Pharmacokinetic Evaluation Study of Chlorogenic Acid Sustained‐Release Capsules Across Species (Rats and Beagle Dogs)

Chlorogenic acid (CA) exhibits significant anti-inflammatory potential for acute disease treatment, but suffers from low oral bioavailability and nonlinear pharmacokinetic behavior due to hepatic rapid metabolism, low solubility and instability. This study developed a sustained-release capsule (CA-CAPC, 1:2) containing both immediate-release CA powder and sustained-release CA-phospholipid complex (CA-PC, 1:1) to enhance bioavailability. Comprehensive characterization (IR, DSC, hygroscopicity, angle of repose, and in vitro dissolution) confirmed the stable formation of the complex through hydrogen bonding and hydrophobic interactions, with improved flowability and low hygroscopicity. The established UPLC-MS/MS method showed good linearity (r² = 0.9967) in the range of 12.5-3200 ng/mL, and its accuracy, precision, recovery rate, matrix effect, and stability all met the requirements for biological sample analysis. Quantify the concentration of CA in plasma using this validated UPLC-MS/MS method. Pharmacokinetic studies in beagle dogs showed CA-CAPC significantly increased AUC_(0-t), AUC_(0-∞), and C_max, advanced T_max, and prolonged MRT_(0-t) and T_1/2 versus CA or CA-PC, indicating enhanced absorption and extended therapeutic coverage. Cross-species consistency in rats further validated the formulation. The CA-CAPC strategy leverages rapid onset from CA powder and sustained release from CA-PC, overcoming CA's pharmacokinetic limitations and providing a promising preclinical foundation for acute disease therapy.