FORMULATION AND EVALUATION OF METRONIDAZOLE BIOADHESIVE MATRICES FOR TREATMENT OF PERIODONTITIS

Metronidazole (Mz) (an anaerobic antibacterial agent) was incorporated into different bioadhesive matrices including gels and films using carbopol 934p (4%), chitosan (3%) and hydroxypropyl methyl cellulose (HPMC) (3%). Penetration enhancers including menthol (1%) or oleic acid (OA) (5%, 10%) were incorporated in such formulations. The bioadhesive forces of the prepared matrices were determined and expressed as detachment stresses (Dyne/cm^2). Permeability of Mz across ear rabbit skin and enhancement ratios (ER) were studied. The effects of selected Mz formulations on the healing rate of experimentally induced periodontitis in guinea pigs were estimated and histologically compared between treated and control groups. The obtained results showed that the gel formulations containing carbopol 934p exhibited maximum bioadhesive force with detachment stress equals to 66.98x10^2 dyne/cm^2 followed by those containing chitosan (42.45x10^2 dyne/cm^2) and HPMC (26.41x10^2 dyne/cm^2). There was a statistically significant difference (P 0.05) between the detachment stresses of gel formulations containing penetration enhancers and the corresponding ones without penetration enhancer. HPMC based films had bioadhesive force (19.33, 16 and 13.67x10^2 dyne/cm^2) higher than those based on chitosan (5.33 and 7.33x10^2 dyne/cm^2). Also, it was noticed that the chitosan gel containing 1% menthol had the highest ER (5.13) among other gel formulations. On the other hand, chitosan based film containing 5% OA has the highest ER (1.73) among films. The effects of the selected formulations on the healing periodontal wound showed that bioadhesive chitosan gel containing menthol had accelerated the periodontal wound healing more than chitosan based film containing oleic acid.