Green HPLC strategy for quantification of carvedilol and hydrochlorothiazide in cardiac medications with in-vitro dissolution kinetics and impurity profiling

Abstract

The introduction of new pharmaceutical formulations necessitates the development of a trustworthy analytical approach capable of quantifying active ingredients in various quality control procedures. A fixed dosage combination of carvedilol (CAR) and hydrochlorothiazide (HCT) has been introduced to treat hypertension with potential recommendation for diabetic patients. Ahigh-performance liquid chromatographic methodology, designed to be ecologically sustainable while maintaining high precision and accuracy, was established. This approach can simultaneously determine both drugs in their pure forms, and dosage form, along with separation and quantification of potential hydrochlorothiazide related impurities; salamide (DSA) and chlorothiazide (CT). Successful separation was performed using YMC^®Triart-Phenyl analytical column via gradient elution employing 0.1% formic acid alongside ethanol at a flow rate of 1.0 mL/min, coupled with photodiode array detection at 254.0 nm. Linearity was obtained across the concentration ranges of 0.1 to 100.0 µg/mL for HCT and CAR and 0.05 to 10.0 µg/mL for DSA and CT. The suggested chromatographic methodology can estimate HCT and CAR in different real samples. Additionally, it facilitates the concurrent monitoring of their dissolution profiles. The studied method's performance was validated in adherence to the guidelines set by the International Conference on Harmonization (ICH). Moreover, its ecological sustainability as well as applicability profile was further affirmed via diverse greenness, blueness, and whiteness assessment tools and compared among official and other reported procedures. In addition, the recently introduced Carbon Footprint Reduction Index tool has been implemented to assess the suggested method with an emphasis on estimating CO₂ emissions. In general, the suggested methodology proves to be effective for conducting the quality control examination of raw forms and commercially accessible preparations.

Keywords: Blueness; Carbon footprint; Cardiac pharmaceutical formulations; Carvedilol; Click analytical chemistry; Dissolution testing; Greenness profile; Hydrochlorothiazide; Impurity profiling; Whiteness assessment..

Fig. 1

Chemical structures of (a) Hydrochlorothiazide (HCT), (b) Carvedilol (CAR), (c) Salamide (DSA) and (d) Chlorothiazide (CT)

Fig. 2

HPLC-DAD chromatogram of a mixture of DSA (5.0 µg/mL), HCT (50.0 µg/mL), CT (5.0 µg/mL) and CAR (50.0 µg/mL) using gradient elution system of 0.1% formic acid and ethanol at 254.0 nm

Fig. 3

Greenness, blueness and whiteness assessment of (a): the proposed HPLC-DAD method, (b): Reported HPLC method [35] and (c): Reported HPLC method [36], via AGREE, Mo GAPI, AGSA, BAGI, CACI and RGB 12 assessment tools

Fig. 4

The results of (a): the proposed HPLC-DAD method, (b): HCT official HPLC method [28], (c): CAR official titrimetric method [28], (d): Reported HPLC method [35] and (e): Reported HPLC method [36] presenting the application of the Carbon Footprint Reduction Index (CaFRI)

Fig. 5

Dissolution profiles of HCT and CAR from Co-Dilatrol^® Tablets in 0.1 N HCl as a dissolution medium