DOI: 10.1002/elan.201500011 Square-Wave Voltammetry as Analytical Tool for Real- Time Study of Controlled Naproxen Releasing from Cellulose Derivative Materials Wilson T. Fonseca, [a, b] Rodrigo F. Santos, [b] Janainne N. Alves, [b] Sabrina D. Ribeiro, [b] Regina M. Takeuchi, [a, b] AndrØ L. Santos, [a, b] Rosana M. N. Assunżo, [a, b] Guimes R. Filho, [b] and Rodrigo A. A. MuÇoz* [b] 1 Introduction Voltammetric techniques, mainly Differential-Pulse Vol- tammetry (DPV) and Square-Wave Voltammetry (SWV), are by far the most used electrochemical techniques for analytical purposes since they clearly present high sensi- tivity making them very suitable for low-level quantifica- tions. These techniques are especially useful for drug analyses, once most of pharmacologically active com- pounds have electroactive groups, which can be voltam- metrically detected. Voltammetry can be easily employed for quantification of drugs in pharmaceutical formula- tions, since excipients usually present in these samples are non-electroactive species such as surfactants, cellulose- based polymers, long-chain organic acids, etc. Therefore, these excipients do not interfere on the voltammetric de- tection. Several works have described voltammetric meth- ods for quantification of drugs [1–6] and literature also brings comprehensive reviews about this topic [7–10]. Voltammetric techniques present several attractive fea- tures for drug analysis such as: high sensitivity and preci- sion, high analytical frequency, low consumption of sample and reagents, and all of this combined with a rela- tively inexpensive instrumentation. On the other hand, the main drawback of voltammetric techniques is their moderate selectivity, which limits their use for analysis of more complex samples containing more than one electro- active species, because in this case the possibility of inter- ference by overlapping of voltammetric peaks is high. An interesting application for voltammetric techniques is the real-time monitoring of drug released from drug delivery systems. This kind of study is usually performed in a buffer solution able to simulate a biological fluid and usually only one drug is released from the drug delivery system. Therefore, these studies require an analytical method with high sensitivity and high analytical frequen- cy with no need for high selectivity, which means an opti- mum condition to employ voltammetry. Analytical tech- niques usually employed to quantify the amount of drug released from drug delivery systems are High Perfor- mance Liquid Chromatography (HPLC) coupled with dif- ferent detection systems, UV-vis spectrophotometry and fluorimetry [11]. A serious limitation of these techniques is that they cannot directly monitor the real-time drug re- leasing which is highly desired in order to obtain com- plete and accurate drug releasing kinetics profile [11]. Moreover, sampling is a challenge when these techniques are used because filtration or centrifugation is required before analysis. Thus, sample/analyte loss during filtration and buffer replacement at releasing vessel can negatively affect the accuracy of the measurements. Voltammetry, on the other hand, can be used to directly measure the concentration of released drug with no need to separate it from the drug-loaded system. In addition, a voltammet- ric technique such as SWV combines very high sensitivity with high speed, enabling the reliable acquisition of re- petitive scans in very short interval times. Therefore, Abstract : This work reports the successful use of square- wave voltammetry (SWV) to directly assess the con- trolled releasing profile of naproxen from lab-made cellu- lose derivative materials (membranes and microparticles) in phosphate buffer (pH 7.4) at 36 8C. Particular advant- age of SWV refers to the direct real-time monitoring of released drug from cellulose derivative microparticles, which cannot be easily assessed by UV-spectrophotome- try. Moreover, SWV was able to detect modifications in the naproxen releasing profile due to morphology and processing of membranes and microparticles. The possible miniaturization and versatility of SWV suggest the prom- ising application on the study of several drug delivery sys- tems, including in vivo studies. Keywords: Controlled release · Drug delivery · Naproxen · Cellulose acetate · Square-wave voltammetry [a] W.T. Fonseca, R. M. Takeuchi, A. L. Santos, R. M. N. Assunżo Universidade Federal de Uberlândia, Faculdade de CiÞncias Integradas do Pontal 38304-402, Ituiutaba, Minas Gerais, Brazil [b] W.T. Fonseca, R. F. Santos, J.N. Alves, S.D. Ribeiro, R. M. Takeuchi, A. L. Santos, R. M. N. Assunżo, G. R. Filho, R. A. A. MuÇoz Universidade Federal de Uberlândia, Instituto de Química 38400-902, Uberlândia, Minas Gerais, Brazil *e-mail: raamunoz@iqufu.ufu.br www.electroanalysis.wiley-vch.de # 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Electroanalysis 2015, 27, 1847 – 1854 1847 Full Paper