitory effect on Staphylococcus aureus (S. aureus) relative to the commercial form of BER. Hence, 2BER-2GA-2 W will be a promising solid-state form of BER for its further development.