Stability-indicating HPLC method for determination of amiodarone hydrochloride and its impurities in tablets: a detailed forced degradation study

Resumo Amiodarone hydrochloride is one of the most important drugs used to treat arrhythmias. The USP monograph for amiodarone hydrochloride describes an HPLC method for the quantification of seven impurities, however, this method shows problems that result in unresolved peaks. Moreover, there is no monograph for tablets in this compendium. Thus, a stability indicating HPLC method was developed for the determination of amiodarone, its known impurities and degradation products in tablets. A detailed forced degradation study was performed submitting amiodarone API, tablets and placebo to different stress conditions: acid and alkaline hydrolysis, oxidation, metal ions, heat, humidity, and light. Amiodarone hydrochloride API was susceptible to degradation in all stress conditions. The tablets also showed degradation in all environments, except in acidic condition. The analytes separation and quantification were achieved on an Agilent Zorbax Eclipse XDB-C18 column (100 x 3.0 mm, 3.5 µm). The mobile phase was composed of 50 mM acetate buffer pH 5.5 (A) and a mixture of methanol-acetonitrile (3:4, v/v) (B) in gradient elution. The method was validated in the range of 350-650 µg/mL for assay and 10-24 µg/mL for impurities determination. Therefore, this method can be used both for stability studies and routine quality control analyses.

Evaluation of in vitro anti-Trypanosoma cruzi activity of medications benznidazole, amiodarone hydrochloride, and their combination

Abstract INTRODUCTION: Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination. METHODS: T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data. RESULTS: On the 4th day, no parasites were observed in any of the treated cultures. CONCLUSIONS: Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again.

Effects of amiodarone combined with succinylmetroprolol sustained-release tablets on cardiac function in patients with atrial fibrillation and congestive heart failure / 中国生化药物杂志

Objective To investigate the clinical efficacy of amiodarone combined with succinylmetroprolol sustained-release tablets in patients with atrial fibrillation and congestive heart failure (CHF) complicated with atrial fibrillation (AF), and to observe the effect of amiodarone on heart function and ventricular rate.MethodsIn people's hospital of Anji county from June 2013 to June 2016 a total of 80 patients with atrial fibrillation and heart failure were enrolled in this study.The patients were randomly divided into control group and treatment group, 40 cases.(Ventricular rate, resting ventricular rate), cardiac function (ejection fraction-EF, stroke volume-SV, cardiac output-CO and left ventricular function) were measured before treatment and 6 months after treatment Ventricular end-diastolic early/late peak velocity ratio-VA/VE).The clinical efficacy and side effects during the treatment were statistically analyzed.ResultsThe ventricular rate and resting ventricular rate after exercise were significantly lower than those before treatment, but the ventricular rate and resting ventricular rate were significantly lower in the treatment group than those in the control group after 6 months of treatment (P<0.05).The VA/VE was significantly lower than that of the control group at 6 months after treatment, and the values of EF, SV and CO were significantly higher than those of the control group at 6 months after the treatment, SV, CO were significantly higher than the control group(P<0.05).Treatment group, the total effective rate was 92.5%, significantly higher than the control group 72.5%(χ2=7.77, P=0.02).No significant adverse reactions during treatment.ConclusionRapid ventricular rate of atrial fibrillation with congestive heart failure were treated with amiodarone combined with metoprolol succinate sustained release tablets can conducive to the ventricular rate and heart function of patients, and the effect is remarkable, safe, so it can be recommended as the drug of choice for clinical treatment of patients.

Effect of amiodarone hydrochloride treatment time on treatment success rate of ventricular premature beats after radiofrequency ablation / 中国生化药物杂志

Objective To investigate the effect of treatment time with amiodarone hydrochloride on treatment success rate of ventricular premature beats after radiofrequency ablation. Methods 46 cases of patients with frequent premature ventricular arrhythmia who received RFCA for the first time in department of gardiology,huangyan hospital of wenzhou medical university from February 2013 to February 2015 were selected,and randomly divided into two groups,the control group were treated with amiodarone hydrochloride for one months,the study group were treated with amiodarone hydrochloride for six months.Left ventricular function and structural parameters,heart rate variability were measured in two groups,the main clinical symptom scores,success rate,efficacy and safety were compared. Results Compared with before treatment,two groups of LVESD,LVEDD and PVC decreased (P<0.05),LVEF increased (P<0.05),SDNN,rMSSD,PNN50,LF and HF increased (P<0.05),scores of palpitation,shortness of breath,chest tightness and main symptom score decreased (P<0.05).Compared with the control group,level of PVC in the study group was lower (P<0.05),LVEF was higher(P<0.05),LVESD and LVEDD were had no significant differences,levels of SDNN,rMSSD,PNN50,LF,HF were higher (P<0.05),scores of palpitations,shortness of breath,chest tightness main symptom score were lower (P<0.05).There were no significant differences in the success rate, clinical efficacy and adverse reaction rate between the two groups. Conclusion The time of taking amiodarone after radiofrequency catheter ablation in patients with PVCs,but taking six months and medication compared to one month,can reduce heart palpitations,chest tightness and other symptoms,and improve left ventricular function,with high security.

