Comparison of PEG 4000 and 6000 in Solid Dispersion of Tadalafil Prepared by Melting Method

Tadalafil is a BCS Class II drug with very low aqueous solubility, limiting its oral bioavailability. Solid dispersion technology using polyethylene glycol (PEG) is an effective strategy to enhance solubility. This study aimed to compare the effectiveness of PEG 4000 and PEG 6000 as carriers in amorphous solid dispersions of tadalafil prepared by the melting method. Solid dispersions were prepared at weight ratios (tadalafil:polymer) of 1:1, 1:2, 1:3, and 1:4 for both PEG 4000 and PEG 6000 using the fusion technique (70 °C). The formulations were characterized by Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared (FTIR) spectroscopy. Solubility studies were conducted in distilled water and phosphate buffer (pH 6.8) and analyzed via a validated HPLC method. Solid dispersions with PEG 6000 at a 1:3 ratio (F7) exhibited the highest solubility enhancement, reaching 16.08 ± 0.6 µg/mL in water. For PEG 4000, the 1:2 ratio (F2) was optimal (8.20 ± 1.3 µg/mL). PXRD and DSC analyses confirmed the transformation of crystalline tadalafil into an amorphous state within the polymer matrix. FTIR spectra indicated shifts in N-H and C=O bands, suggesting hydrogen bond formation. In conclusion, PEG 6000 produced a superior solid dispersion for tadalafil compared to PEG 4000. The primary mechanism is the formation of an amorphous system stabilized by hydrogen bonding. This study provides a formulation basis for improving the oral delivery of tadalafil.