Effect of non-cross-linked calcium on characteristics, swelling behaviour, drug release and mucoadhesiveness of calcium alginate beads

•Calcium alginate beads with different amounts of Ca2+ were prepared.•Beads washing resulted in removing non-cross-linked Ca2+ (NCL-Ca) only.•Ca2+ release was bimodal; NCL-Ca was burst-released followed by CL-Ca release.•NCL-Ca had a significant impact on bead swelling and drug release in SIFs.•NCL-Ca had a significant impact on the mucoadhesive properties of beads.

In this study, ibuprofen-loaded calcium alginate beads (CABs) with varying amounts of non-cross-linked calcium (NCL-Ca) were prepared using different washing methods. The influence of NCL-Ca on beads properties was investigated. Increasing the number or duration of washes led to significant decreases in the amount of NCL-Ca whereas the impact of the volume of washes was not significant. Approximately 70% of the initial amount of Ca2+ was NCL-Ca which was removable by washing while only 30% was cross-linked (CL-Ca). Ca2+ release from the CABs was bimodal; NCL-Ca was burst-released followed by a slower release of CL-Ca. Washing methods and the amount of NCL-Ca had significant influences on the encapsulation efficiency, beads weight, beads swelling, drug release profile and the mucoadhesiveness of CABs. This study highlighted the importance of washing methods and the amount of NCL-Ca to establish CABs properties and understand their behaviour in the simulated intestinal fluids (SIFs).