Resumen Las herramientas de transformada continua de wavelets fueron empleadas para el procesamiento de espectros de absorción UV con el fin de lograr la cuantificación y la comprensión del comportamiento de fumarato de disoproxilo de tenofovir (TEN) y de emtricitabina (EMT) en la disolución in vitro de las tabletas comerciales, con bajo costo y corto tiempo de análisis. Se realizaron pruebas preliminares de análisis de señales para determinar la familia o familias de ondículas más adecuadas para monitorear los perfiles de disolución in vitro y para cuantificar los fármacos de interés. Entre ellos, las herramientas Daubechies (db6), Symlets 3 (sym3), Biorthogonal 1.5 (bior1.5) y Coiflets 5 (coif5) resultaron ser óptimas proporcionando resultados deseados. Funciones de calibración obtenidas mediante el análisis de regresión de señales de ondículas transformadas (variable dependiente) obtenidas para soluciones de calibración (concentración - variable independiente) presentaron buena linealidad en el intervalo de concentraciones 4.0-52.0 µg/mL para ambos fármacos. La validez de procesamiento de señales CWT fue demostrada mediante el análisis de mezclas de conocidas concentraciones, preparadas en el laboratorio. La cuantificación de TEN y EMT no requiere su separación previa. El procedimiento fue empleado en el ensayo de monitoreo de la disolución in vitro de los fármacos y en las tabletas con contenían los dos fármacos. En este trabajo se propone un procedimiento basado en CWT, alternativo respecto a la tradicional espectrofotometría de derivadas para resolución de mezclas binarias sin necesidad de separación previa de dos componentes.

Abstract Wavelet signal processing tools were applied to the UV spectral dataset for the quantification and understanding the in vitro dissolution behaviors of tenofovir disoproxil fumarate (TEN) and emtricitabine (EMT) in commercial tablets with low-cost and short analysis time. Preliminary signal analysis tests were staged to determine the most suitable wavelet family or families to monitor in vitro dissolution profiles and quantify the drugs of interest. Of these, Daubechies (db6), Symlets 3 (sym3), Biorthogonal 1.5 (bior1.5) and Coiflets 5 (coif5) continuous wavelet tools have been found to be optimal as they provide the desired results. Calibration curves obtained by regression analysis of the continuous wavelet signal (dependent variable) on concentration (independent variable) were found to be linear in the range of 4.0-52.0 µg/mL for both drugs. The validity of CWT signal processing tools was tested by analyzing mixtures made in the laboratory. The Quantitation of TEN and EMT by the proposed signal processing tools did not require a pre-separation procedure. They were successfully utilized for the assay and in vitro dissolution monitoring of the two drugs in their combined tablets. Consequently, the presented work provided alternative tools based on wavelet signal processing to traditional derivative spectrophotometry to resolve a two-component mixture without using a priori separation step.

ABSTRACT Continuous wavelet transform (CWT) was proposed for the simultaneous determination and dissolution profiles of valsartan (VAL) and hydrochlorothiazide (HCT) in tablets, without the use of a chemical separation procedure. The CWT approach was applied to the original UV spectra and their ratio spectra in the optimal wavelength ranges. After testing several wavelet families, Mexican hat function-CWT and Daubechies7-CWT (mexh-CWT and db7-CWT, respectively) were found to be suitable for the transformation of the original UV spectra. In the following procedure, mexh-CWT and Coiflets3-CWT (coif3-CWT) were found to be appropriate for the signal analysis of ratio spectra (RS) of VAL/HCT and HCT/VAL. Calibration graphs for VAL and HCT were obtained by measuring db7-CWT and mexh-CWT amplitudes in the transformation of the original absorption spectra and RS-coif-CWT and RS-mexh-CWT amplitudes in the transformation of the ratio spectra. The validity and applicability of the proposed CWT methods were evaluated through the analysis of an independent set of synthetic binary mixtures consisting of VAL and HCT. The proposed signal processing methods were then successfully applied to the simultaneous quantitative evaluation and simultaneous dissolution profiles of the related drugs in commercial tablets, with good agreement reported for the experimental results.

A new spectral continuous wavelet transform (CWT) methods are proposed for the quantitative analysis of the binary mixtures. The simultaneous spectral resolution of binary mixtures and tablets containing paracetamol (PAR) and chloroxozone (CHL) with overlapping absorption spectra is performed by six wavelet families with no chemical separation procedure. The calibration graphs for the six wavelet families are obtained by the help of the data collected from the CWT- signal amplitudes corresponding to the zero crossing points inthe spectral range of 210 nm-310nm. The validation of each wavelet family is carriedoutby analyzing various synthetic binary mixtures of the above mentioned drugs. The second derivative spectrophotometry (D2) is used to compare the experimental results provided by the analyzed continuous wavelet families and a good coincidence is reported for the proposed analytical approaches.

Signal processing methods based on the combined use of the continuous wavelet transform (CWT) and zero-crossing technique were applied to the simultaneous spectrophotometric determination of perindopril (PER) and indapamide (IND) in tablets. These signal processing methods do not require any priory separation step. Initially, various wavelet families were tested to identify the optimum signal processing giving the best recovery results. From this procedure, the Haar and Biorthogonal1.5 continuous wavelet transform (HAAR-CWT and BIOR1.5-CWT, respectively) were found suitable for the analysis of the related compounds. After transformation of the absorbance vectors by using HAAR-CWT and BIOR1.5-CWT, the CWT-coefficients were drawn as a graph versus wavelength and then the HAAR-CWT and BIOR1.5-CWT spectra were obtained. Calibration graphs for PER and IND were obtained by measuring the CWT amplitudes at 231.1 and 291.0 nm in the HAAR-CWT spectra and at 228.5 and 246.8 nm in BIOR1.5-CWT spectra, respectively. In order to compare the performance of HAAR-CWT and BIOR1.5-CWT approaches, derivative spectrophotometric (DS) method and HPLC as comparison methods, were applied to the PER-IND samples. In this DS method, first derivative absorbance values at 221.6 for PER and 282.7 nm for IND were used to obtain the calibration graphs. The validation of the CWT and DS signal processing methods was carried out by using the recovery study and standard addition technique. In the following step, these methods were successfully applied to the commercial tablets containing PER and IND compounds and good accuracy and precision were reported for the experimental results obtained by all proposed signal processing methods.

