| Summary: | Background: Hypertension is a common chronic disease that increases the risk of cardiovascular disease. Sustained-release formulations are designed to maintain therapeutic levels of drugs throughout the course of hypertension treatment, thereby increasing patient compliance and enhancing patient outcomes. MT-1207 is a novel multi-target antihypertensive agent that has been indicated to be effective in treating hypertension.
Objective: This project is focused on the optimisation of a once-a-day oral sustained-release tablet of MT-1207 that may provide better properties, in vitro and in vivo sustained-release behaviour than the one developed previously by Vrettos et al.
Design and methods: Tablets containing different polymers, including HPMC K15M, HPMC K100M, Kollidon® SR and, Eudragit® RSPO, as well as combinations of them were prepared and characterised in terms of pre- and post-compression parameters, physicochemical properties and in vitro drug release. Apart from these tests, kinetic analysis was also conducted on the in vitro release data of the optimised formulation, along with in vitro release testing at 200 rpm.
Results: Each of the formulations tested in the project showed good flowability and compressibility. The most promising formulation containing 31% w/w HPMC K15M and 20%w/w Kollidon® SR provided a complete 24-hour sustained release of MT-1207 with more than 80% of the drug released at the 24-hour timepoint. The physicochemical characterisation showed that the drug was compatible with all the excipients. The drug release followed first-order model kinetics and the mechanism of release was found to be non-Fickian diffusion. Finally, the in vitro release data at 200 rpm had no statistically significant difference to those collected at 75 rpm which indicated that the tablets could probably provide a robust sustained release for in vivo study.
Conclusion: In the present study, a new 24-hour sustained-release tablet for MT-1207 was successfully optimised and could be considered for further in vivo tests.
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