Abstract
The objective of this study was to investigate the physicochemical properties, drug release and in situ depot-forming behavior of alginate hydrogel containing poorly water-soluble aripiprazole (ARP) for achieving free-flowing injectability, clinically accessible gelation time and sustained drug release. The balanced ratio of pyridoxal phosphate (PLP) and glucono-delta-lactone (GDL) was crucial to modulate gelation time of the alginate solution in the presence of calcium carbonate. Our results demonstrated that the sol state alginate hydrogel before gelation was free-flowing, stable and readily injectable using a small 23 G needle. In addition, the ratio (w/w) of PLP and GDL altered the gelation time, which was longer as the PLP content increased but shorter as the GDL content increased. The alginate hydrogel with a ratio of PLP to GDL of 15:9 had the optimal physicochemical properties in terms of a clinically acceptable gelation time (9.1 min), in situ-depot formation with muscle-mimicking stiffness (3.55 kPa) and sustained release over a two-week period. The alginate hydrogel, which is tunable by varying the ratio of PLP and GDL, could provide a controllable pharmaceutical preparation to meet the need for long-acting performance of antipsychotic drugs like ARP.