IL FARMACO 60 (2005) 43–46

http://france.elsevier.com/direct/FARMAC/

Original article

Differential pulse voltammetric determination of carvedilol in tablets

dosage form using glassy carbon electrode
A. Radi *, T. Elmogy
Department of Chemistry, Faculty of Science, Mansoura University, 34517 Dumyat, Egypt
Received 19 May 2004; accepted 29 July 2004

Available online 11 November 2004

Abstract

The electrochemical oxidation of antihypertensive drug carvedilol has been studied in pH range 2.0–11.0 at a glassy carbon electrode by
cyclic and differential pulse voltammetry. Two oxidation processes were produced in different supporting electrolyte media. Both oxidation
processes were irreversible and diffusion-controlled. The first oxidation process was chosen for the analysis of carvedilol. A very resolved
voltammetric peak was obtained in Britton–Robinson buffer at pH 8.0 using differential pulse mode. The linear response was obtained in the
range of 0.25–10.00 µg ml–1. The limit of detection was found to be 0.10 µg ml–1. The developed method was used for the determination of
carvedilol in tablet dosage form.
© 2004 Elsevier SAS. All rights reserved.

Keywords: Carvedilol; Differential pulse voltammetry; Pharmaceutical; Glassy carbon electrode, Dilatrend® tablets

