Formulation development and evaluation of spray-dried astaxanthin-loaded self-microemulsifying delivery systems in tablets

An antioxidant activity of astaxanthin (AST) is one of the desirable bioactive properties for nutraceutical and pharmaceutical products. However, poor aqueous solubility and high possibility of degradation of AST limit its efficacy of oral absorption and bioavailability. Therefore, the aim of this study was to develop and optimize the spray-dried astaxanthin-loaded self-microemulsifying delivery system (SMEDS) in tablets to improve solubility, dissolution, and bioavailability of AST. By using a mixture design, liquid AST SMEDS (L-AST SMEDS) formulations containing rice bran oil, Kolliphor® RH40, and Span® 20 were optimized based on the desirability function. The optimal L-AST SMEDS composed of rice bran oil (33.67%), Kolliphor® RH40 (34.70%), and Span® 20 (31.63%) successfully provided acceptable physicochemical properties of the self-assembling microemulsion. Furthermore, the optimized L-AST SMEDS was mixed with a precipitation inhibitor (PI) (hydroxypropyl methylcellulose, HPMC, or polyvinyl alcohol, PVA) and a solid carrier (microcrystalline cellulose, MCC) then solidified into powders by spray drying. The spray-dried AST SMEDS powders with desirable physicochemical properties were satisfactorily obtained. Subsequently, solid AST SMEDS powder was thoroughly blended with MCC, Aerosil® 200, croscarmellose sodium, and stearic acid followed by compressing into AST SMEDS tablets F1 (HPMC) or F2 (PVA). According to the in vitro dissolution study, the release rates of F1 and F2 tablets were slightly slower than that of L-AST SMEDS in pH 1.2; however, their release profiles were similar to that of L-AST SMEDS in pH 6.8. From Caco-2 cells studies, AST SMEDS tablets both F1 and F2 exhibited concentration-dependent cellular antioxidant activities, and their cellular uptakes (absorption efficiencies) were significantly higher than AST raw material. This research suggested that our successfully developed SMEDS tablets could be an appropriate platform to deliver a highly lipophilic compound like AST and improve loading capacity, dissolution profiles, cellular uptake, and oral bioavailability of AST.