Preparation Optimization and Screening of the Effect of Processing Variables on Agar Nanospheres Loaded with Bupropion HCl by a D-Optimal Design

摘要

Bupropion is an atypical antidepressant drug. Fluctuating in its serum levels following oral administration of immediate release dosage forms leads to occasional seizure. The aim of the present work was designing of sustained release bupropion HCl nanospheres suited for pulmonary delivery. Agar nanospheres were prepared by transferring the w/o emulsion to solid in oil (s/o) suspension. Calcium chloride was used as cross-linking agent and hydroxypropyl β-cyclodextrin (HPβCD) was used as permeability enhancer. A response surface D-optimal design was used for optimization of nanospheres. Independent factors included in the design were calcium chloride percent, speed of homogenization, agar percent, and HPβCD percent. Optimum condition was predicted to be achieved when the calcium chloride was set at 7.19%, homogenization speed at 8500 rpm, agar content at 2%, and HPβCD at 0.12%. The optimized nanoparticles showed particle size of 587 nm, zeta potential of −30.9 mV, drug loading efficiency of 38.6%, and release efficiency of 51% until 5 h. The nanospheres showed high degree of bioadhesiveness. D-optimal response surface method is a satisfactory design to optimize the fabrication of bupropion HCl loaded agar nanospheres and these nanospheres can be successively exploited to deliver bupropion in a controlled manner for a sufficiently extended period.