Sustained-release alginate-chitosan pellets prepared by melt pelletization technique

Context: Alginate-chitosan pellets prepared by extrusion-spheronization technique exhibited fast drug dissolution.

Objective: This study aimed to design sustained-release alginate pellets through rapid in situ matrix coacervation by chitosan during dissolution.

Methods: Pellets made of alginate with chitosan and/or calcium acetate were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed such reaction to occur only in dissolution phase.

Results: Drug release was retarded in pH 2.2 medium when pellets were formulated with calcium acetate or chitosan till a change in medium pH to 6.8. The sustained-release characteristics of calcium alginate pellets were attributed to pellet dispersion and rapid cross-linking by soluble Ca²⁺ during dissolution. The slow drug release characteristics of alginate-chitosan pellets were attributed to polyelectrolyte complexation and pellet aggregation into swollen structures with reduced erosion. The drug release was, however, not retarded when both calcium acetate and chitosan coexisted in the same matrix as a result of chitosan shielding of Ca²⁺ to initiate alginate cross-linkages and rapid in situ solvation of calcium acetate induced fast pellet dispersion and chitosan losses from matrix.

Conclusion: Similar to calcium alginate pellets, alginate-chitosan pellets demonstrated sustained drug release property though via different mechanisms. Combination of alginate, chitosan and calcium acetate in the same matrix nevertheless failed to retard drug release via complementary drug release pattern.