Natural Clinoptilolite as a Functional Mineral Component in Alginate Hybrid Microcapsules for Controlled Amoxicillin Release

Background/Objectives: Natural clinoptilolite–amoxicillin hybrids (CNZ@AMOX) were incorporated into alginate microcapsules via ionic gelation to develop a hybrid mineral–polymer delivery system for the controlled release of amoxicillin. Methods: A face-centered central composite design combined with response surface methodology (FCCD-RSM) was utilized to assess the effects of the zeolite/sodium alginate ratio, alginate concentration, calcium chloride concentration and curing time on the encapsulation efficiency (EE), sphericity factor (SF), and roundness (Rn). Results: The EE ranged from 5.9% to 91.3%, depending on the formulation composition. Numerical optimization identified the optimal conditions as 70.962% EE, 0.05 SF and 1.00 Rn, with a desirability score of 0.873. The incorporation of natural clinoptilolite improved microcapsule structural integrity and reduced the initial burst release by modulating diffusion pathways within the hybrid matrix. The optimized CNZ@AMOX exhibited pH-dependent release behavior, with minimal drug release in simulated gastric fluid (SGF) and diffusion-controlled release in simulated intestinal fluid (SIF), which was best described by the Korsmeyer–Peppas model. Conclusions: These findings demonstrate that zeolite–alginate hybrid microcapsules represent promising inorganic–organic composite carriers for the pH-responsive and controlled delivery of AMOX.