Hansen Solubility Parameters and QbD-Oriented HPLC Method Development and Validation for Dermatokinetic Study of a Miconazole-Loaded Cationic Nanoemulsion in Rat Model

Abstract

Miconazole (MCZ) is a potential antifungal drug to treat skin infections caused by Candida , Tinea pedis (athlete’s foot fungal infection), Tinea cruris (jock itching in the groin and buttocks), and Tinea corporis (red scaly rash on the skin). The current study focused on Hansen parameter-based solvent selection (HSPiP software) and method development optimization using an experimental design tool for sensitive, accurate, reproducible, economic, rapid, robust, and precise methodology to quantify MCZ in rat plasma. Moreover, a Taguchi design was used for screening two independent factors (flow rate and ACN content). Quality by design (QbD) was employed to optimize and identify the right ratio of mobile phase composition and its impact on the peak and retention time. The elution of MCZ was achieved using methanol and acetonitrile (15:85 v/v ratio) at a retention time of 6 min and optimal flow rate (1 mL/min). Finally, the method was validated based on accuracy, precision, linearity, selectiveness, and high recovery at varied concentrations as per the International Council for Harmonization (ICH) guidelines. The method was linear ( r 2 = 0.999) over the explored concentration range (250–2000 ng/mL) at 270 nm detection wavelength. The optimized method was used to quantify in vivo pharmacokinetic (PK) study after transdermal application of MCZ-loaded formulations (MCNE11, MNE11, MCZ-Sol, and MCZ-MKT). HSP-oriented solvent selection and quality by design-based optimized process variables and composition in the optimized analytical methodology were quite convincing and have been a cutting-edge MCZ analysis method so far. The validated method was robust, economic, and rapid with high specificity and selectivity.

HSPiP, Computational Modeling, and QbD-Assisted Optimized Method Validation of 5-Fluorouracil for Transdermal Products

“…This reduced the long-term developmental period and excess waste of organic solvents generally consumed in the hit-and-trial method. An analytical method fundamentally operates on relative polarity-based interaction existing between the solute and mobile phase . QbD-based optimization helped to identify critical factors having an impact on the analytical method of the investigated drug from the biological sample.…”

“…QbD-based optimization helped to identify critical factors having an impact on the analytical method of the investigated drug from the biological sample. Furthermore, both programs were implemented to get low optimal rum time to save organic solvents and analytical time with high reproducibility, accuracy, sensitivity, and precision following the method reported before …”