Formulation development of periodontal gel base to control metronidazole release for periodontitis patients

Abstract

Generally, antimicrobial agents are orally administered to periodontitis patients. This could induce some side effects, poor local concentrations of drug, superinfections and bacterial resistance. The purpose of this study was to develop a localized drug delivery system that offered prolonged administration of metronidazole, an anaerobe antimicrobial agent. In preliminary study, various components were used to prepare gel base system such as hydrophilic gel base including carbopol, hydroxyl ethyl cellulose, hydroxyl propyl methyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxy methyl cellulose and poloxamer 407, hydrophobic gel base including insoluble polymers (ethylcellulose, Eudragit® RS, Eudragit® RL), polyethylene, Aerosil® , hydrocarbon compounds (white soft paraffin), glyceryl monostearate, stearic acid, isopropyl myristate, mineral oil and the combination of hydrophilic and hydrophobic component, hydrophilic-hydrophobic gel base. Each formulation was characterized in terms of physical appearances, viscosity, syringeability, spreadability, disappearance property test, ex vivo mucoadhesion time, ex vivo mucoadhesion force and in vivo evaluation in patient. The viscosity was closely related with syringeability and spreadability. Increasing concentration of components especially hydrophilic polymers could present to increasing viscosity, decreasing syringeability and spreadability. The mucoadhesion on porcine intestinal mucosa of hydrophilic gel base was more than those form hydrophobic and hydrophilic- hydrophobic gel base system. Disappearance of hydrophilic gel base was polymers dissolution due to swelling erosion. The selected of periodontal gels which showed good application such as low viscosity and high syringeability. When selected of periodontal gel base systems containing 5% metronidazole were evaluated in patients with periodontal pocket deeper than 3 mm, highly or extremely bleeding was occurred. All selected gels were then removed by bleeding, except hydrophilic-hydrophobic gel based on insoluble polymers and hydrocarbon compound (system 3-3) which was remained for more than 24 hours. Afterward, this system was evaluated by increasing of drug concentration, microbial sensitivity test, drug release and stability test. The release rate of drug was decreased due to the dense of poor crystal drug solubility in the matrix of gel structure. All selected gels could not tolerate room temperature, Thai-FDA stability test (45°C and 75% RH) and 6 freeze-thaw cycles and but remained intact when storage at refrigerated temperature.