Enhanced oral bioavailability of etodolac by self-emulsifying systems: in-vitro and in-vivo evaluation.
OBJECTIVE
The objective of this study was to prepare a self-emulsifying drug delivery system (SEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, etodolac. The SEDDS formulations were optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation, and by determination of the particle size of the resulting emulsion.


METHODS
An optimized formulation of SEDDS (composed of 20% etodolac, 30% oil Labrafac WL1349, 10% Lauroglycol 90 and 40% Labrasol) was selected for bioavailability assessment in rabbits. The anti-inflammatory effect was also determined in rats, and compared with powder drug and etodolac suspension in water (50 mg/kg).


RESULTS
The peak plasma concentration of 16.4 +/- 1.1 microg/ml appeared after 1.3 +/- 0.2 h, whereas with powder drug and etodolac suspension the values were 7.5 +/- 0.5 and 10.6 +/- 0.7 microg/ml at 4.2 +/- 0.4 and 2.4 +/- 0.2 h, respectively. The AUC(0-8) of the etodolac SEDDS formulation was 2.3 times that of the pure drug and 1.4 times that of the suspension form. SEDDS formulation exhibits a 21% increase in paw thickness compared with a 39% increase on oral administration of etodolac suspension after 4 h at the same dose of the drug (20 mg/kg).


CONCLUSIONS
The result indicates the utility of SEDDS for the oral delivery of etodolac and potentially other lipophilic drugs.
Barakat
Nahla S
NS
Department of Pharmaceutics, King Saud University, Riyadh, Kingdom of Saudi Arabia. nsybarakat@yahoo.com
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D004487:Edema / Q000188:drug therapy; D004655:Emulsions; D017308:Etodolac / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D010316:Particle Size; D011208:Powders; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013535:Suspensions
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D011208:Powders; D013535:Suspensions; D017308:Etodolac