A determinação simultânea de ácido ascórbico (AA), ácido acetilsalicílico (ASP) e paracetamol (PAR) em misturas sintéticas e tabletes efervescentes foi realizada usando-se as técnicas de transformações de Haar e transformações de onda pequena tipo chapéu mexicano (HAAR-CWT e MEXH-CWT, respectivamente), juntamente com a técnica de divisor duplo. Os métodos de processamento de sinal são baseados na aplicação de HAAR-CWT e MEXH-CWT aos espectros relativos com divisor duplo (DDRS). Estes espectros foram obtidos pela divisão do espectro de absorção do composto puro e suas misturas ternárias, por um divisor duplo ou espectro padrão correspondente à mistura de dois compostos em mistura ternária. O uso combinado de HAAR-CWT e MEXH-CWT com espectros relativos com divisor duplo (DDRS) foi denominado DDRS-HAAR CWT e DDRS-MEXH CWT. Para avaliar a habilidade ou aplicabilidade dos métodos desenvolvidos DDRS-CWT, foi aplicado como comparação, o método espectrofotométrico por derivada de espectros relativos com divisor duplo (DDRS-DS), às amostras mencionadas acima, contendo AA, ASP e PAR. Resultados satisfatórios foram obtidos.

Simultaneous determination of ascorbic acid (AA), acetylsalicylic acid (ASP) and paracetamol (PAR) in their synthetic mixtures and effervescent tablets were performed by Haar and Mexican continuous wavelet transforms (HAAR-CWT and MEXH-CWT, respectively) together with double divisor technique. The signal processing methods are based on the application of HAAR-CWT and MEXH-CWT to the double divisor-ratio spectra (DDRS). These spectra were obtained by dividing the absorption spectra of pure compound and its ternary mixtures by a double-divisor or standard spectrum corresponding to a mixture of two compounds in ternary mixture. A combined use of HAAR-CWT and MEXH-CWT with double divisor-ratio spectra (DDRS) was denoted by DDRS-HAAR CWT and DDRS-MEXH CWT. To check the ability or applicability of the developed DDRS-CWT methods, the double divisor-ratio spectra-derivative spectrophotometric (DDRS-DS) method, as a comparison method, was applied to the above mentioned samples containing AA, ASP and PAR and satisfactory results were obtained.

A resolução quantitativa da mistura de quinapril e hidroclorotiazida em comprimidos foi realizada com o uso da transformada de ondas contínuas e métodos quimiométricos. No caso da transformada de ondas contínuas, uma série de famílias de ondas foram testadas para achar o ponto ótimo da técnica de processamento de sinais das ondas. A função de onda tipo chapéu mexicano apresentou o melhor resultado. Essa função onda tipo chapéu mexicano foi aplicada aos espectros de absorção do quinapril e da hidroxiclorotiazida na faixa de 200-320 nm para um conjunto padrão de medicamentos na concentração de quinapril de 4,0-20,0 µg mL-1 e hidroclorotiazida de 2,5-12,5 µg mL-1. As funções de calibração do quinapril em 230,6 nm e da hidroclorotiazida em 271,1 nm foram calculadas em função da relação entre as medidas dos sinais de ondas contínuas e das concentrações. De acordo com o enfoque quimiométrico, foram utilizadas calibrações por regressão dos mínimos quadrados e dos componentes principais, baseadas em um conjunto de teste de 21 misturas, contendo os dois medicamentos e os dados de absorbância correspondentes, na faixa de comprimento de onda igual a 205-290 nm. Todos os métodos propostos foram validados pela análise separada das misturas sintéticas e pela técnica de adição padrão. A utilização do método desenvolvido indicou que a seletividade e a sensibilidade foram satisfatórias na análise dos comprimidos.

Quantitative resolution of the quinapril and hydrochlorothiazide mixture in tablets was achieved by using continuous wavelet transform and chemometric methods. In the case of the continuous wavelet transform, various continuous wavelet families were tested in order to find the optimum point of the wavelet signal processing technique. The Mexican hat wavelet function was reported to be the optimal one. The Mexican hat wavelet function was applied to the absorption spectra of quinapril and hydrochlorothiazide in the spectral range of 200-320 nm for standard series of drugs in the concentration range of 4.0-20.0 µg mL-1 quinapril and 2.5-12.5 µg mL-1 hydrochlorothiazide. The calibration functions for quinapril at 230.6 nm and for hydrochlorothiazide at 271.1 nm were calculated based on the relationship between the measurements of continuous wavelet signals and their concentrations. According to the chemometric approach, partial least squares and principal component regression calibrations were constructed by a training set of 21 mixtures, containing two drugs and their corresponding absorbance data, in the wavelength range of 205-290 nm. All proposed methods were validated by the independent analysis of the synthetic mixtures and by the standard addition technique. The application of the methods indicated that their selectivity and the sensitivity were satisfactory. The investigated methods were successfully applied to tablet analysis.