1. Introduction

Carvedilol (Fig. 1), (±)-1-(carbazol-4-yloxy)-3-[[2-(O-

methoxyphenoxy)ethyl]amino]-2-propanol, which has been
prescribed as an antihypertensive agent [1,2], is accepted as
an effective agent for the treatment of congestive heart fail-
Fig. 1. Chemical structure of carvedilol.
ure (CHF) [3–5]. It causes non-cardioselective b/a1-adreno-
ceptor blockade and also has an anti-oxidant effect [6,7].
range of pharmaceuticals with the advantage that there is, in
No methods for determination of carvedilol in pharmaceu-
most instances, no need for derivatizations, and that these
tical dosage forms can be found in the literature. Several ana-
methods are less sensitive to matrix effects than other ana-
lytical methods for the determination of carvedilol in various
lytical techniques [17]. Thus, the sensitive determination of
biological media [8–14] or the separation of enantiomers
compounds, even in complex matrices, is possible without
[15,16] are described, including liquid chromatographic, high-
tedious extraction procedures being necessary before the
performance liquid chromatographic and capillary electro-
voltammetric measurements. Currently, no report about the
phoresis.
electrochemical redox properties of carvedilol is available in
Electroanalytical techniques, such as cyclic voltammetry, the literature. Consequently, quantitative determination of
linear sweep voltammetry, and differential pulse voltamme- this drug using electrochemical techniques is a non-explored
try, have been used for the sensitive determination of a wide matter up today except a HPLC method with electrochemical
detection [8]. Therefore, the purpose of this work is to inves-
tigate the electrochemical characterization of carvedilol on
glassy carbon electrode and devise a suitable differential
* Corresponding author. Tel.: +20-57-403-866; fax: +20-57-403-868. pulse voltammetric method for the analysis of carvedilol in
E-mail address: abdradi@yahoo.com (A. Radi). tablets.
0014-827X/$ - see front matter © 2004 Elsevier SAS. All rights reserved.
doi:10.1016/j.farmac.2004.07.016
44 A. Radi, T. Elmogy / IL FARMACO 60 (2005) 43–46
2. Experimental
2.1. Reagents
Bulk carvedilol drug and Dilatrend® tablets were kindly
supplied by Boehringer Mannheim GmbH. A stock solution
of 100.00 µg ml–1 carvedilol was prepared by dissolving an
accurate mass of the drug in an appropriate volume of metha-
nol, which was then stored in the dark at 4 °C. More dilute
solutions were prepared daily by accurate dilution just before
use. The standard stock solutions were protected from light
through out the experimental procedures and their concentra-
tions did not change with time. Britton–Robinson buffer
solutions were prepared using 0.04 M o-phosphoric, acetic,
and boric acids, and desired pH was adjusted by the addition
of 0.2 M sodium hydroxide solution. High-purity reagents
were employed in all experiments. Acetic acid and sodium
hydroxide were from Sigma (Saint Louis, USA); boric acid
and o-phosphoric were supplied from Merck (Darmstadt,
Germany) and methanol from Carlo Erba (Milan, Italy). All
solutions were prepared using doubly distilled water.
2.2. Apparatus
The cyclic, linear sweep and differential pulse voltammet-
ric experiments were performed using an AEW2 analytical
electrochemical workstation controlled by the ECprog3 elec-
trochemistry software (Sycopel, UK). A three-electrode cell
system incorporating the glassy carbon disc electrode (BAS
model MF-2012, U = 3 mm) as working electrode, an Ag–
AgCl (3 M KCl) (BAS model MF-2063) reference electrode
and a platinum-wire (BAS model MW-1032) auxiliary elec-
trode were also used. Operating conditions for the DPV
were: pulse amplitude, 50 mV; pulse width, 50 ms; scan rate,
20 mVs–1.
The pH was measured using A Schott Geräte CG 808 digi-
tal pH-meter with H 61 pH combination electrode (Mainz,
Germany) with an accuracy of ±0.02 pH.
2.3. Procedure
For voltammetric measurement, 10 ml of the electrolyte
solution were transferred into the voltammetric cell. After
measurement of the blank solution, the appropriate amount
of carvedilol solution is added and the anodic potential sweep
was carried under different operational parameters. Before
each measurement the glassy carbon electrode was polished
manually with 0.5 mm alumina dispersed in bidistilled water
on a smooth polishing cloth and gently dried with a tissue
paper. All measurements were carried out at room tempera-
ture, and peak heights were evaluated by means of the tan-
gent method.
2.3.1. Tablet assay procedure
Ten Dilatrend® tablets were reduced to a homogeneous
fine powder in a mortar. An amount of this powder corre-
sponding to about 10.00 µg ml–1 stock solution was accu-
rately weighed and transferred into a 50 ml calibrated flask
and filled up to the volume with methanol. The contents of
the flask were sonicated for 10 min to achieve complete
dissolution. Analyzed solutions were prepared by taking ali-
quots of the clear supernatant and diluting with the selected
supporting electrolyte. Voltammograms were recorded in a
similar way as for standard solutions of carvedilol.
3. Results and discussion
3.1. Differential pulse voltammetry
In general, pH is one of the variables that commonly and
strongly influence the shapes of voltammograms, and it is
important to investigate the effects of pH on electrochemical
systems. Carvedilol was electrochemically oxidized at the
glassy carbon electrode in two steps over the pH range
investigated. Due to the well-resolved signal obtained by
DPV, the effect of solution acidity on peak potential and peak
intensity were studied using this technique. As shown in
Fig. 2, the first oxidation process was more pronounced,
while the second process was less distinct at all pH values
tested. Thus, the study was focused mainly on the first oxida-
tion peak because of its analytical interest. The plot Ep1 vs.
pH showed two straight lines (Fig. 3a), with a break at pH
values of 4.0 and 9.0, implying the involvement of different
