Experimental Design Utilizing Mixed Micellar Monolithic Liquid Chromatography and Ethanol for Rapid Simultaneous Determination of Four Antipsoriatics: A Blue–Green Approach

Abstract

Utilizing chromatography with green chemistry principles helps minimize harm to people and the environment. Since its recent release, the new combination of tazarotene (TAZ) and halobetasol propionate has gained popularity. Crisaborole (CRB) has recently also shown potential for treating psoriasis and can be coformulated with drugs like TAZ and anthralin. Currently, no method has been reported for the simultaneous determination of these drugs. In addition, an environmentally friendly high-performance liquid chromatography (HPLC) method for any of them has yet to be developed. The challenge arises mainly due to TAZ's strong retention on reversed phase (RP) columns, which prompts the use of high amounts of organic solvent. To develop a green isocratic HPLC-photodiode array (PDA) method, the central composite and Box–Behnken quality-by-design approaches were employed to study the impact of various factors and their interactions on multiple responses. Since TAZ could not be eluted using micellar phases alone, ethanol was selected as an organic modifier due to its accessibility, environmental friendliness, and limited studies on its use in micellar HPLC. The separation was achieved using a mobile phase of 0.01 M Brij-35, 0.143 M sodium dodecyl sulfate (SDS), and 0.015 M ammonium acetate (pH 4.95): ethanol (83:17, v/v) at a 1.5 mL/min flow rate. The method utilized the monolithic Chromolith performance RP-C<inf>18</inf> column (100 mm × 4.6 mm × 5µm) at 40°C with a run time less than 10 min. The linear range established was (3.00–150.00 µg/mL) with limits of detection (0.59–0.78 µg/mL) and quantification (1.79–2.37 µg/mL). The proposed method was applied to different dosage forms (ointment, cream, lotion) after optimizing a microextraction procedure with recoveries > 98.5%. It scored 0.7 on analytical greenness (AGREE), 76 on modified Green Analytical Procedure Index (MoGAPI), and 82.5 on Blue Applicability Grade Index (BAGI). Comparing these scores with reported methods underlines the value of incorporating a scoring system into GAPI and evaluating methods from the blue and green perspectives.