Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers

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

Abstract

In the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers, namely polyethylene oxide and Kollidon® SR. A factorial experiment was conducted, and the results revealed a non-effervescent gastroretentive layer that, unlike most gastroretentive layers reported in the literature, was easy to prepare, and provided immediate tablet buoyancy (mean floating lag time of 1.5 s) that lasted over 24 h in fasted state simulated gastric fluid (FaSSGF) pH 1.6, irrespective of the drug layer, thereby allowing a 24-hour sustained release of MT-1207 from the drug layer of the tablets. Furthermore, during in vitro buoyancy testing of the optimised bilayer tablets in media of different pH values (1.0, 3.0, 6.0), the significant difference (one-way ANOVA, p < 0.001) between the respective total floating times indicated that stomach pH effects on tablet buoyancy are important to be considered during the development of non-effervescent gastroretentive formulations and the choice of dosing regimen. To the best of our knowledge, this has not been reported before, and it should probably be factored in when designing dosing regimens. Finally, a pharmacokinetic study in Beagle dogs indicated a successful in vivo 24-hour sustained release of MT-1207 from the optimised gastroretentive bilayer tablet formulations with the drug plasma concentration remaining above the estimated minimum effective concentration of 1 ng/mL at the 24-hour timepoint and also demonstrated the gastroretentive capabilities of the hydrophilic and hydrophobic polymer combination. The optimised formulations will be forwarded to clinical development.

Citation

Vrettos, N., Wang, P., Wang, Y., Roberts, C. J., Xu, J., Yao, H., & Zhu, Z. (2023). Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers. Pharmaceutical Development and Technology, 28(8), 724-742. https://doi.org/10.1080/10837450.2023.2238822

• Journal Article Type: Article
• Acceptance Date: Jul 17, 2023
• Online Publication Date: Jul 28, 2023
• Publication Date: Oct 1, 2023
• Deposit Date: Jul 27, 2023
• Publicly Available Date: Jul 29, 2024
• Journal: Pharmaceutical Development and Technology
• Print ISSN: 1083-7450
• Electronic ISSN: 1097-9867
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 8
• Pages: 724-742
• DOI: https://doi.org/10.1080/10837450.2023.2238822
• Keywords: MT-1207; gastroretentive tablets; bilayer tablets; novel gastroretentive layer; pH effect; buoyancy
• Public URL: https://nottingham-repository.worktribe.com/output/23480562
• Publisher URL: https://www.tandfonline.com/doi/full/10.1080/10837450.2023.2238822
• Additional Information: Peer Review Statement: The publishing and review policy for this title is described in its Aims & Scope.; Aim & Scope: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=iphd20; Received: 2023-03-13; Revised: 2023-07-17; Accepted: 2023-07-17; Published: 2023-07-26