Physicochemical stability of an extemporaneously prepared crushed tadalafil tablet formulation for pediatric pulmonary arterial hypertension

Abstract Background and purpose Pediatric formulations of cardiovascular drugs are limited, and tablets are often crushed to create individualized doses. In clinical practice, pre-processed crushed formulations may be stored for later use; however, information on their long-term physicochemical stability remains limited. This study evaluated the storage stability of a crushed formulation of tadalafil, a drug used for pediatric pulmonary arterial hypertension (PAH). Methods Tadalafil (TAD) 20 mg tablets were crushed, sieved, and mixed with lactose monohydrate to prepare a crushed tadalafil formulation (cTAD, 40 mg/g). TAD crystals were used as controls. Samples were stored for 90 d at 25 °C with 57.6 ± 0.4% relative humidity under diffused light (approximately 600 lx) or in light-shielded conditions. The thermal and solid-state properties were characterized using DSC, TGA, and PXRD. The moisture content was determined using Karl Fischer titration. Color changes were measured using a colorimeter, and intermolecular interactions were analyzed using Fourier-transform infrared (FTIR) spectroscopy. Results After 90 days, slight yellowing appeared in crystalline TAD stored under diffused light, whereas no color changes occurred in samples stored under light-shielded conditions or in cTAD. The moisture content remained unchanged in both cTAD and crystalline TAD. DSC and PXRD analyses showed no appreciable changes in the thermal behavior or crystalline state of TAD during storage. The FTIR spectra showed no shifts in the characteristic TAD peaks, indicating that neither crushing nor storage induced any intermolecular interactions. Conclusion These results show that the crushed tadalafil formulation prepared from tablets and mixed with lactose remained physicochemically stable for at least 90 days under tested storage conditions.