Formulation and Optimization of Sustained-Release Gastroretentive Microspheres of Vonoprazan Using Box–Behnken Design
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Abstract
Background: Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) with potent acid-suppressive activity; however, its therapeutic efficacy may be limited by rapid gastric emptying. The present study aimed to formulate and optimize sustained-release gastroretentive microspheres of vonoprazan using the ionotropic gelation technique to prolong gastric residence time and achieve controlled drug release.
Methods: Gastroretentive microspheres were prepared using sodium alginate and HPMC K100M as matrix-forming polymers and calcium chloride as the cross-linking agent. A three-factor, three-level Box–Behnken design was employed to optimize sodium alginate concentration (1–3% w/v), HPMC K100M concentration (0.5–1.5% w/v), and calcium chloride concentration (2–6% w/v). The formulations were evaluated for encapsulation efficiency, particle size, percentage yield, drug loading, swelling index, floating behavior, and in vitro drug release. Numerical optimization was performed using the desirability function approach.
Results: The encapsulation efficiency ranged from 85.18% to 94.21%, particle size varied between 171 and 221 nm, and cumulative drug release after 12 h ranged from 66.7% to 79.8%. ANOVA confirmed that the developed models were statistically significant (p < 0.05), with sodium alginate concentration significantly affecting encapsulation efficiency, while sodium alginate and HPMC K100M significantly influenced particle size and drug release. The optimized formulation contained 3.0% w/v sodium alginate, 1.5% w/v HPMC K100M, and 4.123% w/v calcium chloride, with predicted values of 93.55% encapsulation efficiency, 172.83 nm particle size, and 79.80% drug release, achieving a desirability of 0.945. The optimized microspheres also demonstrated excellent floating ability, high swelling capacity, and satisfactory stability.
Conclusion: The optimized gastroretentive microspheres of vonoprazan successfully provided sustained drug release with high encapsulation efficiency and desirable physicochemical characteristics. The Box–Behnken design proved to be an effective optimization tool for developing a robust gastroretentive delivery system with potential to improve the therapeutic performance of vonoprazan.