Reduction of gastric ulcerogenicity during multiple administration of diclofenac sodium by a novel solid-in-oil suspension.
This article reports a significant reduction of gastric ulcerogenicity by complex formation of a nonsteroidal anti-inflammatory drug with surfactants. Diclofenac sodium (DFNa) was suspended in medium chain triglyceride (MCT) by forming a complex with an edible lipophilic surfactant. Two types of suspensions, prepared through a membrane emulsification with different pore sizes, were evaluated according to the degree of gastric damage following multiple oral administration in rats. It was shown that gastric ulcerogenicity of DFNa was reduced by the surfactant-drug complexes, at doses up to 12 mg/kg, whereas severe gastric damage was observed upon oral administration of the aqueous solution at doses of 6 mg/kg. Comparable blood levels of DFNa were observed after administration of solution and suspension formulations.
Piao
Hongyu
H
Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, Fukuoka, Japan.
Hirata
Akihiko
A
Yokoyama
Hideakira
H
Fujii
Takeru
T
Shimizu
Ichiro
I
Ito
Susumu
S
Kamiya
Noriho
N
Goto
Masahiro
M
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use*; D004008:Diclofenac / Q000008:administration & dosage* / Q000627:therapeutic use*; D009821:Oils / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000473:pathology; D013276:Stomach Ulcer / Q000188:drug therapy*; D013535:Suspensions
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009821:Oils; D013535:Suspensions; D004008:Diclofenac