Journal of Pharmaceutical and Biomedical Analysis 57 (2012) 115–119 Contents lists available at SciVerse ScienceDirect Journal of Pharmaceutical and Biomedical Analysis jou rn al h om epage: www.elsevier.com/locate/jpba Short communication Dissolution testing of isoniazid, rifampicin, pyrazinamide and ethambutol tablets using near-infrared spectroscopy (NIRS) and multivariate calibration Ana Carolina de Oliveira Neves a , Gustavo Mesquita Soares a , Stéphanie Cavalcante de Morais a , Fernanda Saadna Lopes da Costa a , Dayanne Lopes Porto b , Kássio Michell Gomes de Lima a,∗ a Institute of Chemistry, Grupo de Pesquisa em Quimiometria Aplicada UFRN, Natal 59072-970, Brazil b Center for Food and Drug Research, UFRN, Natal 59072-970, Brazil a r t i c l e i n f o Article history: Received 2 March 2011 Received in revised form 16 August 2011 Accepted 17 August 2011 Available online 24 August 2011 Keywords: NIR diffuse reflectance Dissolution testing Tuberculosis tablets PLS a b s t r a c t This work utilized the near-infrared spectroscopy (NIRS) and multivariate calibration to measure the percentage drug dissolution of four active pharmaceutical ingredients (APIs) (isoniazid, rifampicin, pyraz- inamide and ethambutol) in finished pharmaceutical products produced in the Federal University of Rio Grande do Norte (Brazil). The conventional analytical method employed in quality control tests of the dis- solution by the pharmaceutical industry is high-performance liquid chromatography (HPLC). The NIRS is a reliable method that offers important advantages for the large-scale production of tablets and for non-destructive analysis. NIR spectra of 38 samples (in triplicate) were measured using a Bomen FT-NIR 160 MB in the range 1100–2500 nm. Each spectrum was the average of 50 scans obtained in the diffuse reflectance mode. The dissolution test, which was initially carried out in 900 mL of 0.1 N hydrochloric acid at 37 ± 0.5 ◦ C, was used to determine the percentage a drug that dissolved from each tablet measured at the same time interval (45 min) at pH 6.8. The measurement of the four API was performed by HPLC (Shi- madzu, Japan) in the gradiente mode. The influence of various spectral pretreatments (Savitzky-Golay smoothing, Multiplicative Scatter Correction (MSC), and Savitzky-Golay derivatives) and multivariate analysis using the partial least squares (PLS) regression algorithm was calculated by the Unscrambler 9.8 (Camo) software. The correlation coefficient (R 2 ) for the HPLC determination versus predicted val- ues (NIRS) ranged from 0.88 to 0.98. The root-mean-square error of prediction (RMSEP) obtained from PLS models were 9.99%, 8.63%, 8.57% and 9.97% for isoniazid, rifampicin, ethambutol and pyrazinamide, respectively, indicating that the NIR method is an effective and non-destructive tool for measurement of drug dissolution from tablets. Crown Copyright © 2011 Published by Elsevier B.V. All rights reserved. 1. Introduction Tuberculosis is a major global health problem because it is easily spread, primarily through the air. Although the disease can strike any organ of the body, the bacillus reproduces and grows quickly in areas with high concentrations of oxygen, which explains the more frequent attacks to the lungs. In 1944, the investigator Selman Waksman discovered streptomycin, the first effective antibiotic action against tuberculosis. Since then, several other drugs have been quite successfully used in the treatment of the disease, includ- ing isoniazid (1952), rifampicin (1965), pyrazinamide (synthesized in 1936, but used only since 1970) and ethambutol (1960), which are shown in Fig. 1 [1]. One methods used to evaluate drug delivery is the study of the dissolution testing, because the dissolution of the active ingredient ∗ Corresponding author. Tel.: +55 84 3215 3828; fax: +55 83 3211 9224. E-mail address: kassio@ufrnet.br (K.M.G. de Lima). in solid dosage forms is considered a key variable in the pro- cess of absorption in the gastrointestinal tract [2]. Dissolution is a dynamic process, strongly dependent on both the medium compo- sition and hydrodynamics. Because the environment of the luminal gastrointestinal tract varies considerably, it is necessary to measure different variables to arrive at a complete picture of the behavior of the drug from its active versions. The procedures for the dissolution test vary according to the number of active ingredients in the formulations. The official meth- ods United States Pharmacopeia (USP) for rifampicin, isoniazid and rifampicin capsule, where the dissolution medium was 0.1 mol L -1 HCl. Procedures for three-drug fixed dose combinations (FDC) became official in USP 24 Supplement 2, whereas four drug (FDC) became official in USP 26 (2003) [3]. Different studies, such as dissolution tests, make use of the technique of high-performance liquid chromatography (HPLC) for quantification of drugs, as regulated by the United States Phar- macopeia (USP). Currently, the use of HPLC methods in studies of dissolution has been increasing because the in vitro dissolution of 0731-7085/$ – see front matter. Crown Copyright © 2011 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jpba.2011.08.029