Nursing of prevention of phlebitis caused by vein medication Amiodarone Hydrochloride / 中国生化药物杂志

Objective To research and analyze nursing measures of phlebitis caused by vein medication Amiodarone Hydrochloride. Methods 150 arrhythmias patients in the Traditional Chinese. Medicine Hospital of Wenling were selected as the subjects. The control group was given routine transfusion nursing, the experimental group was given comprehensive nursing intervention on the basis of the control group, saline irrigation before and after transfusion, observed the local reaction of patients, and controlled the concentration and external application of potato chips. Results After the corresponding nursing measures, in the control group, accounting for 46.7%. 35 cases of phlebitis occurred in the experimental group. The incidence of phlebitis in the experimental group was 16.0%, which was significantly lower than that (46.7%) in the control group, which was statistically significant (P<0.05). In the experimental group, the number of patients with I degree phlebitis was 8, and the proportion was 66.67%. In the control group, there were 7 cases of I degree phlebitis, accounting for 20%, which was statistically significant (P<0.05). In the experimental group, there were 4 cases of II degree phlebitis, the proportion was 33.33%, significantly lower than that (54.28%) of the control group (19 cases of II degree phlebitis) with statistical significance (P<0.05). Conclusion The application of comprehensive nursing measures in arrhythmia patients treated with Amiodarone Hydrochloride vein medication, could significantly reduce the occurrence of phlebitis and improve the curative effect with high safety and clinical significance.

Nursing of prevention of phlebitis caused by vein medication Amiodarone Hydrochloride / 中国生化药物杂志

Objective To research and analyze nursing measures of phlebitis caused by vein medication Amiodarone Hydrochloride. Methods 150 arrhythmias patients in the Traditional Chinese. Medicine Hospital of Wenling were selected as the subjects. The control group was given routine transfusion nursing, the experimental group was given comprehensive nursing intervention on the basis of the control group, saline irrigation before and after transfusion, observed the local reaction of patients, and controlled the concentration and external application of potato chips. Results After the corresponding nursing measures, in the control group, accounting for 46.7%. 35 cases of phlebitis occurred in the experimental group. The incidence of phlebitis in the experimental group was 16.0%, which was significantly lower than that (46.7%) in the control group, which was statistically significant (P<0.05). In the experimental group, the number of patients with I degree phlebitis was 8, and the proportion was 66.67%. In the control group, there were 7 cases of I degree phlebitis, accounting for 20%, which was statistically significant (P<0.05). In the experimental group, there were 4 cases of II degree phlebitis, the proportion was 33.33%, significantly lower than that (54.28%) of the control group (19 cases of II degree phlebitis) with statistical significance (P<0.05). Conclusion The application of comprehensive nursing measures in arrhythmia patients treated with Amiodarone Hydrochloride vein medication, could significantly reduce the occurrence of phlebitis and improve the curative effect with high safety and clinical significance.

Amiodarone hydrochloride: enhancement of solubility and dissolution rate by solid dispersion technique

abstract Amiodarone HCl is an antiarrhythmic agent, which has low aqueous solubility and presents absorption problems. This study aimed to develop inclusion complexes containing hydrophilic carriers PEG 1500, 4000 and 6000 by fusion and kneading methods in order to evaluate the increase in solubility and dissolution rate of amiodarone HCl. The solid dispersion and physical mixtures were characterized by X-ray diffraction, FT-IR spectra, water solubility and dissolution profiles. Both methods and carriers increased the solubility of drug, however PEG 6000 enhanced the drug solubility in solid dispersion better than other carriers. Different media were evaluated for the solubility study, including distilled water, acid buffer pH 1.2, acetate buffer pH 4.5 and phosphate buffer pH 6.8 at 37 ºC. Based on the evaluation of the results obtained in the study phase solubility carriers PEG 4000 and PEG 6000 were selected for the preparation of the physical mixture and solid dispersion. All formulations were prepared at drug-carrier ratios of 1:1 to 1:10(w/w). The results of in vitro release studies indicated that the solid dispersion technique by fusion method in proportion of 1:10 (w/w) increased significantly the dissolution rate of the drug. X-ray diffraction studies showed reduced drug crystallinity in the solid dispersions. FT-IR demonstrated interactions between the drug and polymers.

resumo Cloridrato de amiodarona é um agente antiarrítmico que possui baixa solubilidade aquosa e apresenta problemas de absorção. Este estudo teve como objetivo desenvolver complexos de inclusão contendo carreadores hidrofílicos PEG 1500, 4000 e 6000 através dos métodos de fusão e amassamento para avaliar o aumento da solubilidade e taxa de dissolução do cloridrato de amiodarona. As dispersões sólidas e misturas físicas foram caracterizadas por difração de raios-X, espectroscopia no infravermelho com transformada de Fourier, solubilidade em água e perfis de dissolução. Ambos os métodos e carreadores aumentaram a solubilidade do fármaco, no entanto o PEG 6000 aumentou a solubilidade do fármaco na dispersão sólida mais que os outros carreadores. Diferentes meios foram avaliados para o estudo de solubilidade, incluindo água destilada, tampão ácido pH 1,2, tampão acetato pH 4,5 e tampão fosfato pH 6,8. Com base na avaliação dos resultados obtidos no estudo de solubilidade de fases, os carreadores PEG 4000 e PEG 6000 foram selecionados para a preparação das misturas físicas e dispersões sólidas. Todas as formulações foram preparadas nas razões fármaco-carreador de 1:1 a 1:10 (p/p). Os resultados de liberação in vitro que a técnica de dispersão sólida pelo método de fusão na proporção 1:10 (p/p) aumentou significativamente a taxa de dissolução do fármaco. Estudos de difração de raios-X mostraram redução da cristalinidade do fármaco na dispersão sólida. Análise por espectroscopia no infravermelho mostrou interações entre o fármaco e o carreador.