Preparation and characterization of andrographolide nano-cocrystals using hummer acoustic resonance technology

Abstract

Andrographolide (AG) is a diterpene lactone with significant anti-inflammatory and antitumor activities. However, the poor water solubility limits its clinical application. An andrographolide-salicylic acid (AG-SLA) nano-cocrystal delivery system was rapidly developed using hummer acoustic resonance (HAR) technology in this research. The formulation of the AG-SLA nano-cocrystal suspension and the process parameters for HAR technology were optimized in a high-throughput manner, with SDS-Tween 80 as the optimal composite stabilizer. Nano-cocrystal suspension of AG-SLA with an average particle size of 190 nm were successfully prepared, and then the optimal formulation were tenfold scaled up. Freeze-drying was adopted to solidify the nano-cocrystal and improve its stability. Various analytical techniques were used to characterize the particle size and solid state of the nano-cocrystals. The high-energy input from the HAR instrument induced partial amorphization of the nano-cocrystals, as confirmed by PXRD and DSC analyses. Saturation solubility experiments demonstrated that the solubility in pH 1.2 hydrochloric acid buffer and pH 6.8 phosphate buffer increased by 5.74 times and 6.82 times, respectively, compared to raw AG. In vitro dissolution tests indicated that the cumulative release over 120 min in pH 1.2 hydrochloric acid buffer and pH 6.8 phosphate buffer increased by 1.60 times and 1.88 times, respectively, compared to raw AG.