Nicotinamide Hydrotropy of the NSAID Piroxicam: Overcoming Dissolution‐Rate Limitation

ABSTRACT

Piroxicam is an NSAID and Biopharmaceutics Classification System (BCS) Class II drug with high membrane permeability but low aqueous solubility, leading to dissolution‐rate‐limited oral absorption. This study evaluates nicotinamide as a safe hydrotropic agent to enhance piroxicam solubility, clarify thermodynamic behavior, enable simple predictive modeling, and reduce biopharmaceutical risk. Equilibrium solubility was determined by the shake‐flask method in water and 10%–30% w/v nicotinamide at 25°C ± 1°C, using a validated UV–Vis assay at 355.38 nm, and analyzed via Gibbs free‐energy change ( ΔG °), hydrotropic efficiency index, solubilizing power ( p ), and dose number ( Do ); Fourier transform infrared (FTIR) and one‐way analysis of variance (ANOVA)/Tukey's test assessed solid‐state interactions and statistical significance. Nicotinamide increased piroxicam solubility from 2.058 to 16.742 µg/mL at 30% w/v, with Δ G ° decreasing from −2.75 to −5.20 kJ/mol and Do from 38.8 to 4.8, whereas FTIR confirmed reversible physical aggregation without covalent modification.