Marianna Ivone, Vita D’Amico, Nunzio Denora, Antonio Lopalco, Rosa Maria Iacobazzi, Angela Lopedota
This study aimed to develop fast-disintegrating cocoa-based microbeads containing β-galactosidase, designed for the management of lactose intolerance in pediatric patients. Microbeads were produced using prilling/vibration technology, employing Kollicoat® Smartseal 30D as the polymer matrix and hydroxypropyl-β-cyclodextrin (HP-β-CD) as a cryoprotectant to preserve enzyme activity during preparation. The process demonstrated high robustness, yielding 91.5% and achieving an encapsulation efficiency of 98.8%. Residual enzyme activity after encapsulation and lyophilization remained high (93.7%), demonstrating the protective effect of HP-β-CD. The microbeads exhibited spherical morphology, narrow size distribution, and excellent flow properties, making them suitable for single-dose delivery systems. They disintegrated completely in milk within 2 min, ensuring immediate enzyme availability. In vitro studies simulating postprandial gastric digestion demonstrated over 90% of lactose hydrolysis within 120 min. Furthermore, the formulation effectively preserved enzymatic stability during storage under different temperature and humidity conditions, maintaining over 90% residual activity after 90 days, whereas the free enzyme showed a progressive loss of activity. Overall, this formulation represents a promising pediatric-friendly oral delivery system that combines enzymatic stability, rapid disintegration in milk, and effective lactose hydrolysis.