Fluorescence-based techniques to assess the miscibility and physical stability of a drug–lipid complex

The objective of this study was to evaluate the feasibility of using fluorescence-based techniques to assess the miscibility and physical stability of a drug-lipid complex pharmaceutical dosage form under a solvent-free condition. An indomethacin-phospholipid complex (IDM-DPC) was used as model complex for this study. The miscibility of indomethacin within the phospholipid was assessed by fluorescence spectroscopy, fluorescence microscopy, and infrared spectroscopy. The miscibility limit of the complex system was determined by fluorescence to be 20%-30% drug loading content, showing good correlation with infrared spectroscopy. The physical stability of the IDM-DPC stored at 40 degrees C was evaluated by fluorescence microscopy. Indomethacin formulated in the lipid complex with an indomethacin loading not more than 30% remained in an amorphous state within a period of 21 days, whereas the samples with a drug loading over 30% started to crystallize earlier with increasing drug content. IDM-DPC having higher miscibilities were found to be more resistant to recrystallization under heating, thus having better physical stability. Fluorescence-based techniques showed convenience and promise in characterizing drug-lipid miscibility and predicting storage stability under a solvent-free condition.