Stability-indicating RP-LC method for determination of azilsartan medoxomil and chlorthalidone in pharmaceutical dosage forms: application to degradation kinetics

Abstract

A RP-LC method was developed and validated for simultaneous determination of the active components, azilsartan medoxomil (AZL) and chlorthalidone (CLT), in their novel antihypertensive combined recipe. The chromatographic separation was achieved on an Eclipse XDB-C18 (4.6 × 150 mm, 5 μm) column using a mobile phase consisting of methanol/potassium hydrogen phosphate buffer (pH 8, 0.05 M) (40:60, v/v) in isocratic mode. The flow rate was maintained at 0.8 mL min(-1) at ambient temperature. Detection was carried out at 210 nm. The method was validated according to the ICH guidelines. Linearity, accuracy, and precision were satisfactory over the concentration range of 5.0-50.0 and 2.5-25.0 μg mL(-1) for AZL and CLT, respectively (r (2) = 0.9999). LODs for AZL and CLT were 0.90 and 0.32 μg mL(-1), whereas LOQs were 2.72 and 0.98 μg mL(-1), respectively. Both drugs were subjected to forced degradation studies under hydrolysis (neutral, acidic, and alkaline), oxidative, and photolytic extensive stress conditions. The proposed method is stability indicating by the resolution of the investigated drugs from their degradation products. Moreover, the kinetics of the acidic degradation of AZL as well as the kinetics of the alkaline degradation of CLT were investigated. Arrhenius plots were constructed and the apparent first-order rate constants, half-life times, shelf-life times, and the activation energies of the degradation processes were calculated. The method was successfully applied for the determination of the studied drugs simultaneously in their coformulated tablet. The developed method is specific and stability indicating for the quality control and routine analysis of the cited medications in their pharmaceutical preparations.

Understanding unconventional routes to impurities from drugs in hydrolytic conditions

“…88 Many drugs degrade through ethereal cleavage even in mild acidic medium at different temperatures. Ambrisentan, 89 azilsartan, 32 Figure 2). Baertschi and Alsante have very clearly outlined the pathway of degradation of duloxetine due to cleavage of ether linkage, 96 which is supported by Bansal et al to explain the similar degradation behaviour of toremifene.…”

A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet Formulation

“…Different analytical methods for the determination of chlorthalidone impurities have been reported. e reported methods describe degradation studies and the estimation of assay and impurity profiles for both drug substance and drug product, as well as in combination with other drug substances [18][19][20][21][22][23]. e proposed analytical method can be performed effectively on chlorthalidone API and chlorthalidone tablets for known EPspecified, process-related, and degradation impurities.…”

Reliable and Sensitive Stability Indicating – Liquid Chromatographic Method for Determination of Azilsartan Medoxomil and Characterization of Common Hydrolytic Degradation Product

“…AZM was approved by the food and drug administration (FDA) in 2011 and available as 80 mg and 40 mg tablets. The literature review on availability of analytical methods for AZM revealed an UV spectroscopic method, 4 stability indicating high performance thin layer chromatographic (HPTLC) method, 5 few liquid chromatographic (LC) methods [6][7][8][9][10][11] and LC-MS methods 12,13 for the quanti fication of AZM in bulk drug, plasma and in combination with other drugs. There are two reports on the estimation of azilsartan medoximil by HPLC viz.…”