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

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 t_1/2 2–2.5 times longer than the immediate-release tablets. Moreover, the AUC_0-24h 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.

Keywords:

• MT-1207
• sustained-release tablets
• hydrophilic matrix
• drug release
• pharmacokinetics

Acknowledgements

The authors thank Professor Xijin Chen (School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University) for his help with the in vivo animal studies on the pharmacokinetics of MT-1207. Also, we thank Mr Colin Wills (School of Pharmacy, The University of Nottingham) for his help with the tabletting process. Finally, we are grateful to the Nanoscale and Microscale Research Centre (nmRC) (The University of Nottingham) for providing us with free access to the scanning and electron microscope that was used in the present study.

Disclosure statement

The authors declare that Shenyang Haiwang Biotechnology Co., Limited which funded the present study is the patent holder of MT-1207 agent.

Additional information

Funding

The present work was funded by Shenyang Haiwang Biotechnology Co., Limited (Shenyang, China, license number 91210102 MAOP4EKG8Y).