Research Article Preparation, Optimization, and Screening of the Effect of Processing Variables on Agar Nanospheres Loaded with Bupropion HCl by a D-Optimal Design Jaleh Varshosaz, 1 Mohammad Reza Zaki, 1,2 Mohsen Minaiyan, 3 and Jaafar Banoozadeh 2 1 Department of Pharmaceutics, Novel Drug Delivery Systems Research Centre, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran 2 Exir Pharmaceutical Company, Borujerd, Iran 3 Department of Pharmacology, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran Correspondence should be addressed to Jaleh Varshosaz; varshosaz@pharm.mui.ac.ir Received 28 August 2014; Revised 7 November 2014; Accepted 17 November 2014 Academic Editor: Paola Laurienzo Copyright © 2015 Jaleh Varshosaz et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Bupropion is an atypical antidepressant drug. Fluctuating in its serum levels following oral administration of immediate release dosage forms leads to occasional seizure. Te 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 -cyclodextrin (HPCD) 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 HPCD 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 HPCD at 0.12%. Te optimized nanoparticles showed particle size of 587 nm, zeta potential of −30.9mV, drug loading efciency of 38.6%, and release efciency of 51% until 5 h. Te 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 sufciently extended period. 1. Introduction Bupropion is an atypical short-acting aminoketone antide- pressants drug [1, 2] which inhibits the reuptake of dopamine and norepinephrine [3]. It was patented for the frst time in 1974 [4] and released onto the world market in 1985 but was briefy withdrawn due to seizures incidence. It was reintroduced in 1989 afer the daily recommended dose was reduced to lower seizure likelihood [3]. To address the dose-related risk of seizures associated with high peak concentration of the drug following oral administration, bupropion hydrochloride is administered in divided doses or as sustained release dosage forms [1, 2, 5, 6]. Bupropion has numerous therapeutic indications includ- ing depression [7], smoking cessation [8], sexual dysfunction [9], obesity [10], attention defcit hyperactivity disorders [11], and seasonal afective disorders [12]. Following oral administration of immediate release forms of bupropion, peak plasma concentration is usually achieved within 2 hours. Te half-life of the postdistributional phase of bupropion ranges from 8 to 24 hours. Bupropion has also a relatively high volume of distribution of 18.6 L/kg [2, 13]. Following absorption from gastrointestinal tract, bupro- pion undergoes extensive frst-pass metabolism with oral bioavailability of only 5% resulting in formation of metabo- lites which are less potent than the parent molecule while being more convulsion inducing [14, 15]. To overcome the shortcomings of currently available dosage forms, that is, (i) fuctuation in plasma level due to immediate release forms and (ii) conversion of parent molecule to its metabolites through frst-pass efect, it is worth it to try other routes of administration in context of Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 571816, 13 pages http://dx.doi.org/10.1155/2015/571816