Oral bioavailability of ketoprofen in suspension and solution formulations in rats: the influence of poloxamer 188.
OBJECTIVE
The aim of the current study was to investigate the effect of poloxamer 188 (P-188) on the bioavailability of the BCS class 2 drug ketoprofen in vivo.


METHODS
Aqueous suspension and solution formulations of ketoprofen with and without P-188 were orally administered to fasted male Wistar rats. The intrinsic dissolution rate and solubility of ketoprofen in simulated intestinal fluid, in both the presence and absence of P-188, was measured.


RESULTS
The AUC and C(max) were found to be significantly enhanced when ketoprofen was administered as suspension and P-188 was present in the formulation (Susp P-188) as compared to the surfactant-free formulation (∼4-fold higher AUC, 7-fold higher C(max) ). While drug solubility appeared to be almost unaffected by P-188, a significantly faster dissolution was observed. In addition, the influence of P-188 on the drug absorption process was investigated by comparison of solution formulations with and without P-188.


CONCLUSIONS
The in-vivo performance of these solutions, a pure buffer solution and a P-188-containing buffer solution showed no significant difference, suggesting that the increase in bioavailability for Susp P-188 was primarily a consequence of the dissolution rate-enhancing effect.
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.
Sarah Maud
SM
Fischer
Johannes
J
Parmentier
Stephen Timothy
ST
Buckley
Isolde
I
Reimold
Martin
M
Brandl
Gert
G
Fricker
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018938:Caco-2 Cells; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D007419:Intestinal Secretions / Q000378:metabolism; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D020442:Poloxamer / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D020442:Poloxamer; D007660:Ketoprofen