Factorial design of in situ gelling two-compartment systems containing chlorhexidine for the treatment of periodontitis.

Periodontitis is one of the most widespread bacterial infectious oral diseases that affects a significant percentage of the population worldwide. Different bacterial strains are responsible for the chronic inflammation and subgingival plaque that could be effectively treated with prolonged exposure to therapeutic levels of antibiotics and antiseptics in the periodontal pockets. Medicated in situ gels of chlorhexidine (CHX), for extended drug release and long-lasting antiseptic effect in the targeted cavities, were prepared in a two-compartment system. One compartment was loaded with sodium alginate solution while other was filled with CHX and calcium solution. The mixing of the solutions during the application resulted in gelation. Two 3 full factorial designs were applied in this study in order to optimize the gel formulation. Initially, the effects of concentration of gelling agent, crosslinker, and pH of the system on the dependent variables such as gel formation and structure characteristics were investigated. Then, the concentration of the crosslinker was optimized. Afterwards, the effect of gelling agent, loading of the drug, and pH of the gel system were correlated with the gel characteristics through another factorial design. Optimized formulations were tested for mucoadhesion, in vitro drug release, and microbiological investigation. Based on the results of the factorial design, mucoadhesiveness, antimicrobial investigation, and drug release, a 4 % alginate composition can be considered optimal. Overall, the optimized in situ periodontal gel was found to be effective with prolonged retention time and desirable outcomes.