Preparation and in vitro characterization of pH/(Na + ) dual sensitive ketoprofen calcium alginate gel beads using multiple hydrophilic polymers

Purpose: To prepare pH/(Na + ) sensitive calcium alginate beads encapsulating ketoprofen (KPF) with different formulations and conditions and investigate the release behaviors under different pH and (Na + ). Methods: Beads formulation was obtained by ionotropic gelation method applying the sodium alginate with various hydrophilic polymers and CaCl2 solution. Poly(vinyl pyrrolidone) (PVP), hydroxyl propyl methyl cellulose (HPMC) and gum xanthan (GX) were added in different formulations. Results: PVPs could eliminate structural bubbles created in the preparation and enhance encapsulation efficiency (EE). Diameters of the beads were increased with more components added. Higher concentration of sodium alginate (SA), lower KPF/SA ratio and longer curing time devoted to slower drug release. PVP could accelerate the drug release in water. HPMC hindered drug releases while GX accelerated the release in simulated gastric fluid (SGF). Three-gel beads had greater dissolution rates in SGF compared to one-gel beads and lower release speeds in simulated intestinal fluid (SIF). The drug release was relatively fast only under the condition of high pH with high (Na + ), the speed was correlated with (Na + ). High affinity of phosphate radicals with Ca-Alg was confirmed through swelling test. With more components added, the surface of bead was more uneven and had more creases. Conclusions: This kind of beads with sensitivities of pH and (Na + ) could be a potential enteric dosage form. EE and release in water and SGF could be enhanced by PVPs while the other hydrophilic polymers retarded the release speed. HPMC can reduce the cumulative released drug to smaller than 10% in SGF. Release mechanism in water and SGF was fit to Ficken diffusion. KPF release could be adjusted by pH and (Na + ).