Enhancing the solubility of celecoxib via lyophilized solid dispersions using computational and experimental approaches

Celecoxib (CLX), a selective COX-2 inhibitor and BCS Class II drug, is widely used for osteoarthritis and rheumatoid arthritis but having poor aqueous solubility (4.2 µg/mL) and limited dissolution, restricting its oral bioavailability. This study aimed to enhance CLX solubility and dissolution using integrated computational and experimental approaches. Simulated crystal morphology revealed a dominant (1 0 0) face, indicating a plate-like crystal habit that may hinder dissolution. Molecular dynamics simulations further identified hydroxypropyl β-cyclodextrin (HP-βCD) as the most compatible polymer, exhibiting the lowest interaction parameter (χ = - 5.86) and mixing energy (Emix = - 3.47 kcal/mol). Physical mixtures (PM1-PM4) were prepared at a 1:1 drug-to-polymer ratio and evaluated for solubility and recrystallization inhibition. PM1 (CLX-HP-βCD) showed the highest solubility (64.18 µg/mL) and longest induction time (140 s), indicating improved supersaturation stability. Lyophilized solid dispersions (SD1-SD4) were then developed and characterized using solubility studies, FTIR spectroscopy, microscopy, and in vitro dissolution testing. SD1 exhibited the greatest solubility enhancement (645 µg/mL), over 150-fold higher than pure CLX. FTIR and microscopy confirmed molecular dispersion and amorphization within the hydrophilic matrix. In vitro dissolution testing showed SD1 achieved 78.5% drug release in 3 h, with release kinetics best described by first-order (R² = 0.9661) and Korsmeyer-Peppas (n = 0.879) models. These dispersions were compressed into tablets (T1-T4) and assessed for mechanical properties and drug release. T1 demonstrated the highest release (99.88% in 3 h), with release kinetics fitting first-order (R² = 0.8996) and Hixson-Crowell (R² = 0.9351) models. Overall, HP-βCD-based lyophilized solid dispersion emerged as a highly effective system for enhancing the solubility, dissolution, and ultimately the oral bioavailability of celecoxib.