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/m(2)), 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.
Department of Pharmacy, University of Yamanashi Hospital, Chuo-city, Yamanashi 409-3898, Japan; Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: auchida@yamanashi.ac.jp.
Atsushi
A
Uchida
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan.
Satomi
S
Onoue
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan.
Hiroto
H
Ohtake
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan.
Yoshiki
Y
Seto
Department of Pharmacy, University of Yamanashi Hospital, Chuo-city, Yamanashi 409-3898, Japan.
Tsuyoshi
T
Teramatsu
Department of Pharmacy, University of Yamanashi Hospital, Chuo-city, Yamanashi 409-3898, Japan.
Tomoko
T
Terajima
Department of Pharmacy, University of Yamanashi Hospital, Chuo-city, Yamanashi 409-3898, Japan.
Toshio
T
Oguchi
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004355:Drug Stability; D015738:Famotidine / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D055668:Photochemical Processes; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012256:Riboflavin / Q000737:chemistry / Q000378:metabolism*
D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D015738:Famotidine; D012256:Riboflavin
UV-VIS spectroscopy; ascorbic acid; famotidine; formulation; injectables; pharmacokinetics; photodegradation; reactive oxygen species; riboflavin; stabilization