In vitro and in vivo evaluation of a sustained-release once-a-day formulation of the novel antihypertensive drug MT-1207

Vrettos, Napoleon-Nikolaos; Wang, Peng; Zhou, Yan; Roberts, Clive J.; Xu, Jinyi; Yao, Hong; Zhu, Zheying

Abstract

Hypertension is one of the most common chronic cardiovascular disorders. Sustained-release formulations are developed to maintain drug therapeutic levels throughout the treatment of hypertension, to promote patient compliance and improve patient outcomes. We have developed and tested in in vivo trials a once-a-day tablet formulation for the novel antihypertensive drug MT-1207. The tablets based upon a hydrophilic polymer matrix underwent post-compression parameter and physicochemical characterisations, along with in vitro drug release testing. The most promising formulation containing 31% w/w HPMC K15M gave a 24-hour release of MT-1207 with an almost constant release rate up to 20 hours. Follow in in vivo studies were carried out in Beagle dogs for the optimised sustained-release tablets in comparison to immediate-release tablets. The results showed that a sustained release of MT-1207 from the new formulation was achieved with a drug t1/2 2–2.5 times longer than the immediate-release tablets. Moreover, the AUC0-24h values of both sustained- and immediate-release tablets were identical at the same dose of 30 mg, indicating that the same amount of drug was absorbed in each case. For treatments based upon MT-1207, this development is significant for future commercial exploitation via scale-up and further trials, and for improved patient outcomes.

Citation

Vrettos, N.-N., Wang, P., Zhou, Y., Roberts, C. J., Xu, J., Yao, H., & Zhu, Z. (2021). In vitro and in vivo evaluation of a sustained-release once-a-day formulation of the novel antihypertensive drug MT-1207. Pharmaceutical Development and Technology, 26(3), 349-361. https://doi.org/10.1080/10837450.2021.1872087

• Journal Article Type: Article
• Acceptance Date: Jan 2, 2021
• Online Publication Date: Jan 13, 2021
• Publication Date: Jan 13, 2021
• Deposit Date: Jan 17, 2021
• Publicly Available Date: Jan 14, 2022
• Journal: Pharmaceutical Development and Technology
• Print ISSN: 1083-7450
• Electronic ISSN: 1097-9867
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 3
• Pages: 349-361
• DOI: https://doi.org/10.1080/10837450.2021.1872087
• Keywords: Pharmaceutical Science; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/5234666
• Publisher URL: https://www.tandfonline.com/doi/full/10.1080/10837450.2021.1872087
• Additional Information: This is an Accepted Manuscript of an article published by Taylor & Francis in Pharmaceutical Development and Technology on 13/1/2021, available online: http://www.tandfonline.com/10.1080/10837450.2021.1872087