Heat-induced formulation inhomogeneity of a three-component suspension.

A suspension formulation containing sarafloxacin HCl, triamcinolone acetonide, and clotrimazole was developed for the treatment of otitis externa in dogs. The potency for the three active ingredients in this suspension was monitored at 25 degrees C and 40 degrees C for up to 3 months. The potencies of triamcinolone and clotrimazole were found unchanged, but the potency of sarafloxacin HCl in the samples stored at 40 degrees C for 1 month varied significantly between samples. However, assay inconsistency for sarafloxacin HCl was not seen in samples stored at 25 degrees C. Under an optical microscope, large crystals were found in the 40 degrees C stability samples but not in the 25 degrees C samples. The large crystals in 40 degrees C samples were identified as sarafloxacin by high-performance liquid chromatography (HPLC). This finding suggests that crystal growth of sarafloxacin took place at 40 degrees C during storage, leading to the formation of larger crystals and the consequent sampling nonuniformity and assay inconsistency. The solid-state properties of these crystals were further evaluated using hot-stage microscopy and Fourier transform infrared (FTIR) analysis. The results indicate that the crystal growth of sarafloxacin was most likely attributed to a change in the hydration form of sarafloxacin.