Fatima Rasool, Ayesha Naseem, Huma Javaid, Zobia Afzal
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.