Evaluation of the bioequivalence of two formulations containing the combination of 400 mg of acetaminophen (paracetamol), 4 mg of phenylephrine and 4 mg of chlorpheniramine in capsules: open-label, three-way crossover study, partially replicated in healthy volunteers of both sexes

This study was carried out in order to compare the relative bioavailability of two different formulations containing 400 mg of acetaminophen + 4 mg of phenylephrine hydrochloride + 4 mg of chlorpheniramine maleate, Test formulation (Cimegripe®) and Reference formulation (Resfenol®) in 84 healthy volunteers of both sexes under fasting conditions. The study was conducted in a single dose, randomized, open-label, crossover 3-way and partially replicated. The tolerability was evaluated by the monitoring of adverse events and vital signs, results of clinical and laboratory tests. Plasma concentrations were quantified by validated bioanalytical methods using the ultra-performance liquid chromatography coupled to tandem mass spectrometry. The Cmax, Tmax, AUC0-t, AUC0-inf, T1/2 and Kel pharmacokinetic parameters were calculated from these obtained concentrations. The 90% confidence intervals were constructed for the ratio reference/test from the geometric average of the Cmax and AUC parameters which were comprised between 80% and 125%. Only the Cmax parameter of the phenylephrine was applied the scaled average bioequivalence due to the intraindividual coefficient of variation > 30% obtained, thus extending the acceptance limits of the interval. It can be concluded that the two formulations were bioequivalent in terms of rate and absorption extent and thus interchangeable

Analysis of chlorpheniramine in human urine samples using dispersive liquid-liquid microextraction combined with high-performance liquid chromatography

A simple and environmentally friendly microextraction technique was used for determination of chlorpheniramine (CPM), an antihistamine drug, in human urine samples using dispersive liquid-liquid microextraction (DLLME) followed by high performance liquid chromatography with diode array detection (HPLC-DAD). In this extraction technique, an appropriate mixture of acetonitrile (disperser solvent) and carbon tetrachloride (extraction solvent) was rapidly injected into the urine sample containing the target analyte. Tiny droplets of extractant were formed and dispersed into the sample solution and then sedimented at the bottom of the conical test tube by centrifugation. Under optimal conditions, the calibration curve was linear in the range of 0.055-5.5 µg mL-1, with a detection limit of 16.5 ng mL-1. This proposed method was successfully applied to the analysis of real urine samples. Low consumption of toxic organic solvents, simplicity of operation, low cost and acceptable figures of merit are the main advantages of the proposed technique.

Utilizou-se uma técnica de microextração simples e ambientalmente amigável para a determinação de clorfeniramina (CPM), anti-histamínico, em amostras de urina humana, utilizando a microextração dispersiva líquido-líquido (DLLME), seguida por cromatografia líquida de alta eficiência com detecção por arranjo de diodos (HPLC-DAD). Nesse método de extração, mistura apropriada de acetonitrila (solvente dispersor) e tetracloreto de carbono (solvente de extração) foi injetada rapidamente na amostra de urina contendo o analito alvo. As pequenas gotículas de agente de extração foram formadas e dispersas na solução da amostra e, em seguida, sedimentadas no fundo do tubo cônico de ensaio por centrifugação. Em condições ótimas, a curva de calibração foi linear no intervalo entre 0,055 e 5,5 µg mL-1, com limite de detecção de 16,5 ng mL-1. O método proposto foi aplicado com sucesso na análise de amostras de urina reais. Baixo consumo de solventes orgânicos tóxicos, simplicidade de operação, baixo custo e figuras de mérito aceitáveis são as principais vantagens do método sugerido.

Simultaneous determination of naphazoline hydrochloride, chlorpheniramine maleate and methylene blue in their ternary mixture

Validated spectrophotometric and chemometric methods were developed for determination of Naphazoline Hydrochloride [NAP], Chlorpheniramine maleate [CLO] and Methylene blue [MB] in their ternary mixture. Method A was a spectrophotometric method, where NAP and MB were determined using second derivative [D2] spectrophoto metric method using the peak amplitudes at 299 nm and 337 nm for NAP and MB respectively, while CLO was determined using second derivative ratio [DD[2]] spectrophotometric method using the peak amplitude at 276.6 nm. Method B used the chemometric techniques; principal component regression [PCR] and partial least squares [PLS] for determination of NAP, CLO and MB using the information contained in the absorption spectra of their ternary mixture solutions. The proposed methods have been successfully applied for the analysis of NAP, CLO and MB in their pharmaceutical formulation and the obtained results were statistically compared with the reported methods

Simultaneous spectrophotometric determination of paracetamol, phenylephrine and chlorpheniramine in pharmaceuticals using chemometric approaches

The linear multivariate calibration models such as principal components regression [PCR] and partial least squares regressions [PLS1 and PLS2] due to the mathematical simplicity and physical or chemical interpretability are sufficient and generally preferred method for analysis of multicomponent drugs. In this study, simultaneous determination of paracetamol, phenylephrine and chlorpheniramine in pharmaceuticals using chemometric methods and UV spectrophotometry is reported as a simple alternative technique. Principal components regression [PCR] and partial least squares regressions [PLS 1 and PLS2] were used for chemometric analyses of data obtained from the spectra of paracetamol, phenylephrine and chlorpheniramine between wavelengths of 200 to 400 nm at several concentrations within their linear ranges. The analytical performance of these chemometric methods were characterized by relative prediction errors and recoveries [%] and compared with each other. PCR, PLS1 and PLS2 were successfully applied to a tablet formulation, with no interference from excipients as indicated by the recovery. However, the PLS1 shows better results due to its flexibility and mathematical principals. The proposed methods are simple and rapid requiring no separation step, and can be easily used as an alternative in the quality control of drugs

Normal-phase LC method for simultaneous analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in tablet formulation

A simple, precise, and accurate method and validated for the analysis of pseudophedrin hydrochloride, dextromethrophan hydrobromide chlorpheniramine maleate, and paracetamol in tablet formulations. The method has shown adequate separation of the four ingredients from each other. Separation was achieved on a silica column [5 micro m, 125 X 4,6 mm inner diameter] using a mobile phase consisting of methanaol/ammonium dihyddrogen phosphate buffer [90:10, v/v] at a flow rate of 1.0 ml/min and UV detection at 220 nm. This new method is validated in accordance with USP requirements for new methods for assay determination, which include accuracy, precision, selectivity, linearity and range, probustness and ruggedness. The current method demonstrates good linearity over the range of 0.15-0.45 mg/ml of pseudophedrine hydrochloride with r[2] of 0.996, and in the range of 0.075-0.225 mg/ml of dextromethorphan hydrobromide with r[2] of 0.992, and in the range of 0.01-0.03 mg/ml of chlorpheniramine maleate with r[2] of 0.994, and in the range of 0.25-0.75 mg/ml of paracetamol with r[2] of 0.991. The average recovery of the method is 99.7%, 98.1%, and 99.2% for pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramien maleate, and paracetamol, respectively. The degree of reproducibility of the results obtained as a result of small deliberate variations in the method parameters and by changing analytical operator has proven that the method is robust and rugged