Stability facilitation of nanoparticles prepared by ultrasound assisted solvent-antisolvent method: Effect of neem gum, acrylamide grafted neem gum and carboxymethylated neem gum over size, morphology and drug release

Abstract

In present research, etoricoxib nanoparticles were prepared using newly developed ultrasonication assisted solvent-antisolvent method. Neem gum (NGP) and their semisynthetic derivatives NGP-g-Am (acrylamide graft copolymer of neem gum) and CMNGP (carboxymethylated neem gum) were used to provide stability to drug nanoprecipitates. In this research response surface methodology based on 32 factorial design was utilized to evaluate the effect of two independent variables (concentration of drug and polymer) over size and entrapment efficiency of nanoparticles (dependent variables). When compared with pure drug nanocrystals, polymer stabilized molecular composite nanoparticles were of smaller size and spherical shape. CMNGP stabilized composite nanoparticles shown smaller size hence better performance in terms of solubility and dissolution rate as compared to NGP and NGP-g-Am. As shown by zeta seizer analysis for the same concentration of drug and stabilizer, size of nanoparticles were found in the range of NGP-g-Am > NGP > CMNGP and reverse case was observed for dissolution rate. Contact angle determination easily predict better hydrophilicity of CMNGP than NGP followed by NGP-g-Am. DSC thermogram predict the amorphous nature of CMNGP than NGP and NGP-g-Am. SEM revealed spherical shaped and non-aggregation of nanoparticles. Prepared nanosuspension show no aggregation and Ostwald repining after 45 days when ultrasonicated for 5 s. t90% of optimized formulations of NGP (N9), NGP-g-Am (A8) and CMNGP (C1) was found to be 249.46 min, 296.63 min and 223.39 min and followed 1° order, Higuchi and 1° order kinetics of drug, respectively. Similarity factor analysis predict that release pattern of drug from three different polymer stabilized nanoparticles are significantly differ to each other. Particle size of nanoparticles was studied in presence of solvent and findings showed no change in size after 45 days.