Electrochemical Behavior and Square-Wave Stripping Voltammetric Determination of Roflumilast in Pharmaceutical Dosage Forms
Authors: Çelebier Mustafa , Dogan Aysegul , Süslü İncilay , Altınöz Sacide 
Published: September 2020

Background:
Bronchial asthma and chronic obstructive pulmonary disease (COPD) are
among the most common chronic diseases. Roflumilast is a novel, potent, selective, and long-acting
phosphodiesterase 4 (PDE-4) inhibitor for the treatment of bronchial asthma and COPD. It has
anti-inflammatory effects, and it has been shown to reduce exacerbations and improve pulmonary
function in patients with COPD. Although there have been some other analytical methodologies reported
for the determination of roflumilast in pharmaceutical dosage forms, there has not yet been
any electrochemical methodology proposed for determination of this unique active pharmaceutical
ingredient in its dosage forms.

Objective:
The aim of this study was to develop an easily applied, selective, sensitive, accurate,
and precise square-wave stripping voltammetric (SWSV) method for the determination of roflumilast
in its pharmaceutical dosage forms. In addition, the electrochemical behavior of roflumilast
was investigated.

Methods:
The proposed method was based on electrochemical reductioThe proposed method was based on electrochemical reduction of roflumilast at a hanging
mercury drop electrode (HMDE) in 0.1 M K2HPO4 and 0.1 M Na2B4O7 (1:1, v/v) buffer at pH
5.0. Two reduction peaks were observed at -1150 mV and -1260 mV with 30 s of accumulation
time and -850 mV of accumulation potential time versus Ag/AgCl reference electrode.n of roflumilast at a hanging mercury drop electrode
(HMDE) in 0.1 M K2HPO4 and 0.1 M Na2B4O7 (1:1, v/v) buffer at pH 5.0. Two reduction peaks were observed at -1150 mV
and -1260 mV with 30 s of accumulation time and -850 mV of accumulation potential time versus Ag/AgCl reference
electrode.

Results:
The higThe highest peak current values with the best peak definition were observed at a frequency
of 50 Hz, scan increment of 5 mV, and pulse amplitude 25 mV. The proposed method was validated
by evaluating validation parameters such as linearity, sensitivity, repeatability, accuracy, precision,
selectivity, recovery, robustness, and ruggedness. A good linear correlation (r=0.9948) was
obtained between the electrochemical response of roflumilast and its concentration in the range of
0.74-3.05 μg mL-1 under the optimum conditions. The obtained accuracy results were between
2.04% and -2.04% while the relative standard deviation of the results was at least 2.78% for intraday
and inter-day studies. The mean recovery for the real applications was 100.63% ± 0.52. The
electrochemical behavior of roflumilast was investigated by cyclic voltammetry. The cyclic voltammogram
of roflumilast exhibited two peaks and the reduction reaction was reversible.hest peak current values with the best peak definition were observed at a frequency of 50 Hz, scan
increment of 5 mV, and pulse amplitude 25 mV. The proposed method was validated by evaluating validation parameters
such as linearity, sensitivity, repeatability, accuracy, precision, selectivity, recovery, robustness, and ruggedness. A good
linear correlation (r=0.9948) was obtained between the electrochemical response of roflumilast and its concentration in the
range of 0.74-3.05 µg mL-1 under the optimum conditions. The obtained accuracy results were between 2.04% and -2.04%
while the relative standard deviation of the results was at least 2.78% for intra-day and inter-day studies. Mean recovery for
the real applications was 100.63% ± 0.52%. The electrochemical behavior of roflumilast was investigated by cyclic
voltammetry. The cyclic voltammogram of roflumilast exhibited two peaks and the reduction reaction was reversible.

Conclusion:
This developed and validated SWSV method was applied successfully for the determination
of roflumilast in tablet dosage form (Daxas®) to assess active roflumilast content. Since high-
-performance liquid chromatography is a dominant technique in industry for quality control of active
pharmaceutical ingredients, the finding in the present study demonstrated that square-wave
stripping voltammetry could be easily utilized in routine applications to determine roflumilast content
in its dosage forms.