Formulation Development of Nanoparticulate Periodontal Drug Delivery System of Metronidazole Benzoate with Combination Processing Method by Using Design of Experiment

Abstract

The objective of present investigation was to develop and evaluate Nanoparticulate Periodontal Drug Delivery System (NPDDS) for local delivery of metronidazole benzoate with combination processing method. Dichloromethane, acetone and ethanol were utilized in combination with, HPMC E15 LV, HPC LF and gelusire 44/14, formulation stabilizers to develop NPDDS. A specific DOE was selected to study the effects and interactions of stabilizers and solvent mixture on particle size distribution and other relevant formulation characterization parameters. We have considered four independent variables X1, X2, X3 and Z4 are HPMC E15 LV, (HPC-LF), Gelusire 44/14 and Solvent mixture, respectively. DOE was used in this investigation to map the system and thus to approximate the Mean particle size (MPS) (Y1), Drug release at 30 minute (%) (Y(30 min)) (Y2), and time for 50% drug release [t50%] (Y3) to find an optimal range of experimental conditions. A two step production process, including combination of high speed homogenization and wet media milling technique was developed. Formulation stabilizer gelusire 44/14 has shown prominent effect over MPS, Y(30 min), and t50%. Overall effect of factors over the responses is graphically represented by the ternary plots. Keywords: Design of experiment, gelusire 44/14, metronidazole benzoate, nanoparticulate drug delivery, periodontitis.