Zhang, C.; Shao, H.; Han, Z.; Liu, B.; Feng, J.; Zhang, J.; Zhang, W.; Zhang, K.; Yang, Q.; Wu, S. Development and In Vitro–In Vivo Correlation Evaluation of IMM-H014 Extended-Release Tablets for the Treatment of Fatty Liver Disease. Int. J. Mol. Sci.2023, 24, 12328.
Zhang, C.; Shao, H.; Han, Z.; Liu, B.; Feng, J.; Zhang, J.; Zhang, W.; Zhang, K.; Yang, Q.; Wu, S. Development and In Vitro–In Vivo Correlation Evaluation of IMM-H014 Extended-Release Tablets for the Treatment of Fatty Liver Disease. Int. J. Mol. Sci. 2023, 24, 12328.
Zhang, C.; Shao, H.; Han, Z.; Liu, B.; Feng, J.; Zhang, J.; Zhang, W.; Zhang, K.; Yang, Q.; Wu, S. Development and In Vitro–In Vivo Correlation Evaluation of IMM-H014 Extended-Release Tablets for the Treatment of Fatty Liver Disease. Int. J. Mol. Sci.2023, 24, 12328.
Zhang, C.; Shao, H.; Han, Z.; Liu, B.; Feng, J.; Zhang, J.; Zhang, W.; Zhang, K.; Yang, Q.; Wu, S. Development and In Vitro–In Vivo Correlation Evaluation of IMM-H014 Extended-Release Tablets for the Treatment of Fatty Liver Disease. Int. J. Mol. Sci. 2023, 24, 12328.
Abstract
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.
Keywords
IMM−H014; extended–release tablet; hydrophilic polymers; in vitro−in vivo correlation; non–alcoholic fatty liver disease
Subject
Medicine and Pharmacology, Pharmacy
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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