Improvement of Tadalafil Solubility through Microwave-Assisted Cyclodextrin Complexation

Research Article

Abstract

Tadalafil, a phosphodiesterase-5 inhibitor used in erectile dysfunction treatment, exhibits poor aqueous solubility leading to limited bioavailability. The aim of this study is to improve tadalafil solubility through inclusion complexation with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) using microwave irradiation technique. Inclusion complexes were prepared in 1:1 and 1:2 molar ratios through physical mixing, kneading, and microwave irradiation methods. Phase solubility analysis revealed AL-type diagrams with stability constants of 410.25 M-1 and 727.73 M-1 for β-CD and HP-β-CD complexes, respectively. The prepared complexes were characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). Microwave-assisted complexation showed better results with aqueous solubility enhancement up to 585 μg/mL compared to pure drug (157 μg/mL). In vitro dissolution studies in different media showed significant improvement in drug release rate, with HP-β-CD complexes exhibiting better performance than β-CD complexes. The optimized formulation (F10) showed 99.80% drug release within 120 minutes compared to 35% for pure drug. Stability studies conducted at room temperature and 40°C for six weeks confirmed the physical and chemical stability of the complexes. The results show that microwave-assisted cyclodextrin complexation as an efficient technique for improving tadalafil solubility and dissolution