Development and Optimization of Spray-Dried Amorphous Solid Dispersions of Celecoxib for Enhanced Solubility and Dissolution: Physicochemical and Solid-State Characterization

Background: Celecoxib is a poorly water-soluble drug whose limited aqueous solubility and dissolution can restrict its biopharmaceutical performance. Amorphous solid dispersion (ASD) technology offers a promising approach for improving the dissolution behavior of poorly water-soluble drugs by reducing crystallinity and increasing the apparent solubility of the drug. Spray drying is particularly useful for producing polymer-stabilized amorphous drug systems with controlled particle characteristics.

Objective: The present study aimed to develop and optimize a spray-dried amorphous solid dispersion of celecoxib using polyvinylpyrrolidone K30 (PVP K30) and to evaluate its physicochemical characteristics, solid-state properties, equilibrium saturation solubility, in vitro dissolution performance, and stability.

Methods: Celecoxib–PVP K30 dispersions were prepared by spray drying using a hydroalcoholic solvent system. Different drug-to-polymer ratios were evaluated during formulation screening, and the optimized formulation was selected based on production yield, drug content, particle size, solubility, dissolution performance, and solid-state characteristics. The formulations were characterized using particle-size analysis, scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction. Equilibrium saturation solubility and in vitro dissolution were evaluated in comparison with untreated crystalline celecoxib. Stability was assessed over the reported six-month observation period.

Results: The optimized celecoxib–PVP K30 ASD exhibited a production yield of 81.4 ± 3.1% and drug content of 98.2 ± 0.6%. The mean particle size decreased from 35.6 ± 4.2 µm for untreated celecoxib to 8.7 ± 1.3 µm for the optimized ASD. Solid-state characterization demonstrated substantial reduction of the characteristic crystalline features of celecoxib, consistent with formation of a predominantly amorphous drug state within the polymeric matrix. Equilibrium saturation solubility increased from 8.5 ± 0.7 µg/mL for untreated celecoxib to 42.6 ± 2.9 µg/mL for the optimized ASD, representing approximately a five-fold enhancement. Endpoint drug release increased from 34.2 ± 2.5% to 86.7 ± 3.4%. During the reported six-month stability period, drug content decreased modestly from 98.2 ± 0.6% to 97.3 ± 0.9%, with no major reported change in physical appearance.

Conclusion: Spray drying with PVP K30 substantially improved the apparent solubility and in vitro dissolution performance of celecoxib while modifying its crystalline state and particle characteristics. The findings support spray-dried ASD technology as a promising formulation strategy for overcoming the solubility and dissolution limitations of celecoxib.

Keywords: Celecoxib; Amorphous solid dispersion; Spray drying; PVP K30; Solubility enhancement; Dissolution enhancement; Amorphization; Solid-state characterization; Pharmaceutical formulation; Physical stability