Stability-indicating HPTLC method for simultaneous estimation of amlodipine besylate, hydrochlorothiazide and olmesartan medoxomil in combined tablet dosage forms

Abstract

Amlodipine besylate, or 3-ethyl-5-methyl-(4RS)-2-[(2-amino-ethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyri-dine-3,5-dicarboxylate benzene sulphonate is a cardiovascular(antianginal), dihydropyridine calcium channel blocker widelyused in antihypertensive pharmaceutical formulations [1–2].Hydrochlorothiazide, or 6-chloro-3,4-dihydro-2H-1,2,4-benzo-thiadiazine-7-sulfonamide-1,1-dioxide, is a diuretic of the class of benzothiadiazines widely used in antihypertensive phar-maceutical formulations, alone or in combination with otherdrugs, which decreases active sodium reabsorption and reducesperipheral vascular resistance [3]. Olmesartan, the medoxomilsalt of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{[2’-(1H-tetrazol-5-yl)[1,1’-biphenyl]-4-yl]methyl}-1H-imidazole-5-carboxylic acid,is the ester prodrug of a new generation of effective and orallyactive angiotensin-II receptor antagonist. It blocks the vasocon-strictor and aldosterone-secreting effects of angiotensin-II, oneof the most important regulators of blood pressure [4]. Thedetermination of OLME from tablet formulation has been car-ried out by high-performance liquid chromatography (HPLC),high-performance thin-layer chromatography (HPTLC) andspectrophotometricaly, alone or in combination [5–7]. Assay ofAMLO and HCTZ in bulk and in dosage form is official in Indi-an Pharmacopoeia and British Pharmacopoeia in differentdosage forms. Several analytical methods have been reportedfor their determination alone or in combination with other drugsin different dosage forms, biological fluids and urine using dif-ferent analytical techniques [8–13]. Forced degradation studiesare used to facilitate the development of analytical methodolo-gy, to gain better understanding of the stability of the activepharmaceutical ingredient (API), drug product, and to provideinformation about degradation pathways and degradation prod-ucts. The objective of this work was to develop a stability-indi-cating HPTLC method for simultaneous analysis of AMLO,HCTZ, and OLME as no reported method is available for theirsimultaneous estimation in combined formulations. Chemicalstructure of the drugs is shown in Figure 1.HPTLC has advantages over other methods because of rapidity,selectivity, economy, and overall versatility in QC aspects ofdrugs. Literature survey revealed that various HPTLC methodshave been reported for determination of AMLO, HCTZ, andOLME individually and in combination with other drugs [3,5–15]. Currently, the HPLC method is the most frequently usedanalytical method for this kind of determinations. However, nosimultaneous estimation of these drugs was reported so far;hence, it was found worthwhile to develop an HPTLC methodfor the simultaneous determination of AMLO, HCTZ, andOLME in the presence of degradation products and relatedimpurities in pharmaceutical formulations.