Preparation, Crystal Structures, and Oral Bioavailability of Two Cocrystals of Emodin with Berberine Chloride

Two cocrystals of emodin (EM) with berberine chloride (BER), EM-BER (1) and 2EM-BER-EtOH (2), were prepared and characterized. There exist reliable O-H···Cl– hydrogen-bonding interactions between the 2-hydroxyl group of emodin and chloride anion. Various π–π interactions dominate the packing structures of 1 and 2. In 1, emodin molecules stack into a supramolecular layer through π–π interactions while π–π interactions between berberine cations also result in a similar layer. In 2, berberine cation simultaneously interacts with two different emodin through π–π interactions to give rise to a 1D chainlike array. Cocrystals 1 and 2 present a low moisture adsorption curve in the range of 0–95% relative humidity values at 25 °C. The sustained release of berberine chloride in pure water could be achieved after forming cocrystals 1 and 2. Emodin in the form of cocrystals 1 and 2 has a higher Cmax and AUC compared with pure emodin.