Antipyretic, analgesic and anti-inflammatory activities of ketoprofen beta-cyclodextrin inclusion complexes in animals.
Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) orally effective in treating fever, pain, and inflammation but gastrointestinal side effects were observed. Preparation of ketoprofen beta-cyclodextrin inclusion complexes was to increase the solubility and reduce the irritation. The complexes were prepared and preliminarily confirmed using X-ray diffraction and dissolution test. Antipyretic, analgesic and anti-inflammatory models were induced by 10% yeast using rabbits, 0.8% acetic acid using mice and 1% carrageenin using rats, respectively. Results showed that the dissolution rate of ketoprofen was significantly improved by complexation. X-Ray diffraction pattern of the complexes exhibited a diffuse pattern that differed from that of physical mixture of ketoprofen and beta-cyclodextrin. Ketoprofen markedly inhibited the fever reactions at a single dose of 2 mg/kg as follows: 64.53% (inhibition rate %) at 1 h for ketoprofen, 73.04% at 1 h for ketoprofen beta-cyclodextrin inclusion complexes, respectively. Alleviating pain reaction rates following a single dose of 8 mg/kg at 20 min were 39.25% for the inclusion complexes and 26.72% for ketoprofen, respectively. Inhibition rates to rat edema following a single dose of 5 mg/kg at 1 h were 39.47% for the inclusion complexes and 23.86% for ketoprofen. Results for antipyretic, analgesic and anti-inflammatory activities showed that the rapid and stronger effects were found in the treatment group of ketoprofen beta-cyclodextrin inclusion complexes in comparison with those of free ketoprofen.
School of Pharmaceutical Sciences, Peking University, Beijing, PR China.
Wan-Liang
WL
Lu
Qiang
Q
Zhang
Li
L
Zheng
Hua
H
Wang
Rong-Yu
RY
Li
Li-Feng
LF
Zhang
Wen-Bin
WB
Shen
Xi-De
XD
Tu
D000277:Adjuvants, Pharmaceutic / Q000737:chemistry; D018712:Analgesics, Non-Narcotic / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000627:therapeutic use*; D004337:Drug Carriers; D005334:Fever / Q000188:drug therapy; D007660:Ketoprofen / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D011817:Rabbits; D051381:Rats; D012995:Solubility; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry
D000277:Adjuvants, Pharmaceutic; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D007660:Ketoprofen; C031215:betadex