Photochemical Mechanism of Riboflavin-Induced Degradation of Famotidine and a Suggested Pharmaceutical Strategy for Improving Photostability

The present study aimed to clarify the mechanism of photodegradation of famotidine with riboflavin (FMT/RF), and to develop a photochemically stabilized formulation of FMT/RF. Photochemical properties of RF were characterized by UV-VIS spectral analysis, reactive oxygen species (ROS) assay, and photostability testing. Pharmacokinetic study was conducted in rats after intravenous administration of FMT (1 mg/kg) formulation containing RF (0.01 mg/kg). The UV-VIS spectral pattern of RF partly overlapped with the sunlight spectrum, and ROS generation from photoirradiated RF was remarkable; thus, RF had high photoreactive potential. In the photostability testing, after irradiation (250 W/m2), degradation rate for FMT in FMT/RF was ca. 11-fold higher than that in FMT alone. The addition of radical scavengers to FMT/RF led to attenuated photodegradation of FMT/RF; in particular, the addition of L-ascorbic acid (vitamin C; VC) to FMT/RF showed ca. 86% inhibition of the photodegradation of FMT/RF. The pharmacokinetic study on FMT indicated that the addition of VC (1 mg/kg) to FMT/RF had no significant impact on the pharmacokinetic behavior of FMT. These findings suggest that ROS-mediated photochemical reaction would be involved in the photodegradation pathway of FMT/RF, and the complementary use of VC might be an attractive approach to improve the photostability of FMT/RF.