HPLC method development for the simultaneous analysis of amlodipine and valsartan in combined dosage forms and in vitro dissolution studies

A simple, rapid and reproducible HPLC method was developed for the simultaneous determination of amlodipine and valsartan in their combined dosage forms, and for drug dissolution studies. A C18 column (ODS 2, 10 μm, 200 x 4.6 mm) and a mobile phase of phosphate buffer (pH 3.6 , 0.01 mol L-1):acetonitrile: methanol (46:44:10 v/v/v) mixture were used for separation and quantification. Analyses were run at a flow-rate of 1 mL min-1 and at ambient temperature. The injection volume was 20 μL and the ultraviolet detector was set at 240 nm. Under these conditions, amlodipine and valsartan were eluted at 7.1 min and 3.4 min, respectively. Total run time was shorter than 9 min. The developed method was validated according to the literature and found to be linear within the range 0.1 - 50 μg mL-1 for amlodipine, and 0.05 - 50 μg mL-1 for valsartan. The developed method was applied successfully for quality control assay of amlodipine and valsartan in their combination drug product and in vitro dissolution studies.

Desenvolveu-se método de HPLC rápido e reprodutível para a determinação simultânea de anlodipino e valsartana em suas formas de associação e para os estudos de dissolução dos fármacos. Utilizaram-se coluna C18 (ODS 2, 10 μm, 200 x 4,6 mm) e fase móvel tampão fosfato (pH 3,6, 0,01 mol L-1):acetonitrila: metanol para a separação e a quantificação. As análises foram efetuadas com velocidade de fluxo de 1 mL min-1 e à temparatura ambiente O volume de injeção foi de 20 μL e utilizou-se detector de ultravioleta a 240 nm. Sob essas condições, anlodipino e valsartana foram eluídas a 7,1 min e 3,4 min, respectivamente. O tempo total de corrida foi menor que 9 min. O método desenvolvido foi validado de acordo com a literatura e se mostrou linear na faixa de 0,1-50 μg mL-1 para anlodipino e de 0,05-50 μg mL-1 para valsartana. O método desenvolvido foi aplicado com sucesso para ensaios de controle de qualidade de associações de anlodipino e valsartana e nos estudos de dissolução in vitro.

Cardiovascular drugs in human mechanical nociception: digoxin, amlodipine, propranolol, pindolol and atenolol

Calcium channel blockers, β adrenergic receptor blockers and Na/K ATPase inhibitors are widely used drugs, mainly for cardiovascular diseases. Their pharmacological targets are not restricted to the cardivascular tissue, nociceptive system structures also express similar targets, which strongly suggests a direct effect on pain sensation. To evaluate the pain intensity changes in outpatient groups, who receive these drugs as a therapy, a cross-sectional sampled, randomized patient groups receiving the calcium channel blocker amlodipine for blood hypertension (n=45), β adrenergic receptor blockers (propranolol, atenolol or pindolol; n=40) for blood hypertension, or digoxin (n=40) for heart failure, were compared to an aparently healthy volunteers control group (n=60). A calibrated noxious pressure of 890 g/mm² was applied for 5 seconds on the patient’s sternum. Subjective pain intensity was reported by the visual analog scale (VAS, 0 to 10). Pain modulation system was evaluated by the application of a second stimulus with a 5 minutes delay. The analgesic effect of the β blockers group (propanolol, atenolol, pindolol) was dosage-dependant (-36.8 percent; P=0.0000003), without differences among them. The calcium channel blocker amlodipine showed lower pain scores (-50.6 percent; P=0.0000003) than β-receptor blockers (P=0.0000003). Digoxin presented the highest pain scores (+56.5 percent; P=0.0000003). All pain scores for the second stimulus were lower than the first stimulus and were differentially affected by β-blockers (atenolol, pindolol and propanolol) and calcium channel blocker (amlodipine), but not by digoxin. These results suggest the influence of widely clinically used cardiovascular drugs on nociception.

Los bloqueadores de los canales de calcio, los bloqueadores de los receptores β adrenérgicos y los inhibidores de la ATPasa Na/K son medicamentos ampliamente usados en enfermedades cardiovasculares. Sus blancos farmacológicos no se restringen al tejido cardiovascular, el sistema nervioso nociceptivo expresa blancos similares, lo que sugiere fuertemente un efecto directo en la sensación del dolor. El objetivo del presente estudio fue evaluar los cambios en la intensidad del dolor en grupos de pacientes ambulatorios que reciban estos medicamentos como terapia. Grupos aleatorios de pacientes que reciben el bloqueador de canales de calcio amlodipina contra la hipertensión arterial (n=45), bloqueadores de receptores β adrenérgicos (propranolol, atenolol or pindolol; n=40) contra la hipertensión arterial o digoxina (n=40) por insuficiencia cardíaca fueron comparados con un grupo control de voluntarios aparentemente sanos (n=60). A todos los grupos se les aplicó una presión nociva calibrada de 890 g/mm² durante 5 segundos sobre el esternón. El paciente reportó la intensidad subjetiva del dolor mediante la escala visual análoga (VAS). El sistema de modulación descendente del dolor fue evaluado mediante la aplicación del mismo estímulo 5 minutos después del primero. Se determinó un efecto analgésico en el grupo de β bloqueantes (propanolol, atenolol, pindolol) dosis dependiente (-36,8 por ciento; P=0,0000003) sin mostrar diferencias entre ellos. El bloqueador de canales de calcio amlodipina mostró un efecto analgésico (-50,6 por ciento; P=0,0000003) que fue mayor que el de los β bloqueantes (P=0,0000003). El grupo con digoxina expresó un efecto hiperalgésico (+56,5 por ciento; P=0,0000003). Todos los valores de dolor para el segundo estímulo fueron menores que para el primero y fueron diferencialmente afectados por los β bloqueantes (atenolol, pindolol and propanolol) y por la amlodipina pero no por la digoxina. Estos...

Spectrophotometric determination of some cardiovascular drugs

The present work described two accurate and selective colorimetric methods for the determination of some cardiovascular drugs. The first method comprises the reaction of DDQ with dipyridamole, celiprolol and diltiazem to develop highly colored radical anion. In the second method Fe [III] hydroxamate reacts with chromonar hydrochloride or diltiazem hydrochloride to produce red colored complex