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Antibacterial Agent-Incorporated Cholesterol Phase Inversion-Based In Situ Forming Matrix for Crevicular Pocket Delivery

Phase inversion in situ forming matrix is one of the promising drug delivery systems for periodontitis treatment owing to the prospective high antimicrobial agent level in the gingival crevicular fluid. Typically, this drug delivery system is a fluid polymeric solution that could change simultaneously to matrix-like after injection into aqueous physiological environment. The main propose of the current study was to achieve successful development of antibacterial agent-incorporated cholesterol phase inversion in situ forming matrix for crevicular pocket delivery. In this study, cholesterol was used as a fat matrix former, while N-methyl pyrrolidone (NMP) was used as the solvent and menthol was used as co-solvent. The 10%w/w metronidazole or doxycycline hyclate was employed as the active compounds. The developed formula were evaluated for viscosity and rheological behavior, antimicrobial activity using cup agar diffusion method and in vitro drug release using dialysis tube method. The consistency index from rheological test of doxycycline hyclate and metronidazole-loaded in situ forming matrices was not significantly different (p<0.05). Interestingly, the viscosity of all formula was quite low; thus, this characteristic provoked an ease of injection. They inhibited against Porphyromonasgingivalis efficiently more than cholesterol in situ forming matrix base (p<0.05). Drug release from systems loaded with doxycycline hyclate and metronidazole were rapid and nearly not different. Owing to the apparent efficiently inhibition against Porphyromonasgingivalis the in situ forming matrix loading doxycline hyclate was selected for further development to minimize the burst release and to prolong the drug release.