Abstract
Experimental design method was used for HPLC determination of irbesartan and hydrochlorothiazide in combined dosage forms. The traditional approach for optimization of experiments is time-consuming, involves a large number of runs and does not allow establishing the multiple interacting parameters. The main advantages of the experimental design method include the simultaneous screening of a larger number of factors affecting response and the estimation of possible interactions. On the basis of preliminary experiments, three factors-independent variables were selected as inputs (methanol content, pH of the mobile phase and temperature) and as dependent variables, five responses (resolution, symmetry of irbesartan peak, symmetry of hydrochlorothiazide peak, retention factor of irbesartan and retention factor of hydrochlorothiazide) were chosen. A full 23 factorial design, where factors were examined at two different levels (“low” and “high”) was used to determine which factors had an effect on the studied response. Afterwards, experimental design was used to optimize these influent parameters in the previously selected experimental domain. The novelty of our method lies in the optimization step accomplished by Derringer′s desirability function. After optimizing the experimental conditions a separation was conducted on a Supelcosil C18 (150 mm × 4.6 mm, 5 μm particle size) column with a mobile phase consisting of methanol-tetrahydrofuran-acetate buffer 47:10:43 v/v/v, pH 6.5 and a column temperature of 25 °C. The developed method was successfully applied to the simultaneous separation of these drug-active compounds in their commercial pharmaceutical dosage forms.
Highlights
Irbesartan [IRB, 2-butyl-3-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]- methyl1-3-diazaspiro-[4,4]non-1-en-4-one, Figure 1(a)] is an angiotensin II blocker
A literature survey revealed that there are a number of HPTLC [2,3,4,5], spectrophotometric [6], and spectrofluorometric [7,8], voltammetric [9], capillary zone electrophoretic [10], HPLC [11,12] and LC-MS [13,14] methods for determination of the individual drugs (IRB and HCT) or IRB/HCT in combination with other drugs
The objective of the first step in the investigation was to perform a screening of the factors that could potentially influence chromatographic retention, the independent variables were defined during the preliminary study
Summary
Irbesartan [IRB, 2-butyl-3-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]- methyl1-3-diazaspiro-[4,4]non-1-en-4-one, Figure 1(a)] is an angiotensin II blocker. Angiotensin II receptor antagonists represent a relatively new pharmacological class [1] which acts mainly by selective blockade of AT1 receptors and reduces the effects of angiotensin II. They may be used alone or in combination with other antihypertensive or diuretic agents. Hydrochlorothiazide [HCT, 6-chloro-3,4-dihydro-2H-1,2,4benzothiadiazine-7-sulphonamide-1,1-dioxide, Figure 1(b)] is a diuretic acting on distal convoluted tubule. Because of their synergistic anti-hypertensive action, irbesartan and hydrochlorothiazide are available on the market as a combined dosage form. A number of methods for the determination of irbesartan and hydrochlorothiazide have been reported, there are a limited number of systematic studies for the optimization of separation parameters
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