Quality control and drug-drug interactions between commercially available Metoprolol and Glimepiride tablets

Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient's safety.

Bioanalytical method development and validation for determination of metoprolol tartarate and hydrochlorothiazide using HPTLC in human plasma

A simple, sensitive, rapid and economic chromatographic method has been developed for determination of metoprolol tartarate and hydrochlorothiazide in human plasma using paracetamol as an internal standard. The analytical technique used for method development was high-performance thin-layer chromatography. HPTLC Camag with precoated silica gel Plate 60F254 (20 cm×10 cm) at 250 µm thicknesses (E. Merck, Darmstadt, Germany) was used as the stationary phase. The mobile phase used consisted of chloroform: methanol: ammonia (9:1:0.5v/v/v). Densitometric analysis was carried out at a wavelength of 239 nm. The rf values for hydrochlorothiazide, paracetamol and metoprolol tartarate were 0.13±0.04, 0.28±0.05, 0.48±0.04, respectively. Plasma samples were extracted by protein precipitation with methanol. Concentration ranges of 200, 400, 600, 800, 1000, 1200 ng/mL and 2000, 4000, 6000, 8000, 10000, 12000 ng/mL of hydrochlorothiazide and metoprolol tartarate, respectively, were used with plasma for the calibration curves. The percent recovery of metoprolol tartarate and hydrochlorothiazide was found to be 77.30 and 77.02 %, respectively. The stability of metoprolol tartarate and hydrochlorothiazide in plasma were confirmed during three freeze-thaw cycles (-20 ºC) on a bench for 24 hours and post-preparatively for 48 hours. The proposed method was validated statistically and proved suitable for determination of metoprolol tartarate and hydrochlorothiazide in human plasma.

Um método simples, sensível, rápido e econômico empregando a cromatografia em camada delgada de alta eficiência (HPTLC) foi desenvolvido para determinação do tartarato de metoprolol e hidroclorotiazida em plasma humano, usando paracetamol como padrão interno. Placas prontas de sílica-gel 60F254 (20 cm×10 cm), 250 µm de espessura, para HPTLC Camag (E. A Merck, Darmstadt, Alemanha) foramutilizadas como fase estacionária. A fase móvel utilizada consistiu de clorofórmio: metanol: amônia (9:1:0,5 v/v/v). A análise densitométrica foi realizada no comprimento de onda 239 nm. Os valores de Rf de hidroclorotiazida, paracetamol e tartarato de metoprolol foram 0.13±0.04, 0.28±0.05, 0.48±0.04 respectivamente. As proteínas do plasma foram extraídas por precipitação com metanol. Para construção das curvas de calibração, empregaram-se intervalos de concentração de 200, 400, 600, 800, 1000, 1200 ng/mL e 2000, 4000, 6000, 8000, 10000, 12000 ng/mL de hidroclorotiazida e tartarato de metoprolol, respectivamente. Os percentuais de recuperação do tartarato de metoprolol e de hidroclorotiazida foram de 77,30 e 77,02, respectivamente. A estabilidade do tartarato de metoprolol e de hidroclorotiazida no plasma foi confirmada durante três ciclos de congelamento e descongelamento (-20 ºC), durante 24 horas e póspreparação durante 48 horas. O método proposto foi validado estatisticamente, sendo adequado para determinação do tartarato de metoprolol e hidroclorotiazida em plasma humano.

Determination of atenolol and metoprolol tartrate in phrmaceutical preparations by tlc densitometry and in urine by hpltc densitometry

Simple, sensitive and accurate quantitative densitometric procedures for the determination of atenolol and metoprolol tartrate in bulk drug, dosage forms and urine were described. In TLC method, atenolol and metoprolol tartrate were determined in dosage forms and the determination of intact atenolol in the presence of its degraded sample. Atenolol and its degraded sample were separated on silica gel with fluorescent indicator in system, acetone-ethanol-ethyl acetate- ammonia, while metoprolol tartrate was separated on silica gel in system, ethyl acetate- methanol-ammonia. Absorbance measurement [detection of reflectance] of separated drugs was carried out in situ at 270 nm. Calibration curves were established in the concentration ranges of 5-80 mug/spot and 5-70 mug/spot for atenolol and metoprolol tartrate, respectively. The results were evaluated by logarithmic regression analysis