Preparation of semaglutide long-acting injectable microcapsules with physicochemical properties, long-term stability, and pharmacokinetics and pharmacodynamics

Purpose: To develop once-a-month long acting semaglutide injectable, its manufacturing process was optimized. The final product to be selected based on improved pharmacokinetics-pharmacodynamics (PK/PD) profiles and decent stability, providing it an advantage over the existing market products. Methods: Semaglutide depot microcapsules were prepared using a double emulsion (W/O/W) process. Effects of different polymers, their ratios, and the amounts of solvents and additives used on the microcapsules’ PK/PD and long-term stability were evaluated. Moreover, the influence of physicochemical properties on the in vitro and in vivo release profiles, weight loss, diabetic control, and long-term stability of the product were investigated. Results: Once-a-month single-dose semaglutide microcapsule was developed, which effectively suppressed the initial burst release down to ⁓10%, maintained therapeutic plasma drug concentration for a month, and improved the surface appearance of microcapsules. The weight loss was achieved up to 15.50%, while the serum insulin level could be elevated by 136% within a month when the optimum formulation was used. Conclusion: The formulation could potentially be an one-month sustained-release injectable therapy with the expectation of anti-obesity effect. It also showed enough assay and stability and hence the SGT-loaded microcapsules could be developed successfully with decent quality and in vivo animal performances.