Controlling swelling and release of hyaluronic acid during aqueous storage by in situ cross-linking during spray drying with alginate

The success of hyaluronic acid in over-the-counter cosmetics has been limited by its poor storage stability in aqueous environments due to premature swelling and hydrolysis. Here, hyaluronic acid was prepared in dry microparticles, encapsulated by spray-drying in patented in situ calcium cross-linked alginate microcapsules (CLAMs) to minimize swelling and release in aqueous formulations. CLAMs prepared with 61% (d.b.) hyaluronic acid (HA-CLAMs) demonstrated restricted plumping, limited water absorption capacity, and reduced leaching; retaining up to 49 % hyaluronic acid after 2 hrs in water. A new method using chelated soluble calcium resulted in particles with significantly improved hyaluronic acid retention in water. Chelate HA-CLAMs exhibited nearly full retention of hyaluronic acid over 2 hr incubation in water, and remained visibly insoluble after 1 year of storage in water at 4{degrees}C. Successful hyaluronic acid retention in CLAMs is likely due to the ability of hyaluronic acid to participate in calcium cross-linking.