Influence of Api Crystal Habit on the in Vitro–in Vivo Performance and Bioequivalence of Celecoxib Capsules

Celecoxib is a Biopharmaceutics Classification System (BCS) Class II drug whose oral absorption is predominantly governed by dissolution and solubilization processes. Consequently, active pharmaceutical ingredient (API) physical attributes may significantly influence pharmaceutical performance and bioavailability. The present investigation evaluated the impact of API crystal habit on the manufacturability, dissolution behavior, stability, and bioequivalence performance of celecoxib capsules. Comparative characterization was performed using microscopic examination, scanning electron microscopy (SEM), particle size distribution analysis, powder flow assessment, dissolution testing in OGD-recommended and multimedia conditions, biorelevant dissolution studies in FaSSIF and FeSSIF media, accelerated stability studies, and fasting-state bioequivalence evaluation. Microscopic and SEM observations revealed distinct differences in crystal habit between the reference listed drug (RLD) API and the test formulation API. The RLD predominantly exhibited rounded or pin-milled particles, whereas the test API consisted primarily of plate-shaped crystals with a greater tendency toward aggregation. Despite these morphological differences, particle size distributions were broadly comparable. The test formulation demonstrated dissolution similarity to the RLD across all evaluated media, including OGD-recommended dissolution conditions, multimedia dissolution testing, and biorelevant FaSSIF and FeSSIF media. Accelerated stability studies conducted at 40°C/75% RH for six months confirmed acceptable assay, dissolution, moisture content, and impurity profiles throughout storage. However, fasting-state bioequivalence evaluation demonstrated supra-bioavailability of the test formulation relative to the RLD. The findings indicate that crystal habit-related API attributes may influence in vivo performance despite comparable dissolution behavior and stability characteristics. The study highlights the limitations of conventional dissolution methodologies in predicting bioequivalence outcomes for celecoxib and emphasizes the importance of comprehensive API morphology assessment during supplier qualification, formulation development, and bioequivalence risk evaluation.