Voltammetric assay of anti-anginal drug nicorandil in different solvents.

Voltammetric behaviour and assay of nicorandil were investigated using square-wave and cyclic voltammetry. Voltammograms in Britton-Robinson (BR) buffer exhibited one well-defined and two merged reduction peaks. The influence of different buffers, electrolytes, pH, scan rates, and concentration of the drug on cathodic peak current was studied. On the basis of electrochemical behaviour of nicorandil, a direct square-wave voltammetric procedure for quantitation of nicorandil has been developed and validated. The proposed square-wave voltammetric method allows quantitation over the range 12.5-62.5 µg mL(-1) with correlation coefficient of 0.992. The limit of quantification and limit of detection were 21.95 µg mL(-1) and 6.58 µg mL(-1) , respectively. Precision and accuracy were also checked and found within limits. The developed square-wave method has also been successfully applied for the determination of nicorandil in pharmaceutical formulations.

Quantitation of nicorandil in pharmaceutical formulations by spectrophotometry using N-(1-naphthyl) ethylenediamine dihydrochloride as coupling agent.

A validated and sensitive spectrophotometric method is developed for the quantitation of nicorandil in pharmaceutical formulations. The method is based on the reduction of nitroxy ethyl group of nicorandil to carbonyl derivative and nitrite ion by Zn/NH4Cl. The nitrite ion undergoes diazotization with sulphanilamide in presence of HCl followed by coupling with N-(1-naphthyl) ethylenediamine dihydrochloride (NED) to form a colored product with lambda(max) at 525 nm. Under the optimized experimental condition, Beer's law is obeyed in the concentration range of 0.4-12.0 microg/ml with molar absorptivity of 1.92 x 10(4) l mol(-1) cm(-1). The statistical analysis of calibration data yields the linear regression equation: A = 6.304 x 10(-4)+9.13 x 10(-2) C with correlation coefficient of 0.9999. The limits of detection and quantification are 0.05 and 0.15 microg/ml, respectively. The results obtained by the proposed method are acceptable with average recoveries of 100.0-100.1%. The results of the proposed method are compared with those of the reference method by point and interval hypothesis tests, which showed excellent agreement and there is no significant difference in accuracy and precision of methods compared.

Determination of inorganic nitrate impurity from nicorandil and its tablet dosage form by simple reversed phase liquid chromatographic method.

A simple, fast, precise, specific and economical reverse phase liquid chromatographic method was developed for determination of nitrate (NIT) impurity from nicorandil (NIC) and its tablet dosage form. NIT is process impurity as well as a degradation product of NIC. This article is based on application of amino propyl silane (APS) column for determination of NIT in presence of NIC and various excipients using potassium nitrate as a standard. The developed method was validated for its intended use by evaluating various important parameters like linearity, accuracy, recovery and specificity. The developed method was applied to evaluate the compatibility study of NIC with various excipients by monitoring the NIT content.

Formulation of an HPMC gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing in vitro transdermal delivery of nicorandil.

The objective of the present study was to formulate a hydroxypropyl methylcellulose (HPMC) gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing the transdermal delivery of nicorandil so as to develop and fabricate a membrane-moderated transdermal therapeutic system (TTS). The in vitro permeation of nicorandil was determined across rat abdominal skin from a solvent system consisting of ethanol or various proportions of ethanol and water. The ethanol-water (70:30 v/v) solvent system that provided an optimal transdermal permeation was used in formulating an HPMC gel drug reservoir system with selected concentrations (0% w/w, 4% w/w, 6% w/w, 8% w/w or 10% w/w) of limonene as a penetration enhancer for further enhancement of transdermal permeation of nicorandil. The amount of nicorandil permeated in 24 h was found increased with an increase in the concentration of limonene in the drug reservoir system up to a concentration of 6% w/w, but beyond this concentration there was no further increase in the amount of drug permeated. The flux of nicorandil was 370.9 +/- 4.2 microg/cm2 x h from the drug reservoir system with 6% w/w of limonene, which is about 2.6 times the required flux to be obtained across rat abdominal skin for producing the desired plasma concentration for the predetermined period in humans. The results of a Fourier Transform Infrared study indicated that limonene enhanced the percutaneous permeation of nicorandil by partially extracting the stratum corneum lipids. It is concluded that the HPMC gel drug reservoir system prepared with a 70:30 v/v ethanol-water solvent system containing 6% w/w of limonene is useful in designing and fabricating a membrane-moderated TTS of nicorandil.

Optimized and validated spectrophotometric methods for the determination of nicorandil in drug formulations and biological fluids.

Two simple, sensitive and economical spectrophotometric methods have been developed for the determination of nicorandil in drug formulations and biological fluids. Method A is based on the reaction of the drug with brucine-sulphanilic acid reagent in sulphuric acid medium producing a yellow-coloured product, which absorbs maximally at 410 nm. Method B depends on the formation of the intensely blue-coloured product which results due to the interaction of an electrophilic intermediate of 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) with oxidized product of 4-(methyl amino) phenol sulphate (metol) in the presence of nicorandil as an oxidizing agent in sulphuric acid medium. The coloured product shows absorbance maximum at 560 nm. Under the optimized experimental conditions, Beer's law is obeyed in the concentration range of 2.5-35.0 and 0.40-2.2 microg ml(-1) for Methods A and B, respectively. Both the methods have been successfully applied to the determination of nicorandil in drug formulations and biological fluids. The results are validated statistically and through recovery studies. In order to establish the bias and the performance of the proposed methods, the point and interval hypothesis tests have been performed. The experimental true bias of all samples is smaller than +/-2%.

Selective and validated spectrophotometric methods for the determination of nicorandil in pharmaceutical formulations.

Two simple and sensitive validated spectrophotometric methods have been described for the assay of nicorandil in drug formulations. Method A is based on the reaction of the drug with phloroglucinol-sulfanilic acid reagent in sulfuric acid medium to give yellow-colored product, which absorbs maximally at 425 nm. Method B uses the oxidative coupling of 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) with DL- 3,4 - dihydroxyphenylalanine (DL-dopa) in the presence of nicorandil as oxidant in sulfuric acid medium to form an intensely colored product having maximum absorbance at 530 nm. Beer's law is obeyed in the concentration range 2.5 to 50.0 and 1.0 to 15.0 microg mL(-1) with methods A and B, respectively. Both methods have been successfully applied for the analysis of drug in pharmaceutical formulations. The reliability and the performance of the proposed methods are established by point and interval hypothesis and through recovery studies. The experimental true bias of all samples is smaller than +/-2%.

Ultrastructural localization of nicorandil in the heart of rats.

To examine the intracellular localization of nicorandil in the heart, [14C]nicorandil and [3H]nicorandil (3 mg kg(-1)) were given orally to rats. The maximum concentration (Cmax) of nicorandil in the myocardium was reached 15 min after the oral dosing. At this time subcellular localization of nicorandil was examined. Nicorandil and its denitrated metabolite, SG-86 were found in mitochondrial fractions and in cytosolic and microsomal fractions of the heart. Electron-microscopic autoradiograms recorded 15min after oral dosing of 3 mg kg(-1) [3H]nicorandil to rats also showed the presence of silver grains generated by the radioactive nicorandil or its metabolites in the mitochondria of the heart. We conclude that nicorandil given orally to rats is distributed in mitochondria of the heart.