Fabrication, characterization and application of ultra-high concentration calcium alginate beads

Calcium alginate hydrogel beads have been widely studied as a carrier matrix for the delivery of food and pharmaceutical compounds due to its non-toxicity, renewability, and the ease of forming hydrogel beads with divalent cations. However, alginate hydrogel beads are known to have low stiffness, i.e., Young’s modulus < 1 MPa, and a short dissolution time of between 1 h to 2 h in the gastrointestinal fluid thus limiting some applications that require prolonged release of compounds. This study was aimed to fabricate calcium alginate beads with high stiffness and extended dissolution profile by increasing the alginate concentration beyond the critical viscosity limit (approximately 5,000 mPa.s) that can be processed using the existing extrusion-dripping system. A temperature-controlled extrusion-dripping method was developed and the feasibility of producing alginate beads at ultra-high concentration (UHC) with an initial viscosity up to 353,000 mPa.s was studied for the first time. The operating temperatures studied were ranged from 40°C to 80°C. Fourier-transform infrared spectroscopy (FTIR) analysis indicated that the chemical properties of the alginate gels were not affected by the operating temperature. The UHC beads have an extraordinary internal structure with thick calcium-alginate matrices and large pores in between the matrices. The dissolution time of the UHC calcium-alginate beads (i.e., 10% w/v) was 2.5 times longer than that of the normal beads (i.e., 2% w/v). The UHC beads had a Young’s modulus value up to 3.6 MPa, which was approximately 8 times higher than the normal beads. The Young’s modulus of the drug loaded UHC alginate beads was found to remain intact after 2.5 h in simulated intestinal fluid (SIF), whereas the normal beads (i.e., 2% w/v) were disintegrated after 30 min. The release of hydrophilic drugs (i.e., paracetamol and methylene blue) from UHC beads was approximately 2.5 times longer than the normal beads. The release kinetics of paracetamol fitted well with the first-order model (r² > 0.96) and followed the Fickian mechanism (n < 0.43). The release kinetics of methylene blue fitted well with the Korsmeyer-peppas model (r² > 0.98) and followed the non-Fickian mechanism (0.43 < n < 0.85). On the other hand, the release kinetics of the water-insoluble drug (i.e., ketoprofen) fitted well with the Korsmeyer-peppas model (r² > 0.98) and followed the Case-II transport mechanism (n > 0.85). It is worth noting that the ketoprofen release from UHC beads exhibited a time lag of 60 min. These findings show that the UHC calcium-alginate beads with high stiffness and extended dissolution profile can be prepared without the need for chemical modification, additional processing steps, or incorporation of additives. The UHC calcium-alginate beads open up the windows of opportunities for applications in sustained delivery of drugs and food ingredients.