number of protons in the current-limiting electrode process
[18]. In the pH ranges 4.0–9.0, a linear dependence is ob-
served with slopes of 79 mV per pH unit. Fig. 3b shows the
influence of pH on peak current. Maximum peak was ob-
tained with Britton–Robinson buffer at pH 8.0. This electro-
lyte was used throughout this study.
3.2. Cyclic voltammetry
To elucidate further the electrode reaction of carvedilol, a
cyclic voltammogram at (GCE) was recorded. As shown in
Fig. 2. Differential pulse voltammograms for 10.00 µg ml–1 carvedilol in
Britton–Robinson buffers of different pH values, at glassy carbon electrode.
Scan rate, 20 mVs–1; pulse amplitude, 50 mV; pulse width, 50 ms.
 A. Radi, T. Elmogy / IL FARMACO 60 (2005) 43–46
Fig. 3. Effect of pH on (a) peak potential and (b) peak current for
10.00 µg ml–1 carvedilol solutions in Britton–Robinson buffer by means of
differential pulse voltammetry at glassy carbon electrode, pulse amplitude
50 mV, pulse width 50 ms, and scan rate 20 mVs–1.
Fig. 4, the cyclic voltammogram of a 30.00 µg ml–1
carvedilol in BRB (0.04 M, pH 8.0) exhibits two anodic
peaks, with no peak on the reverse scan, indicating the
irreversible nature of the electrode reaction. The anodic
peaks may be attributed to the irreversible oxidation of the
N-heterocyclic nitrogen of the carbazole moiety and the
nitrogen of secondary amino group in the side chain. The
study of the influence of scans rate shows that the peak
current of the first oxidation step (ipa1) changes linearly with
scan rate (V) according to the equation ipa1 = AVx. The x
values 1.0 and 0.5 are expected for adsorption-controlled and
diffusion-controlled reaction [19]. The regression of log ipa1
vs. log V gave a slope value of 0.52, indicating that the
oxidation current is of diffusional nature. On the other hand,
as scan rate was increased from 20 to 500 mVs–1, the peak
potential shifted toward more positive potential as expected
for an irreversible oxidation process [20]. The value of ␣na,
product of transfer coefficient and number of electrons trans-
Fig. 4. Cyclic voltammograms of 30.00 µg ml–1 carvedilol solution on
glassy carbon electrode in Britton–Robinson buffer at pH 8.0. Scan rate,
100 mVs–1. The dotted lines represent blank solution.
45
ferred in the rate-determining step, was determined from
treatment (log i vs. E) of the voltammetric curves. The value
obtained (0.43) shows the total irreversibility of the electron
transfer process.
3.3. Analytical applications
Based on the voltammetric behavior of carvedilol, a quan-
titative method was developed. To select the best electro-
chemical method, the anodic peak obtained by CV and DPV
were compared with each other. The best ratio of the peak to
background currents was obtained with DPV. Best results
were obtained at pulse amplitude 50 mV, pulse width 50 ms,
and scan rate 20 mVs–1. A set of DP voltammograms in BRB
(0.04 M, pH 8.0) illustrating the variation of peak height with
carvedilol concentration is shown in Fig. 5. A linear range
was observed for concentrations between 0.25 and
10 µg ml–1. The variation of peak current (ipa1) with
carvedilol concentration is represented by a straight-line
equation ipa1 (µA) = 0.07439 + 0.06583 c (µg ml–1),
r = 0.9996 (n = 10), where r is the correlation coefficient and
n is the number of points. Statistical evaluation of the data
[21] was performed through determination of the standard
deviation of the residuals (Sy/x = 0.00271), standard deviation
of the intercept (Sa = 0.00166), and standard deviation of the
slope (Sb = 3.4 × 10–4). The small figures obtained refer to the
high precision of the method. The detection limit LD
(0.10 µg ml–1) of carvedilol was calculated by using the
equation LD = 3Sy/x/b, where Sy/x is the standard deviation of
the blank and b is the slope of the calibration curve.
Specificity of the optimized procedure for the assay of
5.00 µg ml–1carvedilol was examined in the presence of
inactive ingredients (sucrose, lactose, povidone, colloidal
Fig. 5. Differential pulse voltammograms for increasing concentrations of
carvedilol in Britton–Robinson buffer at pH 8.0 on glassy carbon electrode.
Scan rate, 20 mVs–1; pulse amplitude, 50 mV; pulse width, 50 ms. Bromo-
criptine concentration: (1) 0.25, (2) 1.25, (3) 2.25, (4) 3.25 µg ml–1; the
dotted lines represent blank solution.
46 A. Radi, T. Elmogy / IL FARMACO 60 (2005) 43–46
anhydrous silica, crospovidone, and magnesium stearate) in
the same ratios of those used in tablets dosage form.
Carvedilol showed no significant excipients interference,
thus the procedures were able to assay carvedilol in the
presence of excipients and hence, it can be considered spe-
cific.
Robustness was examined by evaluating the influence of
small variations in some of the most important procedural
variables including pH and concentration. The results
showed that none of these variables significantly affect the
recovery of carvedilol and provide an indication of the reli-
ability of the proposed procedures for assay of the drug: these
could be considered robust.
3.3.1. Assay of carvedilol in tablets
The proposed analysis procedure was successfully applied
for the assay of carvedilol in a pharmaceutical formulation
(Dilatrend® tablets labeled to contain 25 mg of carvedilol
per tablet). Five determinations of three different samples of
the drug gave an average carvedilol content of 25.13 mg per
tablet corresponding to a mean recovery of 100.81%. The
relative standard deviation was 0.94%.
4. Conclusion
The developed electroanalytical method presented in this
work is a good technique for the determination of carvedilol
with adequate reproducibility and recovery. No interferences
were observed by the excipients present in the formulation.
The described method is a direct method for the determina-
tion of carvedilol and does not include any extraction pro-
cess. Electroanalytical method is a considerable timesaver
and the overall cost of analysis is lower when compared with
the chromatographic methods.
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