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Alginate (ALG) cross-linking by CaCl₂ is a promising strategy to obtain modified-release drug delivery systems with mucoadhesive properties. However, current technologies to produce CaCl₂ cross-linked alginate microparticles possess major disadvantages, such as a poor encapsulation efficiency of water-soluble drugs and a difficulty in controlling the process. Hence, this study presents a novel method that streamlines microparticle production by spray drying; a rapid, continuous, reproducible, and scalable technique enabling obtainment of a product with low moisture content, high drug loading, and a high production yield. To model a freely water-soluble drug, metformin hydrochloride (MF) was selected. It was observed that MF was successfully encapsulated in alginate microparticles cross-linked by CaCl₂ using a one-step drying process. Modification of ALG provided drug release prolongation-particles obtained from 2% ALG cross-linked by 0.1% CaCl₂ with a prolonged MF rate of dissolution of up to 12 h. Cross-linking of the ALG microparticles structure by CaCl₂ decreased the swelling ratio and improved the mucoadhesive properties which were evaluated using porcine stomach mucosa.

Calcium Chloride Modified Alginate Microparticles Formulated by the Spray Drying Process: A Strategy to Prolong the Release of Freely Soluble Drugs