Formulation design and optimization of triclosan loaded nanoparticles for enhanced drug delivery across gingival sulcus by Resolution IV modeling of Design Expert®

Nafiu Aminu, Siok-Yee Chan, Seok-Ming Toh


The aim of this study was to design and systematically optimize triclosan loaded nanoparticles (TCS-loaded NPs) formulation for the treatment of periodontal disease. Triclosan (TCS) is a broad spectrum antimicrobial agent that has been used in the treatment of the disease. The free drug has poor aqueous solubility and therefore may encounter permeability problems when applied to the oral cavity. Resolution IV model of Design-Expert® software (version 10) was used for the design of experiment and optimization of TCS-loaded NPs. The nanoparticles (NPs) were prepared using the solvent displacement method. Effect of factors that were investigated include drug-polymer ratio, surfactant concentration, stirring speed, stirring duration, and drug-polymer injection rate. Particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (EE) were the critical quality attributes selected for the study. Desirability function determined by the software for optimized TCS-loaded NPs was 0.704. The observed particle size, PDI, zeta potential and EE of the optimized TCS-loaded NPs was found to be 135 ± 2.3 nm, 0.1 ± 0.012, -30 ± -4 mV and 75 ± 6%, respectively. It was found that particle size increases by elevating the concentration of polymer and decreases with an increase in surfactant concentration and stirring speed. Zeta potential was found to increase when surfactant concentration was reduced. Both surfactant concentration and drug to polymer ratio were found to negatively affect PDI while % EE was positively influenced by the increase in polymer concentration and decrease in surfactant concentration. The use of Design-Expert® software helped in identifying suitable levels of critical quality parameters for preparing improved NPs formulation for delivery of TCS into the periodontal pocket.


Design-Expert®; Resolution IV; design of experiment; periodontal disease; triclosan

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