This study aimed to develop extended–release tablets containing 25 mg IMM−H014, an original drug formulated by a direct powder pressing method based on pharmaceutical–grade hydrophilic matrix polymers, such as hydroxypropyl methylcellulose, to establish an in vitro−in vivo corre-lation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were de-termined in five dissolution media, in which the drug released from the hydrophilic tablets fol-lowed Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate buffer saline medium (pH 7.5) for further 24 h. Accelerated stability studies (40°C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmaco-kinetics study in beagle dogs showed that compared to the IMM−H014 immediate release prep-aration, the maximum plasma concentration of the extended release (ER) preparation was sig-nificantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on an area under curve, indicating that the optimal formulation has an obvious ER profile. And a good IVIVC was established, which could be used to predict in vivo pharmacokinetics from the formulation composition.

This study aimed to develop extended-release tablets containing 25 mg IMM-H014, an original drug formulated by a direct powder pressing method based on pharmaceutical-grade hydrophilic matrix polymers such as hydroxypropyl methylcellulose, to establish an in vitro–in vivo correlation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single-factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were determined in five dissolution media, in which the drug released from the hydrophilic tablets followed the Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate-buffered saline medium (pH 7.5) for a further 24 h. Accelerated stability studies (40 °C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmacokinetics study in beagle dogs showed that compared to the IMM-H014 immediate release preparation, the maximum plasma concentration of the extended-release (ER) preparation was significantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on the area under curve, indicating that the optimal formulation has an obvious ER profile, and a good IVIVC was established, which could be used to predict in vivo pharmacokinetics based on the formulation composition.

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.