A REVIEW ON ANALYTICAL METHODS FOR IVABRADINE DETERMINATION IN PHARMACEUTICAL DOSAGE FORMS

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ABOUT AUTHORS
Tabassum I. Hangad *, Rani S. Potawale
Department of Pharmaceutical Chemistry,
M. C. E. Society's Allana College of Pharmacy, Azam Campus ,Camp, Pune 411001.

ABSTRACT
Ivabradine is a specific heart rate lowering agent, acting by reducing the rate of pacemaker
activity in the sinoatrial node. Ivabradine is a novel heart rate lowering medicine for the symptomatic management of stable angina pectoralis and symptomatic chronic heart failure. In multicenter clinical trials, it has been proved that Ivabradine is superior to beta-blocking agents during complex therapy of chronic heart failure accompanied with its beneficial effects related to cardiac remodeling, improvement of the currency of heart failure and diminution of patients rehospitalisation. It is suggested that Ivabradine as a newer agent is a valuable perspective drug for the treatment of congestive heart failure. This review is useful for the future study for researcher involved in formulation development and quality control of Ivabradine.

This review article represents the various analytical methods which have been reported for estimation of Ivabradine in pharmaceutical dosage form. The spectrophotometric techniques and Q-absorbance ratio method were reported by the various authors. Many researchers also worked in chromatographic areas like Thin layer chromatography, High performance liquid chromatography, and High performance thin layer chromatography. Ivabradine is also studied by various hyphenated techniques .We reviewed and reported almost all analytical methods with more emphasis on chromatographic mrthodsfor Ivabradine. 

Reference Id: PHARMATUTOR-ART-2612

INTRODUCTION
Ivabradine is a specific heart rate lowering agent, acting by reducing the rate of pacemaker activity in the sinoatrial node. Chemically 3-[3-({[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1, 3, 5-trien-7yl] methyl} methylamino) propyl]-1, 3, 4, 5-tetrahydro-7,8-dimethoxy-2H-3-benzazepin -2-One and available in the form of hydrochloride salt Ivabradine is the  new class of drugs that have the ability of slowing the depolarization slope, reducing heart rate and show the activity similar to that of β-blockers. Ivabradine is freely soluble in water, methanol, and acetonitrile. The drug is a basic drug and having pKa values≈ 8.02. (O’Neil MJ., 2006, Sulfi et al., 2006 , Seerapu et al., 2010).

An increase in heart rate  is a common occurrence in cardiac pathophysiology, particularly in heart failure, mediated by β-adrenergic receptors (βARs) following activation of the sympathetic nervous system.  Although an elevated heart rate may initially compensate for insufficient cardiac output, sustained tachycardia usually leads to adverse haemodynamic consequences. Ivabradine is a novel pharmacological agent specifically inhibiting the hyperpolarization-activated pacemaker If–current (If) that underlies the rate of spontaneous diastolic depolarization in sinoatrial pacemaker cells. This drug is introduced in medical practice in the last decade is a pure heart rate-slowing agent. A large number of studies in patients with cardiovascular disease have demonstrated that heart rate is a very important and major independent risk factor for prognosis, because lowering of heart rate reduces cardiac work and diminished myocardial oxygen requirement. It was shown that ivabradine a selective inhibitor of the hyperpolarisation activated sodium channel (If) is involved in pacemaker generation and responsiveness of the sino-atrial node resulting in the heart rate reduction without negative inotropic action. Ivabradine in chronic heart failure improves diastolic function and attenuates cardiac tissue hypoxia. Long-term reduction of heart rate induced by Ivabradine reduced remodeling and preserved nitric oxide (NO) bioavailability, resulting from processes triggered early after reduction of heart rate. (Sulfi et al., 2006).

Structure of Ivabradine

Fig.1 Structure of Ivabradine

Mechanism of action-
Ivabradine blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel, and inhibit the If–current (If) which  reduces the cardiac pacemaker activity of the sinus node  which decreases heart rate without an effect on ventricular repolarization or myocardial contractility. Ivabradine is recommended for angina pectoralis and symptomatic chronic heart failure. Ivabradine inhibit the "funny" channel pacemaker current (If) in the sinoatrial node in a dose-dependent fashion, resulting in a lower heart rate and thus more blood to flow to the myocardium. When we use  calcium channel blockers and beta blockers for lowering heart rate, they are good in actiot but show adverse effcts due to their negative ionotropic effects. Therefore, Ivabradine is designed as a "pure" heart rate-lowering drug. It causes no serious adverse effects. (Corlanor® is a first-in-class, HCN channel blocker that lowers heart rate).

Fig.2 Mechanism of Ivabradine

Analytical methods

Chromatographic method
Table no. 1 Summary of chromatographic methods for Ivabradine

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UV Spectroscopic Method
First order derivative spectroscopy and Area Under the curve spectroscopic technique was developed for simultaneous determination of Ivabradine was developed

Table no 2. Summary of Spectroscopic methods for Ivabradine

DISCUSSION
The presented systematic review covers the current analytical methods for the determination of Ivabradine and its combination in pharmaceutical and biological samples like serum and plasma. HPLC method were found to be most widely use for Ivabradine. Various chromatographic conditions are presented in table.

CONCLUSION
The sensitivity, specificity, and better separation efficiency enable HPLC to be used frequently for simultaneous qualitative and quantitative determination of Ivabradine. The presented information is useful for the future study for researcher involved in formulation development and quality control of Ivabradine.

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