Calcium alginate multi-unit oral dosage form for delayed release of celecoxib

Calcium alginate beads containing celecoxib dissolved in a self-emulsifying phase were developed and characterized with the aim of ensuring a control on the site of drug release. The influence of different variables (concentration of the cross-linking agent, hardening time and amount of loaded drug) on the physico-chemical and biopharmaceutical properties was evaluated. Microscope images showed spherical dried beads and DSC revealed the absence of drug in crystalline state. The swelling behaviour of the beads was pH-sensitive and was not significantly influenced by the different variables selected. All the formulations were able to reduce the drug release at low pH and guaranteed a complete drug release at intestinal pH. In particular, at pH 7.4 the effect of the concentration of the cross-linking agent was evident: the rate and the extent of celecoxib release decreased significantly as the cross-linking agent concentration increased. According to the results presented in this study, adopting 15 min of hardening time in a solution of 100 mM CaCl₂ and high drug loading, it is possible to obtain multi-unit systems characterized by good mechanical resistance, scarce swelling and release in acidic environment and good drug availability performances in the intestinal fluids.