Development and Evaluation of a Phospholipid Complex-Loaded SMEDDS for Enhanced Oral Delivery of H007, a Novel Anti-Hyperlipidemic Drug.

Background

H007 is a novel selective AMP-activated protein kinase (AMPK) activator with demonstrated efficacy against hyperlipidemia; however, its oral bioavailability is limited by poor solubility and low intestinal permeability. This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) incorporating a H007-phospholipid complex (H007-PC) to improve both solubility and intestinal permeability.

Methods

H007-PC-SME was prepared by integrating phospholipid complexes into an SMEDDS formulation. The formulation was optimized on the basis of emulsification efficiency, droplet size, and zeta potential, and was then evaluated for stability, in vitro drug release, and cellular uptake. Different H007 formulations were orally administered to golden hamsters to assess bioavailability, and a chylomicron flow blockade hamster model was used to evaluate lymphatic transport.

Results

The optimized H007-PC-SME showed good stability, rapid self-emulsification, and improved drug solubility. Relative to ordinary H007 tablets, the relative bioavailability of H007-SME and H007-PC-SME was 376.65% and 464.62%, respectively, when calculated from M1 exposure, and 314.01% and 463.55%, respectively, when calculated from MP exposure. When evaluated in a cycloheximide model, H007-SME and H007-PC-SME increased the lymphatic transport fraction of M1 from approximately 0% to 22% and 54%, and that of MP from approximately 1% to 28% and 52% compared with ordinary H007 tablets.

Conclusions

H007-PC-SME combines stable phospholipid complex formation with strong self-emulsification performance and effective drug dissolution. By overcoming the intrinsic limitations of the H007 active pharmaceutical ingredient and ordinary H007 tablets, this formulation improves membrane permeability and lymphatic transport, thereby enhancing oral bioavailability and therapeutic potential. The formulation shows good stability and acceptable in vitro biocompatibility under the tested conditions. The preparation process is straightforward, reproducible, and suitable for further pharmaceutical development.